The Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Antigen Testing.

BACKGROUND: Immunoassays designed to detect SARS-CoV-2 protein antigens (Ag) are commonly used to diagnose COVID-19. The most widely used tests are lateral flow assays that generate results in approximately 15 minutes for diagnosis at the point-of-care. Higher throughput, laboratory-based SARS-CoV-2 Ag assays have also been developed. The number of commercially available SARS-CoV-2 Ag detection tests has increased rapidly, as has the COVID-19 diagnostic literature. 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 an update to the third in a series of frequently updated COVID-19 diagnostic guidelines developed by the IDSA. OBJECTIVE: The 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 non-medical settings. 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 Ag tests. A review of relevant, peer-reviewed published literature was conducted through April 1, 2022. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. RESULTS: The panel made ten diagnostic recommendations. These recommendations address Ag testing in symptomatic and asymptomatic individuals and assess single versus repeat testing strategies. CONCLUSIONS: U.S. Food and Drug Administration (FDA) SARS-CoV-2 Ag tests with Emergency Use Authorization (EUA) have high specificity and low to moderate sensitivity compared to nucleic acid amplification testing (NAAT). Ag test sensitivity is dependent on the presence or absence of symptoms, and in symptomatic patients, on timing of testing after symptom onset. In contrast, Ag tests have high specificity, and, in most cases, positive Ag results can be acted upon without confirmation. Results of point-of-care testing are comparable to those of laboratory-based testing, and observed or unobserved self-collection of specimens for testing yields similar results. Modeling suggests that repeat Ag testing increases sensitivity compared to testing once, but no empirical data were available to inform this question. Based on these observations, rapid RT-PCR or laboratory-based NAAT remains the testing method of choice for diagnosing SARS-CoV-2 infection. However, when timely molecular testing is not readily available or is logistically infeasible, Ag testing helps identify individuals with SARS-CoV-2 infection. Data were insufficient to make a recommendation about the utility of Ag testing to guide release of patients with COVID-19 from isolation. The overall quality of available evidence supporting use of Ag testing was graded as very low to moderate.

American Society of Hematology living guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19: January 2022 update on the use of therapeutic-intensity anticoagulation in acutely ill patients.

BACKGROUND: COVID-19-related acute illness is associated with an increased risk of venous thromboembolism (VTE). OBJECTIVE: These evidence-based guidelines from the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in making decisions about the use of anticoagulation in patients with COVID-19. METHODS: ASH formed a multidisciplinary guideline panel that included patient representatives and applied strategies to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process and performed systematic evidence reviews (through November 2021). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess evidence and make recommendations, which were subject to public comment. This is an update to guidelines published in February 2021 as part of the living phase of these guidelines. RESULTS: The panel made one additional recommendation. The panel issued a conditional recommendation in favor of therapeutic-intensity over prophylactic-intensity anticoagulation in patients with COVID-19-related acute illness who do not have suspected or confirmed VTE. The panel emphasized the need for an individualized assessment of risk of thrombosis and bleeding. The panel also noted that heparin (unfractionated or low molecular weight) may be preferred because of a preponderance of evidence with this class of anticoagulants. CONCLUSION: This conditional recommendation was based on very low certainty in the evidence, underscoring the need for additional, high-quality, randomized controlled trials comparing different intensities of anticoagulation in patients with COVID-19-related acute illness.

The Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Antigen Testing.

BACKGROUND: 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 approximately 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. OBJECTIVE: 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 non-medical settings. 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 Ag 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 five diagnostic recommendations. These recommendations address antigen testing in symptomatic and asymptomatic individuals as well as assess single versus repeat testing strategies. CONCLUSIONS: Data on the clinical performance of U.S. Food and Drug Administration SARS-CoV-2 Ag tests with Emergency Use Authorization is 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 to reference NAAT methods. Antigen test sensitivity is heavily dependent on viral load, with differences observed between symptomatic compared to asymptomatic individuals and the time of testing post onset of symptoms. Based on these observations, rapid 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.

American Society of Hematology living guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19: July 2021 update on postdischarge thromboprophylaxis.

BACKGROUND: COVID-19-related acute illness is associated with an increased risk of venous thromboembolism (VTE). OBJECTIVE: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about the use of anticoagulation for thromboprophylaxis in patients with COVID-19 who do not have confirmed or suspected VTE. METHODS: ASH formed a multidisciplinary guideline panel, including 3 patient representatives, and applied strategies to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process, including performing systematic evidence reviews (up to March 2021). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the grading of recommendations assessment, development, and evaluation (GRADE) approach to assess evidence and make recommendations, which were subject to public comment. RESULTS: The panel agreed on 1 additional recommendation. The panel issued a conditional recommendation against the use of outpatient anticoagulant prophylaxis in patients with COVID-19 who are discharged from the hospital and who do not have suspected or confirmed VTE or another indication for anticoagulation. CONCLUSIONS: This recommendation was based on very low certainty in the evidence, underscoring the need for high-quality randomized controlled trials assessing the role of postdischarge thromboprophylaxis. Other key research priorities include better evidence on assessing risk of thrombosis and bleeding outcomes in patients with COVID-19 after hospital discharge.

COVID-19 and chronic kidney disease: an updated overview of reviews.

BACKGROUND: Coronavirus disease (COVID-19) has resulted in the death of more than 3.5 million people worldwide. While COVID-19 mostly affects the lungs, different comorbidities can have an impact on its outcomes. We performed an overview of reviews to assess the effect of Chronic Kidney Disease (CKD) on contracting COVID-19, hospitalization, mortality, and disease severity. METHODS: We searched published and preprint databases. We updated the reviews by searching for primary studies published after August 2020, and prioritized reviews that are most updated and of higher quality using the AMSTAR tool. RESULTS: We included 69 systematic reviews and 66 primary studies. Twenty-eight reviews reported on the prevalence of CKD among patients with COVID-19, which ranged from 0.4 to 49.0%. One systematic review showed an increased risk of hospitalization in patients with CKD and COVID-19 (RR = 1.63, 95% CI 1.03-2.58) (Moderate certainty). Primary studies also showed a statistically significant increase of hospitalization in such patients. Thirty-seven systematic reviews assessed mortality risk in patients with CKD and COVID-19. The pooled estimates from primary studies for mortality in patients with CKD and COVID-19 showed a HR of 1.48 (95% CI 1.33-1.65) (Moderate certainty), an OR of 1.77 (95% CI 1.54-2.02) (Moderate certainty) and a RR of 1.6 (95% CI 0.88-2.92) (Low certainty). CONCLUSIONS: Our review highlights the impact of CKD on the poor outcomes of COVID-19, underscoring the importance of identifying strategies to prevent COVID-19 infection among patients with CKD.

American Society of Hematology living guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19: May 2021 update on the use of intermediate-intensity anticoagulation in critically ill patients.

BACKGROUND: COVID-19-related critical illness is associated with an increased risk of venous thromboembolism (VTE). OBJECTIVE: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in making decisions about the use of anticoagulation for thromboprophylaxis in patients with COVID-19-related critical illness who do not have confirmed or suspected VTE. METHODS: ASH formed a multidisciplinary guideline panel that included 3 patient representatives and applied strategies to minimize potential bias from conflicts of interest. The McMaster University Grading of Recommendations Assessment, Development and Evaluation (GRADE) Centre supported the guideline development process by performing systematic evidence reviews (up to 5 March 2021). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the GRADE approach to assess evidence and make recommendations, which were subject to public comment. This is an update on guidelines published in February 2021. RESULTS: The panel agreed on 1 additional recommendation. The panel issued a conditional recommendation in favor of prophylactic-intensity over intermediate-intensity anticoagulation in patients with COVID-19-related critical illness who do not have confirmed or suspected VTE. CONCLUSIONS: This recommendation was based on low certainty in the evidence, which underscores the need for additional high-quality, randomized, controlled trials comparing different intensities of anticoagulation in critically ill patients. Other key research priorities include better evidence regarding predictors of thrombosis and bleeding risk in critically ill patients with COVID-19 and the impact of nonanticoagulant therapies (eg, antiviral agents, corticosteroids) on thrombotic risk.

Ethical Considerations for Treating Cancer Patients During the SARS-CoV-2 Virus Crisis: To Treat or Not to Treat? A Literature Review and Perspective From a Cancer Center in Low-Middle Income Country.

Providing routine healthcare to patients with serious health illnesses represents a challenge to healthcare providers amid the SARS-CoV-2 pandemic. Treating cancer patients during this pandemic is even more complex due to their heightened vulnerability, as both cancer and cancer treatment weaken the immune system leading to a higher risk of both infections and severe complications. In addition to the need to protect cancer patients from unnecessary exposure to SARS-CoV-2 infection during their routine care, interruption, and discontinuation of cancer treatment can result in negative consequences on patients' health, in addition to the ghost of rationing healthcare resources in high demand during a global health crisis. This article aims to explore the ethical dilemmas faced by decision-makers and healthcare providers caring for cancer patients during the SARS-CoV-2 pandemic. This includes setting triage criteria for non-infected cancer patients, fairly allocating limited healthcare resources between cancer patients and SARS-CoV-2 patients, prioritizing SARS-CoV-2 treatment or vaccine, once developed, for cancer patients and non-cancer patients, patient-physician communication on matters such as end-of-life and do-not-resuscitate (DNR), and lastly, shifting physicians' priorities from treating their own cancer patients to treating critically ill SARS-CoV-2 infected patients. Ultimately, no straightforward decision can be easily made at such exceptionally difficult times. Applying different ethical principles can result in very different scenarios and consequences. In the end, we will briefly share the experience of the King Hussein Cancer Center (KHCC), the only standalone comprehensive cancer center in the region.

DNR and COVID-19: The Ethical Dilemma and Suggested Solutions.

Ethics are considered a basic aptitude in healthcare, and the capacity to handle ethical dilemmas in tough times calls for an adequate, responsible, and blame-free environment. While do-not-resuscitate (DNR) decisions are made in advance in certain medical situations, in particular in the setting of poor prognosis like in advanced oncology, the discussion of DNR in relation to acute medical conditions, the COVID-19 pandemic in this example, might impose ethical dilemmas to the patient and family, healthcare providers (HCPs) including physicians and nurses, and to the institution. The literature on DNR decisions in the more recent pandemics and outbreaks is scarce. DNR was only discussed amid the H1N1 influenza pandemic in 2009, with clear global recommendations. The unprecedented condition of the COVID-19 pandemic leaves healthcare systems worldwide confronting tough decisions. DNR has been implemented in some countries where the healthcare system is limited in capacity to admit, and thus intubating and resuscitating patients when needed is jeopardized. Some countries were forced to adopt a unilateral DNR policy for certain patient groups. Younger age was used as a discriminator in some, while general medical condition with anticipated good outcome was used in others. The ethical challenge of how to balance patient autonomy vs. beneficence, equality vs. equity, is a pressing concern. In the current difficult situation, when cases top 100 million globally and the death toll surges past 2.7 million, difficult decisions are to be made. Societal rather than individual benefits might prevail. Pre-hospital triaging of cases, engagement of other sectors including mental health specialists and religious scholars to support patients, families, and HCPs in the frontline might help in addressing the psychological stress these groups might encounter in addressing DNR in the current situation.

American Society of Hematology 2021 guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19)-related critical illness and acute illness are associated with a risk of venous thromboembolism (VTE). OBJECTIVE: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about the use of anticoagulation for thromboprophylaxis for patients with COVID-19-related critical illness and acute illness who do not have confirmed or suspected VTE. METHODS: ASH formed a multidisciplinary guideline panel and applied strict management strategies to minimize potential bias from conflicts of interest. The panel included 3 patient representatives. The McMaster University GRADE Centre supported the guideline-development process, including performing systematic evidence reviews (up to 19 August 2020). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment. RESULTS: The panel agreed on 2 recommendations. The panel issued conditional recommendations in favor of prophylactic-intensity anticoagulation over intermediate-intensity or therapeutic-intensity anticoagulation for patients with COVID-19-related critical illness or acute illness who do not have confirmed or suspected VTE. CONCLUSIONS: These recommendations were based on very low certainty in the evidence, underscoring the need for high-quality, randomized controlled trials comparing different intensities of anticoagulation. They will be updated using a living recommendation approach as new evidence becomes available.

The Fair Allocation of Scarce Medical Resources: A Comparative Study From Jordan.

The allocation strategies during challenging situations among the different social groups is based on 9 principles which can be considered either individually: sickest first, waiting list, prognosis, youngest first, instrumental values, lottery, monetary contribution, reciprocity, and individual behavior, or in combination; youngest first and prognosis, for example. In this study, we aim to look into the most important prioritization principles amongst different groups in the Jordanian population, in order to facilitate the decision-making process for any potential medical crisis. We conducted an online survey that tackled how individuals would deal with three different scenarios of medical scarcity: (1) organ donation, (2) limited hospital beds during an influenza epidemic, and (3) allocation of novel therapeutics for lung cancer. In addition, a free-comment option was included at the end of the survey if respondents wished to contribute further. Seven hundred and fifty-four survey responses were gathered, including 372 males (49.3%), and 382 females (50.7%). Five groups of individuals were represented including religion scholars, physicians, medical students, allied health practitioners, and lay people. Of the five surveyed groups, four found "sickest-first" to be the most important prioritization principle in all three scenarios, and only the physicians group documented a disagreement. In the first scenario, physicians regarded "sickest-first" and "combined-criteria" to be of equal importance. In general, no differences were documented between the examined groups in comparison with lay people in the preference of options in all three scenarios; however, physicians were more likely to choose "combination" in both the second and third scenarios (OR 3.70, 95% CI 1.62-8.44, and 2.62, 95% CI 1.48-4.59; p < 0.01), and were less likely to choose "sickest-first" as the single most important prioritization principle (OR 0.57, CI 0.37-0.88, and 0.57; 95% CI 0.36-0.88; p < 0.01). Out of 100 free comments, 27 (27.0%) thought that the "social-value" of patients should also be considered, adding the 10th potential allocation principle. Our findings are concordant with literature in terms of allocating scarce medical resources. However, "social-value" appeared as an important principle that should be addressed when prioritizing scarce medical resources in Jordan.