Pulmonology

Lung transplants are increasing, with 2,562 performed in the United States in 2018 – a 31% increase over the preceding 5 years. With this increased demand for donor lungs, waitlist mortality in the United States is 9.4 deaths per 100 waitlist-years for obstructive lung diseases and as high as 29.7 deaths per 100 waitlist-years for restrictive lung diseases (Valapour M, et al. Lung. Am J Transplant. 2020;20[suppl s1]:427). Conversely, lungs are utilized from eligible multiorgan donors only 15% to 20% of the time, usually due to concerns over donor history or organ quality (Young KA, et al. Chest. 2019;155[3]:465). In light of this imbalance of supply and demand, lung transplant specialists are making significant efforts to expand the donor pool of available organs. Three of these strategies include: (1) applications of ex-vivo lung perfusion (EVLP) technology; (2) use of lungs from hepatitis C-positive donors for hep-C negative recipients; and (3) increasing utilization of donation after cardiac death.

Normothermic ex-vivo lung perfusion is a technology which allows donor lungs to be perfused and ventilated after removal from the donor but before transplant into the recipient. This is in contrast to the traditional method of cold static preservation. The proposed advantage of using this technology is to allow time for a more thorough assessment of graft quality and to improve function of grafts not meeting established criteria for transplant, all-the-while decreasing organ ischemia despite an increased cross-clamp time. There are currently four commercial systems available capable of EVLP. Broadly speaking, three EVLP management protocols exist (Toronto, Lund, and OCS), which differ in perfusate composition, target flow, pulmonary arterial pressure, left atrial pressure, and ventilatory settings. Notably, the Toronto protocol uses a closed left atrium, whereas the Lund and OCS protocol use an open left atrium. There are excellent published reviews of the different systems (Possoz J, et al. J Thorac Dis. 2019;11[4]:1635). EVLP has now been studied for two different goals: (1) to allow an extended evaluation of lungs of questionable quality before transplant; or (2) for routine use in all lung transplantations in place of cold static preservation.

In most studies concerning the use of EVLP for reconditioning of donor lungs, “high risk” or “extended criteria” refers to one or more of the following: P/F ratios < 300 on arterial blood gas, macroscopic abnormalities (eg, pulmonary edema, poor lung compliance), donation after circulatory death, or high-risk history (eg, aspiration). The largest cohort with the longest follow-up addressing the role of EVLP for donation of lungs with extended criteria was published from the Toronto Lung Transplant Group. Their results have demonstrated equivalent graft survival and rates of chronic lung allograft dysfunction (CLAD) up to 9 years posttransplant compared with standard criteria donor lungs, despite utilizing lower quality lungs and having a longer median preservation (Divithotawela C, et al. JAMA Surg. 2019;154[12]:1143). The group’s subsequent lung transplant rates have increased over the past decade.

A separate study addressed the same question but differed in that it was a single-arm, multicenter, international trial that tracked the outcomes of 93 extended criteria lungs placed on EVLP (including a large proportion acquired via donation after circulatory death) (Loor G, et al. Lancet Respir Med. 2019;7[11]:975). Among these, 87% of eligible lungs were transplanted, and outcomes were excellent, albeit shorter in follow-up compared with the Toronto cohort (eg, primary graft dysfunction grade 3 (PGD3) within 72 hours was 44% and 1-year survival was 91%). Based on these trials and many other retrospective reports, it has been concluded by many experts in the field that EVLP-treated extended criteria donor lungs perform equally well to standard criteria donor lungs.

Two RCTs have been conducted to evaluate whether EVLP is noninferior to static cold storage with donor lungs meeting “standard criteria” for transplant. The first was a single center study at the Medical University of Vienna, that looked at 80 recipient/donor pairs. Lungs in the EVLP arm underwent 4 hours of perfusion with frequent reassessment of quality before transplant, whereas the lungs in the control arm went directly to transplant. This study met noninferiority criteria looking at primary outcomes of PGD grade >1 and 30-day survival (Slama A, et al. J Heart Lung Transplant. 2017;36[7]:744). The second study was a phase 3, multicenter, international trial that included 320 recipient/donor pairs randomized to either EVLP (without a prespecified time on the EVLP system) or static cold storage. This trial met noninferiority for safety endpoints (lung graft-related adverse events within 30 days) and a composite primary outcome of PGD grade 3 incidence within 72 hours and 30-day survival (Warnecke G, et al. Lancet Respir Med. 2018;6[5]:357). The authors also tested and found superiority of EVLP in lower PGD grade 3 frequency compared with control. While these RCTs may suggest a role for EVLP in the procurement process of standard criteria organs in addition to extended criteria organs in the future, major criticisms for these trials include the lack of a demonstrable clinical benefit over cold storage beyond the lower PGD3 rates.

In the era of direct-acting antiviral agents available to treat HCV infection, there has been efforts to study the early use of anti-HCV medications to prevent infection as a result of heart or lung transplant from HCV viremic donors to HCV-negative recipients. In one major trial on efficacy, it was found that 4 weeks of sofosbuvir and velpatasvir, when started within a few hours of transplant, was sufficient to achieve a sustained (undetectable) virologic response at 12 weeks after completion of the antiviral regimen (Woolley AE, et al. N Engl J Med. 2019;380[17]:1606). Therefore, many transplant centers have adopted protocols to increase the donor pool (by CDC estimates about 4% of solid organ donors are HCV-positive) by accepting HCV nucleic acid amplification test (NAT)-positive donors for HCV-negative recipients, after appropriate informed consent.

Donation after cardiac death (DCD), which is alternatively known as donation after circulatory determination of death (DCDD), generally refers to organ procurement taking place after cessation of circulation, often after inpatient withdrawal of support. This is in contrast to the much more common practice of donation after brain death (DBD). Addressing concerns over the quality of lungs donated in the context of DCD compared with DBD, analyses of ISHLT registry data have demonstrated no differences in hospital length of stay or survival at 1 or 5 years (Van Raemdonck D, et al. J Heart Lung Transplant. 2019;38[12]:1235). Outcomes comparing specific mechanisms of donor death in DCD remain relatively unknown, such as outcomes from donors withdrawn from life support vs donors who had an uncontrolled cardiac death.

These methods for expanding the donor pool are not mutually exclusive, and, in fact, application of EVLP for lungs obtained in the context of DCD seems to be increasingly common. Optimization of protocols with collaboration between lung transplant centers will be paramount as we move forward in advancing this field. As we do so, efforts to successfully increase the donor pool will serve to provide a life-saving therapy to an ever-growing number of patients with end-stage lung disease.

Dr. Sala and Dr. Tomic are with the Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois.

Lung transplants are increasing, with 2,562 performed in the United States in 2018 – a 31% increase over the preceding 5 years. With this increased demand for donor lungs, waitlist mortality in the United States is 9.4 deaths per 100 waitlist-years for obstructive lung diseases and as high as 29.7 deaths per 100 waitlist-years for restrictive lung diseases (Valapour M, et al. Lung. Am J Transplant. 2020;20[suppl s1]:427). Conversely, lungs are utilized from eligible multiorgan donors only 15% to 20% of the time, usually due to concerns over donor history or organ quality (Young KA, et al. Chest. 2019;155[3]:465). In light of this imbalance of supply and demand, lung transplant specialists are making significant efforts to expand the donor pool of available organs. Three of these strategies include: (1) applications of ex-vivo lung perfusion (EVLP) technology; (2) use of lungs from hepatitis C-positive donors for hep-C negative recipients; and (3) increasing utilization of donation after cardiac death.

Normothermic ex-vivo lung perfusion is a technology which allows donor lungs to be perfused and ventilated after removal from the donor but before transplant into the recipient. This is in contrast to the traditional method of cold static preservation. The proposed advantage of using this technology is to allow time for a more thorough assessment of graft quality and to improve function of grafts not meeting established criteria for transplant, all-the-while decreasing organ ischemia despite an increased cross-clamp time. There are currently four commercial systems available capable of EVLP. Broadly speaking, three EVLP management protocols exist (Toronto, Lund, and OCS), which differ in perfusate composition, target flow, pulmonary arterial pressure, left atrial pressure, and ventilatory settings. Notably, the Toronto protocol uses a closed left atrium, whereas the Lund and OCS protocol use an open left atrium. There are excellent published reviews of the different systems (Possoz J, et al. J Thorac Dis. 2019;11[4]:1635). EVLP has now been studied for two different goals: (1) to allow an extended evaluation of lungs of questionable quality before transplant; or (2) for routine use in all lung transplantations in place of cold static preservation.

In most studies concerning the use of EVLP for reconditioning of donor lungs, “high risk” or “extended criteria” refers to one or more of the following: P/F ratios < 300 on arterial blood gas, macroscopic abnormalities (eg, pulmonary edema, poor lung compliance), donation after circulatory death, or high-risk history (eg, aspiration). The largest cohort with the longest follow-up addressing the role of EVLP for donation of lungs with extended criteria was published from the Toronto Lung Transplant Group. Their results have demonstrated equivalent graft survival and rates of chronic lung allograft dysfunction (CLAD) up to 9 years posttransplant compared with standard criteria donor lungs, despite utilizing lower quality lungs and having a longer median preservation (Divithotawela C, et al. JAMA Surg. 2019;154[12]:1143). The group’s subsequent lung transplant rates have increased over the past decade.

A separate study addressed the same question but differed in that it was a single-arm, multicenter, international trial that tracked the outcomes of 93 extended criteria lungs placed on EVLP (including a large proportion acquired via donation after circulatory death) (Loor G, et al. Lancet Respir Med. 2019;7[11]:975). Among these, 87% of eligible lungs were transplanted, and outcomes were excellent, albeit shorter in follow-up compared with the Toronto cohort (eg, primary graft dysfunction grade 3 (PGD3) within 72 hours was 44% and 1-year survival was 91%). Based on these trials and many other retrospective reports, it has been concluded by many experts in the field that EVLP-treated extended criteria donor lungs perform equally well to standard criteria donor lungs.

Two RCTs have been conducted to evaluate whether EVLP is noninferior to static cold storage with donor lungs meeting “standard criteria” for transplant. The first was a single center study at the Medical University of Vienna, that looked at 80 recipient/donor pairs. Lungs in the EVLP arm underwent 4 hours of perfusion with frequent reassessment of quality before transplant, whereas the lungs in the control arm went directly to transplant. This study met noninferiority criteria looking at primary outcomes of PGD grade >1 and 30-day survival (Slama A, et al. J Heart Lung Transplant. 2017;36[7]:744). The second study was a phase 3, multicenter, international trial that included 320 recipient/donor pairs randomized to either EVLP (without a prespecified time on the EVLP system) or static cold storage. This trial met noninferiority for safety endpoints (lung graft-related adverse events within 30 days) and a composite primary outcome of PGD grade 3 incidence within 72 hours and 30-day survival (Warnecke G, et al. Lancet Respir Med. 2018;6[5]:357). The authors also tested and found superiority of EVLP in lower PGD grade 3 frequency compared with control. While these RCTs may suggest a role for EVLP in the procurement process of standard criteria organs in addition to extended criteria organs in the future, major criticisms for these trials include the lack of a demonstrable clinical benefit over cold storage beyond the lower PGD3 rates.

In the era of direct-acting antiviral agents available to treat HCV infection, there has been efforts to study the early use of anti-HCV medications to prevent infection as a result of heart or lung transplant from HCV viremic donors to HCV-negative recipients. In one major trial on efficacy, it was found that 4 weeks of sofosbuvir and velpatasvir, when started within a few hours of transplant, was sufficient to achieve a sustained (undetectable) virologic response at 12 weeks after completion of the antiviral regimen (Woolley AE, et al. N Engl J Med. 2019;380[17]:1606). Therefore, many transplant centers have adopted protocols to increase the donor pool (by CDC estimates about 4% of solid organ donors are HCV-positive) by accepting HCV nucleic acid amplification test (NAT)-positive donors for HCV-negative recipients, after appropriate informed consent.

Donation after cardiac death (DCD), which is alternatively known as donation after circulatory determination of death (DCDD), generally refers to organ procurement taking place after cessation of circulation, often after inpatient withdrawal of support. This is in contrast to the much more common practice of donation after brain death (DBD). Addressing concerns over the quality of lungs donated in the context of DCD compared with DBD, analyses of ISHLT registry data have demonstrated no differences in hospital length of stay or survival at 1 or 5 years (Van Raemdonck D, et al. J Heart Lung Transplant. 2019;38[12]:1235). Outcomes comparing specific mechanisms of donor death in DCD remain relatively unknown, such as outcomes from donors withdrawn from life support vs donors who had an uncontrolled cardiac death.

These methods for expanding the donor pool are not mutually exclusive, and, in fact, application of EVLP for lungs obtained in the context of DCD seems to be increasingly common. Optimization of protocols with collaboration between lung transplant centers will be paramount as we move forward in advancing this field. As we do so, efforts to successfully increase the donor pool will serve to provide a life-saving therapy to an ever-growing number of patients with end-stage lung disease.

Dr. Sala and Dr. Tomic are with the Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois.

Lung transplants are increasing, with 2,562 performed in the United States in 2018 – a 31% increase over the preceding 5 years. With this increased demand for donor lungs, waitlist mortality in the United States is 9.4 deaths per 100 waitlist-years for obstructive lung diseases and as high as 29.7 deaths per 100 waitlist-years for restrictive lung diseases (Valapour M, et al. Lung. Am J Transplant. 2020;20[suppl s1]:427). Conversely, lungs are utilized from eligible multiorgan donors only 15% to 20% of the time, usually due to concerns over donor history or organ quality (Young KA, et al. Chest. 2019;155[3]:465). In light of this imbalance of supply and demand, lung transplant specialists are making significant efforts to expand the donor pool of available organs. Three of these strategies include: (1) applications of ex-vivo lung perfusion (EVLP) technology; (2) use of lungs from hepatitis C-positive donors for hep-C negative recipients; and (3) increasing utilization of donation after cardiac death.

Normothermic ex-vivo lung perfusion is a technology which allows donor lungs to be perfused and ventilated after removal from the donor but before transplant into the recipient. This is in contrast to the traditional method of cold static preservation. The proposed advantage of using this technology is to allow time for a more thorough assessment of graft quality and to improve function of grafts not meeting established criteria for transplant, all-the-while decreasing organ ischemia despite an increased cross-clamp time. There are currently four commercial systems available capable of EVLP. Broadly speaking, three EVLP management protocols exist (Toronto, Lund, and OCS), which differ in perfusate composition, target flow, pulmonary arterial pressure, left atrial pressure, and ventilatory settings. Notably, the Toronto protocol uses a closed left atrium, whereas the Lund and OCS protocol use an open left atrium. There are excellent published reviews of the different systems (Possoz J, et al. J Thorac Dis. 2019;11[4]:1635). EVLP has now been studied for two different goals: (1) to allow an extended evaluation of lungs of questionable quality before transplant; or (2) for routine use in all lung transplantations in place of cold static preservation.

In most studies concerning the use of EVLP for reconditioning of donor lungs, “high risk” or “extended criteria” refers to one or more of the following: P/F ratios < 300 on arterial blood gas, macroscopic abnormalities (eg, pulmonary edema, poor lung compliance), donation after circulatory death, or high-risk history (eg, aspiration). The largest cohort with the longest follow-up addressing the role of EVLP for donation of lungs with extended criteria was published from the Toronto Lung Transplant Group. Their results have demonstrated equivalent graft survival and rates of chronic lung allograft dysfunction (CLAD) up to 9 years posttransplant compared with standard criteria donor lungs, despite utilizing lower quality lungs and having a longer median preservation (Divithotawela C, et al. JAMA Surg. 2019;154[12]:1143). The group’s subsequent lung transplant rates have increased over the past decade.

A separate study addressed the same question but differed in that it was a single-arm, multicenter, international trial that tracked the outcomes of 93 extended criteria lungs placed on EVLP (including a large proportion acquired via donation after circulatory death) (Loor G, et al. Lancet Respir Med. 2019;7[11]:975). Among these, 87% of eligible lungs were transplanted, and outcomes were excellent, albeit shorter in follow-up compared with the Toronto cohort (eg, primary graft dysfunction grade 3 (PGD3) within 72 hours was 44% and 1-year survival was 91%). Based on these trials and many other retrospective reports, it has been concluded by many experts in the field that EVLP-treated extended criteria donor lungs perform equally well to standard criteria donor lungs.

Two RCTs have been conducted to evaluate whether EVLP is noninferior to static cold storage with donor lungs meeting “standard criteria” for transplant. The first was a single center study at the Medical University of Vienna, that looked at 80 recipient/donor pairs. Lungs in the EVLP arm underwent 4 hours of perfusion with frequent reassessment of quality before transplant, whereas the lungs in the control arm went directly to transplant. This study met noninferiority criteria looking at primary outcomes of PGD grade >1 and 30-day survival (Slama A, et al. J Heart Lung Transplant. 2017;36[7]:744). The second study was a phase 3, multicenter, international trial that included 320 recipient/donor pairs randomized to either EVLP (without a prespecified time on the EVLP system) or static cold storage. This trial met noninferiority for safety endpoints (lung graft-related adverse events within 30 days) and a composite primary outcome of PGD grade 3 incidence within 72 hours and 30-day survival (Warnecke G, et al. Lancet Respir Med. 2018;6[5]:357). The authors also tested and found superiority of EVLP in lower PGD grade 3 frequency compared with control. While these RCTs may suggest a role for EVLP in the procurement process of standard criteria organs in addition to extended criteria organs in the future, major criticisms for these trials include the lack of a demonstrable clinical benefit over cold storage beyond the lower PGD3 rates.

In the era of direct-acting antiviral agents available to treat HCV infection, there has been efforts to study the early use of anti-HCV medications to prevent infection as a result of heart or lung transplant from HCV viremic donors to HCV-negative recipients. In one major trial on efficacy, it was found that 4 weeks of sofosbuvir and velpatasvir, when started within a few hours of transplant, was sufficient to achieve a sustained (undetectable) virologic response at 12 weeks after completion of the antiviral regimen (Woolley AE, et al. N Engl J Med. 2019;380[17]:1606). Therefore, many transplant centers have adopted protocols to increase the donor pool (by CDC estimates about 4% of solid organ donors are HCV-positive) by accepting HCV nucleic acid amplification test (NAT)-positive donors for HCV-negative recipients, after appropriate informed consent.

Donation after cardiac death (DCD), which is alternatively known as donation after circulatory determination of death (DCDD), generally refers to organ procurement taking place after cessation of circulation, often after inpatient withdrawal of support. This is in contrast to the much more common practice of donation after brain death (DBD). Addressing concerns over the quality of lungs donated in the context of DCD compared with DBD, analyses of ISHLT registry data have demonstrated no differences in hospital length of stay or survival at 1 or 5 years (Van Raemdonck D, et al. J Heart Lung Transplant. 2019;38[12]:1235). Outcomes comparing specific mechanisms of donor death in DCD remain relatively unknown, such as outcomes from donors withdrawn from life support vs donors who had an uncontrolled cardiac death.

These methods for expanding the donor pool are not mutually exclusive, and, in fact, application of EVLP for lungs obtained in the context of DCD seems to be increasingly common. Optimization of protocols with collaboration between lung transplant centers will be paramount as we move forward in advancing this field. As we do so, efforts to successfully increase the donor pool will serve to provide a life-saving therapy to an ever-growing number of patients with end-stage lung disease.

Dr. Sala and Dr. Tomic are with the Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois.

Cystic fibrosis transmembrane conductance regulator modulators are bringing new hope to many patients with CF. But what do physicians and patients need to know about the latest CFTR modulator therapies?

Susan M. Millard, MD, is a pediatric pulmonologist at Helen DeVos Children's Hospital in Grand Rapids, Mich. In an audio interview, Dr. Millard discusses the new Food and Drug Administration-approved combination therapy of elexacaftor, tezacaftor, and ivacaftor (Trikafta). It's a trio that could make a significant difference for the roughly 90% of patients with at least one F508del mutation.

Dr. Millard outlines which patients are candidates for the combination therapy,  what physicians and patients can expect with Trikafta use, and how the drug affects patients' use of other CF therapies. She also explains the steps physicians should take before starting patients on the therapy, and what side effects to watch for during treatment.

Dr. Millard is the local principal investigator for CF research at Helen DeVos Children’s Hospital, including Mylan, Therapeutic Development Network, and Vertex clinical studies.

Cystic fibrosis transmembrane conductance regulator modulators are bringing new hope to many patients with CF. But what do physicians and patients need to know about the latest CFTR modulator therapies?

Susan M. Millard, MD, is a pediatric pulmonologist at Helen DeVos Children's Hospital in Grand Rapids, Mich. In an audio interview, Dr. Millard discusses the new Food and Drug Administration-approved combination therapy of elexacaftor, tezacaftor, and ivacaftor (Trikafta). It's a trio that could make a significant difference for the roughly 90% of patients with at least one F508del mutation.

Dr. Millard outlines which patients are candidates for the combination therapy,  what physicians and patients can expect with Trikafta use, and how the drug affects patients' use of other CF therapies. She also explains the steps physicians should take before starting patients on the therapy, and what side effects to watch for during treatment.

Dr. Millard is the local principal investigator for CF research at Helen DeVos Children’s Hospital, including Mylan, Therapeutic Development Network, and Vertex clinical studies.

Cystic fibrosis transmembrane conductance regulator modulators are bringing new hope to many patients with CF. But what do physicians and patients need to know about the latest CFTR modulator therapies?

Susan M. Millard, MD, is a pediatric pulmonologist at Helen DeVos Children's Hospital in Grand Rapids, Mich. In an audio interview, Dr. Millard discusses the new Food and Drug Administration-approved combination therapy of elexacaftor, tezacaftor, and ivacaftor (Trikafta). It's a trio that could make a significant difference for the roughly 90% of patients with at least one F508del mutation.

Dr. Millard outlines which patients are candidates for the combination therapy,  what physicians and patients can expect with Trikafta use, and how the drug affects patients' use of other CF therapies. She also explains the steps physicians should take before starting patients on the therapy, and what side effects to watch for during treatment.

Dr. Millard is the local principal investigator for CF research at Helen DeVos Children’s Hospital, including Mylan, Therapeutic Development Network, and Vertex clinical studies.

Patients with both type 2 diabetes and asthma who were on glucagonlike peptide receptor–1 (GLP-1R) agonists for glucose control had lower levels of a key biomarker of airway inflammation than similar patients on other types of glucose-control medications, according to results of a study to have been presented at the annual meeting of the American Academy of Asthma, Allergy, and Immunology. The AAAAI canceled their annual meeting and provided abstracts and access to presenters for press coverage.

The findings from this study potentially replicated findings in humans that have been reported in preclinical trials.

“Our work showed that type 2 diabetics with asthma who were treated with GLP-1 receptor agonists had lower levels of periostin, and this provides really one of the first human data to show that these drugs may impact key inflammation pathways in the airway,” Dinah Foer, MD, of Brigham and Women’s Hospital, Boston, said in an interview. She described periostin as “a known critical inducer of airway mucous production and airway responsiveness.”

The study retrospectively evaluated serum samples from the Partners HealthCare Biobank of 161 adults with both asthma and type 2 diabetes, 42 of whom were on GLP-1R agonists and 119 of whom were taking non-GLP-1R agonist diabetes medications. The study used the Partners Healthcare EHR to identify eligible patients.

The study found that periostin levels were significantly decreased in GLP-1R agonist users: 19.1 ng/mL (standard deviation, +8.7) versus 27.4 ng/mL (SD, +14) in the non-GLP-1R agonist group (P = .001), Dr. Foer said. The other known mediators of asthma inflammatory pathways that were measured – interleukin-6, IL-8, sCD163, total IgE, and sST2 (soluble suppression of tumorigenesis–2) – showed no differences between the two groups, Dr. Foer said.

She said that this was the first human study to show similar results to preclinical models of asthma pathways. “What was interesting to us was that our findings were robust even when we controlled for covariates,” she added.

These findings lay the groundwork for further research into the potential therapeutic role GLP-1R agonists in asthma, Dr. Foer said. “This supports using periostin as a biomarker for novel therapeutic use of GLP-1R [agonists] in asthma,” she said. “At this point further study is needed to understand the clinical impact of GPL-1R [agonists] in asthma both for patients with type 2 diabetes and potentially in the future for patients who don’t have type 2 diabetes or metabolic disease.”

She added: “I don’t think we’re there yet; this is just one foot forward.”

The next step for researchers involves analyzing outcomes in asthmatics with type 2 diabetes on GLP-1R agonist therapy using a larger sample size as well as patients with asthma and metabolic disease, Dr. Foer said. The goal would be to identify corresponding biomarkers.

“There’s a terrific conversation in the field about the relationships between metabolism and asthma,” she said. “What our data contributes to that is, it suggests a role for metabolic pathways, specifically as it’s related GLP-1R [agonist] signaling pathways in regulating airway inflammation.”

Mark Moss, MD, associate professor of allergy & immunology at the University of Wisconsin–Madison, who was to serve as the moderator of the session, was positive about the GLP-1R agonist findings. He said in an interview: “This is promising research that provides a possible new target for the treatment of asthma.”

Dr. Foer disclosed that she has no relevant financial relationships.

SOURCE: Foer D et al. AAAAI Session 462, Abstract 784.

Patients with both type 2 diabetes and asthma who were on glucagonlike peptide receptor–1 (GLP-1R) agonists for glucose control had lower levels of a key biomarker of airway inflammation than similar patients on other types of glucose-control medications, according to results of a study to have been presented at the annual meeting of the American Academy of Asthma, Allergy, and Immunology. The AAAAI canceled their annual meeting and provided abstracts and access to presenters for press coverage.

The findings from this study potentially replicated findings in humans that have been reported in preclinical trials.

“Our work showed that type 2 diabetics with asthma who were treated with GLP-1 receptor agonists had lower levels of periostin, and this provides really one of the first human data to show that these drugs may impact key inflammation pathways in the airway,” Dinah Foer, MD, of Brigham and Women’s Hospital, Boston, said in an interview. She described periostin as “a known critical inducer of airway mucous production and airway responsiveness.”

The study retrospectively evaluated serum samples from the Partners HealthCare Biobank of 161 adults with both asthma and type 2 diabetes, 42 of whom were on GLP-1R agonists and 119 of whom were taking non-GLP-1R agonist diabetes medications. The study used the Partners Healthcare EHR to identify eligible patients.

The study found that periostin levels were significantly decreased in GLP-1R agonist users: 19.1 ng/mL (standard deviation, +8.7) versus 27.4 ng/mL (SD, +14) in the non-GLP-1R agonist group (P = .001), Dr. Foer said. The other known mediators of asthma inflammatory pathways that were measured – interleukin-6, IL-8, sCD163, total IgE, and sST2 (soluble suppression of tumorigenesis–2) – showed no differences between the two groups, Dr. Foer said.

She said that this was the first human study to show similar results to preclinical models of asthma pathways. “What was interesting to us was that our findings were robust even when we controlled for covariates,” she added.

These findings lay the groundwork for further research into the potential therapeutic role GLP-1R agonists in asthma, Dr. Foer said. “This supports using periostin as a biomarker for novel therapeutic use of GLP-1R [agonists] in asthma,” she said. “At this point further study is needed to understand the clinical impact of GPL-1R [agonists] in asthma both for patients with type 2 diabetes and potentially in the future for patients who don’t have type 2 diabetes or metabolic disease.”

She added: “I don’t think we’re there yet; this is just one foot forward.”

The next step for researchers involves analyzing outcomes in asthmatics with type 2 diabetes on GLP-1R agonist therapy using a larger sample size as well as patients with asthma and metabolic disease, Dr. Foer said. The goal would be to identify corresponding biomarkers.

“There’s a terrific conversation in the field about the relationships between metabolism and asthma,” she said. “What our data contributes to that is, it suggests a role for metabolic pathways, specifically as it’s related GLP-1R [agonist] signaling pathways in regulating airway inflammation.”

Mark Moss, MD, associate professor of allergy & immunology at the University of Wisconsin–Madison, who was to serve as the moderator of the session, was positive about the GLP-1R agonist findings. He said in an interview: “This is promising research that provides a possible new target for the treatment of asthma.”

Dr. Foer disclosed that she has no relevant financial relationships.

SOURCE: Foer D et al. AAAAI Session 462, Abstract 784.

Patients with both type 2 diabetes and asthma who were on glucagonlike peptide receptor–1 (GLP-1R) agonists for glucose control had lower levels of a key biomarker of airway inflammation than similar patients on other types of glucose-control medications, according to results of a study to have been presented at the annual meeting of the American Academy of Asthma, Allergy, and Immunology. The AAAAI canceled their annual meeting and provided abstracts and access to presenters for press coverage.

The findings from this study potentially replicated findings in humans that have been reported in preclinical trials.

“Our work showed that type 2 diabetics with asthma who were treated with GLP-1 receptor agonists had lower levels of periostin, and this provides really one of the first human data to show that these drugs may impact key inflammation pathways in the airway,” Dinah Foer, MD, of Brigham and Women’s Hospital, Boston, said in an interview. She described periostin as “a known critical inducer of airway mucous production and airway responsiveness.”

The study retrospectively evaluated serum samples from the Partners HealthCare Biobank of 161 adults with both asthma and type 2 diabetes, 42 of whom were on GLP-1R agonists and 119 of whom were taking non-GLP-1R agonist diabetes medications. The study used the Partners Healthcare EHR to identify eligible patients.

The study found that periostin levels were significantly decreased in GLP-1R agonist users: 19.1 ng/mL (standard deviation, +8.7) versus 27.4 ng/mL (SD, +14) in the non-GLP-1R agonist group (P = .001), Dr. Foer said. The other known mediators of asthma inflammatory pathways that were measured – interleukin-6, IL-8, sCD163, total IgE, and sST2 (soluble suppression of tumorigenesis–2) – showed no differences between the two groups, Dr. Foer said.

She said that this was the first human study to show similar results to preclinical models of asthma pathways. “What was interesting to us was that our findings were robust even when we controlled for covariates,” she added.

These findings lay the groundwork for further research into the potential therapeutic role GLP-1R agonists in asthma, Dr. Foer said. “This supports using periostin as a biomarker for novel therapeutic use of GLP-1R [agonists] in asthma,” she said. “At this point further study is needed to understand the clinical impact of GPL-1R [agonists] in asthma both for patients with type 2 diabetes and potentially in the future for patients who don’t have type 2 diabetes or metabolic disease.”

She added: “I don’t think we’re there yet; this is just one foot forward.”

The next step for researchers involves analyzing outcomes in asthmatics with type 2 diabetes on GLP-1R agonist therapy using a larger sample size as well as patients with asthma and metabolic disease, Dr. Foer said. The goal would be to identify corresponding biomarkers.

“There’s a terrific conversation in the field about the relationships between metabolism and asthma,” she said. “What our data contributes to that is, it suggests a role for metabolic pathways, specifically as it’s related GLP-1R [agonist] signaling pathways in regulating airway inflammation.”

Mark Moss, MD, associate professor of allergy & immunology at the University of Wisconsin–Madison, who was to serve as the moderator of the session, was positive about the GLP-1R agonist findings. He said in an interview: “This is promising research that provides a possible new target for the treatment of asthma.”

Dr. Foer disclosed that she has no relevant financial relationships.

SOURCE: Foer D et al. AAAAI Session 462, Abstract 784.

Patients with allergic rhinitis receiving oral tree sublingual immunotherapy (SLIT) during pollen season showed improvement in their symptoms, according to recent research released as an abstract for the annual meeting of the American Academy of Allergy, Asthma & Immunology.

Photo courtesy Oak Ridge National Laboratory

Tree pollen season is generally considered to be between February and June, with alder and hazel allergens affecting patients early and oak pollen affecting patients later in the season. Since a major birch allergen, Betula verrucosa 1 (Bet v 1), cross-reacts with alder, hazel, and oak allergens, some patients may experience allergies across the entire tree pollen season from members of this so-called birth homologous group, Hendrik Nolte, MD, senior vice president of research and development at ALK-Abello Americas and International, said in an interview.

According to the U.S. National Health and Nutrition Examination Survey 2005-2006, 16% of 8,086 participants 6 years or older with allergy had a specific immunoglobulin E (IgE) to birch, while 18% had a specific IgE to oak. Patients who reported having hay fever had a specific IgE to birch of 23% and a specific IgE to oak of 26% (J Allergy Clin Immunol. 2011 May;127[5]:1226-1235.e7).

“Patients who are allergic to birch pollen often experience symptoms in response to pollen from other members of the birch homologous group, which prolong the tree season and increase the symptom burden for these patients,” Dr. Nolte said. “Thus, treatment with SLIT-tablet immunotherapy may be an important treatment option for many allergy sufferers.”

Dr. Nolte and colleagues performed a randomized, double-blind, multinational trial of 634 patients before and during tree pollen season in which participants received a daily SLIT tablet or placebo. Patients were between ages 12 and 65 years with allergic rhinitis, and investigators enrolled patients or without conjunctivitis and with or without asthma. The investigations evaluated the patients’ daily symptom score and daily medication score, which was grouped into the total combined score. The patients were also allowed to use their rescue medications during the trial.
 

SLIT demonstrates symptom improvement

“Improvement in allergic rhinoconjunctivitis symptoms and reduction in symptom-relieving medication use with the tree SLIT-tablet during birch, alder/hazel, and oak pollen seasons were significant versus placebo and showed internal consistency across almost 4 months of birch and related tree pollen exposure,” Dr. Nolte said.

Patients showed relative improvements in their total combined score of 39.6% for birch, 29.7% for alder and hazel, 36.0% during oak pollen season, and 35.0% during the entire tree pollen season, compared with placebo (all P ≤ .002). Relative daily symptom scores also improved in the group that received oral SLIT, with 36.8% of patients showing improvement during birch season, 26.0% during alder and hazel season, 31.6% during oak season, and 31.6% across all pollen seasons, compared with those taking placebo (all P ≤ .003). A greater number of patients also achieved a relative improvement in daily medication score during birch season (49.2%), alder and hazel season (43.8%), oak season (45.9%) and during the whole of tree pollen season (45.3%), compared with placebo (P ≤ .002).

“The results support the clinical relevance of cross-reactivity between birch, alder/hazel, and oak pollen homologous allergens,” Dr. Nolte said. “Immunologic cross-reactivity is supported by alder, hazel, and oak specific IgE data and IgG4 in responses to the tree SLIT tablet.”

Dr. Nolte said the next step in his team’s research was to evaluate oral SLIT in a phase 3 trial for children aged 5-17 years.

This study was funded by ALK, and the authors received medical writing and editorial assistance from Scott Medical Communications. Dr. Nolte reported that he is a paid employee of ALK.

SOURCE: Nolte H et al. AAAAI, Abstract 267.

.

Patients with allergic rhinitis receiving oral tree sublingual immunotherapy (SLIT) during pollen season showed improvement in their symptoms, according to recent research released as an abstract for the annual meeting of the American Academy of Allergy, Asthma & Immunology.

Photo courtesy Oak Ridge National Laboratory

Tree pollen season is generally considered to be between February and June, with alder and hazel allergens affecting patients early and oak pollen affecting patients later in the season. Since a major birch allergen, Betula verrucosa 1 (Bet v 1), cross-reacts with alder, hazel, and oak allergens, some patients may experience allergies across the entire tree pollen season from members of this so-called birth homologous group, Hendrik Nolte, MD, senior vice president of research and development at ALK-Abello Americas and International, said in an interview.

According to the U.S. National Health and Nutrition Examination Survey 2005-2006, 16% of 8,086 participants 6 years or older with allergy had a specific immunoglobulin E (IgE) to birch, while 18% had a specific IgE to oak. Patients who reported having hay fever had a specific IgE to birch of 23% and a specific IgE to oak of 26% (J Allergy Clin Immunol. 2011 May;127[5]:1226-1235.e7).

“Patients who are allergic to birch pollen often experience symptoms in response to pollen from other members of the birch homologous group, which prolong the tree season and increase the symptom burden for these patients,” Dr. Nolte said. “Thus, treatment with SLIT-tablet immunotherapy may be an important treatment option for many allergy sufferers.”

Dr. Nolte and colleagues performed a randomized, double-blind, multinational trial of 634 patients before and during tree pollen season in which participants received a daily SLIT tablet or placebo. Patients were between ages 12 and 65 years with allergic rhinitis, and investigators enrolled patients or without conjunctivitis and with or without asthma. The investigations evaluated the patients’ daily symptom score and daily medication score, which was grouped into the total combined score. The patients were also allowed to use their rescue medications during the trial.
 

SLIT demonstrates symptom improvement

“Improvement in allergic rhinoconjunctivitis symptoms and reduction in symptom-relieving medication use with the tree SLIT-tablet during birch, alder/hazel, and oak pollen seasons were significant versus placebo and showed internal consistency across almost 4 months of birch and related tree pollen exposure,” Dr. Nolte said.

Patients showed relative improvements in their total combined score of 39.6% for birch, 29.7% for alder and hazel, 36.0% during oak pollen season, and 35.0% during the entire tree pollen season, compared with placebo (all P ≤ .002). Relative daily symptom scores also improved in the group that received oral SLIT, with 36.8% of patients showing improvement during birch season, 26.0% during alder and hazel season, 31.6% during oak season, and 31.6% across all pollen seasons, compared with those taking placebo (all P ≤ .003). A greater number of patients also achieved a relative improvement in daily medication score during birch season (49.2%), alder and hazel season (43.8%), oak season (45.9%) and during the whole of tree pollen season (45.3%), compared with placebo (P ≤ .002).

“The results support the clinical relevance of cross-reactivity between birch, alder/hazel, and oak pollen homologous allergens,” Dr. Nolte said. “Immunologic cross-reactivity is supported by alder, hazel, and oak specific IgE data and IgG4 in responses to the tree SLIT tablet.”

Dr. Nolte said the next step in his team’s research was to evaluate oral SLIT in a phase 3 trial for children aged 5-17 years.

This study was funded by ALK, and the authors received medical writing and editorial assistance from Scott Medical Communications. Dr. Nolte reported that he is a paid employee of ALK.

SOURCE: Nolte H et al. AAAAI, Abstract 267.

.

Patients with allergic rhinitis receiving oral tree sublingual immunotherapy (SLIT) during pollen season showed improvement in their symptoms, according to recent research released as an abstract for the annual meeting of the American Academy of Allergy, Asthma & Immunology.

Photo courtesy Oak Ridge National Laboratory

Tree pollen season is generally considered to be between February and June, with alder and hazel allergens affecting patients early and oak pollen affecting patients later in the season. Since a major birch allergen, Betula verrucosa 1 (Bet v 1), cross-reacts with alder, hazel, and oak allergens, some patients may experience allergies across the entire tree pollen season from members of this so-called birth homologous group, Hendrik Nolte, MD, senior vice president of research and development at ALK-Abello Americas and International, said in an interview.

According to the U.S. National Health and Nutrition Examination Survey 2005-2006, 16% of 8,086 participants 6 years or older with allergy had a specific immunoglobulin E (IgE) to birch, while 18% had a specific IgE to oak. Patients who reported having hay fever had a specific IgE to birch of 23% and a specific IgE to oak of 26% (J Allergy Clin Immunol. 2011 May;127[5]:1226-1235.e7).

“Patients who are allergic to birch pollen often experience symptoms in response to pollen from other members of the birch homologous group, which prolong the tree season and increase the symptom burden for these patients,” Dr. Nolte said. “Thus, treatment with SLIT-tablet immunotherapy may be an important treatment option for many allergy sufferers.”

Dr. Nolte and colleagues performed a randomized, double-blind, multinational trial of 634 patients before and during tree pollen season in which participants received a daily SLIT tablet or placebo. Patients were between ages 12 and 65 years with allergic rhinitis, and investigators enrolled patients or without conjunctivitis and with or without asthma. The investigations evaluated the patients’ daily symptom score and daily medication score, which was grouped into the total combined score. The patients were also allowed to use their rescue medications during the trial.
 

SLIT demonstrates symptom improvement

“Improvement in allergic rhinoconjunctivitis symptoms and reduction in symptom-relieving medication use with the tree SLIT-tablet during birch, alder/hazel, and oak pollen seasons were significant versus placebo and showed internal consistency across almost 4 months of birch and related tree pollen exposure,” Dr. Nolte said.

Patients showed relative improvements in their total combined score of 39.6% for birch, 29.7% for alder and hazel, 36.0% during oak pollen season, and 35.0% during the entire tree pollen season, compared with placebo (all P ≤ .002). Relative daily symptom scores also improved in the group that received oral SLIT, with 36.8% of patients showing improvement during birch season, 26.0% during alder and hazel season, 31.6% during oak season, and 31.6% across all pollen seasons, compared with those taking placebo (all P ≤ .003). A greater number of patients also achieved a relative improvement in daily medication score during birch season (49.2%), alder and hazel season (43.8%), oak season (45.9%) and during the whole of tree pollen season (45.3%), compared with placebo (P ≤ .002).

“The results support the clinical relevance of cross-reactivity between birch, alder/hazel, and oak pollen homologous allergens,” Dr. Nolte said. “Immunologic cross-reactivity is supported by alder, hazel, and oak specific IgE data and IgG4 in responses to the tree SLIT tablet.”

Dr. Nolte said the next step in his team’s research was to evaluate oral SLIT in a phase 3 trial for children aged 5-17 years.

This study was funded by ALK, and the authors received medical writing and editorial assistance from Scott Medical Communications. Dr. Nolte reported that he is a paid employee of ALK.

SOURCE: Nolte H et al. AAAAI, Abstract 267.

.

Coronavirus disease (COVID-19) was declared a pandemic by the World Health Organization on March 11. This rapidly spreading disease is caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The infection has spread to more than 140 countries, including the United States. As of March 16, more than 170,400 people had tested positive for SARS-CoV-2 and more than 6,619 people have died across the globe.

The number of new COVID-19 cases appears to be decreasing in China, but the number of cases are rapidly increasing worldwide. Based on available data, primarily from China, children (aged 0-19 years) account for only about 2% of all cases. Despite the probable low virulence and incidence of infection in children, they could act as potential vectors and transmit infection to more vulnerable populations. As of March 16, approximately 3,823 cases and more than 67 deaths had been reported in the United States with few pediatric patients testing positive for the disease.

SARS-CoV2 transmission mainly occurs via respiratory route through close contact with infected individuals and through fomites. The incubation period ranges from 2-14 days with an average of about 5 days. Adult patients present with cough and fever, which may progress to lower respiratory tract symptoms, including shortness of breath. Approximately 10% of all patients develop severe disease and acute respiratory distress syndrome (ARDS), requiring mechanical ventilation.

COVID-19 carries a mortality rate of up to 3%, but has been significantly higher in the elderly population, and those with chronic health conditions. Available data so far shows that children are at lower risk and the severity of the disease has been milder compared to adults. The reasons for this are not clear at this time. As of March 16, there were no reported COVID-19 related deaths in children under age 9 years.
 

The pediatric population: Disease patterns and transmission

The epidemiology and spectrum of disease for COVID-19 is poorly understood in pediatrics because of the low number of reported pediatric cases and limited data available from these patients. Small numbers of reported cases in children has led some to believe that children are relatively immune to the infection by SARS-CoV-2. However, Oifang et al. found that children are equally as likely as adults to be infected.¹

Liu et al. found that of 366 children admitted to a hospital in Wuhan with respiratory infections in January 2020, 1.6% (six patients) cases were positive for SARS-CoV-2.² These six children were aged 1-7 years and had all been previously healthy; all six presented with cough and fever of 102.2° F or greater. Four of the children also had vomiting. Laboratory findings were notable for lymphopenia (six of six), leukopenia (four of six), and neutropenia (3/6) with mild to moderate elevation in C-reactive protein (6.8-58.8 mg/L). Five of six children had chest CT scans. One child’s CT scan showed “bilateral ground-glass opacities” (similar to what is reported in adults), three showed “bilateral patchy shadows,” and one was normal. One child (aged 3 years) was admitted to the ICU. All of the children were treated with supportive measures, empiric antibiotics, and antivirals (six of six received oseltamivir and four of six received ribavirin). All six children recovered completely and their median hospital stay was 7.5 days with a range of 5-13 days.

Xia et al. reviewed 20 children (aged 1 day to 14 years) admitted to a hospital in Wuhan during Jan. 23–Feb. 8.³ The study reported that fever and cough were the most common presenting symptoms (approximately 65%). Less common symptoms included rhinorrhea (15%), diarrhea (15%), vomiting (10%), and sore throat (5%). WBC count was normal in majority of children (70%) with leukopenia in 20% and leukocytosis in 10%. Lymphopenia was noted to be 35%. Elevated procalcitonin was noted in 80% of children, although the degree of elevation is unclear. In this study, 8 of 20 children were coinfected with other respiratory pathogens such as influenza, respiratory syncytial virus, mycoplasma, and cytomegalovirus. All children had chest CT scans. Ten of 20 children had bilateral pulmonary lesions, 6 of 20 had unilateral pulmonary lesions, 12 of 20 had ground-glass opacities and 10 of 20 had lung consolidations with halo signs.

Wei et al., retrospective chart review of nine infants admitted for COVID-19 found that all nine had at least one infected family member.⁴ This study reported that seven of nine were female infants, four of nine had fever, two had mild upper respiratory infection symptoms, and one had no symptoms. The study did report that two infants did not have any information available related to symptoms. None of the infants developed severe symptoms or required ICU admission.

Current challenges

Given the aggressive transmission of COVID-19, these numbers seem to be increasing exponentially with a significant impact on the life of the entire country. Therefore, we must focus on containing the spread and mitigating the transmission with a multimodality approach.

Some of the initial challenges faced by physicians in the United States were related to difficulty in access to testing in persons under investigation (PUI), which in turn resulted in a delay in diagnosis and infection control. At this time, the need is to increase surge testing capabilities across the country through a variety of innovative approaches including public-private partnerships with commercial labs through Emergency Use Authorization (EUA) issued by the Centers for Disease Control and Prevention and the Department of Health and Human Services. To minimize exposure to health care professionals, telemedicine and telehealth capabilities should be exploited. This will minimize the exposure to infected patients and reduce the need for already limited personal protective equipment (PPE). As the number of cases rise, hospitals should expect and prepare for a surge in COVID-19–related hospitalizations and health care utilization.
 

Conclusion

Various theories are being proposed as to why children are not experiencing severe disease with COVID-19. Children may have cross-protective immunity from infection with other coronaviruses. Children may not have the same exposures from work, travel, and caregiving that adults experience as they are typically exposed by someone in their home. At this time, not enough is known about clinical presentations in children as the situation continues to evolve across the globe.

Respiratory infections in children pose unique infection control challenges with respect to compliant hand hygiene, cough etiquette, and the use of PPE when indicated. There is also concern for persistent fecal shedding of virus in infected pediatric patients, which could be another mode of transmission.⁶ Children could, however, be very efficient vectors of COVID-19, similar to flu, and potentially spread the pathogen to very vulnerable populations leading to high morbidity and mortality. School closures are an effective social distancing measure needed to flatten the curve and avoid overwhelming the health care structure of the United States.
 

Dr. Konanki is a board-certified pediatrician doing inpatient work at Wellspan Chambersburg Hospital and outpatient work at Keystone Pediatrics in Chambersburg, Pa. He also serves as the physician member of the hospital’s Code Blue Jr. committee and as a member of Quality Metrics committee at Keystone Health. Dr. Tirupathi is the medical director of Keystone Infectious Diseases/HIV in Chambersburg, Pa., and currently chair of infection prevention at Wellspan Chambersburg and Waynesboro (Pa.) Hospitals. He also is the lead physician for antibiotic stewardship at these hospitals. Dr. Palabindala is hospital medicine division chief at the University of Mississippi Medical Center, Jackson.

References

1. Bi Q et al. Epidemiology and transmission of COVID-19 in Shenzhen China: Analysis of 391 cases and 1,286 of their close contacts. medRxiv 2020.03.03.20028423.

2. Liu W et al. Detection of Covid-19 in children in early January 2020 in Wuhan, China. N Engl J Med. 2020 Mar 12. doi: 10.1056/NEJMc2003717.

3. Xia W et al. Clinical and CT features in pediatric patients with COVID‐19 infection: Different points from adults. Pediatr Pulmonol. 2020 Mar 5. doi: 10.1002/ppul.24718.

4. Wei M et al. Novel Coronavirus infection in hospitalized infants under 1 year of age in China. JAMA. 2020 Feb. 14. doi: 10.1001/jama.2020.2131.

5. Huijun C et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: A retrospective review of medical records. Lancet. 2020 Mar 7 395;10226:809-15.

6. Xu Y et al. Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding. Nat Med. 2020 Mar 13. doi. org/10.1038/s41591-020-0817-4.

Coronavirus disease (COVID-19) was declared a pandemic by the World Health Organization on March 11. This rapidly spreading disease is caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The infection has spread to more than 140 countries, including the United States. As of March 16, more than 170,400 people had tested positive for SARS-CoV-2 and more than 6,619 people have died across the globe.

The number of new COVID-19 cases appears to be decreasing in China, but the number of cases are rapidly increasing worldwide. Based on available data, primarily from China, children (aged 0-19 years) account for only about 2% of all cases. Despite the probable low virulence and incidence of infection in children, they could act as potential vectors and transmit infection to more vulnerable populations. As of March 16, approximately 3,823 cases and more than 67 deaths had been reported in the United States with few pediatric patients testing positive for the disease.

SARS-CoV2 transmission mainly occurs via respiratory route through close contact with infected individuals and through fomites. The incubation period ranges from 2-14 days with an average of about 5 days. Adult patients present with cough and fever, which may progress to lower respiratory tract symptoms, including shortness of breath. Approximately 10% of all patients develop severe disease and acute respiratory distress syndrome (ARDS), requiring mechanical ventilation.

COVID-19 carries a mortality rate of up to 3%, but has been significantly higher in the elderly population, and those with chronic health conditions. Available data so far shows that children are at lower risk and the severity of the disease has been milder compared to adults. The reasons for this are not clear at this time. As of March 16, there were no reported COVID-19 related deaths in children under age 9 years.
 

The pediatric population: Disease patterns and transmission

The epidemiology and spectrum of disease for COVID-19 is poorly understood in pediatrics because of the low number of reported pediatric cases and limited data available from these patients. Small numbers of reported cases in children has led some to believe that children are relatively immune to the infection by SARS-CoV-2. However, Oifang et al. found that children are equally as likely as adults to be infected.¹

Liu et al. found that of 366 children admitted to a hospital in Wuhan with respiratory infections in January 2020, 1.6% (six patients) cases were positive for SARS-CoV-2.² These six children were aged 1-7 years and had all been previously healthy; all six presented with cough and fever of 102.2° F or greater. Four of the children also had vomiting. Laboratory findings were notable for lymphopenia (six of six), leukopenia (four of six), and neutropenia (3/6) with mild to moderate elevation in C-reactive protein (6.8-58.8 mg/L). Five of six children had chest CT scans. One child’s CT scan showed “bilateral ground-glass opacities” (similar to what is reported in adults), three showed “bilateral patchy shadows,” and one was normal. One child (aged 3 years) was admitted to the ICU. All of the children were treated with supportive measures, empiric antibiotics, and antivirals (six of six received oseltamivir and four of six received ribavirin). All six children recovered completely and their median hospital stay was 7.5 days with a range of 5-13 days.

Xia et al. reviewed 20 children (aged 1 day to 14 years) admitted to a hospital in Wuhan during Jan. 23–Feb. 8.³ The study reported that fever and cough were the most common presenting symptoms (approximately 65%). Less common symptoms included rhinorrhea (15%), diarrhea (15%), vomiting (10%), and sore throat (5%). WBC count was normal in majority of children (70%) with leukopenia in 20% and leukocytosis in 10%. Lymphopenia was noted to be 35%. Elevated procalcitonin was noted in 80% of children, although the degree of elevation is unclear. In this study, 8 of 20 children were coinfected with other respiratory pathogens such as influenza, respiratory syncytial virus, mycoplasma, and cytomegalovirus. All children had chest CT scans. Ten of 20 children had bilateral pulmonary lesions, 6 of 20 had unilateral pulmonary lesions, 12 of 20 had ground-glass opacities and 10 of 20 had lung consolidations with halo signs.

Wei et al., retrospective chart review of nine infants admitted for COVID-19 found that all nine had at least one infected family member.⁴ This study reported that seven of nine were female infants, four of nine had fever, two had mild upper respiratory infection symptoms, and one had no symptoms. The study did report that two infants did not have any information available related to symptoms. None of the infants developed severe symptoms or required ICU admission.

Current challenges

Given the aggressive transmission of COVID-19, these numbers seem to be increasing exponentially with a significant impact on the life of the entire country. Therefore, we must focus on containing the spread and mitigating the transmission with a multimodality approach.

Some of the initial challenges faced by physicians in the United States were related to difficulty in access to testing in persons under investigation (PUI), which in turn resulted in a delay in diagnosis and infection control. At this time, the need is to increase surge testing capabilities across the country through a variety of innovative approaches including public-private partnerships with commercial labs through Emergency Use Authorization (EUA) issued by the Centers for Disease Control and Prevention and the Department of Health and Human Services. To minimize exposure to health care professionals, telemedicine and telehealth capabilities should be exploited. This will minimize the exposure to infected patients and reduce the need for already limited personal protective equipment (PPE). As the number of cases rise, hospitals should expect and prepare for a surge in COVID-19–related hospitalizations and health care utilization.
 

Conclusion

Various theories are being proposed as to why children are not experiencing severe disease with COVID-19. Children may have cross-protective immunity from infection with other coronaviruses. Children may not have the same exposures from work, travel, and caregiving that adults experience as they are typically exposed by someone in their home. At this time, not enough is known about clinical presentations in children as the situation continues to evolve across the globe.

Respiratory infections in children pose unique infection control challenges with respect to compliant hand hygiene, cough etiquette, and the use of PPE when indicated. There is also concern for persistent fecal shedding of virus in infected pediatric patients, which could be another mode of transmission.⁶ Children could, however, be very efficient vectors of COVID-19, similar to flu, and potentially spread the pathogen to very vulnerable populations leading to high morbidity and mortality. School closures are an effective social distancing measure needed to flatten the curve and avoid overwhelming the health care structure of the United States.
 

Dr. Konanki is a board-certified pediatrician doing inpatient work at Wellspan Chambersburg Hospital and outpatient work at Keystone Pediatrics in Chambersburg, Pa. He also serves as the physician member of the hospital’s Code Blue Jr. committee and as a member of Quality Metrics committee at Keystone Health. Dr. Tirupathi is the medical director of Keystone Infectious Diseases/HIV in Chambersburg, Pa., and currently chair of infection prevention at Wellspan Chambersburg and Waynesboro (Pa.) Hospitals. He also is the lead physician for antibiotic stewardship at these hospitals. Dr. Palabindala is hospital medicine division chief at the University of Mississippi Medical Center, Jackson.

References

1. Bi Q et al. Epidemiology and transmission of COVID-19 in Shenzhen China: Analysis of 391 cases and 1,286 of their close contacts. medRxiv 2020.03.03.20028423.

2. Liu W et al. Detection of Covid-19 in children in early January 2020 in Wuhan, China. N Engl J Med. 2020 Mar 12. doi: 10.1056/NEJMc2003717.

3. Xia W et al. Clinical and CT features in pediatric patients with COVID‐19 infection: Different points from adults. Pediatr Pulmonol. 2020 Mar 5. doi: 10.1002/ppul.24718.

4. Wei M et al. Novel Coronavirus infection in hospitalized infants under 1 year of age in China. JAMA. 2020 Feb. 14. doi: 10.1001/jama.2020.2131.

5. Huijun C et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: A retrospective review of medical records. Lancet. 2020 Mar 7 395;10226:809-15.

6. Xu Y et al. Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding. Nat Med. 2020 Mar 13. doi. org/10.1038/s41591-020-0817-4.

Coronavirus disease (COVID-19) was declared a pandemic by the World Health Organization on March 11. This rapidly spreading disease is caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The infection has spread to more than 140 countries, including the United States. As of March 16, more than 170,400 people had tested positive for SARS-CoV-2 and more than 6,619 people have died across the globe.

The number of new COVID-19 cases appears to be decreasing in China, but the number of cases are rapidly increasing worldwide. Based on available data, primarily from China, children (aged 0-19 years) account for only about 2% of all cases. Despite the probable low virulence and incidence of infection in children, they could act as potential vectors and transmit infection to more vulnerable populations. As of March 16, approximately 3,823 cases and more than 67 deaths had been reported in the United States with few pediatric patients testing positive for the disease.

SARS-CoV2 transmission mainly occurs via respiratory route through close contact with infected individuals and through fomites. The incubation period ranges from 2-14 days with an average of about 5 days. Adult patients present with cough and fever, which may progress to lower respiratory tract symptoms, including shortness of breath. Approximately 10% of all patients develop severe disease and acute respiratory distress syndrome (ARDS), requiring mechanical ventilation.

COVID-19 carries a mortality rate of up to 3%, but has been significantly higher in the elderly population, and those with chronic health conditions. Available data so far shows that children are at lower risk and the severity of the disease has been milder compared to adults. The reasons for this are not clear at this time. As of March 16, there were no reported COVID-19 related deaths in children under age 9 years.
 

The pediatric population: Disease patterns and transmission

The epidemiology and spectrum of disease for COVID-19 is poorly understood in pediatrics because of the low number of reported pediatric cases and limited data available from these patients. Small numbers of reported cases in children has led some to believe that children are relatively immune to the infection by SARS-CoV-2. However, Oifang et al. found that children are equally as likely as adults to be infected.¹

Liu et al. found that of 366 children admitted to a hospital in Wuhan with respiratory infections in January 2020, 1.6% (six patients) cases were positive for SARS-CoV-2.² These six children were aged 1-7 years and had all been previously healthy; all six presented with cough and fever of 102.2° F or greater. Four of the children also had vomiting. Laboratory findings were notable for lymphopenia (six of six), leukopenia (four of six), and neutropenia (3/6) with mild to moderate elevation in C-reactive protein (6.8-58.8 mg/L). Five of six children had chest CT scans. One child’s CT scan showed “bilateral ground-glass opacities” (similar to what is reported in adults), three showed “bilateral patchy shadows,” and one was normal. One child (aged 3 years) was admitted to the ICU. All of the children were treated with supportive measures, empiric antibiotics, and antivirals (six of six received oseltamivir and four of six received ribavirin). All six children recovered completely and their median hospital stay was 7.5 days with a range of 5-13 days.

Xia et al. reviewed 20 children (aged 1 day to 14 years) admitted to a hospital in Wuhan during Jan. 23–Feb. 8.³ The study reported that fever and cough were the most common presenting symptoms (approximately 65%). Less common symptoms included rhinorrhea (15%), diarrhea (15%), vomiting (10%), and sore throat (5%). WBC count was normal in majority of children (70%) with leukopenia in 20% and leukocytosis in 10%. Lymphopenia was noted to be 35%. Elevated procalcitonin was noted in 80% of children, although the degree of elevation is unclear. In this study, 8 of 20 children were coinfected with other respiratory pathogens such as influenza, respiratory syncytial virus, mycoplasma, and cytomegalovirus. All children had chest CT scans. Ten of 20 children had bilateral pulmonary lesions, 6 of 20 had unilateral pulmonary lesions, 12 of 20 had ground-glass opacities and 10 of 20 had lung consolidations with halo signs.

Wei et al., retrospective chart review of nine infants admitted for COVID-19 found that all nine had at least one infected family member.⁴ This study reported that seven of nine were female infants, four of nine had fever, two had mild upper respiratory infection symptoms, and one had no symptoms. The study did report that two infants did not have any information available related to symptoms. None of the infants developed severe symptoms or required ICU admission.

Current challenges

Given the aggressive transmission of COVID-19, these numbers seem to be increasing exponentially with a significant impact on the life of the entire country. Therefore, we must focus on containing the spread and mitigating the transmission with a multimodality approach.

Some of the initial challenges faced by physicians in the United States were related to difficulty in access to testing in persons under investigation (PUI), which in turn resulted in a delay in diagnosis and infection control. At this time, the need is to increase surge testing capabilities across the country through a variety of innovative approaches including public-private partnerships with commercial labs through Emergency Use Authorization (EUA) issued by the Centers for Disease Control and Prevention and the Department of Health and Human Services. To minimize exposure to health care professionals, telemedicine and telehealth capabilities should be exploited. This will minimize the exposure to infected patients and reduce the need for already limited personal protective equipment (PPE). As the number of cases rise, hospitals should expect and prepare for a surge in COVID-19–related hospitalizations and health care utilization.
 

Conclusion

Various theories are being proposed as to why children are not experiencing severe disease with COVID-19. Children may have cross-protective immunity from infection with other coronaviruses. Children may not have the same exposures from work, travel, and caregiving that adults experience as they are typically exposed by someone in their home. At this time, not enough is known about clinical presentations in children as the situation continues to evolve across the globe.

Respiratory infections in children pose unique infection control challenges with respect to compliant hand hygiene, cough etiquette, and the use of PPE when indicated. There is also concern for persistent fecal shedding of virus in infected pediatric patients, which could be another mode of transmission.⁶ Children could, however, be very efficient vectors of COVID-19, similar to flu, and potentially spread the pathogen to very vulnerable populations leading to high morbidity and mortality. School closures are an effective social distancing measure needed to flatten the curve and avoid overwhelming the health care structure of the United States.
 

Dr. Konanki is a board-certified pediatrician doing inpatient work at Wellspan Chambersburg Hospital and outpatient work at Keystone Pediatrics in Chambersburg, Pa. He also serves as the physician member of the hospital’s Code Blue Jr. committee and as a member of Quality Metrics committee at Keystone Health. Dr. Tirupathi is the medical director of Keystone Infectious Diseases/HIV in Chambersburg, Pa., and currently chair of infection prevention at Wellspan Chambersburg and Waynesboro (Pa.) Hospitals. He also is the lead physician for antibiotic stewardship at these hospitals. Dr. Palabindala is hospital medicine division chief at the University of Mississippi Medical Center, Jackson.

References

1. Bi Q et al. Epidemiology and transmission of COVID-19 in Shenzhen China: Analysis of 391 cases and 1,286 of their close contacts. medRxiv 2020.03.03.20028423.

2. Liu W et al. Detection of Covid-19 in children in early January 2020 in Wuhan, China. N Engl J Med. 2020 Mar 12. doi: 10.1056/NEJMc2003717.

3. Xia W et al. Clinical and CT features in pediatric patients with COVID‐19 infection: Different points from adults. Pediatr Pulmonol. 2020 Mar 5. doi: 10.1002/ppul.24718.

4. Wei M et al. Novel Coronavirus infection in hospitalized infants under 1 year of age in China. JAMA. 2020 Feb. 14. doi: 10.1001/jama.2020.2131.

5. Huijun C et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: A retrospective review of medical records. Lancet. 2020 Mar 7 395;10226:809-15.

6. Xu Y et al. Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding. Nat Med. 2020 Mar 13. doi. org/10.1038/s41591-020-0817-4.

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.

As COVID-19 spreads across the United States, it is important to understand the extent of the nation’s ICU resources, according to the Society of Critical Care Medicine. The SCCM has updated its statistics on the resources available to care for what could become “an overwhelming number of critically ill patients, many of whom may require mechanical ventilation,” the society said in a blog post on March 13.

That overwhelming number was considered at an American Hospital Association webinar in February: Investigators projected that 4.8 million patients could be hospitalized with COVID-19, of whom 1.9 million would be admitted to ICUs and 960,000 would require ventilator support, Neil A. Halpern, MD, director of the critical care center at Memorial Sloan Kettering Cancer Center, New York, and Kay See Tan, PhD, of the hospital’s department of epidemiology and biostatistics, reported in that post.

As far as critical care beds are concerned, the United States is in better shape than are other countries dealing with the coronavirus. The United States’ 34.7 critical care beds per 100,000 population put it a good bit ahead of Germany, which has 29.2 beds per 100,000, while other countries in both Europe and Asia are well behind, Dr. Halpern and Dr. Tan noted.

More recent data from the AHA show that just over half of its registered community hospitals deliver ICU services and have at least 10 acute care beds and one ICU bed, they reported.

Those 2,704 hospitals have nearly 535,000 acute care beds, of which almost 97,000 are ICU beds. Almost 71% of those ICU beds are for adults, with the rest located in neonatal and pediatric units, data from an AHA 2018 survey show.

Since patients with COVID-19 are most often admitted to ICUs with severe hypoxic respiratory failure, the nation’s supply of ventilators also may be tested. U.S. acute care hospitals own about 62,000 full-featured mechanical ventilators and almost 99,000 older ventilators that “may not be capable of adequately supporting patients with severe acute respiratory failure,” Dr. Halpern and Dr. Tan said.

As U.S. hospitals reach the crisis levels anticipated in the COVID-19 pandemic, staffing shortages can be expected as well. Almost half (48%) of acute care hospitals have no intensivists, so “other physicians (e.g., pulmonologists, surgeons, anesthesiologists, etc) may be pressed into service as outpatient clinics and elective surgery are suspended,” they wrote.

The blog post includes a tiered staffing strategy that the SCCM “encourages hospitals to adopt in pandemic situations such as COVID-19.”

[email protected]

As COVID-19 spreads across the United States, it is important to understand the extent of the nation’s ICU resources, according to the Society of Critical Care Medicine. The SCCM has updated its statistics on the resources available to care for what could become “an overwhelming number of critically ill patients, many of whom may require mechanical ventilation,” the society said in a blog post on March 13.

That overwhelming number was considered at an American Hospital Association webinar in February: Investigators projected that 4.8 million patients could be hospitalized with COVID-19, of whom 1.9 million would be admitted to ICUs and 960,000 would require ventilator support, Neil A. Halpern, MD, director of the critical care center at Memorial Sloan Kettering Cancer Center, New York, and Kay See Tan, PhD, of the hospital’s department of epidemiology and biostatistics, reported in that post.

As far as critical care beds are concerned, the United States is in better shape than are other countries dealing with the coronavirus. The United States’ 34.7 critical care beds per 100,000 population put it a good bit ahead of Germany, which has 29.2 beds per 100,000, while other countries in both Europe and Asia are well behind, Dr. Halpern and Dr. Tan noted.

More recent data from the AHA show that just over half of its registered community hospitals deliver ICU services and have at least 10 acute care beds and one ICU bed, they reported.

Those 2,704 hospitals have nearly 535,000 acute care beds, of which almost 97,000 are ICU beds. Almost 71% of those ICU beds are for adults, with the rest located in neonatal and pediatric units, data from an AHA 2018 survey show.

Since patients with COVID-19 are most often admitted to ICUs with severe hypoxic respiratory failure, the nation’s supply of ventilators also may be tested. U.S. acute care hospitals own about 62,000 full-featured mechanical ventilators and almost 99,000 older ventilators that “may not be capable of adequately supporting patients with severe acute respiratory failure,” Dr. Halpern and Dr. Tan said.

As U.S. hospitals reach the crisis levels anticipated in the COVID-19 pandemic, staffing shortages can be expected as well. Almost half (48%) of acute care hospitals have no intensivists, so “other physicians (e.g., pulmonologists, surgeons, anesthesiologists, etc) may be pressed into service as outpatient clinics and elective surgery are suspended,” they wrote.

The blog post includes a tiered staffing strategy that the SCCM “encourages hospitals to adopt in pandemic situations such as COVID-19.”

[email protected]

As COVID-19 spreads across the United States, it is important to understand the extent of the nation’s ICU resources, according to the Society of Critical Care Medicine. The SCCM has updated its statistics on the resources available to care for what could become “an overwhelming number of critically ill patients, many of whom may require mechanical ventilation,” the society said in a blog post on March 13.

That overwhelming number was considered at an American Hospital Association webinar in February: Investigators projected that 4.8 million patients could be hospitalized with COVID-19, of whom 1.9 million would be admitted to ICUs and 960,000 would require ventilator support, Neil A. Halpern, MD, director of the critical care center at Memorial Sloan Kettering Cancer Center, New York, and Kay See Tan, PhD, of the hospital’s department of epidemiology and biostatistics, reported in that post.

As far as critical care beds are concerned, the United States is in better shape than are other countries dealing with the coronavirus. The United States’ 34.7 critical care beds per 100,000 population put it a good bit ahead of Germany, which has 29.2 beds per 100,000, while other countries in both Europe and Asia are well behind, Dr. Halpern and Dr. Tan noted.

More recent data from the AHA show that just over half of its registered community hospitals deliver ICU services and have at least 10 acute care beds and one ICU bed, they reported.

Those 2,704 hospitals have nearly 535,000 acute care beds, of which almost 97,000 are ICU beds. Almost 71% of those ICU beds are for adults, with the rest located in neonatal and pediatric units, data from an AHA 2018 survey show.

Since patients with COVID-19 are most often admitted to ICUs with severe hypoxic respiratory failure, the nation’s supply of ventilators also may be tested. U.S. acute care hospitals own about 62,000 full-featured mechanical ventilators and almost 99,000 older ventilators that “may not be capable of adequately supporting patients with severe acute respiratory failure,” Dr. Halpern and Dr. Tan said.

As U.S. hospitals reach the crisis levels anticipated in the COVID-19 pandemic, staffing shortages can be expected as well. Almost half (48%) of acute care hospitals have no intensivists, so “other physicians (e.g., pulmonologists, surgeons, anesthesiologists, etc) may be pressed into service as outpatient clinics and elective surgery are suspended,” they wrote.

The blog post includes a tiered staffing strategy that the SCCM “encourages hospitals to adopt in pandemic situations such as COVID-19.”

[email protected]