Morgan, Rebecca L.

Abstract Background Since its emergence in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to pose a risk to healthcare personnel (HCP) and patients in healthcare settings. Although all clinical interactions likely carry some risk of transmission, human actions, such as coughing, and care activities, such as aerosol-generating procedures, likely have a higher risk of transmission. The rapid emergence and global spread of SARS-CoV-2 continues to create significant challenges in healthcare facilities, particularly with shortages of the personal protective equipment (PPE) used by HCP. Evidence-based recommendations for what PPE to use in conventional, contingency, and crisis standards of care continue to be needed. Where evidence is lacking, the development of specific research questions can help direct funders and investigators. The purpose of the current study was to develop evidence-based rapid guidelines intended to support HCP in their decisions about infection prevention when caring for patients with suspected or known coronavirus disease 2019 (COVID-19). Methods The Infectious Diseases Society of America (IDSA) formed a multidisciplinary guideline panel including frontline clinicians, infectious disease specialists, experts in infection control, and guideline methodologists, with representation from the disciplines of public health, medical microbiology, pediatrics, critical care medicine and gastroenterology. The process followed a rapid recommendation checklist. The panel prioritized questions and outcomes. Then a systematic review of the peer-reviewed and gray literature was conducted. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence and make recommendations. Results The IDSA guideline panel agreed on 8 recommendations, including 2 updated recommendations and 1 new recommendation added since the first version of the guideline. Narrative summaries of other interventions undergoing evaluations are also included. Conclusions Using a combination of direct and indirect evidence, the panel was able to provide recommendations for 8 specific questions on the use of PPE by HCP providing care for patients with suspected or known COVID-19. Where evidence was lacking, attempts were made to provide potential avenues for investigation. There remain significant gaps in the understanding of the transmission dynamics of SARS-CoV-2, and PPE recommendations may need to be modified in response to new evidence. These recommendations should serve as a minimum for PPE use in healthcare facilities and do not preclude decisions based on local risk assessments or requirements of local health jurisdictions or other regulatory bodies.

Abstract Despite the challenges of the pandemic, there has been substantial progress with coronavirus disease 2019 (COVID-19) therapies. Pivotal COVID-19 trials like SOLIDARITY, RECOVERY, and ACCT-1 were rapidly conducted and data disseminated to support effective therapies. However, critical shortcomings remain on trial conduct, dissemination and interpretation of study results, and regulatory guidance in pandemic settings. The lessons that we learned have implications for both the current pandemic and future emerging infectious diseases. There is a need for establishing and standardizing clinical meaningful outcomes in therapeutic trials and for targeting defined populations and phenotypes that will most benefit from specific therapies. Standardized processes should be established for rapid and critical data review and dissemination to ensure scientific integrity. Clarity around the evidence standards needed for issuance of both emergency use authorization (EUA) and biologic license application (BLA) should be established and an infrastructure for executing rapid trials in epidemic settings maintained.

Abstract Given the urgent need for treatments during the coronavirus disease 2019 pandemic, the US Food and Drug Administration issued emergency use authorizations (EUAs) for multiple therapies. In several instances, however, these EUAs were issued before sufficient evidence of a given therapy’s efficacy and safety were available, potentially promoting ineffective or even harmful therapies and undermining the generation of definitive evidence. We describe the strengths and weaknesses of the different therapeutic EUAs issued during this pandemic. We also contrast them to the vaccine EUAs and suggest a framework and criteria for an evidence-based, trustworthy, and publicly transparent therapeutic EUA process for future pandemics.

Abstract Immunoassays designed to detect SARS-CoV-2 protein antigens are now commercially available. The most widely used tests are rapid lateral flow assays that generate results in ~15 minutes for diagnosis at the point-of-care. Higher throughput, laboratory-based SARS-CoV-2 antigen (Ag) assays have also been developed. The overall accuracy of SARS-CoV-2 Ag tests, however, is not well defined. The Infectious Diseases Society of America (IDSA) convened an expert panel to perform a systematic review of the literature and develop best-practice guidance related to SARS-CoV-2 Ag testing. This guideline is the third in a series of rapid, frequently updated COVID-19 diagnostic guidelines developed by IDSA. IDSA’s goal was to develop evidence-based recommendations or suggestions that assist clinicians, clinical laboratories, patients, public health authorities, administrators, and policymakers in decisions related to the optimal use of SARS-CoV-2 Ag tests in both medical and nonmedical settings. A multidisciplinary panel of infectious diseases clinicians, clinical microbiologists, and experts in systematic literature review identified and prioritized clinical questions related to the use of SARS-CoV-2 Ag tests. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. The panel agreed on 5 diagnostic recommendations. These recommendations address Ag testing in symptomatic and asymptomatic individuals as well as assess single versus repeat testing strategies. Data on the clinical performance of US Food and Drug Administration SARS-CoV-2 Ag tests with Emergency Use Authorization are mostly limited to single, one-time testing versus standard nucleic acid amplification testing (NAAT) as the reference standard. Rapid Ag tests have high specificity and low to modest sensitivity compared with reference NAAT methods. Antigen test sensitivity is heavily dependent on viral load, with differences observed between symptomatic compared with asymptomatic individuals and the time of testing post-onset of symptoms. Based on these observations, rapid reverse transcriptase–polymerase chain reaction (RT-PCR) or laboratory-based NAAT remain the diagnostic methods of choice for diagnosing SARS-CoV-2 infection. However, when molecular testing is not readily available or is logistically infeasible, Ag testing can help identify some individuals with SARS-CoV-2 infection. The overall quality of available evidence supporting use of Ag testing was graded as very low to moderate.

Abstract Background Accurate molecular diagnostic tests are necessary for confirming a diagnosis of coronavirus disease 2019 (COVID-19). Direct detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acids in respiratory tract specimens informs patient, healthcare institution and public health level decision-making. The numbers of available SARS-CoV-2 nucleic acid detection tests are rapidly increasing, as is the COVID-19 diagnostic literature. Thus, the Infectious Diseases Society of America (IDSA) recognized a significant need for frequently updated systematic reviews of the literature to inform evidence-based best practice guidance. Objective The IDSA’s goal was to develop an evidence-based diagnostic guideline to assist clinicians, clinical laboratorians, patients and policymakers in decisions related to the optimal use of SARS-CoV-2 nucleic acid amplification tests. In addition, we provide a conceptual framework for understanding molecular diagnostic test performance, discuss the nuance of test result interpretation in a variety of practice settings and highlight important unmet research needs in the COVID-19 diagnostic testing space. Methods IDSA convened a multidisciplinary panel of infectious diseases clinicians, clinical microbiologists, and experts in systematic literature review to identify and prioritize clinical questions and outcomes related to the use of SARS-CoV-2 molecular diagnostics. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. Results The panel agreed on 17 diagnostic recommendations. Conclusions Universal access to accurate SARS-CoV-2 nucleic acid testing is critical for patient care, hospital infection prevention and the public response to the COVID-19 pandemic. Information on the clinical performance of available tests is rapidly emerging, but the quality of evidence of the current literature is considered moderate to very low. Recognizing these limitations, the IDSA panel weighed available diagnostic evidence and recommends nucleic acid testing for all symptomatic individuals suspected of having COVID-19. In addition, testing is recommended for asymptomatic individuals with known or suspected contact with a COVID-19 case. Testing asymptomatic individuals without known exposure is suggested when the results will impact isolation/quarantine/personal protective equipment (PPE) usage decisions, dictate eligibility for surgery, or inform solid organ or hematopoietic stem cell transplantation timing. Ultimately, prioritization of testing will depend on institutional-specific resources and the needs of different patient populations.

While numerous guidelines for the prescription of physical activity are released each year, the quality and practicability of these guidelines is unknown. We assessed the quality of 95 guidance documents published since 2000 that included recommendations about physical activity for the promotion of general health and prevention of cardiometabolic disease. We used 3 tools: Appraisal of Guidelines for Research and Evaluation (AGREE II), the National Academy of Medicine’s (NAM) Standards for Trustworthy Clinical Practice Guidelines, and the Frequency, Intensity, Time, and Type (FITT) score. Average AGREE II domain scores ranged from 38%−84%, and the portion of criteria fulfilled per NAM domain ranged from 7%–39%. The average FITT score for all recommendations was 2.48 out of 4. While guidelines improved according to both AGREE II and the NAM standards over time, their practicability as assessed by FITT score did not improve. Guidelines produced by governmental agencies or other nonprofit organizations, using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, or fulfilling a higher number of NAM criteria tended to be of higher quality. Organizations producing physical activity guidelines can improve their quality by establishing and reporting processes for public representation, external review, and conflict of interest (COI) management. Future recommendations about physical activity should be more specific and include strategies to improve implementation. Registration no.: PROSPERO CRD42019126364. Novelty: Most physical activity recommendations are not sufficiently specific to be practically implemented. The overall quality of guidelines has improved over time, but the specificity of recommendations has not. Improved public representation, external review, and COI disclosure and management processes would improve guideline quality.

Abstract Background The availability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serologic testing has rapidly increased. Current assays use a variety of technologies, measure different classes of immunoglobulin or immunoglobulin combinations, and detect antibodies directed against different portions of the virus. The overall accuracy of these tests, however, has not been well defined. The Infectious Diseases Society of America (IDSA) convened an expert panel to perform a systematic review of the coronavirus disease 2019 (COVID-19) serology literature and construct best-practice guidance related to SARS-CoV-2 serologic testing. This guideline is the fourth in a series of rapid, frequently updated COVID-19 guidelines developed by IDSA. Objective IDSA’s goal was to develop evidence-based recommendations that assist clinicians, clinical laboratories, patients, and policymakers in decisions related to the optimal use of SARS-CoV-2 serologic tests in a variety of settings. We also highlight important unmet research needs pertaining to the use of anti–SARS-CoV-2 antibody tests for diagnosis, public health surveillance, vaccine development, and the selection of convalescent plasma donors. Methods A multidisciplinary panel of infectious diseases clinicians, clinical microbiologists, and experts in systematic literature review identified and prioritized clinical questions related to the use of SARS-CoV-2 serologic tests. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. Results The panel agreed on 8 diagnostic recommendations. Conclusions Information on the clinical performance and utility of SARS-CoV-2 serologic tests is rapidly emerging. Based on available evidence, detection of anti–SARS-CoV-2 antibodies may be useful for confirming the presence of current or past infection in selected situations. The panel identified 3 potential indications for serologic testing, including (1) evaluation of patients with a high clinical suspicion for COVID-19 when molecular diagnostic testing is negative and ≥2 weeks have passed since symptom onset, (2) assessment of multisystem inflammatory syndrome in children, and (3) conducting serosurveillance studies. The certainty of available evidence supporting the use of serology for either diagnosis or epidemiology was, however, graded as very low to moderate. For the most updated version of these guidelines, please go to https://www.idsociety.org/covid19guidelines.

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible virus that can infect healthcare personnel (HCP) and patients in healthcare settings. Specific care activities, in particular, aerosol-generating procedures, may have a higher risk of transmission. The rapid emergence and global spread of SARS-CoV-2 has created significant challenges in healthcare facilities, particularly with severe shortages of personal protective equipment (PPE) used to protect HCP. Evidence-based recommendations for what PPE to use in conventional, contingency, and crisis standards of care are needed. Where evidence is lacking, the development of specific research questions can help direct funders and investigators. Objective Our objective was to develop evidence-based rapid guidelines intended to support HCP in their decisions about infection prevention when caring for patients with suspected or known coronavirus disease 2019 (COVID-19). Methods The Infectious Diseases Society of America (IDSA) formed a multidisciplinary guideline panel that included front-line clinicians, infectious diseases specialists, experts in infection control, and guideline methodologists with representation from the disciplines of preventive care, public health, medical microbiology, pediatrics, critical care medicine, and gastroenterology. The process followed a rapid recommendation checklist. The panel prioritized questions and outcomes. Then, a systematic review of the peer-reviewed and gray literature was conducted. The Grading of Recommendations Assessment, Development and Evaluation approach was used to assess the certainty of evidence and make recommendations. Results The IDSA guideline panel agreed on 8 recommendations and provided narrative summaries of other interventions undergoing evaluations. Conclusions Using a combination of direct and indirect evidence, the panel was able to provide recommendations for 8 specific questions on the use of PPE for HCP who provide care for patients with suspected or known COVID-19. Where evidence was lacking, attempts were made to provide potential avenues for investigation. Significant gaps in the understanding of the transmission dynamics of SARS-CoV-2 remain, and PPE recommendations may need to be modified in response to new evidence.

Abstract IDSA Disclaimer As of the time of this publication, updates have been made to IDSA’s Guidelines on the Diagnosis of COVID-19. For the most updated version of these guidelines, please go to https://www.idsociety.org/covid19guidelines. Background Accurate molecular diagnostic tests are necessary for confirming a diagnosis of coronavirus disease 2019 (COVID-19). Direct detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acids in respiratory tract specimens informs patient, healthcare institution, and public health–level decision-making. The number of available SARS-CoV-2 nucleic acid detection tests is rapidly increasing, as is the COVID-19 diagnostic literature. Thus, the Infectious Diseases Society of America (IDSA) recognized a significant need for frequently updated systematic reviews of the literature to inform evidence-based best practice guidance. Objective The IDSA’s goal was to develop an evidence-based diagnostic guidelines to assist clinicians, clinical laboratorians, patients, and policy makers in decisions related to the optimal use of SARS-CoV-2 nucleic acid amplification tests. In addition, the society provides a conceptual framework for understanding molecular diagnostic test performance, discusses the nuance of test result interpretation in a variety of practice settings, and highlights important unmet research needs in the COVID-19 diagnostic testing arena. Methods IDSA convened a multidisciplinary panel of infectious diseases clinicians, clinical microbiologists, and experts in systematic literature review to identify and prioritize clinical questions and outcomes related to the use of SARS-CoV-2 molecular diagnostics. Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the certainty of evidence and make testing recommendations. Results The panel agreed on 15 diagnostic recommendations. Conclusions Universal access to accurate SARS-CoV-2 nucleic acid testing is critical for patient care, hospital infection prevention, and the public response to the COVID-19 pandemic. Information on the clinical performance of available tests is rapidly emerging, but the quality of evidence of the current literature is considered low to very low. Recognizing these limitations, the IDSA panel weighed available diagnostic evidence and recommends nucleic acid testing for all symptomatic individuals suspected of having COVID-19. In addition, testing is recommended for asymptomatic individuals who have had a known or suspected contact with a COVID-19 case. Testing asymptomatic individuals without known exposure is suggested when the results will impact isolation/quarantine/personal protective equipment usage decisions, dictate eligibility for surgery, or inform administration of immunosuppressive therapy. Ultimately, prioritization of testing will depend on institution-specific resources and the needs of different patient populations.