Journal of Clinical Outcomes Management

LOS ANGELES – Intracerebral hemorrhage (ICH) appears to be not nearly as uniformly devastating to patients as its reputation suggests. Recent study results documented unexpectedly decent recovery prospects for hemorrhagic stroke patients assessed after 1 year who were earlier considered moderately severe or severely disabled based on their 30-day status. And these data provide further support for the growing impression among clinicians that a way forward for improving outcomes even more is with a “gentle” surgical intervention designed to substantially reduce ICH clot volume.

“Historically, there’s been a lot of nihilism around these patients. Intracerebral hemorrhage has always been the deadliest stroke type, but one of the great advances of the past 10-20 years is that ICH survival has improved. Patients do better than we used to think,” said Kevin N. Sheth, MD, professor of neurology and neurosurgery, and chief of neurocritical care and emergency neurology at Yale University in New Haven, Conn. “Even though ICH remains a difficult disease, this change has two big implications,” Dr. Sheth said in an interview during the International Stroke Conference sponsored by the American Heart Association. First, increased ICH survival offers an opportunity to expand the reach of recent management advances through quality improvement programs that emphasize new strategies that work better and incentivize delivery of these successful strategies to more patients.

The second implication is simply a growing number of ICH survivors, expanding the population of patients who stand to gain from these new management strategies. Dr. Sheth is working with the Get With the Guidelines – Stroke program, a quality-improvement program begun in 2003 and until now aimed at patients with acute ischemic stroke, to develop a 15-site pilot program planned to start in 2020 that will begin implementing and studying a Get With the Guidelines – Stroke quality-improvement program focused on patients with an ICH. The current conception of a quality measurement and improvement program like Get with the Guidelines – Stroke for patients with ICH stems from an important, earlier milestone in the emergence of effective ICH treatments, the 2018 publication of performance measures for ICH care that identified nine key management steps for assessing quality of care and documented the evidence behind them.

“Evidence for optimal treatment of ICH has lagged behind that for ischemic stroke, and consequently, metrics specific to ICH care have not been widely promulgated,” said the authors of the 2018 ICH performance measures, a panel that included Dr. Sheth. “However, numerous more recent studies and clinical trials of various medical and surgical interventions for ICH have been published and form the basis of evidence-based guidelines for the management of ICH,” they explained.
 

MISTIE III showcases better ICH outcomes

Perhaps the most dramatic recent evidence of brighter prospects for ICH patients came in data collected during the MISTIE III (Minimally Invasive Surgery with Thrombolysis in Intracerebral Hemorrhage Evacuation III) trial, which randomized 506 ICH patients with a hematoma of at least 30 mL to standard care or to a “gentle” clot-reduction protocol using a small-bore catheter placed with stereotactic guidance to both evacuate clot and introduce a serial infusion of alteplase into the clot to try to shrink its volume to less than 15 mL. The study’s results showed a neutral effect for the primary outcome, the incidence of recovery to a modified Rankin Scale (mRS) score of 0-3 at 1 year after entry, which occurred in 45% of the surgically treated patients and 41% of the controls in a modified intention-to-treat analysis that included 499 of the randomized patients, a difference that did not reach statistical significance.

However, when the analysis focused on the 146 of 247 patients (59%) randomized to surgical plus lytic intervention who underwent the procedure and actually had their clot volume reduced to 15 mL or less per protocol, the adjusted incidence of the primary endpoint was double that of patients who underwent the procedure but failed to have their residual clot reduced to this size. A similar doubling of good outcomes occurred when MISTIE patients had their residual clot cut to 20 mL or less, compared with those who didn’t reach this, with the differences in both analyses statistically significant. The actual rates showed patients with clot cut to 15 mL or less having a 53% rate of a mRS score of 0-3 after 1 year, compared with 33% of patients who received the intervention but had their residual clot remain above 15 mL.

The MISTIE III investigators looked at their data to try to get better insight into the outcome of all “poor prognosis” patients in the study regardless of their treatment arm assignment, and how patients and their family members made decisions for withdrawal of life-sustaining therapy. In MISTIE III, 61 patients had withdrawal of life-sustaining treatment (WoLST), with more than 40% of the WoLST occurring with patients randomized to the intervention arm including 10 patients treated to a residual clot volume of 15 mL or less. To quantify the disease severity in these 61 patients, the researchers applied a six-item formula at 30 days after the stroke, a metric their 2019 report described in detail. They then used these severity scores to identify 104 matched patients who were alive at 30 days and remained on life-sustaining treatment to see their 1-year outcomes. At 30 days, the 104 matched patients included 82 (79%) with a mRS score of 5 (severe disability) and 22 patients (21%) with a mRS score of 4 (moderately severe disability). Overall, an mRS score of 4 or 5 was quite prevalent 30 days after the stroke, with 87% of the patients treated with the MISTIE intervention and 90% of the control patients having this degree of disability at 30 days.

When the MISTIE III investigators followed these patients for a year, they made an unexpected finding: A substantial incidence of patients whose condition had improved since day 30. One year out, 40 (39%) of these 104 patients had improved to a mRS score of 1-3, including 10 (10%) with a mRS score of 1 or 2. Another indicator of the reasonable outcome many of these patients achieved was that after 1 year 69% were living at home.

“Our data show that many ICH subjects with clinical factors that suggest ‘poor prognosis,’ when given time, can achieve a favorable outcome and return home,” concluded Noeleen Ostapkovich, who presented these results at the Stroke Conference.

She cited these findings as potentially helpful for refining the information given to patients and families on the prognosis for ICH patients at about 30 days after their event, the usual time for assessment. “These patients looked like they weren’t going to do well after 30 days, but by 365 days they had improved physically and in their ability to care for themselves at home,” noted Ms. Ostapkovich, a researcher in the Brain Injury Outcomes Clinical Trial Coordinating Center of Johns Hopkins University in Baltimore.
 

A message for acute-care clinicians

She and her colleagues highlighted the implications these new findings have for clinical decision making in the first weeks after an ICH.

“Acute-care physicians see these patients at day 30, not at day 365, so it’s important that they have a clear picture of what these patients could look like a year later. It’s an important message,” Ms. Ostapkovich said in an interview.

In fact, a colleague of hers at Johns Hopkins ran an analysis that looked at factors that contributed to families opting for WoLST for 61 of the MISTIE III patients, and found that 38 family groups (62%) cited the anticipated outcome of the patient in a dependent state as their primary reason for opting for WoLST, Lourdes J. Carhuapoma reported in a separate talk at the conference.

Mitchel L. Zoler/MDedge News

“The main message is that many patients with significant ICH did well and recovered despite having very poor prognostic factors at 30 days, but it took more time. A concern is that the [prognostic] information families receive may be wrong. There is a disconnect,” between what families get told to expect and what actually happens, said Ms. Carhuapoma, an acute care nurse practitioner at Johns Hopkins.

“When physicians, nurses, and family members get together” to discuss ICH patients like these after 30 days, “they see the glass as empty. But the real message is that the glass is half full,” summed up Daniel F. Hanley, MD, lead investigator of MISTIE III and professor of neurology at Johns Hopkins. “These data show a large amount of improvement between 30 and 180 days.” The 104 patients with exclusively mRS scores of 4 or 5 at day 30 had a 30% incidence of improvement to an mRS score of 2 or 3 after 180 days, on their way to a 39% rate of mRS scores of 1-3 at 1 year.

An additional analysis that has not yet been presented showed that the “strongest predictor” of whether or not patients who presented with a mRS score of 4 or 5 after 30 days improved their status at 1 year was if their residual hematoma volume shrank to 15 mL or less, Dr. Hanley said in an interview. “It’s not rocket science. If you had to choose between a 45-mL hematoma and less than 15 mL, which would you choose? What’s new here is how this recovery can play out,” taking 180 days or longer in some patients to become apparent.
 

More evidence needed to prove MISTIE’s hypothesis

According to Dr. Hanley, the MISTIE III findings have begun to influence practice despite its neutral primary finding, with more attention being paid to reducing residual clot volume following an ICH. And evidence continues to mount that more aggressive minimization of hematoma size can have an important effect on outcomes. For example, another study presented at the conference assessed the incremental change in prognostic accuracy when the ICH score, a five-item formula for estimating the prognosis of an ICH patient, substituted a precise quantification of residual hematoma volume rather than the original, dichotomous entry for either a hematoma volume of 30 mL or greater, or less than 30 mL, and when the severity score also quantified intraventricular hemorrhage (IVH) volume rather than simply designating IVH as present or absent.

Using data from 933 patients who had been enrolled in either MISTIE III or in another study of hematoma volume reduction, CLEAR III, the analysis showed that including specific quantification of both residual ICH volume as well as residual IVH volume improved the area under the receiver operating characteristic curve of the ICH score as a prognostic assessment from 0.70 to 0.75 in the intervention arms of the two trials, and from 0.60 to 0.68 in the two combined control arms, Adam de Havenon, MD, reported in a talk at the conference. “These data show that quantifying ICH and IVH volume improves mortality prognostication,” concluded Dr. de Havenon, a vascular and stroke neurologist at the University of Utah in Salt Lake City.

Mitchel L. Zoler/MDedge News

Furthermore, it’s “certainly evidence for the importance of volume reduction,” he said during discussion of his talk. “The MISTIE procedure can reset patients” so that their outcomes become more like patients with much smaller clot volumes even if they start with large hematomas. “In our experience, if the volume is reduced to 5 mL, there is real benefit regardless of how big the clot was initially,” Dr. de Havenon said.

But the neutral result for the MISTIE III primary endpoint will, for the time being, hobble application of this concept and keep the MISTIE intervention from rising to a level I recommendation until greater evidence for its efficacy comes out.

“It’s been known for many years that clot size matters when it comes to ICH. The MISTIE team has made a very compelling case that [reducing clot volume] is a very reasonable hypothesis, but we must continue to acquire data that can confirm it,” Dr. Sheth commented.

Dr. Sheth’s institution receives research funding from Novartis and Bard for studies that Dr. Sheth helps run. The MISTIE III study received the alteplase used in the study at no cost from Genentech. Ms. Ostapkovich and Ms. Carhuapoma had no disclosures. Dr. Hanley has received personal fees from BrainScope, Medtronic, Neurotrope, Op2Lysis, and Portola. Dr. de Havenon has received research funding from Regeneron.

[email protected]

LOS ANGELES – Intracerebral hemorrhage (ICH) appears to be not nearly as uniformly devastating to patients as its reputation suggests. Recent study results documented unexpectedly decent recovery prospects for hemorrhagic stroke patients assessed after 1 year who were earlier considered moderately severe or severely disabled based on their 30-day status. And these data provide further support for the growing impression among clinicians that a way forward for improving outcomes even more is with a “gentle” surgical intervention designed to substantially reduce ICH clot volume.

“Historically, there’s been a lot of nihilism around these patients. Intracerebral hemorrhage has always been the deadliest stroke type, but one of the great advances of the past 10-20 years is that ICH survival has improved. Patients do better than we used to think,” said Kevin N. Sheth, MD, professor of neurology and neurosurgery, and chief of neurocritical care and emergency neurology at Yale University in New Haven, Conn. “Even though ICH remains a difficult disease, this change has two big implications,” Dr. Sheth said in an interview during the International Stroke Conference sponsored by the American Heart Association. First, increased ICH survival offers an opportunity to expand the reach of recent management advances through quality improvement programs that emphasize new strategies that work better and incentivize delivery of these successful strategies to more patients.

The second implication is simply a growing number of ICH survivors, expanding the population of patients who stand to gain from these new management strategies. Dr. Sheth is working with the Get With the Guidelines – Stroke program, a quality-improvement program begun in 2003 and until now aimed at patients with acute ischemic stroke, to develop a 15-site pilot program planned to start in 2020 that will begin implementing and studying a Get With the Guidelines – Stroke quality-improvement program focused on patients with an ICH. The current conception of a quality measurement and improvement program like Get with the Guidelines – Stroke for patients with ICH stems from an important, earlier milestone in the emergence of effective ICH treatments, the 2018 publication of performance measures for ICH care that identified nine key management steps for assessing quality of care and documented the evidence behind them.

“Evidence for optimal treatment of ICH has lagged behind that for ischemic stroke, and consequently, metrics specific to ICH care have not been widely promulgated,” said the authors of the 2018 ICH performance measures, a panel that included Dr. Sheth. “However, numerous more recent studies and clinical trials of various medical and surgical interventions for ICH have been published and form the basis of evidence-based guidelines for the management of ICH,” they explained.
 

MISTIE III showcases better ICH outcomes

Perhaps the most dramatic recent evidence of brighter prospects for ICH patients came in data collected during the MISTIE III (Minimally Invasive Surgery with Thrombolysis in Intracerebral Hemorrhage Evacuation III) trial, which randomized 506 ICH patients with a hematoma of at least 30 mL to standard care or to a “gentle” clot-reduction protocol using a small-bore catheter placed with stereotactic guidance to both evacuate clot and introduce a serial infusion of alteplase into the clot to try to shrink its volume to less than 15 mL. The study’s results showed a neutral effect for the primary outcome, the incidence of recovery to a modified Rankin Scale (mRS) score of 0-3 at 1 year after entry, which occurred in 45% of the surgically treated patients and 41% of the controls in a modified intention-to-treat analysis that included 499 of the randomized patients, a difference that did not reach statistical significance.

However, when the analysis focused on the 146 of 247 patients (59%) randomized to surgical plus lytic intervention who underwent the procedure and actually had their clot volume reduced to 15 mL or less per protocol, the adjusted incidence of the primary endpoint was double that of patients who underwent the procedure but failed to have their residual clot reduced to this size. A similar doubling of good outcomes occurred when MISTIE patients had their residual clot cut to 20 mL or less, compared with those who didn’t reach this, with the differences in both analyses statistically significant. The actual rates showed patients with clot cut to 15 mL or less having a 53% rate of a mRS score of 0-3 after 1 year, compared with 33% of patients who received the intervention but had their residual clot remain above 15 mL.

The MISTIE III investigators looked at their data to try to get better insight into the outcome of all “poor prognosis” patients in the study regardless of their treatment arm assignment, and how patients and their family members made decisions for withdrawal of life-sustaining therapy. In MISTIE III, 61 patients had withdrawal of life-sustaining treatment (WoLST), with more than 40% of the WoLST occurring with patients randomized to the intervention arm including 10 patients treated to a residual clot volume of 15 mL or less. To quantify the disease severity in these 61 patients, the researchers applied a six-item formula at 30 days after the stroke, a metric their 2019 report described in detail. They then used these severity scores to identify 104 matched patients who were alive at 30 days and remained on life-sustaining treatment to see their 1-year outcomes. At 30 days, the 104 matched patients included 82 (79%) with a mRS score of 5 (severe disability) and 22 patients (21%) with a mRS score of 4 (moderately severe disability). Overall, an mRS score of 4 or 5 was quite prevalent 30 days after the stroke, with 87% of the patients treated with the MISTIE intervention and 90% of the control patients having this degree of disability at 30 days.

When the MISTIE III investigators followed these patients for a year, they made an unexpected finding: A substantial incidence of patients whose condition had improved since day 30. One year out, 40 (39%) of these 104 patients had improved to a mRS score of 1-3, including 10 (10%) with a mRS score of 1 or 2. Another indicator of the reasonable outcome many of these patients achieved was that after 1 year 69% were living at home.

“Our data show that many ICH subjects with clinical factors that suggest ‘poor prognosis,’ when given time, can achieve a favorable outcome and return home,” concluded Noeleen Ostapkovich, who presented these results at the Stroke Conference.

She cited these findings as potentially helpful for refining the information given to patients and families on the prognosis for ICH patients at about 30 days after their event, the usual time for assessment. “These patients looked like they weren’t going to do well after 30 days, but by 365 days they had improved physically and in their ability to care for themselves at home,” noted Ms. Ostapkovich, a researcher in the Brain Injury Outcomes Clinical Trial Coordinating Center of Johns Hopkins University in Baltimore.
 

A message for acute-care clinicians

She and her colleagues highlighted the implications these new findings have for clinical decision making in the first weeks after an ICH.

“Acute-care physicians see these patients at day 30, not at day 365, so it’s important that they have a clear picture of what these patients could look like a year later. It’s an important message,” Ms. Ostapkovich said in an interview.

In fact, a colleague of hers at Johns Hopkins ran an analysis that looked at factors that contributed to families opting for WoLST for 61 of the MISTIE III patients, and found that 38 family groups (62%) cited the anticipated outcome of the patient in a dependent state as their primary reason for opting for WoLST, Lourdes J. Carhuapoma reported in a separate talk at the conference.

Mitchel L. Zoler/MDedge News

“The main message is that many patients with significant ICH did well and recovered despite having very poor prognostic factors at 30 days, but it took more time. A concern is that the [prognostic] information families receive may be wrong. There is a disconnect,” between what families get told to expect and what actually happens, said Ms. Carhuapoma, an acute care nurse practitioner at Johns Hopkins.

“When physicians, nurses, and family members get together” to discuss ICH patients like these after 30 days, “they see the glass as empty. But the real message is that the glass is half full,” summed up Daniel F. Hanley, MD, lead investigator of MISTIE III and professor of neurology at Johns Hopkins. “These data show a large amount of improvement between 30 and 180 days.” The 104 patients with exclusively mRS scores of 4 or 5 at day 30 had a 30% incidence of improvement to an mRS score of 2 or 3 after 180 days, on their way to a 39% rate of mRS scores of 1-3 at 1 year.

An additional analysis that has not yet been presented showed that the “strongest predictor” of whether or not patients who presented with a mRS score of 4 or 5 after 30 days improved their status at 1 year was if their residual hematoma volume shrank to 15 mL or less, Dr. Hanley said in an interview. “It’s not rocket science. If you had to choose between a 45-mL hematoma and less than 15 mL, which would you choose? What’s new here is how this recovery can play out,” taking 180 days or longer in some patients to become apparent.
 

More evidence needed to prove MISTIE’s hypothesis

According to Dr. Hanley, the MISTIE III findings have begun to influence practice despite its neutral primary finding, with more attention being paid to reducing residual clot volume following an ICH. And evidence continues to mount that more aggressive minimization of hematoma size can have an important effect on outcomes. For example, another study presented at the conference assessed the incremental change in prognostic accuracy when the ICH score, a five-item formula for estimating the prognosis of an ICH patient, substituted a precise quantification of residual hematoma volume rather than the original, dichotomous entry for either a hematoma volume of 30 mL or greater, or less than 30 mL, and when the severity score also quantified intraventricular hemorrhage (IVH) volume rather than simply designating IVH as present or absent.

Using data from 933 patients who had been enrolled in either MISTIE III or in another study of hematoma volume reduction, CLEAR III, the analysis showed that including specific quantification of both residual ICH volume as well as residual IVH volume improved the area under the receiver operating characteristic curve of the ICH score as a prognostic assessment from 0.70 to 0.75 in the intervention arms of the two trials, and from 0.60 to 0.68 in the two combined control arms, Adam de Havenon, MD, reported in a talk at the conference. “These data show that quantifying ICH and IVH volume improves mortality prognostication,” concluded Dr. de Havenon, a vascular and stroke neurologist at the University of Utah in Salt Lake City.

Mitchel L. Zoler/MDedge News

Furthermore, it’s “certainly evidence for the importance of volume reduction,” he said during discussion of his talk. “The MISTIE procedure can reset patients” so that their outcomes become more like patients with much smaller clot volumes even if they start with large hematomas. “In our experience, if the volume is reduced to 5 mL, there is real benefit regardless of how big the clot was initially,” Dr. de Havenon said.

But the neutral result for the MISTIE III primary endpoint will, for the time being, hobble application of this concept and keep the MISTIE intervention from rising to a level I recommendation until greater evidence for its efficacy comes out.

“It’s been known for many years that clot size matters when it comes to ICH. The MISTIE team has made a very compelling case that [reducing clot volume] is a very reasonable hypothesis, but we must continue to acquire data that can confirm it,” Dr. Sheth commented.

Dr. Sheth’s institution receives research funding from Novartis and Bard for studies that Dr. Sheth helps run. The MISTIE III study received the alteplase used in the study at no cost from Genentech. Ms. Ostapkovich and Ms. Carhuapoma had no disclosures. Dr. Hanley has received personal fees from BrainScope, Medtronic, Neurotrope, Op2Lysis, and Portola. Dr. de Havenon has received research funding from Regeneron.

[email protected]

LOS ANGELES – Intracerebral hemorrhage (ICH) appears to be not nearly as uniformly devastating to patients as its reputation suggests. Recent study results documented unexpectedly decent recovery prospects for hemorrhagic stroke patients assessed after 1 year who were earlier considered moderately severe or severely disabled based on their 30-day status. And these data provide further support for the growing impression among clinicians that a way forward for improving outcomes even more is with a “gentle” surgical intervention designed to substantially reduce ICH clot volume.

“Historically, there’s been a lot of nihilism around these patients. Intracerebral hemorrhage has always been the deadliest stroke type, but one of the great advances of the past 10-20 years is that ICH survival has improved. Patients do better than we used to think,” said Kevin N. Sheth, MD, professor of neurology and neurosurgery, and chief of neurocritical care and emergency neurology at Yale University in New Haven, Conn. “Even though ICH remains a difficult disease, this change has two big implications,” Dr. Sheth said in an interview during the International Stroke Conference sponsored by the American Heart Association. First, increased ICH survival offers an opportunity to expand the reach of recent management advances through quality improvement programs that emphasize new strategies that work better and incentivize delivery of these successful strategies to more patients.

The second implication is simply a growing number of ICH survivors, expanding the population of patients who stand to gain from these new management strategies. Dr. Sheth is working with the Get With the Guidelines – Stroke program, a quality-improvement program begun in 2003 and until now aimed at patients with acute ischemic stroke, to develop a 15-site pilot program planned to start in 2020 that will begin implementing and studying a Get With the Guidelines – Stroke quality-improvement program focused on patients with an ICH. The current conception of a quality measurement and improvement program like Get with the Guidelines – Stroke for patients with ICH stems from an important, earlier milestone in the emergence of effective ICH treatments, the 2018 publication of performance measures for ICH care that identified nine key management steps for assessing quality of care and documented the evidence behind them.

“Evidence for optimal treatment of ICH has lagged behind that for ischemic stroke, and consequently, metrics specific to ICH care have not been widely promulgated,” said the authors of the 2018 ICH performance measures, a panel that included Dr. Sheth. “However, numerous more recent studies and clinical trials of various medical and surgical interventions for ICH have been published and form the basis of evidence-based guidelines for the management of ICH,” they explained.
 

MISTIE III showcases better ICH outcomes

Perhaps the most dramatic recent evidence of brighter prospects for ICH patients came in data collected during the MISTIE III (Minimally Invasive Surgery with Thrombolysis in Intracerebral Hemorrhage Evacuation III) trial, which randomized 506 ICH patients with a hematoma of at least 30 mL to standard care or to a “gentle” clot-reduction protocol using a small-bore catheter placed with stereotactic guidance to both evacuate clot and introduce a serial infusion of alteplase into the clot to try to shrink its volume to less than 15 mL. The study’s results showed a neutral effect for the primary outcome, the incidence of recovery to a modified Rankin Scale (mRS) score of 0-3 at 1 year after entry, which occurred in 45% of the surgically treated patients and 41% of the controls in a modified intention-to-treat analysis that included 499 of the randomized patients, a difference that did not reach statistical significance.

However, when the analysis focused on the 146 of 247 patients (59%) randomized to surgical plus lytic intervention who underwent the procedure and actually had their clot volume reduced to 15 mL or less per protocol, the adjusted incidence of the primary endpoint was double that of patients who underwent the procedure but failed to have their residual clot reduced to this size. A similar doubling of good outcomes occurred when MISTIE patients had their residual clot cut to 20 mL or less, compared with those who didn’t reach this, with the differences in both analyses statistically significant. The actual rates showed patients with clot cut to 15 mL or less having a 53% rate of a mRS score of 0-3 after 1 year, compared with 33% of patients who received the intervention but had their residual clot remain above 15 mL.

The MISTIE III investigators looked at their data to try to get better insight into the outcome of all “poor prognosis” patients in the study regardless of their treatment arm assignment, and how patients and their family members made decisions for withdrawal of life-sustaining therapy. In MISTIE III, 61 patients had withdrawal of life-sustaining treatment (WoLST), with more than 40% of the WoLST occurring with patients randomized to the intervention arm including 10 patients treated to a residual clot volume of 15 mL or less. To quantify the disease severity in these 61 patients, the researchers applied a six-item formula at 30 days after the stroke, a metric their 2019 report described in detail. They then used these severity scores to identify 104 matched patients who were alive at 30 days and remained on life-sustaining treatment to see their 1-year outcomes. At 30 days, the 104 matched patients included 82 (79%) with a mRS score of 5 (severe disability) and 22 patients (21%) with a mRS score of 4 (moderately severe disability). Overall, an mRS score of 4 or 5 was quite prevalent 30 days after the stroke, with 87% of the patients treated with the MISTIE intervention and 90% of the control patients having this degree of disability at 30 days.

When the MISTIE III investigators followed these patients for a year, they made an unexpected finding: A substantial incidence of patients whose condition had improved since day 30. One year out, 40 (39%) of these 104 patients had improved to a mRS score of 1-3, including 10 (10%) with a mRS score of 1 or 2. Another indicator of the reasonable outcome many of these patients achieved was that after 1 year 69% were living at home.

“Our data show that many ICH subjects with clinical factors that suggest ‘poor prognosis,’ when given time, can achieve a favorable outcome and return home,” concluded Noeleen Ostapkovich, who presented these results at the Stroke Conference.

She cited these findings as potentially helpful for refining the information given to patients and families on the prognosis for ICH patients at about 30 days after their event, the usual time for assessment. “These patients looked like they weren’t going to do well after 30 days, but by 365 days they had improved physically and in their ability to care for themselves at home,” noted Ms. Ostapkovich, a researcher in the Brain Injury Outcomes Clinical Trial Coordinating Center of Johns Hopkins University in Baltimore.
 

A message for acute-care clinicians

She and her colleagues highlighted the implications these new findings have for clinical decision making in the first weeks after an ICH.

“Acute-care physicians see these patients at day 30, not at day 365, so it’s important that they have a clear picture of what these patients could look like a year later. It’s an important message,” Ms. Ostapkovich said in an interview.

In fact, a colleague of hers at Johns Hopkins ran an analysis that looked at factors that contributed to families opting for WoLST for 61 of the MISTIE III patients, and found that 38 family groups (62%) cited the anticipated outcome of the patient in a dependent state as their primary reason for opting for WoLST, Lourdes J. Carhuapoma reported in a separate talk at the conference.

Mitchel L. Zoler/MDedge News

“The main message is that many patients with significant ICH did well and recovered despite having very poor prognostic factors at 30 days, but it took more time. A concern is that the [prognostic] information families receive may be wrong. There is a disconnect,” between what families get told to expect and what actually happens, said Ms. Carhuapoma, an acute care nurse practitioner at Johns Hopkins.

“When physicians, nurses, and family members get together” to discuss ICH patients like these after 30 days, “they see the glass as empty. But the real message is that the glass is half full,” summed up Daniel F. Hanley, MD, lead investigator of MISTIE III and professor of neurology at Johns Hopkins. “These data show a large amount of improvement between 30 and 180 days.” The 104 patients with exclusively mRS scores of 4 or 5 at day 30 had a 30% incidence of improvement to an mRS score of 2 or 3 after 180 days, on their way to a 39% rate of mRS scores of 1-3 at 1 year.

An additional analysis that has not yet been presented showed that the “strongest predictor” of whether or not patients who presented with a mRS score of 4 or 5 after 30 days improved their status at 1 year was if their residual hematoma volume shrank to 15 mL or less, Dr. Hanley said in an interview. “It’s not rocket science. If you had to choose between a 45-mL hematoma and less than 15 mL, which would you choose? What’s new here is how this recovery can play out,” taking 180 days or longer in some patients to become apparent.
 

More evidence needed to prove MISTIE’s hypothesis

According to Dr. Hanley, the MISTIE III findings have begun to influence practice despite its neutral primary finding, with more attention being paid to reducing residual clot volume following an ICH. And evidence continues to mount that more aggressive minimization of hematoma size can have an important effect on outcomes. For example, another study presented at the conference assessed the incremental change in prognostic accuracy when the ICH score, a five-item formula for estimating the prognosis of an ICH patient, substituted a precise quantification of residual hematoma volume rather than the original, dichotomous entry for either a hematoma volume of 30 mL or greater, or less than 30 mL, and when the severity score also quantified intraventricular hemorrhage (IVH) volume rather than simply designating IVH as present or absent.

Using data from 933 patients who had been enrolled in either MISTIE III or in another study of hematoma volume reduction, CLEAR III, the analysis showed that including specific quantification of both residual ICH volume as well as residual IVH volume improved the area under the receiver operating characteristic curve of the ICH score as a prognostic assessment from 0.70 to 0.75 in the intervention arms of the two trials, and from 0.60 to 0.68 in the two combined control arms, Adam de Havenon, MD, reported in a talk at the conference. “These data show that quantifying ICH and IVH volume improves mortality prognostication,” concluded Dr. de Havenon, a vascular and stroke neurologist at the University of Utah in Salt Lake City.

Mitchel L. Zoler/MDedge News

Furthermore, it’s “certainly evidence for the importance of volume reduction,” he said during discussion of his talk. “The MISTIE procedure can reset patients” so that their outcomes become more like patients with much smaller clot volumes even if they start with large hematomas. “In our experience, if the volume is reduced to 5 mL, there is real benefit regardless of how big the clot was initially,” Dr. de Havenon said.

But the neutral result for the MISTIE III primary endpoint will, for the time being, hobble application of this concept and keep the MISTIE intervention from rising to a level I recommendation until greater evidence for its efficacy comes out.

“It’s been known for many years that clot size matters when it comes to ICH. The MISTIE team has made a very compelling case that [reducing clot volume] is a very reasonable hypothesis, but we must continue to acquire data that can confirm it,” Dr. Sheth commented.

Dr. Sheth’s institution receives research funding from Novartis and Bard for studies that Dr. Sheth helps run. The MISTIE III study received the alteplase used in the study at no cost from Genentech. Ms. Ostapkovich and Ms. Carhuapoma had no disclosures. Dr. Hanley has received personal fees from BrainScope, Medtronic, Neurotrope, Op2Lysis, and Portola. Dr. de Havenon has received research funding from Regeneron.

[email protected]

Patients with diabetes may be at extra risk for coronavirus disease (COVID-19) mortality, and doctors treating them need to keep up with the latest guidelines and expert advice.

Most health advisories about COVID-19 mention diabetes as one of the high-risk categories for the disease, likely because early data coming out of China, where the disease was first reported, indicated an elevated case-fatality rate for COVID-19 patients who also had diabetes.

In an article published in JAMA, Zunyou Wu, MD, and Jennifer M. McGoogan, PhD, summarized the findings from a February report on 44,672 confirmed cases of the disease from the Chinese Center for Disease Control and Prevention. The overall case-fatality rate (CFR) at that stage was 2.3% (1,023 deaths of the 44,672 confirmed cases). The data indicated that the CFR was elevated among COVID-19 patients with preexisting comorbid conditions, specifically, cardiovascular disease (CFR, 10.5%), diabetes (7.3%), chronic respiratory disease (6.3%), hypertension (6%), and cancer (5.6%).

The data also showed an aged-related trend in the CFR, with patients aged 80 years or older having a CFR of 14.8% and those aged 70-79 years, a rate of 8.0%, while there were no fatal cases reported in patients aged 9 years or younger (JAMA. 2020 Feb 24. doi: 10.1001/jama.2020.2648).

Those findings have been echoed by the U.S. Centers of Disease Control and Prevention. The American Diabetes Association and the American Association of Clinical Endocrinologists have in turn referenced the CDC in their COVID-19 guidance recommendations for patients with diabetes.

Guidelines were already in place for treatment of infections in patients with diabetes, and at this stage, it seems that the same guidelines would extend to those patients who are also diagnosed with COVID-19, which is caused by the novel coronavirus, SARS-CoV-2.

In general, patients with diabetes – especially those whose disease is not controlled, or not well controlled – can be more susceptible to more common infections, such as influenza and pneumonia, possibly because hyperglycemia can subdue immunity by disrupting function of the white blood cells.
 

Glucose control is key

An important factor in any form of infection control in patients with diabetes seems to be whether or not a patient’s glucose levels are well controlled, according to comments from members of the editorial advisory board for Clinical Endocrinology News. Good glucose control, therefore, could be instrumental in reducing both the risk for and severity of infection.

Paul Jellinger, MD, of the Center for Diabetes & Endocrine Care, Hollywood, Fla., said that, over the years, he had not observed higher infection rates in general in patients with hemoglobin A_1c levels below 7, or even higher. However, “a bigger question for me, given the broad category of ‘diabetes’ listed as a risk for serious coronavirus complications by the CDC, has been: Just which individuals with diabetes are really at risk? Are patients with well-controlled diabetes at increased risk as much as those with significant hyperglycemia and uncontrolled diabetes? In my view, not likely.”

Alan Jay Cohen, MD, agreed with Dr. Jellinger. “Many patients have called the office in the last 10 days to ask if there are special precautions they should take because they are reading that they are in the high-risk group because they have diabetes. Many of them are in superb, or at least pretty good, control. I have not seen where they have had a higher incidence of infection than the general population, and I have not seen data with COVID-19 that specifically demonstrates that a person with diabetes in good control has an increased risk,” he said.

“My recommendations to these patients have been the same as those given to the general population,” added Dr. Cohen, medical director at Baptist Medical Group: The Endocrine Clinic, Memphis.

Herbert I. Rettinger, MD, also conceded that poorly controlled blood sugars and confounding illnesses, such as renal and cardiac conditions, are common in patients with long-standing diabetes, but “there is a huge population of patients with type 1 diabetes, and very few seem to be more susceptible to infection. Perhaps I am missing those with poor diet and glucose control.”

Philip Levy, MD, picked up on that latter point, emphasizing that “endocrinologists take care of fewer patients with diabetes than do primary care physicians. Most patients with type 2 diabetes are not seen by us unless the PCP has problems [treating them],” so it could be that PCPs may see a higher number of patients who are at a greater risk for infections.

Ultimately, “good glucose control is very helpful in avoiding infections,” said Dr. Levy, of the Banner University Medical Group Endocrinology & Diabetes, Phoenix.
 

For sick patients

Guidelines for patients at the Joslin Diabetes Center in Boston advise patients who are feeling sick to continue taking their diabetes medications, unless instructed otherwise by their providers, and to monitor their glucose more frequently because it can spike suddenly.

Patients with type 1 diabetes should check for ketones if their glucose passes 250 mg/dL, according to the guidelines, and patients should remain hydrated at all times and get plenty of rest.

“Sick-day guidelines definitely apply, but patients should be advised to get tested if they have any symptoms they are concerned about,” said Dr. Rettinger, of the Endocrinology Medical Group of Orange County, Orange, Calif.

If patients with diabetes develop COVID-19, then home management may still be possible, according to Ritesh Gupta, MD, of Fortis C-DOC Hospital, New Delhi, and colleagues (Diabetes Metab Syndr. 2020 Mar 10;14[3]:211-2. doi: 10.1016/j.dsx.2020.03.002).

Dr. Rettinger agreed, noting that home management would be feasible as long as “everything is going well, that is, the patient is not experiencing respiratory problems or difficulties in controlling glucose levels. Consider patients with type 1 diabetes who have COVID-19 as you would a nursing home patient – ever vigilant.”

Dr. Gupta and coauthors also recommended basic treatment measures such as maintaining hydration and managing symptoms with acetaminophen and steam inhalation, and home isolation for 14 days or until the symptoms resolve. However, the ADA warns in its guidelines that patients should “be aware that some constant glucose monitoring sensors (Dexcom G5, Medtronic Enlite, and Guardian) are impacted by acetaminophen (Tylenol), and that patients should check with finger sticks to ensure accuracy [if they are taking acetaminophen].”

In the event of hyperglycemia with fever in patients with type 1 diabetes, blood glucose and urinary ketones should be monitored often, the authors wrote, cautioning that “frequent changes in dosage and correctional bolus may be required to maintain normoglycemia.” Dr Rettinger emphasized that “hyperglycemia, as always, is best treated with fluids and insulin and frequent checks of sugars to be sure the treatment regimen is successful.”

In regard to diabetic drug regimens, patients with type 1 or 2 disease should continue on their current medications, advised Yehuda Handelsman, MD. “Some, especially those on insulin, may require more of it. And the patient should increase fluid intake to prevent fluid depletion. We do not reduce antihyperglycemic medication to preserve fluids.

Preventive measures

In the interest of maintaining good glucose control, patients also should monitor their glucose levels more frequently so that fluctuations can be detected early and quickly addressed with the appropriate medication adjustments, according to guidelines from the ADA and AACE. They should continue to follow a healthy diet that includes adequate protein and they should exercise regularly.

Patients should ensure that they have enough medication and testing supplies – for at least 14 days, and longer, if costs permit – in case they have to go into quarantine.

General preventive measures, such as frequent hand washing with soap and water, practicing good respiratory hygiene by sneezing or coughing into a facial tissue or bent elbow, also apply for reducing the risk of infection. Touching of the face should be avoided, as should nonessential travel and contact with infected individuals.

Patients with diabetes should always be current with their influenza and pneumonia shots.

Dr. Rettinger said that he always recommends the following preventative measures to his patients and he is using the current health crisis to reinforce them:

• Eat lots of multicolored fruits and vegetables.
• Eat yogurt and take probiotics to keep the intestinal biome strong and functional.
• Be extra vigilant regarding sugars and sugar control to avoid peaks and valleys wherever possible.
• Keep the immune system strong with at least 7-8 hours sleep and reduce stress levels whenever possible.
• Avoid crowds and handshaking.
• Wash hands regularly.

Possible therapies

There are currently no drugs that have been approved specifically for the treatment of COVID-19, although a vaccine against the disease is currently under development.

Dr. Gupta and his colleagues noted in their article that there have been reports of the anecdotal use of antiviral drugs such as lopinavir, ritonavir, interferon-beta, the RNA polymerase inhibitor remdesivir, and chloroquine.

However, Dr. Handelsman said that, as far as he knows, none of these drugs has been shown to be beneficial for COVID-19. “Some [providers] have tried Tamiflu, but with no clear outcomes, and for severely sick patients, they tried medications for anti-HIV, hepatitis C, and malaria, but so far, there has been no breakthrough.”

Dr. Cohen, Dr. Handelsman, Dr. Jellinger, Dr. Levy, and Dr. Rettinger are members of the editorial advisory board of Clinical Endocrinology News. Dr. Gupta and Dr. Wu, and their colleagues, reported no conflicts of interest.

[email protected]

Patients with diabetes may be at extra risk for coronavirus disease (COVID-19) mortality, and doctors treating them need to keep up with the latest guidelines and expert advice.

Most health advisories about COVID-19 mention diabetes as one of the high-risk categories for the disease, likely because early data coming out of China, where the disease was first reported, indicated an elevated case-fatality rate for COVID-19 patients who also had diabetes.

In an article published in JAMA, Zunyou Wu, MD, and Jennifer M. McGoogan, PhD, summarized the findings from a February report on 44,672 confirmed cases of the disease from the Chinese Center for Disease Control and Prevention. The overall case-fatality rate (CFR) at that stage was 2.3% (1,023 deaths of the 44,672 confirmed cases). The data indicated that the CFR was elevated among COVID-19 patients with preexisting comorbid conditions, specifically, cardiovascular disease (CFR, 10.5%), diabetes (7.3%), chronic respiratory disease (6.3%), hypertension (6%), and cancer (5.6%).

The data also showed an aged-related trend in the CFR, with patients aged 80 years or older having a CFR of 14.8% and those aged 70-79 years, a rate of 8.0%, while there were no fatal cases reported in patients aged 9 years or younger (JAMA. 2020 Feb 24. doi: 10.1001/jama.2020.2648).

Those findings have been echoed by the U.S. Centers of Disease Control and Prevention. The American Diabetes Association and the American Association of Clinical Endocrinologists have in turn referenced the CDC in their COVID-19 guidance recommendations for patients with diabetes.

Guidelines were already in place for treatment of infections in patients with diabetes, and at this stage, it seems that the same guidelines would extend to those patients who are also diagnosed with COVID-19, which is caused by the novel coronavirus, SARS-CoV-2.

In general, patients with diabetes – especially those whose disease is not controlled, or not well controlled – can be more susceptible to more common infections, such as influenza and pneumonia, possibly because hyperglycemia can subdue immunity by disrupting function of the white blood cells.
 

Glucose control is key

An important factor in any form of infection control in patients with diabetes seems to be whether or not a patient’s glucose levels are well controlled, according to comments from members of the editorial advisory board for Clinical Endocrinology News. Good glucose control, therefore, could be instrumental in reducing both the risk for and severity of infection.

Paul Jellinger, MD, of the Center for Diabetes & Endocrine Care, Hollywood, Fla., said that, over the years, he had not observed higher infection rates in general in patients with hemoglobin A_1c levels below 7, or even higher. However, “a bigger question for me, given the broad category of ‘diabetes’ listed as a risk for serious coronavirus complications by the CDC, has been: Just which individuals with diabetes are really at risk? Are patients with well-controlled diabetes at increased risk as much as those with significant hyperglycemia and uncontrolled diabetes? In my view, not likely.”

Alan Jay Cohen, MD, agreed with Dr. Jellinger. “Many patients have called the office in the last 10 days to ask if there are special precautions they should take because they are reading that they are in the high-risk group because they have diabetes. Many of them are in superb, or at least pretty good, control. I have not seen where they have had a higher incidence of infection than the general population, and I have not seen data with COVID-19 that specifically demonstrates that a person with diabetes in good control has an increased risk,” he said.

“My recommendations to these patients have been the same as those given to the general population,” added Dr. Cohen, medical director at Baptist Medical Group: The Endocrine Clinic, Memphis.

Herbert I. Rettinger, MD, also conceded that poorly controlled blood sugars and confounding illnesses, such as renal and cardiac conditions, are common in patients with long-standing diabetes, but “there is a huge population of patients with type 1 diabetes, and very few seem to be more susceptible to infection. Perhaps I am missing those with poor diet and glucose control.”

Philip Levy, MD, picked up on that latter point, emphasizing that “endocrinologists take care of fewer patients with diabetes than do primary care physicians. Most patients with type 2 diabetes are not seen by us unless the PCP has problems [treating them],” so it could be that PCPs may see a higher number of patients who are at a greater risk for infections.

Ultimately, “good glucose control is very helpful in avoiding infections,” said Dr. Levy, of the Banner University Medical Group Endocrinology & Diabetes, Phoenix.
 

For sick patients

Guidelines for patients at the Joslin Diabetes Center in Boston advise patients who are feeling sick to continue taking their diabetes medications, unless instructed otherwise by their providers, and to monitor their glucose more frequently because it can spike suddenly.

Patients with type 1 diabetes should check for ketones if their glucose passes 250 mg/dL, according to the guidelines, and patients should remain hydrated at all times and get plenty of rest.

“Sick-day guidelines definitely apply, but patients should be advised to get tested if they have any symptoms they are concerned about,” said Dr. Rettinger, of the Endocrinology Medical Group of Orange County, Orange, Calif.

If patients with diabetes develop COVID-19, then home management may still be possible, according to Ritesh Gupta, MD, of Fortis C-DOC Hospital, New Delhi, and colleagues (Diabetes Metab Syndr. 2020 Mar 10;14[3]:211-2. doi: 10.1016/j.dsx.2020.03.002).

Dr. Rettinger agreed, noting that home management would be feasible as long as “everything is going well, that is, the patient is not experiencing respiratory problems or difficulties in controlling glucose levels. Consider patients with type 1 diabetes who have COVID-19 as you would a nursing home patient – ever vigilant.”

Dr. Gupta and coauthors also recommended basic treatment measures such as maintaining hydration and managing symptoms with acetaminophen and steam inhalation, and home isolation for 14 days or until the symptoms resolve. However, the ADA warns in its guidelines that patients should “be aware that some constant glucose monitoring sensors (Dexcom G5, Medtronic Enlite, and Guardian) are impacted by acetaminophen (Tylenol), and that patients should check with finger sticks to ensure accuracy [if they are taking acetaminophen].”

In the event of hyperglycemia with fever in patients with type 1 diabetes, blood glucose and urinary ketones should be monitored often, the authors wrote, cautioning that “frequent changes in dosage and correctional bolus may be required to maintain normoglycemia.” Dr Rettinger emphasized that “hyperglycemia, as always, is best treated with fluids and insulin and frequent checks of sugars to be sure the treatment regimen is successful.”

In regard to diabetic drug regimens, patients with type 1 or 2 disease should continue on their current medications, advised Yehuda Handelsman, MD. “Some, especially those on insulin, may require more of it. And the patient should increase fluid intake to prevent fluid depletion. We do not reduce antihyperglycemic medication to preserve fluids.

Preventive measures

In the interest of maintaining good glucose control, patients also should monitor their glucose levels more frequently so that fluctuations can be detected early and quickly addressed with the appropriate medication adjustments, according to guidelines from the ADA and AACE. They should continue to follow a healthy diet that includes adequate protein and they should exercise regularly.

Patients should ensure that they have enough medication and testing supplies – for at least 14 days, and longer, if costs permit – in case they have to go into quarantine.

General preventive measures, such as frequent hand washing with soap and water, practicing good respiratory hygiene by sneezing or coughing into a facial tissue or bent elbow, also apply for reducing the risk of infection. Touching of the face should be avoided, as should nonessential travel and contact with infected individuals.

Patients with diabetes should always be current with their influenza and pneumonia shots.

Dr. Rettinger said that he always recommends the following preventative measures to his patients and he is using the current health crisis to reinforce them:

• Eat lots of multicolored fruits and vegetables.
• Eat yogurt and take probiotics to keep the intestinal biome strong and functional.
• Be extra vigilant regarding sugars and sugar control to avoid peaks and valleys wherever possible.
• Keep the immune system strong with at least 7-8 hours sleep and reduce stress levels whenever possible.
• Avoid crowds and handshaking.
• Wash hands regularly.

Possible therapies

There are currently no drugs that have been approved specifically for the treatment of COVID-19, although a vaccine against the disease is currently under development.

Dr. Gupta and his colleagues noted in their article that there have been reports of the anecdotal use of antiviral drugs such as lopinavir, ritonavir, interferon-beta, the RNA polymerase inhibitor remdesivir, and chloroquine.

However, Dr. Handelsman said that, as far as he knows, none of these drugs has been shown to be beneficial for COVID-19. “Some [providers] have tried Tamiflu, but with no clear outcomes, and for severely sick patients, they tried medications for anti-HIV, hepatitis C, and malaria, but so far, there has been no breakthrough.”

Dr. Cohen, Dr. Handelsman, Dr. Jellinger, Dr. Levy, and Dr. Rettinger are members of the editorial advisory board of Clinical Endocrinology News. Dr. Gupta and Dr. Wu, and their colleagues, reported no conflicts of interest.

[email protected]

Patients with diabetes may be at extra risk for coronavirus disease (COVID-19) mortality, and doctors treating them need to keep up with the latest guidelines and expert advice.

Most health advisories about COVID-19 mention diabetes as one of the high-risk categories for the disease, likely because early data coming out of China, where the disease was first reported, indicated an elevated case-fatality rate for COVID-19 patients who also had diabetes.

In an article published in JAMA, Zunyou Wu, MD, and Jennifer M. McGoogan, PhD, summarized the findings from a February report on 44,672 confirmed cases of the disease from the Chinese Center for Disease Control and Prevention. The overall case-fatality rate (CFR) at that stage was 2.3% (1,023 deaths of the 44,672 confirmed cases). The data indicated that the CFR was elevated among COVID-19 patients with preexisting comorbid conditions, specifically, cardiovascular disease (CFR, 10.5%), diabetes (7.3%), chronic respiratory disease (6.3%), hypertension (6%), and cancer (5.6%).

The data also showed an aged-related trend in the CFR, with patients aged 80 years or older having a CFR of 14.8% and those aged 70-79 years, a rate of 8.0%, while there were no fatal cases reported in patients aged 9 years or younger (JAMA. 2020 Feb 24. doi: 10.1001/jama.2020.2648).

Those findings have been echoed by the U.S. Centers of Disease Control and Prevention. The American Diabetes Association and the American Association of Clinical Endocrinologists have in turn referenced the CDC in their COVID-19 guidance recommendations for patients with diabetes.

Guidelines were already in place for treatment of infections in patients with diabetes, and at this stage, it seems that the same guidelines would extend to those patients who are also diagnosed with COVID-19, which is caused by the novel coronavirus, SARS-CoV-2.

In general, patients with diabetes – especially those whose disease is not controlled, or not well controlled – can be more susceptible to more common infections, such as influenza and pneumonia, possibly because hyperglycemia can subdue immunity by disrupting function of the white blood cells.
 

Glucose control is key

An important factor in any form of infection control in patients with diabetes seems to be whether or not a patient’s glucose levels are well controlled, according to comments from members of the editorial advisory board for Clinical Endocrinology News. Good glucose control, therefore, could be instrumental in reducing both the risk for and severity of infection.

Paul Jellinger, MD, of the Center for Diabetes & Endocrine Care, Hollywood, Fla., said that, over the years, he had not observed higher infection rates in general in patients with hemoglobin A_1c levels below 7, or even higher. However, “a bigger question for me, given the broad category of ‘diabetes’ listed as a risk for serious coronavirus complications by the CDC, has been: Just which individuals with diabetes are really at risk? Are patients with well-controlled diabetes at increased risk as much as those with significant hyperglycemia and uncontrolled diabetes? In my view, not likely.”

Alan Jay Cohen, MD, agreed with Dr. Jellinger. “Many patients have called the office in the last 10 days to ask if there are special precautions they should take because they are reading that they are in the high-risk group because they have diabetes. Many of them are in superb, or at least pretty good, control. I have not seen where they have had a higher incidence of infection than the general population, and I have not seen data with COVID-19 that specifically demonstrates that a person with diabetes in good control has an increased risk,” he said.

“My recommendations to these patients have been the same as those given to the general population,” added Dr. Cohen, medical director at Baptist Medical Group: The Endocrine Clinic, Memphis.

Herbert I. Rettinger, MD, also conceded that poorly controlled blood sugars and confounding illnesses, such as renal and cardiac conditions, are common in patients with long-standing diabetes, but “there is a huge population of patients with type 1 diabetes, and very few seem to be more susceptible to infection. Perhaps I am missing those with poor diet and glucose control.”

Philip Levy, MD, picked up on that latter point, emphasizing that “endocrinologists take care of fewer patients with diabetes than do primary care physicians. Most patients with type 2 diabetes are not seen by us unless the PCP has problems [treating them],” so it could be that PCPs may see a higher number of patients who are at a greater risk for infections.

Ultimately, “good glucose control is very helpful in avoiding infections,” said Dr. Levy, of the Banner University Medical Group Endocrinology & Diabetes, Phoenix.
 

For sick patients

Guidelines for patients at the Joslin Diabetes Center in Boston advise patients who are feeling sick to continue taking their diabetes medications, unless instructed otherwise by their providers, and to monitor their glucose more frequently because it can spike suddenly.

Patients with type 1 diabetes should check for ketones if their glucose passes 250 mg/dL, according to the guidelines, and patients should remain hydrated at all times and get plenty of rest.

“Sick-day guidelines definitely apply, but patients should be advised to get tested if they have any symptoms they are concerned about,” said Dr. Rettinger, of the Endocrinology Medical Group of Orange County, Orange, Calif.

If patients with diabetes develop COVID-19, then home management may still be possible, according to Ritesh Gupta, MD, of Fortis C-DOC Hospital, New Delhi, and colleagues (Diabetes Metab Syndr. 2020 Mar 10;14[3]:211-2. doi: 10.1016/j.dsx.2020.03.002).

Dr. Rettinger agreed, noting that home management would be feasible as long as “everything is going well, that is, the patient is not experiencing respiratory problems or difficulties in controlling glucose levels. Consider patients with type 1 diabetes who have COVID-19 as you would a nursing home patient – ever vigilant.”

Dr. Gupta and coauthors also recommended basic treatment measures such as maintaining hydration and managing symptoms with acetaminophen and steam inhalation, and home isolation for 14 days or until the symptoms resolve. However, the ADA warns in its guidelines that patients should “be aware that some constant glucose monitoring sensors (Dexcom G5, Medtronic Enlite, and Guardian) are impacted by acetaminophen (Tylenol), and that patients should check with finger sticks to ensure accuracy [if they are taking acetaminophen].”

In the event of hyperglycemia with fever in patients with type 1 diabetes, blood glucose and urinary ketones should be monitored often, the authors wrote, cautioning that “frequent changes in dosage and correctional bolus may be required to maintain normoglycemia.” Dr Rettinger emphasized that “hyperglycemia, as always, is best treated with fluids and insulin and frequent checks of sugars to be sure the treatment regimen is successful.”

In regard to diabetic drug regimens, patients with type 1 or 2 disease should continue on their current medications, advised Yehuda Handelsman, MD. “Some, especially those on insulin, may require more of it. And the patient should increase fluid intake to prevent fluid depletion. We do not reduce antihyperglycemic medication to preserve fluids.

Preventive measures

In the interest of maintaining good glucose control, patients also should monitor their glucose levels more frequently so that fluctuations can be detected early and quickly addressed with the appropriate medication adjustments, according to guidelines from the ADA and AACE. They should continue to follow a healthy diet that includes adequate protein and they should exercise regularly.

Patients should ensure that they have enough medication and testing supplies – for at least 14 days, and longer, if costs permit – in case they have to go into quarantine.

General preventive measures, such as frequent hand washing with soap and water, practicing good respiratory hygiene by sneezing or coughing into a facial tissue or bent elbow, also apply for reducing the risk of infection. Touching of the face should be avoided, as should nonessential travel and contact with infected individuals.

Patients with diabetes should always be current with their influenza and pneumonia shots.

Dr. Rettinger said that he always recommends the following preventative measures to his patients and he is using the current health crisis to reinforce them:

• Eat lots of multicolored fruits and vegetables.
• Eat yogurt and take probiotics to keep the intestinal biome strong and functional.
• Be extra vigilant regarding sugars and sugar control to avoid peaks and valleys wherever possible.
• Keep the immune system strong with at least 7-8 hours sleep and reduce stress levels whenever possible.
• Avoid crowds and handshaking.
• Wash hands regularly.

Possible therapies

There are currently no drugs that have been approved specifically for the treatment of COVID-19, although a vaccine against the disease is currently under development.

Dr. Gupta and his colleagues noted in their article that there have been reports of the anecdotal use of antiviral drugs such as lopinavir, ritonavir, interferon-beta, the RNA polymerase inhibitor remdesivir, and chloroquine.

However, Dr. Handelsman said that, as far as he knows, none of these drugs has been shown to be beneficial for COVID-19. “Some [providers] have tried Tamiflu, but with no clear outcomes, and for severely sick patients, they tried medications for anti-HIV, hepatitis C, and malaria, but so far, there has been no breakthrough.”

Dr. Cohen, Dr. Handelsman, Dr. Jellinger, Dr. Levy, and Dr. Rettinger are members of the editorial advisory board of Clinical Endocrinology News. Dr. Gupta and Dr. Wu, and their colleagues, reported no conflicts of interest.

[email protected]

Patients with diabetes may have an increased risk of developing coronavirus infection (COVID-19), along with increased risks of morbidity and mortality, according to researchers writing in Diabetes & Metabolic Syndrome.

Although relevant clinical data remain scarce, patients with diabetes should take extra precautions to avoid infection and, if infected, may require special care, reported Ritesh Gupta, MD, of Fortis C-DOC Hospital, New Delhi, and colleagues.

“The disease severity [with COVID-19] has varied from mild, self-limiting, flu-like illness to fulminant pneumonia, respiratory failure, and death,” the authors wrote.

As of March 16, 2020, the World Health Organization reported 167,515 confirmed cases of COVID-19 and 6,606 deaths from around the world, with a mortality rate of 3.9%. But the actual mortality rate may be lower, the authors suggested, because a study involving more than 1,000 confirmed cases reported a mortality rate of 1.4%.

“Considering that the number of unreported and unconfirmed cases is likely to be much higher than the reported cases, the actual mortality may be less than 1%, which is similar to that of severe seasonal influenza,” the authors said, in reference to an editorial by Anthony S. Fauci, MD, and colleagues in the New England Journal of Medicine. In addition, they noted, mortality rates may vary by region.

The largest study relevant to patients with diabetes, which involved 72,314 cases of COVID-19, showed that patients with diabetes had a threefold higher mortality rate than did those without diabetes (7.3% vs. 2.3%, respectively). These figures were reported by the Chinese Centre for Disease Control and Prevention.

However, data from smaller cohorts with diabetes and COVID-19 have yielded mixed results. For instance, one study, involving 140 patients from Wuhan, suggested that diabetes was not a risk factor for severe disease, and in an analysis of 11 studies reporting on laboratory abnormalities in patients with a diagnosis of COVID-19, raised blood sugar levels or diabetes were not mentioned among the predictors of severe disease.

“Our knowledge about the prevalence of COVID-19 and disease course in people with diabetes will evolve as more detailed analyses are carried out,” the authors wrote. “For now, it is reasonable to assume that people with diabetes are at increased risk of developing infection. Coexisting heart disease, kidney disease, advanced age, and frailty are likely to further increase the severity of disease.”
 

Prevention first

“It is important that people with diabetes maintain good glycemic control, because it might help in reducing the risk of infection and the severity,” the authors wrote.

In addition to more frequent monitoring of blood glucose levels, they recommended other preventive measures, such as getting adequate nutrition, exercising, and being current with vaccinations for influenza and pneumonia. The latter, they said, may also reduce the risk of secondary bacterial pneumonia after a respiratory viral infection.

In regard to nutrition, adequate protein intake is important and “any deficiencies of minerals and vitamins need to be taken care of,” they advised. Likewise, exercise is known to improve immunity and should continue, but they suggest avoiding gyms and swimming pools.

For patients with coexisting heart and/or kidney disease, they also recommended efforts to stabilize cardiac/renal status.

In addition, the general preventive measures, such as regular and thorough hand washing with soap and water, practicing good respiratory hygiene by sneezing and coughing into a bent elbow or a facial tissue, and avoiding contact with anyone who is infected, should be observed.

As with other patients with chronic diseases that are managed long-term medications, patients with diabetes should always ensure that they have a sufficient supply of their medications and refills, if possible.
 

After a diagnosis

If patients with diabetes develop COVID-19, then home management may still be possible, wrote the authors, who recommended basic treatment measures such as maintaining hydration and managing symptoms with acetaminophen and steam inhalation, and home isolation for 14 days or until the symptoms resolve.

In the event of hyperglycemia with fever in patients with type 1 diabetes, blood glucose and urinary ketones should be monitored often. “Frequent changes in dosage and correctional bolus may be required to maintain normoglycemia,” they cautioned.

Concerning diabetic drug regimens, they suggest patients avoid antihyperglycemic agents that can cause volume depletion or hypoglycemia and, if necessary, that they reduce oral antidiabetic drugs and follow sick-day guidelines.

For hospitalized patients, the investigators strengthened that statement, advising that oral agents need to be stopped, particularly sodium-glucose cotransporter 2 inhibitors and metformin. “Insulin is the preferred agent for control of hyperglycemia in hospitalized sick patients,” they wrote.

Untested therapies

The authors also discussed a range of untested therapies that may help fight COVID-19, such as antiviral drugs (such as lopinavir and ritonavir), zinc nanoparticles, and vitamin C. Supplementing those recommendations, Dr. Gupta and colleagues provided a concise review of COVID-19 epidemiology and extant data relevant to patients with diabetes.

The investigators reported no conflicts of interest.

SOURCE: Gupta et al. Diabetes Metab Syndr. 2020;14(3):211-12.

Patients with diabetes may have an increased risk of developing coronavirus infection (COVID-19), along with increased risks of morbidity and mortality, according to researchers writing in Diabetes & Metabolic Syndrome.

Although relevant clinical data remain scarce, patients with diabetes should take extra precautions to avoid infection and, if infected, may require special care, reported Ritesh Gupta, MD, of Fortis C-DOC Hospital, New Delhi, and colleagues.

“The disease severity [with COVID-19] has varied from mild, self-limiting, flu-like illness to fulminant pneumonia, respiratory failure, and death,” the authors wrote.

As of March 16, 2020, the World Health Organization reported 167,515 confirmed cases of COVID-19 and 6,606 deaths from around the world, with a mortality rate of 3.9%. But the actual mortality rate may be lower, the authors suggested, because a study involving more than 1,000 confirmed cases reported a mortality rate of 1.4%.

“Considering that the number of unreported and unconfirmed cases is likely to be much higher than the reported cases, the actual mortality may be less than 1%, which is similar to that of severe seasonal influenza,” the authors said, in reference to an editorial by Anthony S. Fauci, MD, and colleagues in the New England Journal of Medicine. In addition, they noted, mortality rates may vary by region.

The largest study relevant to patients with diabetes, which involved 72,314 cases of COVID-19, showed that patients with diabetes had a threefold higher mortality rate than did those without diabetes (7.3% vs. 2.3%, respectively). These figures were reported by the Chinese Centre for Disease Control and Prevention.

However, data from smaller cohorts with diabetes and COVID-19 have yielded mixed results. For instance, one study, involving 140 patients from Wuhan, suggested that diabetes was not a risk factor for severe disease, and in an analysis of 11 studies reporting on laboratory abnormalities in patients with a diagnosis of COVID-19, raised blood sugar levels or diabetes were not mentioned among the predictors of severe disease.

“Our knowledge about the prevalence of COVID-19 and disease course in people with diabetes will evolve as more detailed analyses are carried out,” the authors wrote. “For now, it is reasonable to assume that people with diabetes are at increased risk of developing infection. Coexisting heart disease, kidney disease, advanced age, and frailty are likely to further increase the severity of disease.”
 

Prevention first

“It is important that people with diabetes maintain good glycemic control, because it might help in reducing the risk of infection and the severity,” the authors wrote.

In addition to more frequent monitoring of blood glucose levels, they recommended other preventive measures, such as getting adequate nutrition, exercising, and being current with vaccinations for influenza and pneumonia. The latter, they said, may also reduce the risk of secondary bacterial pneumonia after a respiratory viral infection.

In regard to nutrition, adequate protein intake is important and “any deficiencies of minerals and vitamins need to be taken care of,” they advised. Likewise, exercise is known to improve immunity and should continue, but they suggest avoiding gyms and swimming pools.

For patients with coexisting heart and/or kidney disease, they also recommended efforts to stabilize cardiac/renal status.

In addition, the general preventive measures, such as regular and thorough hand washing with soap and water, practicing good respiratory hygiene by sneezing and coughing into a bent elbow or a facial tissue, and avoiding contact with anyone who is infected, should be observed.

As with other patients with chronic diseases that are managed long-term medications, patients with diabetes should always ensure that they have a sufficient supply of their medications and refills, if possible.
 

After a diagnosis

If patients with diabetes develop COVID-19, then home management may still be possible, wrote the authors, who recommended basic treatment measures such as maintaining hydration and managing symptoms with acetaminophen and steam inhalation, and home isolation for 14 days or until the symptoms resolve.

In the event of hyperglycemia with fever in patients with type 1 diabetes, blood glucose and urinary ketones should be monitored often. “Frequent changes in dosage and correctional bolus may be required to maintain normoglycemia,” they cautioned.

Concerning diabetic drug regimens, they suggest patients avoid antihyperglycemic agents that can cause volume depletion or hypoglycemia and, if necessary, that they reduce oral antidiabetic drugs and follow sick-day guidelines.

For hospitalized patients, the investigators strengthened that statement, advising that oral agents need to be stopped, particularly sodium-glucose cotransporter 2 inhibitors and metformin. “Insulin is the preferred agent for control of hyperglycemia in hospitalized sick patients,” they wrote.

Untested therapies

The authors also discussed a range of untested therapies that may help fight COVID-19, such as antiviral drugs (such as lopinavir and ritonavir), zinc nanoparticles, and vitamin C. Supplementing those recommendations, Dr. Gupta and colleagues provided a concise review of COVID-19 epidemiology and extant data relevant to patients with diabetes.

The investigators reported no conflicts of interest.

SOURCE: Gupta et al. Diabetes Metab Syndr. 2020;14(3):211-12.

Patients with diabetes may have an increased risk of developing coronavirus infection (COVID-19), along with increased risks of morbidity and mortality, according to researchers writing in Diabetes & Metabolic Syndrome.

Although relevant clinical data remain scarce, patients with diabetes should take extra precautions to avoid infection and, if infected, may require special care, reported Ritesh Gupta, MD, of Fortis C-DOC Hospital, New Delhi, and colleagues.

“The disease severity [with COVID-19] has varied from mild, self-limiting, flu-like illness to fulminant pneumonia, respiratory failure, and death,” the authors wrote.

As of March 16, 2020, the World Health Organization reported 167,515 confirmed cases of COVID-19 and 6,606 deaths from around the world, with a mortality rate of 3.9%. But the actual mortality rate may be lower, the authors suggested, because a study involving more than 1,000 confirmed cases reported a mortality rate of 1.4%.

“Considering that the number of unreported and unconfirmed cases is likely to be much higher than the reported cases, the actual mortality may be less than 1%, which is similar to that of severe seasonal influenza,” the authors said, in reference to an editorial by Anthony S. Fauci, MD, and colleagues in the New England Journal of Medicine. In addition, they noted, mortality rates may vary by region.

The largest study relevant to patients with diabetes, which involved 72,314 cases of COVID-19, showed that patients with diabetes had a threefold higher mortality rate than did those without diabetes (7.3% vs. 2.3%, respectively). These figures were reported by the Chinese Centre for Disease Control and Prevention.

However, data from smaller cohorts with diabetes and COVID-19 have yielded mixed results. For instance, one study, involving 140 patients from Wuhan, suggested that diabetes was not a risk factor for severe disease, and in an analysis of 11 studies reporting on laboratory abnormalities in patients with a diagnosis of COVID-19, raised blood sugar levels or diabetes were not mentioned among the predictors of severe disease.

“Our knowledge about the prevalence of COVID-19 and disease course in people with diabetes will evolve as more detailed analyses are carried out,” the authors wrote. “For now, it is reasonable to assume that people with diabetes are at increased risk of developing infection. Coexisting heart disease, kidney disease, advanced age, and frailty are likely to further increase the severity of disease.”
 

Prevention first

“It is important that people with diabetes maintain good glycemic control, because it might help in reducing the risk of infection and the severity,” the authors wrote.

In addition to more frequent monitoring of blood glucose levels, they recommended other preventive measures, such as getting adequate nutrition, exercising, and being current with vaccinations for influenza and pneumonia. The latter, they said, may also reduce the risk of secondary bacterial pneumonia after a respiratory viral infection.

In regard to nutrition, adequate protein intake is important and “any deficiencies of minerals and vitamins need to be taken care of,” they advised. Likewise, exercise is known to improve immunity and should continue, but they suggest avoiding gyms and swimming pools.

For patients with coexisting heart and/or kidney disease, they also recommended efforts to stabilize cardiac/renal status.

In addition, the general preventive measures, such as regular and thorough hand washing with soap and water, practicing good respiratory hygiene by sneezing and coughing into a bent elbow or a facial tissue, and avoiding contact with anyone who is infected, should be observed.

As with other patients with chronic diseases that are managed long-term medications, patients with diabetes should always ensure that they have a sufficient supply of their medications and refills, if possible.
 

After a diagnosis

If patients with diabetes develop COVID-19, then home management may still be possible, wrote the authors, who recommended basic treatment measures such as maintaining hydration and managing symptoms with acetaminophen and steam inhalation, and home isolation for 14 days or until the symptoms resolve.

In the event of hyperglycemia with fever in patients with type 1 diabetes, blood glucose and urinary ketones should be monitored often. “Frequent changes in dosage and correctional bolus may be required to maintain normoglycemia,” they cautioned.

Concerning diabetic drug regimens, they suggest patients avoid antihyperglycemic agents that can cause volume depletion or hypoglycemia and, if necessary, that they reduce oral antidiabetic drugs and follow sick-day guidelines.

For hospitalized patients, the investigators strengthened that statement, advising that oral agents need to be stopped, particularly sodium-glucose cotransporter 2 inhibitors and metformin. “Insulin is the preferred agent for control of hyperglycemia in hospitalized sick patients,” they wrote.

Untested therapies

The authors also discussed a range of untested therapies that may help fight COVID-19, such as antiviral drugs (such as lopinavir and ritonavir), zinc nanoparticles, and vitamin C. Supplementing those recommendations, Dr. Gupta and colleagues provided a concise review of COVID-19 epidemiology and extant data relevant to patients with diabetes.

The investigators reported no conflicts of interest.

SOURCE: Gupta et al. Diabetes Metab Syndr. 2020;14(3):211-12.

The Food and Drug Administration announced three measures aimed at improving the testing capacity for COVID-19.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

First, the FDA is giving states more flexibility to approve and implement testing for COVID-19.

“States can set up a system in which they take responsibility for authorizing such tests and the laboratories will not engage with the FDA,” agency Commissioner Stephen Hahn, MD, said in a March 16 statement announcing the policy updates. “Laboratories developing tests in these states can engage directly with the appropriate state authorities, instead of with the FDA.”

A copy of the updated guidance document can be found here.

Dr. Hahn added that laboratories working within this authority granted to states will not have to pursue an emergency use authorization (EUA). New York state was previously granted a waiver to allow for more state oversight over the introduction of diagnostic testing.

Second, the FDA is expanding guidance issued on Feb. 29 on who can develop diagnostic tests. Originally, the Feb. 29 guidance was aimed at labs certified to perform high-complexity testing consistent with requirements outlined in the Clinical Laboratory Improvement Amendments.

“Under the update published today, the agency does not intend to object to commercial manufacturers distributing and labs using new commercially developed tests prior to the FDA granting an EUA, under certain circumstances,” Commissioner Hahn said, adding that a number of commercial manufacturers are developing tests for the coronavirus with the intent of submitting an EUA request.

“During this public health emergency, the FDA does not intend to object to the distribution and use of these tests for specimen testing for a reasonable period of time after the manufacturer’s validation of the test while the manufacturer is preparing its EUA request,” he added.

The updated guidance also provides recommendations for test developers working on serologic tests for COVID-19.

During a March 16 conference call with reporters, Commissioner Hahn said the flexibility would add a “significant number of tests and we believe this will be a surge to meet the demand that we expect to see, although it is somewhat difficult” to quantify the number of tests this new flexibility will bring to the market.

[email protected]

The Food and Drug Administration announced three measures aimed at improving the testing capacity for COVID-19.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

First, the FDA is giving states more flexibility to approve and implement testing for COVID-19.

“States can set up a system in which they take responsibility for authorizing such tests and the laboratories will not engage with the FDA,” agency Commissioner Stephen Hahn, MD, said in a March 16 statement announcing the policy updates. “Laboratories developing tests in these states can engage directly with the appropriate state authorities, instead of with the FDA.”

A copy of the updated guidance document can be found here.

Dr. Hahn added that laboratories working within this authority granted to states will not have to pursue an emergency use authorization (EUA). New York state was previously granted a waiver to allow for more state oversight over the introduction of diagnostic testing.

Second, the FDA is expanding guidance issued on Feb. 29 on who can develop diagnostic tests. Originally, the Feb. 29 guidance was aimed at labs certified to perform high-complexity testing consistent with requirements outlined in the Clinical Laboratory Improvement Amendments.

“Under the update published today, the agency does not intend to object to commercial manufacturers distributing and labs using new commercially developed tests prior to the FDA granting an EUA, under certain circumstances,” Commissioner Hahn said, adding that a number of commercial manufacturers are developing tests for the coronavirus with the intent of submitting an EUA request.

“During this public health emergency, the FDA does not intend to object to the distribution and use of these tests for specimen testing for a reasonable period of time after the manufacturer’s validation of the test while the manufacturer is preparing its EUA request,” he added.

The updated guidance also provides recommendations for test developers working on serologic tests for COVID-19.

During a March 16 conference call with reporters, Commissioner Hahn said the flexibility would add a “significant number of tests and we believe this will be a surge to meet the demand that we expect to see, although it is somewhat difficult” to quantify the number of tests this new flexibility will bring to the market.

[email protected]

The Food and Drug Administration announced three measures aimed at improving the testing capacity for COVID-19.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

First, the FDA is giving states more flexibility to approve and implement testing for COVID-19.

“States can set up a system in which they take responsibility for authorizing such tests and the laboratories will not engage with the FDA,” agency Commissioner Stephen Hahn, MD, said in a March 16 statement announcing the policy updates. “Laboratories developing tests in these states can engage directly with the appropriate state authorities, instead of with the FDA.”

A copy of the updated guidance document can be found here.

Dr. Hahn added that laboratories working within this authority granted to states will not have to pursue an emergency use authorization (EUA). New York state was previously granted a waiver to allow for more state oversight over the introduction of diagnostic testing.

Second, the FDA is expanding guidance issued on Feb. 29 on who can develop diagnostic tests. Originally, the Feb. 29 guidance was aimed at labs certified to perform high-complexity testing consistent with requirements outlined in the Clinical Laboratory Improvement Amendments.

“Under the update published today, the agency does not intend to object to commercial manufacturers distributing and labs using new commercially developed tests prior to the FDA granting an EUA, under certain circumstances,” Commissioner Hahn said, adding that a number of commercial manufacturers are developing tests for the coronavirus with the intent of submitting an EUA request.

“During this public health emergency, the FDA does not intend to object to the distribution and use of these tests for specimen testing for a reasonable period of time after the manufacturer’s validation of the test while the manufacturer is preparing its EUA request,” he added.

The updated guidance also provides recommendations for test developers working on serologic tests for COVID-19.

During a March 16 conference call with reporters, Commissioner Hahn said the flexibility would add a “significant number of tests and we believe this will be a surge to meet the demand that we expect to see, although it is somewhat difficult” to quantify the number of tests this new flexibility will bring to the market.

[email protected]

With new developments daily and lingering uncertainty about COVID-19, questions about testing and treatment for the coronavirus are at the forefront.

To address these top questions, Jay C. Butler, MD, deputy director for infectious diseases at the Centers for Disease Control and Prevention, sat down with JAMA editor Howard Bauchner, MD, to discuss the latest data on COVID-19 and to outline updated guidance from the agency. The following question-and-answer session was part of a live stream interview hosted by JAMA on March 16, 2020. The questions have been edited for length and clarity.
 

What test is being used to identify COVID-19?

In the United States, the most common and widely available test is the RT-polymerase chain reaction (rRT-PCR), which over the past few weeks has become available at public health labs across the country, Dr. Butler said during the JAMA interview. Capacity for the test is now possible in all 50 states and in Washington, D.C.

“More recently, there’s been a number of commercial labs that have come online to be able to do the testing,” Dr. Butler said. “Additionally, a number of academic centers are now able to run [Food and Drug Administration]–approved testing using slightly different PCR platforms.”
 

How accurate is the test?

Dr. Butler called PCR the “gold standard,” for testing COVID-19, and said it’s safe to say the test’s likelihood of identifying infection or past infection is extremely high. However, data on test sensitivity is limited.

“This may be frustrating to those of us who really like to know specifics of how to interpret the test results, but it’s important to keep in mind, we’re talking about a virus that we didn’t know existed 3 months ago,” he said.
 

At what point does a person with coronavirus test positive?

When exactly a test becomes positive is an unknown, Dr. Butler said. The assumption is that a patient who tests positive is more likely to be infectious, and data suggest the level of infectiousness is greatest after the onset of symptoms.

“There is at least some anecdotal reports that suggest that transmission could occur before onset of symptoms, but the data is still very limited,” he said. “Of course that has big implications in terms of how well we can really slow the spread of the virus.”
 

Who should get tested?

Dr. Butler said the focus should be individuals who are symptomatic with evidence of respiratory tract infection. People who are concerned about the virus and want a test are not the target.

“It’s important when talking to patients to help them to understand, this is different than a test for HIV or hepatitis C, where much of the message is: ‘Please get tested.’ ” he said. “This a situation where we’re trying to diagnose an acute infection. We do have a resource that may become limited again as some of the equipment required for running the test or collecting the specimen may come into short supply, so we want to focus on those people who are symptomatic and particularly on people who may be at higher risk of more severe illness.”
 

If a previously infected patient tests negative, can they still shed virus?

The CDC is currently analyzing how a negative PCR test relates to viral load, according to Dr. Butler. He added there have been situations in which a patient has twice tested negative for the virus, but a third swab resulted in a weakly positive result.

“It’s not clear if those are people who are actually infectious,” he said. “The PCR is detecting viral RNA, it doesn’t necessarily indicate there is viable virus present in the respiratory tract. So in general, I think it is safe to go back to work, but a positive test in a situation like that can be very difficult to interpret because we think it probably doesn’t reflect infectivity, but we don’t know for sure.”
 

Do we have an adequate supply of tests in the United States?

The CDC has addressed supply concerns by broadening the number of PCR platforms that can be used to run COVID-19 analyses, Dr. Butler said. Expansion of these platforms has been one way the government is furthering testing options and enabling consumer labs and academic centers to contribute to testing.

When can people who test positive go back to work?

The CDC is still researching that question and reviewing the data, Dr. Butler said. The current recommendation is that a patient who tests positive is considered clear to return to work after two negative tests at least 24 hours apart, following the resolution of symptoms. The CDC has not yet made an official recommendation on an exact time frame, but the CDC is considering a 14-day minimum of quarantine.

“The one caveat I’ll add is that someone who is a health care worker, even if they have resolved symptoms, it’s still a good idea to wear a surgical mask [when they return to work], just as an extra precaution.”
 

What do we know about immunity? Can patients get reinfected?

Long-term immunity after exposure and infection is virtually unknown, Dr. Butler said. Investigators know those with COVID-19 have an antibody response, but whether that is protective or not, is unclear. In regard to older coronaviruses, such as those that cause colds, patients generally develop an antibody response and may have a period of immunity, but that immunity eventually wanes and reinfection can occur.

What is the latest on therapies?

A number of trials are underway in China and in the United States to test possible therapies for COVID-19, Dr. Butler said. One of the candidate drugs is the broad spectrum antiviral drug remdesivir, which was developed for the treatment of the Ebola virus. Additionally, the National Institutes of Health is studying the potential for monoclonal antibodies to treat COVID-19.

“Of course these are drugs not yet FDA approved,” he said. “We all want to have them in our toolbox as soon as possible, but we want to make sure these drugs are going to benefit and not harm, and that they really do have the utility that we hope for.”
 

Is there specific guidance for healthcare workers about COVID-19?

Health care workers have a much higher likelihood of being exposed or exposing others who are at high risk of severe infection, Dr. Butler said. That’s why, if a health care worker becomes infected and recovers, it’s still important to take extra precautions when going back to work, such as wearing a mask.

“These are recommendations that are in-draft,” he said. “I want to be clear, I’m floating concepts out there that people can consider. ... I recognize as a former infection control medical director at a hospital that sometimes you have to adapt those guidelines based on your local conditions.”

[email protected]

With new developments daily and lingering uncertainty about COVID-19, questions about testing and treatment for the coronavirus are at the forefront.

To address these top questions, Jay C. Butler, MD, deputy director for infectious diseases at the Centers for Disease Control and Prevention, sat down with JAMA editor Howard Bauchner, MD, to discuss the latest data on COVID-19 and to outline updated guidance from the agency. The following question-and-answer session was part of a live stream interview hosted by JAMA on March 16, 2020. The questions have been edited for length and clarity.
 

What test is being used to identify COVID-19?

In the United States, the most common and widely available test is the RT-polymerase chain reaction (rRT-PCR), which over the past few weeks has become available at public health labs across the country, Dr. Butler said during the JAMA interview. Capacity for the test is now possible in all 50 states and in Washington, D.C.

“More recently, there’s been a number of commercial labs that have come online to be able to do the testing,” Dr. Butler said. “Additionally, a number of academic centers are now able to run [Food and Drug Administration]–approved testing using slightly different PCR platforms.”
 

How accurate is the test?

Dr. Butler called PCR the “gold standard,” for testing COVID-19, and said it’s safe to say the test’s likelihood of identifying infection or past infection is extremely high. However, data on test sensitivity is limited.

“This may be frustrating to those of us who really like to know specifics of how to interpret the test results, but it’s important to keep in mind, we’re talking about a virus that we didn’t know existed 3 months ago,” he said.
 

At what point does a person with coronavirus test positive?

When exactly a test becomes positive is an unknown, Dr. Butler said. The assumption is that a patient who tests positive is more likely to be infectious, and data suggest the level of infectiousness is greatest after the onset of symptoms.

“There is at least some anecdotal reports that suggest that transmission could occur before onset of symptoms, but the data is still very limited,” he said. “Of course that has big implications in terms of how well we can really slow the spread of the virus.”
 

Who should get tested?

Dr. Butler said the focus should be individuals who are symptomatic with evidence of respiratory tract infection. People who are concerned about the virus and want a test are not the target.

“It’s important when talking to patients to help them to understand, this is different than a test for HIV or hepatitis C, where much of the message is: ‘Please get tested.’ ” he said. “This a situation where we’re trying to diagnose an acute infection. We do have a resource that may become limited again as some of the equipment required for running the test or collecting the specimen may come into short supply, so we want to focus on those people who are symptomatic and particularly on people who may be at higher risk of more severe illness.”
 

If a previously infected patient tests negative, can they still shed virus?

The CDC is currently analyzing how a negative PCR test relates to viral load, according to Dr. Butler. He added there have been situations in which a patient has twice tested negative for the virus, but a third swab resulted in a weakly positive result.

“It’s not clear if those are people who are actually infectious,” he said. “The PCR is detecting viral RNA, it doesn’t necessarily indicate there is viable virus present in the respiratory tract. So in general, I think it is safe to go back to work, but a positive test in a situation like that can be very difficult to interpret because we think it probably doesn’t reflect infectivity, but we don’t know for sure.”
 

Do we have an adequate supply of tests in the United States?

The CDC has addressed supply concerns by broadening the number of PCR platforms that can be used to run COVID-19 analyses, Dr. Butler said. Expansion of these platforms has been one way the government is furthering testing options and enabling consumer labs and academic centers to contribute to testing.

When can people who test positive go back to work?

The CDC is still researching that question and reviewing the data, Dr. Butler said. The current recommendation is that a patient who tests positive is considered clear to return to work after two negative tests at least 24 hours apart, following the resolution of symptoms. The CDC has not yet made an official recommendation on an exact time frame, but the CDC is considering a 14-day minimum of quarantine.

“The one caveat I’ll add is that someone who is a health care worker, even if they have resolved symptoms, it’s still a good idea to wear a surgical mask [when they return to work], just as an extra precaution.”
 

What do we know about immunity? Can patients get reinfected?

Long-term immunity after exposure and infection is virtually unknown, Dr. Butler said. Investigators know those with COVID-19 have an antibody response, but whether that is protective or not, is unclear. In regard to older coronaviruses, such as those that cause colds, patients generally develop an antibody response and may have a period of immunity, but that immunity eventually wanes and reinfection can occur.

What is the latest on therapies?

A number of trials are underway in China and in the United States to test possible therapies for COVID-19, Dr. Butler said. One of the candidate drugs is the broad spectrum antiviral drug remdesivir, which was developed for the treatment of the Ebola virus. Additionally, the National Institutes of Health is studying the potential for monoclonal antibodies to treat COVID-19.

“Of course these are drugs not yet FDA approved,” he said. “We all want to have them in our toolbox as soon as possible, but we want to make sure these drugs are going to benefit and not harm, and that they really do have the utility that we hope for.”
 

Is there specific guidance for healthcare workers about COVID-19?

Health care workers have a much higher likelihood of being exposed or exposing others who are at high risk of severe infection, Dr. Butler said. That’s why, if a health care worker becomes infected and recovers, it’s still important to take extra precautions when going back to work, such as wearing a mask.

“These are recommendations that are in-draft,” he said. “I want to be clear, I’m floating concepts out there that people can consider. ... I recognize as a former infection control medical director at a hospital that sometimes you have to adapt those guidelines based on your local conditions.”

[email protected]

With new developments daily and lingering uncertainty about COVID-19, questions about testing and treatment for the coronavirus are at the forefront.

To address these top questions, Jay C. Butler, MD, deputy director for infectious diseases at the Centers for Disease Control and Prevention, sat down with JAMA editor Howard Bauchner, MD, to discuss the latest data on COVID-19 and to outline updated guidance from the agency. The following question-and-answer session was part of a live stream interview hosted by JAMA on March 16, 2020. The questions have been edited for length and clarity.
 

What test is being used to identify COVID-19?

In the United States, the most common and widely available test is the RT-polymerase chain reaction (rRT-PCR), which over the past few weeks has become available at public health labs across the country, Dr. Butler said during the JAMA interview. Capacity for the test is now possible in all 50 states and in Washington, D.C.

“More recently, there’s been a number of commercial labs that have come online to be able to do the testing,” Dr. Butler said. “Additionally, a number of academic centers are now able to run [Food and Drug Administration]–approved testing using slightly different PCR platforms.”
 

How accurate is the test?

Dr. Butler called PCR the “gold standard,” for testing COVID-19, and said it’s safe to say the test’s likelihood of identifying infection or past infection is extremely high. However, data on test sensitivity is limited.

“This may be frustrating to those of us who really like to know specifics of how to interpret the test results, but it’s important to keep in mind, we’re talking about a virus that we didn’t know existed 3 months ago,” he said.
 

At what point does a person with coronavirus test positive?

When exactly a test becomes positive is an unknown, Dr. Butler said. The assumption is that a patient who tests positive is more likely to be infectious, and data suggest the level of infectiousness is greatest after the onset of symptoms.

“There is at least some anecdotal reports that suggest that transmission could occur before onset of symptoms, but the data is still very limited,” he said. “Of course that has big implications in terms of how well we can really slow the spread of the virus.”
 

Who should get tested?

Dr. Butler said the focus should be individuals who are symptomatic with evidence of respiratory tract infection. People who are concerned about the virus and want a test are not the target.

“It’s important when talking to patients to help them to understand, this is different than a test for HIV or hepatitis C, where much of the message is: ‘Please get tested.’ ” he said. “This a situation where we’re trying to diagnose an acute infection. We do have a resource that may become limited again as some of the equipment required for running the test or collecting the specimen may come into short supply, so we want to focus on those people who are symptomatic and particularly on people who may be at higher risk of more severe illness.”
 

If a previously infected patient tests negative, can they still shed virus?

The CDC is currently analyzing how a negative PCR test relates to viral load, according to Dr. Butler. He added there have been situations in which a patient has twice tested negative for the virus, but a third swab resulted in a weakly positive result.

“It’s not clear if those are people who are actually infectious,” he said. “The PCR is detecting viral RNA, it doesn’t necessarily indicate there is viable virus present in the respiratory tract. So in general, I think it is safe to go back to work, but a positive test in a situation like that can be very difficult to interpret because we think it probably doesn’t reflect infectivity, but we don’t know for sure.”
 

Do we have an adequate supply of tests in the United States?

The CDC has addressed supply concerns by broadening the number of PCR platforms that can be used to run COVID-19 analyses, Dr. Butler said. Expansion of these platforms has been one way the government is furthering testing options and enabling consumer labs and academic centers to contribute to testing.

When can people who test positive go back to work?

The CDC is still researching that question and reviewing the data, Dr. Butler said. The current recommendation is that a patient who tests positive is considered clear to return to work after two negative tests at least 24 hours apart, following the resolution of symptoms. The CDC has not yet made an official recommendation on an exact time frame, but the CDC is considering a 14-day minimum of quarantine.

“The one caveat I’ll add is that someone who is a health care worker, even if they have resolved symptoms, it’s still a good idea to wear a surgical mask [when they return to work], just as an extra precaution.”
 

What do we know about immunity? Can patients get reinfected?

Long-term immunity after exposure and infection is virtually unknown, Dr. Butler said. Investigators know those with COVID-19 have an antibody response, but whether that is protective or not, is unclear. In regard to older coronaviruses, such as those that cause colds, patients generally develop an antibody response and may have a period of immunity, but that immunity eventually wanes and reinfection can occur.

What is the latest on therapies?

A number of trials are underway in China and in the United States to test possible therapies for COVID-19, Dr. Butler said. One of the candidate drugs is the broad spectrum antiviral drug remdesivir, which was developed for the treatment of the Ebola virus. Additionally, the National Institutes of Health is studying the potential for monoclonal antibodies to treat COVID-19.

“Of course these are drugs not yet FDA approved,” he said. “We all want to have them in our toolbox as soon as possible, but we want to make sure these drugs are going to benefit and not harm, and that they really do have the utility that we hope for.”
 

Is there specific guidance for healthcare workers about COVID-19?

Health care workers have a much higher likelihood of being exposed or exposing others who are at high risk of severe infection, Dr. Butler said. That’s why, if a health care worker becomes infected and recovers, it’s still important to take extra precautions when going back to work, such as wearing a mask.

“These are recommendations that are in-draft,” he said. “I want to be clear, I’m floating concepts out there that people can consider. ... I recognize as a former infection control medical director at a hospital that sometimes you have to adapt those guidelines based on your local conditions.”

[email protected]

President Donald Trump has advised state governors not to wait on the federal government when it comes to ensuring readiness for a surge in patients from the COVID-19 outbreak.

Courtesy CDC

“If they are able to get ventilators, respirators, if they are able to get certain things without having to go through the longer process of federal government,” they should order on their own and bypass the federal government ordering system, the president stated during a March 16 press briefing.

That being said, he noted that the federal government is “ordering tremendous numbers of ventilators, respirators, [and] masks,” although he could not give a specific number on how much has been ordered or how many has already been stockpiled.

“It is always going to be faster if they can get them directly, if they need them, and I have given them authorization to order directly,” President Trump said.

The comments came as the White House revised recommendations on gatherings. The new guidelines now limit gatherings to no more than 10 people. Officials are further advising Americans to self-quarantine for 2 weeks if they are sick, if someone in their house is sick, or if someone in their house has tested positive for COVID-19.

Additionally, the White House called on Americans to limit discretionary travel and to avoid eating and drinking in restaurants, bars, and food courts during the next 15 days, even if they are feeling healthy and are asymptomatic.

“With several weeks of focused action, we can turn the corner and turn it quickly,” the president said.

In terms of testing, the Food and Drug Administration has granted emergency use authorization to two commercial diagnostic tests: Thermo Fisher for its TaqPath COVID-19 Combo Kit and Roche for its cobas SARS-CoV-2 test. White House officials said up to 1 million tests will be available this week, with 2 million next week.

The president also announced that phase 1 testing of a vaccine has begun. The test involves more than 40 healthy volunteers in the Seattle area who will receive three shots over the trial period. Phase 1 testing is generally conducted to determine safety of a new therapeutic.

[email protected]

President Donald Trump has advised state governors not to wait on the federal government when it comes to ensuring readiness for a surge in patients from the COVID-19 outbreak.

Courtesy CDC

“If they are able to get ventilators, respirators, if they are able to get certain things without having to go through the longer process of federal government,” they should order on their own and bypass the federal government ordering system, the president stated during a March 16 press briefing.

That being said, he noted that the federal government is “ordering tremendous numbers of ventilators, respirators, [and] masks,” although he could not give a specific number on how much has been ordered or how many has already been stockpiled.

“It is always going to be faster if they can get them directly, if they need them, and I have given them authorization to order directly,” President Trump said.

The comments came as the White House revised recommendations on gatherings. The new guidelines now limit gatherings to no more than 10 people. Officials are further advising Americans to self-quarantine for 2 weeks if they are sick, if someone in their house is sick, or if someone in their house has tested positive for COVID-19.

Additionally, the White House called on Americans to limit discretionary travel and to avoid eating and drinking in restaurants, bars, and food courts during the next 15 days, even if they are feeling healthy and are asymptomatic.

“With several weeks of focused action, we can turn the corner and turn it quickly,” the president said.

In terms of testing, the Food and Drug Administration has granted emergency use authorization to two commercial diagnostic tests: Thermo Fisher for its TaqPath COVID-19 Combo Kit and Roche for its cobas SARS-CoV-2 test. White House officials said up to 1 million tests will be available this week, with 2 million next week.

The president also announced that phase 1 testing of a vaccine has begun. The test involves more than 40 healthy volunteers in the Seattle area who will receive three shots over the trial period. Phase 1 testing is generally conducted to determine safety of a new therapeutic.

[email protected]

President Donald Trump has advised state governors not to wait on the federal government when it comes to ensuring readiness for a surge in patients from the COVID-19 outbreak.

Courtesy CDC

“If they are able to get ventilators, respirators, if they are able to get certain things without having to go through the longer process of federal government,” they should order on their own and bypass the federal government ordering system, the president stated during a March 16 press briefing.

That being said, he noted that the federal government is “ordering tremendous numbers of ventilators, respirators, [and] masks,” although he could not give a specific number on how much has been ordered or how many has already been stockpiled.

“It is always going to be faster if they can get them directly, if they need them, and I have given them authorization to order directly,” President Trump said.

The comments came as the White House revised recommendations on gatherings. The new guidelines now limit gatherings to no more than 10 people. Officials are further advising Americans to self-quarantine for 2 weeks if they are sick, if someone in their house is sick, or if someone in their house has tested positive for COVID-19.

Additionally, the White House called on Americans to limit discretionary travel and to avoid eating and drinking in restaurants, bars, and food courts during the next 15 days, even if they are feeling healthy and are asymptomatic.

“With several weeks of focused action, we can turn the corner and turn it quickly,” the president said.

In terms of testing, the Food and Drug Administration has granted emergency use authorization to two commercial diagnostic tests: Thermo Fisher for its TaqPath COVID-19 Combo Kit and Roche for its cobas SARS-CoV-2 test. White House officials said up to 1 million tests will be available this week, with 2 million next week.

The president also announced that phase 1 testing of a vaccine has begun. The test involves more than 40 healthy volunteers in the Seattle area who will receive three shots over the trial period. Phase 1 testing is generally conducted to determine safety of a new therapeutic.

[email protected]

Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s Coronavirus Resource Center.

The European Society of Cardiology (ESC) has issued a statement urging physicians and patients to continue treatment with angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), in light of a newly described theory that those agents could increase the risk of developing COVID-19 and/or worsen its severity.

The concern arises from the observation that the new coronavirus SARS-CoV-2 causing COVID-19 binds to angiotensin-converting enzyme 2 (ACE2) to infect cells, and both ACE inhibitors and ARBs increase ACE2 levels.

This mechanism has been theorized as a possible risk factor for facilitating the acquisition of COVID-19 infection and worsening its severity. However, paradoxically, it has also been hypothesized to protect against acute lung injury from the disease.

Meanwhile, a Lancet Respiratory Medicine article was published March 11 entitled, “Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?”

“We ... hypothesize that diabetes and hypertension treatment with ACE2-stimulating drugs increases the risk of developing severe and fatal COVID-19,” said the authors.

This prompted some media coverage in the United Kingdom and “social media-related amplification,” leading to concern and, in some cases, discontinuation of the drugs by patients.

But on March 13, the ESC Council on Hypertension dismissed the concerns as entirely speculative, in a statement posted to the ESC website.

It said that the council “strongly recommend that physicians and patients should continue treatment with their usual antihypertensive therapy because there is no clinical or scientific evidence to suggest that treatment with ACE inhibitors or ARBs should be discontinued because of the COVID-19 infection.”

The statement, signed by Council Chair Professor Giovanni de Simone, MD, on behalf of the nucleus members, also says that in regard to the theorized protective effect against serious lung complications in individuals with COVID-19, the data come only from animal, and not human, studies.

“Speculation about the safety of ACE-inhibitor or ARB treatment in relation to COVID-19 does not have a sound scientific basis or evidence to support it,” the ESC panel concludes.

This article first appeared on Medscape.com.

Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s Coronavirus Resource Center.

The European Society of Cardiology (ESC) has issued a statement urging physicians and patients to continue treatment with angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), in light of a newly described theory that those agents could increase the risk of developing COVID-19 and/or worsen its severity.

The concern arises from the observation that the new coronavirus SARS-CoV-2 causing COVID-19 binds to angiotensin-converting enzyme 2 (ACE2) to infect cells, and both ACE inhibitors and ARBs increase ACE2 levels.

This mechanism has been theorized as a possible risk factor for facilitating the acquisition of COVID-19 infection and worsening its severity. However, paradoxically, it has also been hypothesized to protect against acute lung injury from the disease.

Meanwhile, a Lancet Respiratory Medicine article was published March 11 entitled, “Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?”

“We ... hypothesize that diabetes and hypertension treatment with ACE2-stimulating drugs increases the risk of developing severe and fatal COVID-19,” said the authors.

This prompted some media coverage in the United Kingdom and “social media-related amplification,” leading to concern and, in some cases, discontinuation of the drugs by patients.

But on March 13, the ESC Council on Hypertension dismissed the concerns as entirely speculative, in a statement posted to the ESC website.

It said that the council “strongly recommend that physicians and patients should continue treatment with their usual antihypertensive therapy because there is no clinical or scientific evidence to suggest that treatment with ACE inhibitors or ARBs should be discontinued because of the COVID-19 infection.”

The statement, signed by Council Chair Professor Giovanni de Simone, MD, on behalf of the nucleus members, also says that in regard to the theorized protective effect against serious lung complications in individuals with COVID-19, the data come only from animal, and not human, studies.

“Speculation about the safety of ACE-inhibitor or ARB treatment in relation to COVID-19 does not have a sound scientific basis or evidence to support it,” the ESC panel concludes.

This article first appeared on Medscape.com.

Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s Coronavirus Resource Center.

The European Society of Cardiology (ESC) has issued a statement urging physicians and patients to continue treatment with angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), in light of a newly described theory that those agents could increase the risk of developing COVID-19 and/or worsen its severity.

The concern arises from the observation that the new coronavirus SARS-CoV-2 causing COVID-19 binds to angiotensin-converting enzyme 2 (ACE2) to infect cells, and both ACE inhibitors and ARBs increase ACE2 levels.

This mechanism has been theorized as a possible risk factor for facilitating the acquisition of COVID-19 infection and worsening its severity. However, paradoxically, it has also been hypothesized to protect against acute lung injury from the disease.

Meanwhile, a Lancet Respiratory Medicine article was published March 11 entitled, “Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?”

“We ... hypothesize that diabetes and hypertension treatment with ACE2-stimulating drugs increases the risk of developing severe and fatal COVID-19,” said the authors.

This prompted some media coverage in the United Kingdom and “social media-related amplification,” leading to concern and, in some cases, discontinuation of the drugs by patients.

But on March 13, the ESC Council on Hypertension dismissed the concerns as entirely speculative, in a statement posted to the ESC website.

It said that the council “strongly recommend that physicians and patients should continue treatment with their usual antihypertensive therapy because there is no clinical or scientific evidence to suggest that treatment with ACE inhibitors or ARBs should be discontinued because of the COVID-19 infection.”

The statement, signed by Council Chair Professor Giovanni de Simone, MD, on behalf of the nucleus members, also says that in regard to the theorized protective effect against serious lung complications in individuals with COVID-19, the data come only from animal, and not human, studies.

“Speculation about the safety of ACE-inhibitor or ARB treatment in relation to COVID-19 does not have a sound scientific basis or evidence to support it,” the ESC panel concludes.

This article first appeared on Medscape.com.

Testing rates for HIV in adolescents and young adults with sexually transmitted infections (STIs) are suboptimal, according to Danielle Petsis, MPH, of the Children’s Hospital of Philadelphia, and associates.

Courtesy Dr. Tom Folks, NIAID/National Institutes of Health

In a study published in Pediatrics, the investigators conducted a retrospective analysis of 1,816 acute STI events from 1,313 patients aged 13-24 years admitted between July 2014 and Dec. 2017 at two urban health care clinics. The most common STIs in the analysis were Chlamydia, gonorrhea, trichomoniasis, and syphilis; the mean age at diagnosis was 17 years, 71% of episodes occurred in females, and 97% occurred in African American patients.

Of the 1,816 events, HIV testing was completed within 90 days of the STI diagnosis for only 55%; there was 1 confirmed HIV diagnosis among the completed tests. When HIV testing did occur, in 38% of cases it was completed concurrently with STI testing or HIV testing was performed in 35% of the 872 follow-up cases. Of the 815 events where HIV testing was not performed, 27% had a test ordered by the provider but not completed by the patient; the patient leaving the laboratory before the test could be performed was the most common reason for test noncompletion (67%), followed by not showing up at all (18%) and errors in the medical record or laboratory (5%); the remaining patients gave as reasons for test noncompletion: declining an HIV test, a closed lab, or no reason.

Logistic regression showed that participants who were female and those with a previous history of STIs had significantly lower adjusted odds of HIV test completion, compared with males and those with no previous history of STIs, respectively, the investigators said. In addition, having insurance and having a family planning visit were associated with decreased odds of HIV testing, compared with not having insurance or a family planning visit.

“As we enter the fourth decade of the HIV epidemic, it remains clear that missed opportunities for diagnosis have the potential to delay HIV diagnosis and linkage to antiretroviral therapy or PrEP and prevention services, thus increasing the population risk of HIV transmission. Our data underscore the need for improved HIV testing education for providers of all levels of training and the need for public health agencies to clearly communicate the need for testing at the time of STI infection to reduce the number of missed opportunities for testing,” Ms. Petsis and colleagues concluded.

The study was supported by the National Institutes of Mental Health and the Children’s Hospital of Philadelphia Research Institute K-Readiness Award. One coauthor reported receiving funding from Bayer Healthcare, the Templeton Foundation, the National Institutes of Health, and Janssen Biotech. She also serves on expert advisory boards for Mylan Pharmaceuticals and Merck. The other authors have no relevant financial disclosures.

[email protected]

SOURCE: Wood S et al. Pediatrics. 2020 Mar 16. doi: 10.1542/peds.2019-2265.

Testing rates for HIV in adolescents and young adults with sexually transmitted infections (STIs) are suboptimal, according to Danielle Petsis, MPH, of the Children’s Hospital of Philadelphia, and associates.

Courtesy Dr. Tom Folks, NIAID/National Institutes of Health

In a study published in Pediatrics, the investigators conducted a retrospective analysis of 1,816 acute STI events from 1,313 patients aged 13-24 years admitted between July 2014 and Dec. 2017 at two urban health care clinics. The most common STIs in the analysis were Chlamydia, gonorrhea, trichomoniasis, and syphilis; the mean age at diagnosis was 17 years, 71% of episodes occurred in females, and 97% occurred in African American patients.

Of the 1,816 events, HIV testing was completed within 90 days of the STI diagnosis for only 55%; there was 1 confirmed HIV diagnosis among the completed tests. When HIV testing did occur, in 38% of cases it was completed concurrently with STI testing or HIV testing was performed in 35% of the 872 follow-up cases. Of the 815 events where HIV testing was not performed, 27% had a test ordered by the provider but not completed by the patient; the patient leaving the laboratory before the test could be performed was the most common reason for test noncompletion (67%), followed by not showing up at all (18%) and errors in the medical record or laboratory (5%); the remaining patients gave as reasons for test noncompletion: declining an HIV test, a closed lab, or no reason.

Logistic regression showed that participants who were female and those with a previous history of STIs had significantly lower adjusted odds of HIV test completion, compared with males and those with no previous history of STIs, respectively, the investigators said. In addition, having insurance and having a family planning visit were associated with decreased odds of HIV testing, compared with not having insurance or a family planning visit.

“As we enter the fourth decade of the HIV epidemic, it remains clear that missed opportunities for diagnosis have the potential to delay HIV diagnosis and linkage to antiretroviral therapy or PrEP and prevention services, thus increasing the population risk of HIV transmission. Our data underscore the need for improved HIV testing education for providers of all levels of training and the need for public health agencies to clearly communicate the need for testing at the time of STI infection to reduce the number of missed opportunities for testing,” Ms. Petsis and colleagues concluded.

The study was supported by the National Institutes of Mental Health and the Children’s Hospital of Philadelphia Research Institute K-Readiness Award. One coauthor reported receiving funding from Bayer Healthcare, the Templeton Foundation, the National Institutes of Health, and Janssen Biotech. She also serves on expert advisory boards for Mylan Pharmaceuticals and Merck. The other authors have no relevant financial disclosures.

[email protected]

SOURCE: Wood S et al. Pediatrics. 2020 Mar 16. doi: 10.1542/peds.2019-2265.

Testing rates for HIV in adolescents and young adults with sexually transmitted infections (STIs) are suboptimal, according to Danielle Petsis, MPH, of the Children’s Hospital of Philadelphia, and associates.

Courtesy Dr. Tom Folks, NIAID/National Institutes of Health

In a study published in Pediatrics, the investigators conducted a retrospective analysis of 1,816 acute STI events from 1,313 patients aged 13-24 years admitted between July 2014 and Dec. 2017 at two urban health care clinics. The most common STIs in the analysis were Chlamydia, gonorrhea, trichomoniasis, and syphilis; the mean age at diagnosis was 17 years, 71% of episodes occurred in females, and 97% occurred in African American patients.

Of the 1,816 events, HIV testing was completed within 90 days of the STI diagnosis for only 55%; there was 1 confirmed HIV diagnosis among the completed tests. When HIV testing did occur, in 38% of cases it was completed concurrently with STI testing or HIV testing was performed in 35% of the 872 follow-up cases. Of the 815 events where HIV testing was not performed, 27% had a test ordered by the provider but not completed by the patient; the patient leaving the laboratory before the test could be performed was the most common reason for test noncompletion (67%), followed by not showing up at all (18%) and errors in the medical record or laboratory (5%); the remaining patients gave as reasons for test noncompletion: declining an HIV test, a closed lab, or no reason.

Logistic regression showed that participants who were female and those with a previous history of STIs had significantly lower adjusted odds of HIV test completion, compared with males and those with no previous history of STIs, respectively, the investigators said. In addition, having insurance and having a family planning visit were associated with decreased odds of HIV testing, compared with not having insurance or a family planning visit.

“As we enter the fourth decade of the HIV epidemic, it remains clear that missed opportunities for diagnosis have the potential to delay HIV diagnosis and linkage to antiretroviral therapy or PrEP and prevention services, thus increasing the population risk of HIV transmission. Our data underscore the need for improved HIV testing education for providers of all levels of training and the need for public health agencies to clearly communicate the need for testing at the time of STI infection to reduce the number of missed opportunities for testing,” Ms. Petsis and colleagues concluded.

The study was supported by the National Institutes of Mental Health and the Children’s Hospital of Philadelphia Research Institute K-Readiness Award. One coauthor reported receiving funding from Bayer Healthcare, the Templeton Foundation, the National Institutes of Health, and Janssen Biotech. She also serves on expert advisory boards for Mylan Pharmaceuticals and Merck. The other authors have no relevant financial disclosures.

[email protected]

SOURCE: Wood S et al. Pediatrics. 2020 Mar 16. doi: 10.1542/peds.2019-2265.

What can psychiatric clinicians do to keep their patients healthy in this coronavirus time?

In the 3 days between starting this column and finishing it, the world has gone into a tailspin. Perhaps what I write is no longer relevant. But hopefully it is.

Below are some of the issues we have been grappling with in my psychiatry department. I have no right or wrong answers here but thoughts about factors to consider.

• On inpatient psychiatry wards, the emphasis is on communal living. On our ward, bedrooms and bathrooms are shared. Patients eat together. There are numerous group therapies.
• We have decided to restrict visitors out of the concern that one may infect a ward of patients and staff. We are hoping to do video visitation, but that may take a while to implement.
• An open question is how we are going to provide our involuntary patients with access to the public defense attorneys. Public defenders still have the ability to come onto the inpatient ward, but we will start screening them first.

• In terms of sanitation, wall sanitizers are forbidden, since sanitizers may be drank or made into a firebomb. So we are incessantly wiping down the shared phones and game board pieces.
• Looking at the outpatient arena, we have moved our chairs around, so that there are 3 feet between chairs. We have opened up another waiting room to provide more distance.
• We are trying to decide whether to cancel groups. We did cancel our senior group, and I think I will cancel the rest of them shortly.
• We are seriously looking at telepsychiatry.
• Schools are closed. Many of my clinicians have young children, so they may be out. We are expecting many patients to cancel and will see how that plays out. Others of us have elderly parents. My mother’s assisted-living facility is on lockdown. So, having been locked out after a visit, she is with me tonight.

• Psychiatrists are expected to keep up their relative value unit count. Can they meet their targets? Probably not. Will it matter?
• And what about all our homeless patients, who cannot disinfect their tents or shelters?
• Conferences no longer seem so important. I am less worried about coverage for the American Psychiatric Association meeting, since the 2020 conference has been canceled.

On the rosy side, maybe this will be a wake-up call about climate change. So we live in interesting times.

Take care of your patients and each other.

Dr. Ritchie is chair of psychiatry at Medstar Washington Hospital Center and professor of psychiatry at Georgetown University, Washington. She has no disclosures.

What can psychiatric clinicians do to keep their patients healthy in this coronavirus time?

In the 3 days between starting this column and finishing it, the world has gone into a tailspin. Perhaps what I write is no longer relevant. But hopefully it is.

Below are some of the issues we have been grappling with in my psychiatry department. I have no right or wrong answers here but thoughts about factors to consider.

• On inpatient psychiatry wards, the emphasis is on communal living. On our ward, bedrooms and bathrooms are shared. Patients eat together. There are numerous group therapies.
• We have decided to restrict visitors out of the concern that one may infect a ward of patients and staff. We are hoping to do video visitation, but that may take a while to implement.
• An open question is how we are going to provide our involuntary patients with access to the public defense attorneys. Public defenders still have the ability to come onto the inpatient ward, but we will start screening them first.

• In terms of sanitation, wall sanitizers are forbidden, since sanitizers may be drank or made into a firebomb. So we are incessantly wiping down the shared phones and game board pieces.
• Looking at the outpatient arena, we have moved our chairs around, so that there are 3 feet between chairs. We have opened up another waiting room to provide more distance.
• We are trying to decide whether to cancel groups. We did cancel our senior group, and I think I will cancel the rest of them shortly.
• We are seriously looking at telepsychiatry.
• Schools are closed. Many of my clinicians have young children, so they may be out. We are expecting many patients to cancel and will see how that plays out. Others of us have elderly parents. My mother’s assisted-living facility is on lockdown. So, having been locked out after a visit, she is with me tonight.

• Psychiatrists are expected to keep up their relative value unit count. Can they meet their targets? Probably not. Will it matter?
• And what about all our homeless patients, who cannot disinfect their tents or shelters?
• Conferences no longer seem so important. I am less worried about coverage for the American Psychiatric Association meeting, since the 2020 conference has been canceled.

On the rosy side, maybe this will be a wake-up call about climate change. So we live in interesting times.

Take care of your patients and each other.

Dr. Ritchie is chair of psychiatry at Medstar Washington Hospital Center and professor of psychiatry at Georgetown University, Washington. She has no disclosures.

What can psychiatric clinicians do to keep their patients healthy in this coronavirus time?

In the 3 days between starting this column and finishing it, the world has gone into a tailspin. Perhaps what I write is no longer relevant. But hopefully it is.

Below are some of the issues we have been grappling with in my psychiatry department. I have no right or wrong answers here but thoughts about factors to consider.

• On inpatient psychiatry wards, the emphasis is on communal living. On our ward, bedrooms and bathrooms are shared. Patients eat together. There are numerous group therapies.
• We have decided to restrict visitors out of the concern that one may infect a ward of patients and staff. We are hoping to do video visitation, but that may take a while to implement.
• An open question is how we are going to provide our involuntary patients with access to the public defense attorneys. Public defenders still have the ability to come onto the inpatient ward, but we will start screening them first.

• In terms of sanitation, wall sanitizers are forbidden, since sanitizers may be drank or made into a firebomb. So we are incessantly wiping down the shared phones and game board pieces.
• Looking at the outpatient arena, we have moved our chairs around, so that there are 3 feet between chairs. We have opened up another waiting room to provide more distance.
• We are trying to decide whether to cancel groups. We did cancel our senior group, and I think I will cancel the rest of them shortly.
• We are seriously looking at telepsychiatry.
• Schools are closed. Many of my clinicians have young children, so they may be out. We are expecting many patients to cancel and will see how that plays out. Others of us have elderly parents. My mother’s assisted-living facility is on lockdown. So, having been locked out after a visit, she is with me tonight.

• Psychiatrists are expected to keep up their relative value unit count. Can they meet their targets? Probably not. Will it matter?
• And what about all our homeless patients, who cannot disinfect their tents or shelters?
• Conferences no longer seem so important. I am less worried about coverage for the American Psychiatric Association meeting, since the 2020 conference has been canceled.

On the rosy side, maybe this will be a wake-up call about climate change. So we live in interesting times.

Take care of your patients and each other.

Dr. Ritchie is chair of psychiatry at Medstar Washington Hospital Center and professor of psychiatry at Georgetown University, Washington. She has no disclosures.

The American Society for Transplantation and Cellular Therapy (ASTCT) has released interim guidelines for the care of hematopoietic cell transplantation (HCT) and cellular therapy patients in the light of the global SARS-CoV-2 pandemic.

The guidelines, summarized briefly below, focus on diagnostic and treatment considerations, evaluation of patients prior to initializing HCT and cellular therapy, and cell donor evaluation. Much of the guideline relies upon recommendations developed by the European Society for Blood and Marrow Transplantation (ESBMT). These guidelines were updated on March 16.

The ASTCT document focuses on patient-treatment specifics and does not cover specific infection-prevention policies and procedures, instead suggesting that local and institutional guidelines, such as those from the Centers for Disease Control and Prevention, should be followed. They did recommend that, in the local presence of COVID-19, “clinic visits that are not critical should be either deferred or substituted with telemedicine visits if deemed appropriate and feasible.”
 

Diagnostic considerations

In any patient with upper or lower respiratory symptoms, obtain polymerase chain reaction (PCR) testing for SARS-CoV-2, where possible, in addition to other respiratory virus PCR testing from any respiratory sample obtained, following CDC recommendations for sample collection and processing, which are continuously being updated on the CDC website.

These recommendations include nasal sampling, rather than oral sampling, and the discouraging of nasal washes where avoidable. If nasal washing is performed, it should be done with appropriate personal protective equipment as described by the CDC. The CDC has also provided additional infection prevention and control information for known and suspected COVID-19 patients in health care settings.

In patients positive for SARS-CoV-2 in an upper respiratory tract sample, chest imaging should be considered.

Preliminary reports suggest that there may be a discrepancy between upper- and lower-tract specimen positivity. Therefore, even when SARS-CoV-2 is not detected in an upper respiratory sample, the ASTCT recommends that chest imaging should be considered for lower respiratory tract infection when clinical symptoms of lower respiratory tract infection are present, including shortness of breath, hypoxia, and tachypnea.

With regard to routine bronchoalveolar lavage, the ASTCT recommends against it if a patient tests positive for SARS-CoV-2 given the risk of transmission among health care workers. The exception is in the case of suspected coinfection based on abnormal chest imaging and in patients for whom it is clinically indicated (for example, those receiving invasive mechanical ventilation). In addition to testing bronchoalveolar lavage samples for SARS-CoV-2, “copathogens should be evaluated and treated.”

Treatment considerations

“At this point no recommendations can be made on specific therapies due to limited data and unknown risk versus benefit; additional recommendations will be forthcoming. Even less data is available for pediatric patients. Treatment for viral, bacterial, and fungal copathogens should be optimized,” according to the ASTCT.

However, the society lists several therapies currently under consideration, which may be available through compassionate-use programs and are being investigated in current clinical trials in several countries, “including lopinavir/ritonavir, ribavirin, hydroxychloroquine, darunavir/cobicistat, and interferons-alpha and -beta.” Remdesivir, in particular, is being evaluated in a National Institutes of Health–sponsored, placebo-controlled clinical trial (NCT04280705).

In case of known or suspected COVID-19 with normal imaging and no or mild symptoms, no therapy is recommended. However, if symptoms progress or imaging is abnormal, an infectious disease specialist or department should be consulted, according to the ASTCT.

Evaluation prior to HCT or cellular therapy

“There is sufficient concern that COVID-19 could have a significant impact on posttransplant or posttherapy outcomes,” according to the guidelines, and the ASTCT provided the following recommendations to be considered in known or suspected COVID-19 patients. In particular, practitioners need to weigh the risk of delaying or altering therapy plans with the risk of progression of underlying disease.

If SARS-CoV-2 is detected in a respiratory specimen, HCT or cellular therapy procedures should be deferred. Therapy should also be deferred in HCT and cellular therapy candidates with close contact with a person infected with SARS-CoV-2 and in those patients who have traveled to a high-risk area or had close contact with a person traveling from an area at high risk for COVID-19.

In the case of a patient in a community with widespread disease, “all HCT and cellular therapy candidates should undergo screening for SARS-CoV-2 infection by PCR in respiratory specimens at the time of initial evaluation and 2 days prior to conditioning/lymphodepletion, regardless of the presence of symptoms, if testing is available.”

Procedures to be deferred include peripheral blood stem cell mobilization, bone marrow harvest, T-cell collections, and conditioning/lymphodepletion. These should not be performed for at least 14 days (preferably 21 days) from the day of last contact, according to the ASTCT. Two consecutive negative PCR tests each approximately 1 week apart (deferral for 14 days minimum), should be obtained, if available.

In areas with high community spread, the guidelines also state that “interim treatment and/or longer deferral of definite therapy should be considered when feasible (for example, multiple myeloma, germ cell tumors, consolidative transplants).”

Similar considerations should be afforded to potential cellular donors. Donors with SARS-CoV-2 detected in a respiratory sample are considered ineligible. Those meeting exposure criteria for patients, as listed above, should be excluded from donation for at least 28 days. “In individual circumstances, a donor may be considered eligible if respiratory samples are negative for SARS-CoV-2 by PCR and donor is asymptomatic. Donor should be closely monitored for COVID-19.”

In the case of unrelated donors, the ASTCT recommends referral to the National Marrow Donor Program (NMDP) guidelines for updated guidance, but points out that, according to the NMDP, the Food and Drug Administration reports that there have been no reported or suspected cases of transfusion-transmitted COVID-19 to date and that “no cases of transfusion-transmission were ever reported for the other two coronaviruses that emerged during the past 2 decades [SARS, the severe acute respiratory syndrome coronavirus, and MERS-CoV, which causes Mideast respiratory syndrome].”

This article was updated 3/26/20.

[email protected]

SOURCE: ASTCT Response to COVID-19. 2020. www.astct.org/connect/astct-response-to-covid-19.

The American Society for Transplantation and Cellular Therapy (ASTCT) has released interim guidelines for the care of hematopoietic cell transplantation (HCT) and cellular therapy patients in the light of the global SARS-CoV-2 pandemic.

The guidelines, summarized briefly below, focus on diagnostic and treatment considerations, evaluation of patients prior to initializing HCT and cellular therapy, and cell donor evaluation. Much of the guideline relies upon recommendations developed by the European Society for Blood and Marrow Transplantation (ESBMT). These guidelines were updated on March 16.

The ASTCT document focuses on patient-treatment specifics and does not cover specific infection-prevention policies and procedures, instead suggesting that local and institutional guidelines, such as those from the Centers for Disease Control and Prevention, should be followed. They did recommend that, in the local presence of COVID-19, “clinic visits that are not critical should be either deferred or substituted with telemedicine visits if deemed appropriate and feasible.”
 

Diagnostic considerations

In any patient with upper or lower respiratory symptoms, obtain polymerase chain reaction (PCR) testing for SARS-CoV-2, where possible, in addition to other respiratory virus PCR testing from any respiratory sample obtained, following CDC recommendations for sample collection and processing, which are continuously being updated on the CDC website.

These recommendations include nasal sampling, rather than oral sampling, and the discouraging of nasal washes where avoidable. If nasal washing is performed, it should be done with appropriate personal protective equipment as described by the CDC. The CDC has also provided additional infection prevention and control information for known and suspected COVID-19 patients in health care settings.

In patients positive for SARS-CoV-2 in an upper respiratory tract sample, chest imaging should be considered.

Preliminary reports suggest that there may be a discrepancy between upper- and lower-tract specimen positivity. Therefore, even when SARS-CoV-2 is not detected in an upper respiratory sample, the ASTCT recommends that chest imaging should be considered for lower respiratory tract infection when clinical symptoms of lower respiratory tract infection are present, including shortness of breath, hypoxia, and tachypnea.

With regard to routine bronchoalveolar lavage, the ASTCT recommends against it if a patient tests positive for SARS-CoV-2 given the risk of transmission among health care workers. The exception is in the case of suspected coinfection based on abnormal chest imaging and in patients for whom it is clinically indicated (for example, those receiving invasive mechanical ventilation). In addition to testing bronchoalveolar lavage samples for SARS-CoV-2, “copathogens should be evaluated and treated.”

Treatment considerations

“At this point no recommendations can be made on specific therapies due to limited data and unknown risk versus benefit; additional recommendations will be forthcoming. Even less data is available for pediatric patients. Treatment for viral, bacterial, and fungal copathogens should be optimized,” according to the ASTCT.

However, the society lists several therapies currently under consideration, which may be available through compassionate-use programs and are being investigated in current clinical trials in several countries, “including lopinavir/ritonavir, ribavirin, hydroxychloroquine, darunavir/cobicistat, and interferons-alpha and -beta.” Remdesivir, in particular, is being evaluated in a National Institutes of Health–sponsored, placebo-controlled clinical trial (NCT04280705).

In case of known or suspected COVID-19 with normal imaging and no or mild symptoms, no therapy is recommended. However, if symptoms progress or imaging is abnormal, an infectious disease specialist or department should be consulted, according to the ASTCT.

Evaluation prior to HCT or cellular therapy

“There is sufficient concern that COVID-19 could have a significant impact on posttransplant or posttherapy outcomes,” according to the guidelines, and the ASTCT provided the following recommendations to be considered in known or suspected COVID-19 patients. In particular, practitioners need to weigh the risk of delaying or altering therapy plans with the risk of progression of underlying disease.

If SARS-CoV-2 is detected in a respiratory specimen, HCT or cellular therapy procedures should be deferred. Therapy should also be deferred in HCT and cellular therapy candidates with close contact with a person infected with SARS-CoV-2 and in those patients who have traveled to a high-risk area or had close contact with a person traveling from an area at high risk for COVID-19.

In the case of a patient in a community with widespread disease, “all HCT and cellular therapy candidates should undergo screening for SARS-CoV-2 infection by PCR in respiratory specimens at the time of initial evaluation and 2 days prior to conditioning/lymphodepletion, regardless of the presence of symptoms, if testing is available.”

Procedures to be deferred include peripheral blood stem cell mobilization, bone marrow harvest, T-cell collections, and conditioning/lymphodepletion. These should not be performed for at least 14 days (preferably 21 days) from the day of last contact, according to the ASTCT. Two consecutive negative PCR tests each approximately 1 week apart (deferral for 14 days minimum), should be obtained, if available.

In areas with high community spread, the guidelines also state that “interim treatment and/or longer deferral of definite therapy should be considered when feasible (for example, multiple myeloma, germ cell tumors, consolidative transplants).”

Similar considerations should be afforded to potential cellular donors. Donors with SARS-CoV-2 detected in a respiratory sample are considered ineligible. Those meeting exposure criteria for patients, as listed above, should be excluded from donation for at least 28 days. “In individual circumstances, a donor may be considered eligible if respiratory samples are negative for SARS-CoV-2 by PCR and donor is asymptomatic. Donor should be closely monitored for COVID-19.”

In the case of unrelated donors, the ASTCT recommends referral to the National Marrow Donor Program (NMDP) guidelines for updated guidance, but points out that, according to the NMDP, the Food and Drug Administration reports that there have been no reported or suspected cases of transfusion-transmitted COVID-19 to date and that “no cases of transfusion-transmission were ever reported for the other two coronaviruses that emerged during the past 2 decades [SARS, the severe acute respiratory syndrome coronavirus, and MERS-CoV, which causes Mideast respiratory syndrome].”

This article was updated 3/26/20.

[email protected]

SOURCE: ASTCT Response to COVID-19. 2020. www.astct.org/connect/astct-response-to-covid-19.

The American Society for Transplantation and Cellular Therapy (ASTCT) has released interim guidelines for the care of hematopoietic cell transplantation (HCT) and cellular therapy patients in the light of the global SARS-CoV-2 pandemic.

The guidelines, summarized briefly below, focus on diagnostic and treatment considerations, evaluation of patients prior to initializing HCT and cellular therapy, and cell donor evaluation. Much of the guideline relies upon recommendations developed by the European Society for Blood and Marrow Transplantation (ESBMT). These guidelines were updated on March 16.

The ASTCT document focuses on patient-treatment specifics and does not cover specific infection-prevention policies and procedures, instead suggesting that local and institutional guidelines, such as those from the Centers for Disease Control and Prevention, should be followed. They did recommend that, in the local presence of COVID-19, “clinic visits that are not critical should be either deferred or substituted with telemedicine visits if deemed appropriate and feasible.”
 

Diagnostic considerations

In any patient with upper or lower respiratory symptoms, obtain polymerase chain reaction (PCR) testing for SARS-CoV-2, where possible, in addition to other respiratory virus PCR testing from any respiratory sample obtained, following CDC recommendations for sample collection and processing, which are continuously being updated on the CDC website.

These recommendations include nasal sampling, rather than oral sampling, and the discouraging of nasal washes where avoidable. If nasal washing is performed, it should be done with appropriate personal protective equipment as described by the CDC. The CDC has also provided additional infection prevention and control information for known and suspected COVID-19 patients in health care settings.

In patients positive for SARS-CoV-2 in an upper respiratory tract sample, chest imaging should be considered.

Preliminary reports suggest that there may be a discrepancy between upper- and lower-tract specimen positivity. Therefore, even when SARS-CoV-2 is not detected in an upper respiratory sample, the ASTCT recommends that chest imaging should be considered for lower respiratory tract infection when clinical symptoms of lower respiratory tract infection are present, including shortness of breath, hypoxia, and tachypnea.

With regard to routine bronchoalveolar lavage, the ASTCT recommends against it if a patient tests positive for SARS-CoV-2 given the risk of transmission among health care workers. The exception is in the case of suspected coinfection based on abnormal chest imaging and in patients for whom it is clinically indicated (for example, those receiving invasive mechanical ventilation). In addition to testing bronchoalveolar lavage samples for SARS-CoV-2, “copathogens should be evaluated and treated.”

Treatment considerations

“At this point no recommendations can be made on specific therapies due to limited data and unknown risk versus benefit; additional recommendations will be forthcoming. Even less data is available for pediatric patients. Treatment for viral, bacterial, and fungal copathogens should be optimized,” according to the ASTCT.

However, the society lists several therapies currently under consideration, which may be available through compassionate-use programs and are being investigated in current clinical trials in several countries, “including lopinavir/ritonavir, ribavirin, hydroxychloroquine, darunavir/cobicistat, and interferons-alpha and -beta.” Remdesivir, in particular, is being evaluated in a National Institutes of Health–sponsored, placebo-controlled clinical trial (NCT04280705).

In case of known or suspected COVID-19 with normal imaging and no or mild symptoms, no therapy is recommended. However, if symptoms progress or imaging is abnormal, an infectious disease specialist or department should be consulted, according to the ASTCT.

Evaluation prior to HCT or cellular therapy

“There is sufficient concern that COVID-19 could have a significant impact on posttransplant or posttherapy outcomes,” according to the guidelines, and the ASTCT provided the following recommendations to be considered in known or suspected COVID-19 patients. In particular, practitioners need to weigh the risk of delaying or altering therapy plans with the risk of progression of underlying disease.

If SARS-CoV-2 is detected in a respiratory specimen, HCT or cellular therapy procedures should be deferred. Therapy should also be deferred in HCT and cellular therapy candidates with close contact with a person infected with SARS-CoV-2 and in those patients who have traveled to a high-risk area or had close contact with a person traveling from an area at high risk for COVID-19.

In the case of a patient in a community with widespread disease, “all HCT and cellular therapy candidates should undergo screening for SARS-CoV-2 infection by PCR in respiratory specimens at the time of initial evaluation and 2 days prior to conditioning/lymphodepletion, regardless of the presence of symptoms, if testing is available.”

Procedures to be deferred include peripheral blood stem cell mobilization, bone marrow harvest, T-cell collections, and conditioning/lymphodepletion. These should not be performed for at least 14 days (preferably 21 days) from the day of last contact, according to the ASTCT. Two consecutive negative PCR tests each approximately 1 week apart (deferral for 14 days minimum), should be obtained, if available.

In areas with high community spread, the guidelines also state that “interim treatment and/or longer deferral of definite therapy should be considered when feasible (for example, multiple myeloma, germ cell tumors, consolidative transplants).”

Similar considerations should be afforded to potential cellular donors. Donors with SARS-CoV-2 detected in a respiratory sample are considered ineligible. Those meeting exposure criteria for patients, as listed above, should be excluded from donation for at least 28 days. “In individual circumstances, a donor may be considered eligible if respiratory samples are negative for SARS-CoV-2 by PCR and donor is asymptomatic. Donor should be closely monitored for COVID-19.”

In the case of unrelated donors, the ASTCT recommends referral to the National Marrow Donor Program (NMDP) guidelines for updated guidance, but points out that, according to the NMDP, the Food and Drug Administration reports that there have been no reported or suspected cases of transfusion-transmitted COVID-19 to date and that “no cases of transfusion-transmission were ever reported for the other two coronaviruses that emerged during the past 2 decades [SARS, the severe acute respiratory syndrome coronavirus, and MERS-CoV, which causes Mideast respiratory syndrome].”

This article was updated 3/26/20.

[email protected]

SOURCE: ASTCT Response to COVID-19. 2020. www.astct.org/connect/astct-response-to-covid-19.