The Saudi Critical Care Society Practice Guidelines on the Management of COVID-19 in the ICU: Therapy Section (preprint)

BackgroundThe 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).MethodsThe 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.ResultsThe 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. ConclusionThe 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.

Adjunctive Therapy with Ascorbic in Critically Ill Patients with COVID-19: A Multicenter Propensity Score Matched Study (preprint)

Background:  Due to its supposed clinical efficacy, relative safety, and low cost, ascorbic acid represents an appealing option for clinicians to utilize in the context of a global health pandemic of COVID-19 patients.Objectives: The aim of this study was to evaluate the efficacy and safety of using ascorbic acid as adjunctive therapy in critically ill patients with COVID-19. Methods: This was a multi-center, non-interventional, retrospective cohort study. All critically ill adult patients admitted to ICU with a confirmed COVID-19 between March 1st to December 31st, 2020 were included in the final analysis. The study was conducted at two large governmental tertiary hospitals in Saudi Arabia. The purpose was to investigate the association between clinical outcomes with ascorbic acid use as an adjunctive therapy in COVID-19 after propensity score matching using baseline severity scores, systemic use of corticosteroids and study centers. Results: A 739 patients were included in this study; 296 patients were included after propensity score matching. There was no association between the administration of ascorbic acid and in-hospital mortality nor 30-day ICU mortality (OR (95%CI): 0.77 (0.476, 1.234), p-value=0.2738 and OR (95%CI): 0.73 (0.438 ,1.204), p-value=0.215 respectively). Using ascorbic acid was associated with lower incidence of thrombosis compared with the non-ascorbic acid group (6.1% vs. 13% respectively); OR (95%CI): 0.42 (0.184, 0.937), p-value=0.0342).Conclusion: Ascorbic acid use as an adjunctive therapy in COVID19 critically ill patients was not associated with mortality benefits; but associated with lower incidence of thrombosis. Further studies are required to confirm these findings.

Nationwide Seroprevalence of SARS-CoV-2 in Saudi Arabia (preprint)

Background: Estimated seroprevalence of Coronavirus Infectious Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is a critical evidence for a better evaluation of the virus spread and monitoring the progress of the COVID-19 pandemic in a population. In the Kingdom of Saudi Arabia (KSA), SARS-CoV-2 seroprevalence has been reported in specific regions, but an extensive nationwide study has not been reported. Here, we report a nationwide study to determine the prevalence of SARS-CoV-2 in the population of KSA during the pandemic, using serum samples from healthy blood donors, non-COVID patients and healthcare workers (HCWs) in six different regions of the kingdom, with addition samples from COVID-19 patients. Methods: A total of 11703 serum samples were collected from different regions of the KSA including; 5395 samples from residual healthy blood donors (D); 5877 samples from non-COVID patients collected through residual sera at clinical biochemistry labs from non-COVID patients (P); and 400 samples from consented HCWs. To determine the seroprevalence of SARS-CoV-2, all serum samples, in addition to positive control sera from RT-PCR confirmed COVID-19 patients, were subjected to in-house ELISA with a sample pooling strategy, which was further validated by testing individual samples that make up some of the pools, with a statistical estimation method to report seroprevalence estimates Results: Overall (combining D and P groups) seroprevalence estimate was around 11% in Saudi Arabia; and was 5.1% (Riyadh), 1.5% (Jazan), 18.4% (Qassim), 20.8% (Hail), 14.7% (ER; Alahsa), and 18.8% in Makkah. Makkah samples were only D group and had a rate of 24.4% and 12.8% in the cities of Makkah and Jeddah, respectively. The seroprevalence in Saudi Arabia across the sampled areas would be 12 times the COVID-19 infection rate. Among HCWs, 7.5% (4.95-10.16 CI 95%) had reactive antibodies to SARS-CoV-2 without reporting any previously confirmed infection. This was higher in HCWs with hypertension. The study also presents the demographics and prevalence of co-morbidities in HCWs and subset of non-COVID-19 population. Interpretation: Our study estimates the overall national serological prevalence of COVID-19 in Saudi Arabia to be 11%, with an apparent disparity between regions.

COVID-19 critical care simulations: An international cross-sectional survey (preprint)

IntroductionMany healthcare systems initiated rapid training with COVID-19 simulations for their healthcare workers (HCWs) to build surge capacity and optimize infection control measures. This study aimed to describe COVID-19 simulation drills in international healthcare centers. MethodsThis is cross-sectional, international survey among simulation team leaders and HCWs, based on each centers debriefing reports from simulation centers from 30 countries in all WHO regions where COVID-19 simulation drills were conducted. The main outcome measures were the COVID-19 simulations characteristics, outcomes, facilitators, obstacles and challenges encountered during the simulation sessions. ResultsInvitation was sent to 500 simulation team leaders and HCWs, 343 responded, and 121 completed the survey. Those who completed the study were from East Mediterranean (EMRO) countries (41.3%); Southeast Asian countries (SERO) (25.6%); and Europe (12.4%) and the remainder from other regions. The frequency of simulation sessions was monthly (27.1%), weekly (24.8%), twice weekly (19.8%), or daily (21.5%). Among participants, 55.6% reported teams full engagement in the simulation sessions. The average session length was 30-60 minutes. The most commonly reported debriefing leaders were ICU staff, simulation lab staff, and ER facilitators, and the least common were infection control staff. A total of 80% reported "a lot" to "a great improvement" in terms of clinical preparedness after simulation sessions, and 70% were satisfied with the COVID-19 simulation sessions and thought they were better than expected. Most of the perceived issues reported were related to infection control measures, followed by team dynamics, logistics, and patient transport issues. ConclusionSimulation centers team leaders and HCWs reported positive feedback on COVID- 19 simulation sessions. The presence of multiprofessional personnel during drills is warranted. These drills are a valuable tool for rehearsing safe dynamics of HCWs on the frontline of COVID-19. Summary boxexplaining the significance of their study by providing each of the following key questions: What is already known?O_LISimulation enhances healthcare systems safety. C_LIO_LIPreparedness to potential disasters includes training for personal protection techniques, environmental contamination, medical management, and training of HCWs. C_LI What are the new findings?O_LIMany hospitals conducted COVID-19 simulations in all WHO regions. C_LIO_LIMost of the team leaders and HCWs reported full engagement and significant clinical preparedness improvement after the COVID-19 simulation sessions. C_LI What do the new findings imply?O_LIThe presence of multiprofessional personnel, including infection control experts, during COVID-19 drills is warranted. C_LIO_LISimulation are a valuable tool for rehearsing safe dynamics of HCWs on the frontline of COVID-19. C_LI

Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19: an international collaborative meta-analysis of randomized trials (preprint)

Background: Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aimed to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. Methods: Rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified published and unpublished RCTs by September 14, 2020 (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, PubMed, Cochrane COVID-19 registry). All-cause mortality was extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine/chloroquine. Prespecified subgroup analyses included patient setting, diagnostic confirmation, control type, and publication status. Results: Sixty-two trials were potentially eligible. We included 16 unpublished trials (1596 patients) and 10 publications/preprints (6317 patients). The combined summary OR on all-cause mortality for hydroxychloroquine was 1.08 (95%CI: 0.99, 1.18; I-square=0%; 24 trials; 7659 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I-square=0%; 4 trials; 307 patients). We identified no subgroup effects. Conclusions: We found no benefit of hydroxychloroquine or chloroquine on the survival of COVID-19 patients. For hydroxychloroquine, the confidence interval is compatible with increased mortality (OR 1.18) or negligibly reduced mortality (OR 0.99). Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.