Venous and arterial thrombosis in COVID-19: An updated narrative review.

Hospitalized patients with coronavirus disease 2019 (COVID-19), particularly those admitted to the intensive care unit (ICU) are at high risk of morbidity and mortality. Several observational studies have described hemostatic derangements and thrombotic complications in patients with COVID-19. The aim of this review article is to summarize the current evidence on pathologic findings, pathophysiology, coagulation and hemostatic abnormalities, D-dimer's role in prognostication epidemiology and risk factors of thrombotic complications, and the role of prophylactic and therapeutic anticoagulation in patients with COVID-19. While existing evidence is limited in quality, COVID-19 appears to increase micro-and macro-vascular thrombosis rates in hospitalized and critically ill patients, which may contribute to the burden of disease. D-dimer can be used for risk stratification of hospitalized patients, but its role to guide anticoagulation therapy remains unclear. Evidence of higher quality is needed to address the role of therapeutic anticoagulation or high-intensity venous thromboembolism prophylaxis in COVID-19 patients. TAKE-HOME POINTS.

Awake proning in patients with COVID-19-related hypoxemic acute respiratory failure: A rapid practice guideline.

This rapid practice guideline provides evidence-based recommendations for the use of awake proning in adult patients with acute hypoxemic respiratory failure due to COVID-19. The panel included 20 experts from 12 countries, including one patient representative, and used a strict conflict of interest policy for potential financial and intellectual conflicts of interest. Methodological support was provided by the guidelines in intensive care, development, and evaluation (GUIDE) group. Based on an updated systematic review, and the grading of recommendations, assessment, development, and evaluation (GRADE) method we evaluated the certainty of evidence and developed recommendations using the Evidence-to-Decision framework. We conducted an electronic vote, requiring >80% agreement amongst the panel for a recommendation to be adopted. The panel made a strong recommendation for a trial of awake proning in adult patients with COVID-19 related hypoxemic acute respiratory failure who are not invasively ventilated. Awake proning appears to reduce the risk of tracheal intubation, although it may not reduce mortality. The panel judged that most patients would want a trial of awake proning, although this may not be feasible in some patients and some patients may not tolerate it. However, given the high risk of clinical deterioration amongst these patients, awake proning should be conducted in an area where patients can be monitored by staff experienced in rapidly detecting and managing clinical deterioration. This RPG panel recommends a trial of awake prone positioning in patients with acute hypoxemic respiratory failure due to COVID-19.

Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19).

BACKGROUND: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed. METHODS: We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations. RESULTS: The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which four are best practice statements, nine are strong recommendations, and 35 are weak recommendations. No recommendation was provided for six questions. The topics were: 1) infection control, 2) laboratory diagnosis and specimens, 3) hemodynamic support, 4) ventilatory support, and 5) COVID-19 therapy. CONCLUSION: The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new evidence in further releases of these guidelines.

Efficacy of awake prone positioning in patients with covid-19 related hypoxemic respiratory failure: systematic review and meta-analysis of randomized trials.

OBJECTIVE: To determine the efficacy and safety of awake prone positioning versus usual care in non-intubated adults with hypoxemic respiratory failure due to covid-19. DESIGN: Systematic review with frequentist and bayesian meta-analyses. STUDY ELIGIBILITY: Randomized trials comparing awake prone positioning versus usual care in adults with covid-19 related hypoxemic respiratory failure. Information sources were Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to 4 March 2022. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data and assessed risk of bias. Random effects meta-analyses were performed for the primary and secondary outcomes. Bayesian meta-analyses were performed for endotracheal intubation and mortality outcomes. GRADE certainty of evidence was assessed for outcomes. MAIN OUTCOME MEASURES: The primary outcome was endotracheal intubation. Secondary outcomes were mortality, ventilator-free days, intensive care unit (ICU) and hospital length of stay, escalation of oxygen modality, change in oxygenation and respiratory rate, and adverse events. RESULTS: 17 trials (2931 patients) met the eligibility criteria. 12 trials were at low risk of bias, three had some concerns, and two were at high risk. Awake prone positioning reduced the risk of endotracheal intubation compared with usual care (crude average 24.2% v 29.8%, relative risk 0.83, 95% confidence interval 0.73 to 0.94; high certainty). This translates to 55 fewer intubations per 1000 patients (95% confidence interval 87 to 19 fewer intubations). Awake prone positioning did not significantly affect secondary outcomes, including mortality (15.6% v 17.2%, relative risk 0.90, 0.76 to 1.07; high certainty), ventilator-free days (mean difference 0.97 days, 95% confidence interval -0.5 to 3.4; low certainty), ICU length of stay (-2.1 days, -4.5 to 0.4; low certainty), hospital length of stay (-0.09 days, -0.69 to 0.51; moderate certainty), and escalation of oxygen modality (21.4% v 23.0%, relative risk 1.04, 0.74 to 1.44; low certainty). Adverse events related to awake prone positioning were uncommon. Bayesian meta-analysis showed a high probability of benefit with awake prone positioning for endotracheal intubation (non-informative prior, mean relative risk 0.83, 95% credible interval 0.70 to 0.97; posterior probability for relative risk <0.95=96%) but lower probability for mortality (0.90, 0.73 to 1.13; <0.95=68%). CONCLUSIONS: Awake prone positioning compared with usual care reduces the risk of endotracheal intubation in adults with hypoxemic respiratory failure due to covid-19 but probably has little to no effect on mortality or other outcomes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022314856.

Ventilation Techniques and Risk for Transmission of Coronavirus Disease, Including COVID-19: A Living Systematic Review of Multiple Streams of Evidence.

BACKGROUND: Mechanical ventilation is used to treat respiratory failure in coronavirus disease 2019 (COVID-19). PURPOSE: To review multiple streams of evidence regarding the benefits and harms of ventilation techniques for coronavirus infections, including that causing COVID-19. DATA SOURCES: 21 standard, World Health Organization-specific and COVID-19-specific databases, without language restrictions, until 1 May 2020. STUDY SELECTION: Studies of any design and language comparing different oxygenation approaches in patients with coronavirus infections, including severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS), or with hypoxemic respiratory failure. Animal, mechanistic, laboratory, and preclinical evidence was gathered regarding aerosol dispersion of coronavirus. Studies evaluating risk for virus transmission to health care workers from aerosol-generating procedures (AGPs) were included. DATA EXTRACTION: Independent and duplicate screening, data abstraction, and risk-of-bias assessment (GRADE for certainty of evidence and AMSTAR 2 for included systematic reviews). DATA SYNTHESIS: 123 studies were eligible (45 on COVID-19, 70 on SARS, 8 on MERS), but only 5 studies (1 on COVID-19, 3 on SARS, 1 on MERS) adjusted for important confounders. A study in hospitalized patients with COVID-19 reported slightly higher mortality with noninvasive ventilation (NIV) than with invasive mechanical ventilation (IMV), but 2 opposing studies, 1 in patients with MERS and 1 in patients with SARS, suggest a reduction in mortality with NIV (very-low-certainty evidence). Two studies in patients with SARS report a reduction in mortality with NIV compared with no mechanical ventilation (low-certainty evidence). Two systematic reviews suggest a large reduction in mortality with NIV compared with conventional oxygen therapy. Other included studies suggest increased odds of transmission from AGPs. LIMITATION: Direct studies in COVID-19 are limited and poorly reported. CONCLUSION: Indirect and low-certainty evidence suggests that use of NIV, similar to IMV, probably reduces mortality but may increase the risk for transmission of COVID-19 to health care workers. PRIMARY FUNDING SOURCE: World Health Organization. (PROSPERO: CRD42020178187).

Effect of Awake Prone Positioning on Endotracheal Intubation in Patients With COVID-19 and Acute Respiratory Failure: A Randomized Clinical Trial.

Importance: The efficacy and safety of prone positioning is unclear in nonintubated patients with acute hypoxemia and COVID-19. Objective: To evaluate the efficacy and adverse events of prone positioning in nonintubated adult patients with acute hypoxemia and COVID-19. Design, Setting, and Participants: Pragmatic, unblinded randomized clinical trial conducted at 21 hospitals in Canada, Kuwait, Saudi Arabia, and the US. Eligible adult patients with COVID-19 were not intubated and required oxygen (≥40%) or noninvasive ventilation. A total of 400 patients were enrolled between May 19, 2020, and May 18, 2021, and final follow-up was completed in July 2021. Intervention: Patients were randomized to awake prone positioning (n = 205) or usual care without prone positioning (control; n = 195). Main Outcomes and Measures: The primary outcome was endotracheal intubation within 30 days of randomization. The secondary outcomes included mortality at 60 days, days free from invasive mechanical ventilation or noninvasive ventilation at 30 days, days free from the intensive care unit or hospital at 60 days, adverse events, and serious adverse events. Results: Among the 400 patients who were randomized (mean age, 57.6 years [SD, 12.83 years]; 117 [29.3%] were women), all (100%) completed the trial. In the first 4 days after randomization, the median duration of prone positioning was 4.8 h/d (IQR, 1.8 to 8.0 h/d) in the awake prone positioning group vs 0 h/d (IQR, 0 to 0 h/d) in the control group. By day 30, 70 of 205 patients (34.1%) in the prone positioning group were intubated vs 79 of 195 patients (40.5%) in the control group (hazard ratio, 0.81 [95% CI, 0.59 to 1.12], P = .20; absolute difference, -6.37% [95% CI, -15.83% to 3.10%]). Prone positioning did not significantly reduce mortality at 60 days (hazard ratio, 0.93 [95% CI, 0.62 to 1.40], P = .54; absolute difference, -1.15% [95% CI, -9.40% to 7.10%]) and had no significant effect on days free from invasive mechanical ventilation or noninvasive ventilation at 30 days or on days free from the intensive care unit or hospital at 60 days. There were no serious adverse events in either group. In the awake prone positioning group, 21 patients (10%) experienced adverse events and the most frequently reported were musculoskeletal pain or discomfort from prone positioning (13 of 205 patients [6.34%]) and desaturation (2 of 205 patients [0.98%]). There were no reported adverse events in the control group. Conclusions and Relevance: In patients with acute hypoxemic respiratory failure from COVID-19, prone positioning, compared with usual care without prone positioning, did not significantly reduce endotracheal intubation at 30 days. However, the effect size for the primary study outcome was imprecise and does not exclude a clinically important benefit. Trial Registration: ClinicalTrials.gov Identifier: NCT04350723.

The Saudi Critical Care Society practice guidelines on the management of COVID-19 in the ICU: Therapy section.

BACKGROUND: The rapid increase in coronavirus disease 2019 (COVID-19) cases during the subsequent waves in Saudi Arabia and other countries prompted the Saudi Critical Care Society (SCCS) to put together a panel of experts to issue evidence-based recommendations for the management of COVID-19 in the intensive care unit (ICU). METHODS: The SCCS COVID-19 panel included 51 experts with expertise in critical care, respirology, infectious disease, epidemiology, emergency medicine, clinical pharmacy, nursing, respiratory therapy, methodology, and health policy. All members completed an electronic conflict of interest disclosure form. The panel addressed 9 questions that are related to the therapy of COVID-19 in the ICU. We identified relevant systematic reviews and clinical trials, then used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach as well as the evidence-to-decision framework (EtD) to assess the quality of evidence and generate recommendations. RESULTS: The SCCS COVID-19 panel issued 12 recommendations on pharmacotherapeutic interventions (immunomodulators, antiviral agents, and anticoagulants) for severe and critical COVID-19, of which 3 were strong recommendations and 9 were weak recommendations. CONCLUSION: The SCCS COVID-19 panel used the GRADE approach to formulate recommendations on therapy for COVID-19 in the ICU. The EtD framework allows adaptation of these recommendations in different contexts. The SCCS guideline committee will update recommendations as new evidence becomes available.

Infection control in the intensive care unit: expert consensus statements for SARS-CoV-2 using a Delphi method.

During the current COVID-19 pandemic, health-care workers and uninfected patients in intensive care units (ICUs) are at risk of being infected with SARS-CoV-2 as a result of transmission from infected patients and health-care workers. In the absence of high-quality evidence on the transmission of SARS-CoV-2, clinical practice of infection control and prevention in ICUs varies widely. Using a Delphi process, international experts in intensive care, infectious diseases, and infection control developed consensus statements on infection control for SARS-CoV-2 in an ICU. Consensus was achieved for 31 (94%) of 33 statements, from which 25 clinical practice statements were issued. These statements include guidance on ICU design and engineering, health-care worker safety, visiting policy, personal protective equipment, patients and procedures, disinfection, and sterilisation. Consensus was not reached on optimal return to work criteria for health-care workers who were infected with SARS-CoV-2 or the acceptable disinfection strategy for heat-sensitive instruments used for airway management of patients with SARS-CoV-2 infection. Well designed studies are needed to assess the effects of these practice statements and address the remaining uncertainties.

High-Flow Nasal Cannula Treatment in Patients with COVID-19 Acute Hypoxemic Respiratory Failure: A Prospective Cohort Study.

BACKGROUND: Early use of high-flow nasal cannula (HFNC) decreases the need for endotracheal intubation (EI) in different respiratory failure causes. While HFNC is used in coronavirus disease 2019 (COVID-19)-related acute hypoxemic respiratory failure (AHRF) under weak recommendations, its efficacy remains to be investigated. OBJECTIVES: The primary objective was to examine HFNC efficacy in preventing EI among COVID-19 patients with AHRF. Secondary objectives were to determine predictors of HFNC success/failure, mortality rate, and length of hospital and intensive care unit (ICU) stay. PATIENTS AND METHODS: This is a prospective cohort study conducted at a single tertiary care centre in Saudi Arabia from April to August 2020. Adult patients admitted to the ICU with AHRF secondary to COVID-19 pneumonia and managed with HFNC were included. We excluded patients who were intubated or managed with non-invasive ventilation before HFNC. RESULTS: Forty-four patients received HFNC for a median duration of 3 days (interquartile range, 1-5 days). The mean age was 57 ± 14 years, and 86% were men. HFNC failure and EI occurred in 29 (66%) patients. Patients in whom HNFC treatment failed had a higher risk of death (52% versus 0%; P = 0.001). After adjusting for confounding factors, a high SOFA score and a low ROX index were significantly associated with HFNC failure (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.04-1.93; P = 0.025; and HR, 0.61; 95% CI, 0.42-0.88; P = 0.008, respectively). CONCLUSIONS: One-third of hypoxemic COVID-19 patients who received HFNC did not require intubation. High SOFA score and low ROX index were associated with HFNC failure.

Use of COVID-19 vaccines in patients with liver disease and post-liver transplantation: Position statement of the Saudi association for the study of liver diseases and transplantation.

Patients with chronic liver disease (CLD) and liver transplant recipients are at increased risk of morbidity and mortality from coronavirus disease 2019 (COVID-19). Although several studies demonstrated the safety and efficacy of COVID-19 vaccines in the general population, data in CLD patients and liver transplant recipients are lacking. Two COVID-19 vaccines were approved by the Saudi Food and Drug Authority and rolled out to several million recipients in Saudi Arabia. These vaccines are mRNA-based vaccine BNT162b2 from Pfizer/BioNTech and adenovirus-based AZD1222 from Oxford/AstraZeneca from three manufacturing sites (EU Nodes, Serum Institute of India, and South Korea Bio). The Saudi Association for the Study of Liver diseases and Transplantation (SASLT) has reviewed the available evidence and issued interim recommendations for COVID-19 vaccination in CLD and liver transplant recipients. Since there is no evidence contradicting the safety and immunogenicity of the currently approved COVID-19 vaccines in patients with CLD and hepatobiliary cancer and liver transplant recipients, the SASLT recommends vaccination in those patient populations. CLD and hepatobiliary cancer patients and liver transplant recipients should be prioritized depending on the risk factors for severe COVID-19. In transplant recipients, the optimal timing of vaccination remains unknown; however, immunization is recommended after the initial immunosuppression phase. Patients with CLD and liver transplant candidates or recipients should be closely monitored after COVID-19 vaccination. These patient populations should be included in future clinical trials to provide further evidence on the efficacy and safety of COVID-19 vaccines.

Corticosteroids in COVID-19 and non-COVID-19 ARDS: a systematic review and meta-analysis.

PURPOSE: Corticosteroids are now recommended for patients with severe COVID-19 including those with COVID-related ARDS. This has generated renewed interest regarding whether corticosteroids should be used in non-COVID ARDS as well. The objective of this study was to summarize all RCTs examining the use of corticosteroids in ARDS. METHODS: The protocol of this study was pre-registered on PROSPERO (CRD42020200659). We searched online databases including MEDLINE, EMBASE, CDC library of COVID research, CINAHL, and COCHRANE. We included RCTs that compared the effect of corticosteroids to placebo or usual care in adult patients with ARDS, including patients with COVID-19. Three reviewers abstracted data independently and in duplicate using a pre-specified standardized form. We assessed individual study risk of bias using the revised Cochrane ROB-2 tool and rated certainty in outcomes using GRADE methodology. We pooled data using a random effects model. The main outcome for this review was 28-day-mortality. RESULTS: We included 18 RCTs enrolling 2826 patients. The use of corticosteroids probably reduced mortality in patients with ARDS of any etiology (2740 patients in 16 trials, RR 0.82, 95% CI 0.72-0.95, ARR 8.0%, 95% CI 2.2-12.5%, moderate certainty). Patients who received a longer course of corticosteroids (over 7 days) had higher rates of survival compared to a shorter course. CONCLUSION: The use of corticosteroids probably reduces mortality in patients with ARDS. This effect was consistent between patients with COVID-19 and non-COVID-19 ARDS, corticosteroid types, and dosage.

Expert consensus statements for the management of COVID-19-related acute respiratory failure using a Delphi method.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented pressure on healthcare system globally. Lack of high-quality evidence on the respiratory management of COVID-19-related acute respiratory failure (C-ARF) has resulted in wide variation in clinical practice. METHODS: Using a Delphi process, an international panel of 39 experts developed clinical practice statements on the respiratory management of C-ARF in areas where evidence is absent or limited. Agreement was defined as achieved when > 70% experts voted for a given option on the Likert scale statement or > 80% voted for a particular option in multiple-choice questions. Stability was assessed between the two concluding rounds for each statement, using the non-parametric Chi-square (χ2) test (p < 0·05 was considered as unstable). RESULTS: Agreement was achieved for 27 (73%) management strategies which were then used to develop expert clinical practice statements. Experts agreed that COVID-19-related acute respiratory distress syndrome (ARDS) is clinically similar to other forms of ARDS. The Delphi process yielded strong suggestions for use of systemic corticosteroids for critical COVID-19; awake self-proning to improve oxygenation and high flow nasal oxygen to potentially reduce tracheal intubation; non-invasive ventilation for patients with mixed hypoxemic-hypercapnic respiratory failure; tracheal intubation for poor mentation, hemodynamic instability or severe hypoxemia; closed suction systems; lung protective ventilation; prone ventilation (for 16-24 h per day) to improve oxygenation; neuromuscular blocking agents for patient-ventilator dyssynchrony; avoiding delay in extubation for the risk of reintubation; and similar timing of tracheostomy as in non-COVID-19 patients. There was no agreement on positive end expiratory pressure titration or the choice of personal protective equipment. CONCLUSION: Using a Delphi method, an agreement among experts was reached for 27 statements from which 20 expert clinical practice statements were derived on the respiratory management of C-ARF, addressing important decisions for patient management in areas where evidence is either absent or limited. TRIAL REGISTRATION: The study was registered with Clinical trials.gov Identifier: NCT04534569.

Surviving Sepsis Campaign Guidelines on the Management of Adults With Coronavirus Disease 2019 (COVID-19) in the ICU: First Update.

BACKGROUND: The coronavirus disease 2019 pandemic continues to affect millions worldwide. Given the rapidly growing evidence base, we implemented a living guideline model to provide guidance on the management of patients with severe or critical coronavirus disease 2019 in the ICU. METHODS: The Surviving Sepsis Campaign Coronavirus Disease 2019 panel has expanded to include 43 experts from 14 countries; all panel members completed an electronic conflict-of-interest disclosure form. In this update, the panel addressed nine questions relevant to managing severe or critical coronavirus disease 2019 in the ICU. We used the World Health Organization's definition of severe and critical coronavirus disease 2019. The systematic reviews team searched the literature for relevant evidence, aiming to identify systematic reviews and clinical trials. When appropriate, we performed a random-effects meta-analysis to summarize treatment effects. We assessed the quality of the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach, then used the evidence-to-decision framework to generate recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. RESULTS: The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued nine statements (three new and six updated) related to ICU patients with severe or critical coronavirus disease 2019. For severe or critical coronavirus disease 2019, the panel strongly recommends using systemic corticosteroids and venous thromboprophylaxis but strongly recommends against using hydroxychloroquine. In addition, the panel suggests using dexamethasone (compared with other corticosteroids) and suggests against using convalescent plasma and therapeutic anticoagulation outside clinical trials. The Surviving Sepsis Campaign Coronavirus Diease 2019 panel suggests using remdesivir in nonventilated patients with severe coronavirus disease 2019 and suggests against starting remdesivir in patients with critical coronavirus disease 2019 outside clinical trials. Because of insufficient evidence, the panel did not issue a recommendation on the use of awake prone positioning. CONCLUSION: The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued several recommendations to guide healthcare professionals caring for adults with critical or severe coronavirus disease 2019 in the ICU. Based on a living guideline model the recommendations will be updated as new evidence becomes available.

The efficacy and safety of hydroxychloroquine for COVID-19 prophylaxis: A systematic review and meta-analysis of randomized trials.

BACKGROUND: Populations such as healthcare workers (HCW) that are unable to practice physical distancing are at high risk of acquiring Coronavirus disease-2019 (COVID-19). In these cases pharmacological prophylaxis would be a solution to reduce severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) transmission. Hydroxychloroquine has in vitro antiviral properties against SARS CoV-2. We therefore sought to determine the efficacy and safety of hydroxychloroquine as prophylaxis for COVID-19. METHODS AND FINDINGS: We electronically searched EMBASE, MEDLINE, the Cochrane COVID-19 Register of Controlled Trials, Epistemonikos COVID-19, clinicaltrials.gov, and the World Health Organization International Clinical Trials Registry Platform up to September 28th, 2020 for randomized controlled trials (RCTs). We calculated pooled relative risks (RRs) for dichotomous outcomes with the corresponding 95% confidence intervals (CIs) using a random-effect model. We identified four RCTs (n = 4921) that met our eligibility criteria. The use of hydroxychloroquine, compared to placebo, did not reduce the risks of developing COVID-19 (RR 0.82, 95% CI 0.65 to 1.04, moderate certainty), hospitalization (RR 0.72, 95% CI 0.34 to 1.50, moderate certainty), or mortality (RR 3.26, 95% CI 0.13 to 79.74, low certainty), however, hydroxychloroquine use increased the risk of adverse events (RR 2.76, 95% CI 1.38 to 5.55, moderate certainty). CONCLUSION: Although pharmacologic prophylaxis is an attractive preventive strategy against COVID-19, the current body of evidence failed to show clinical benefit for prophylactic hydroxychloroquine and showed a higher risk of adverse events when compared to placebo or no prophylaxis.

Perspective of the Surviving Sepsis Campaign on the Management of Pediatric Sepsis in the Era of Coronavirus Disease 2019.

Severe acute respiratory syndrome coronavirus 2 is a novel cause of organ dysfunction in children, presenting as either coronavirus disease 2019 with sepsis and/or respiratory failure or a hyperinflammatory shock syndrome. Clinicians must now consider these diagnoses when evaluating children for septic shock and sepsis-associated organ dysfunction. The Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-associated Organ Dysfunction in Children provide an appropriate framework for the early recognition and initial resuscitation of children with sepsis or septic shock caused by all pathogens, including severe acute respiratory syndrome coronavirus 2. However, the potential benefits of select adjunctive therapies may differ from non-coronavirus disease 2019 sepsis.