The use and safety risk of repurposed drugs for COVID-19 patients: lessons learned utilizing the Food and Drug Administration's Adverse Event Reporting System.

Objectives: This study was designed to assess the disproportionality analyses of adverse drug reactions (ADRs) related to hydroxychloroquine and remdesivir and how ADR reporting fluctuated during the COVID-19 pandemic. Methods: A retrospective observational study was conducted utilizing the Food and Drug Administration's Adverse Event Reporting System (FAERS) data between 2019 and 2021. The study was conducted in two phases. In the first phase, all reports associated with the drugs of interest were evaluated to assess all related adverse drug reactions. In the second phase, specific outcomes of interest (i.e., QT prolongation and renal and hepatic events) were determined to study their association with the drugs of interest. A descriptive analysis was conducted for all adverse reactions related to the drugs being studied. In addition, disproportionality analyses were conducted to compute the reporting odds ratio, the proportional reporting ratio, the information component, and the empirical Bayes geometric mean. All analyses were conducted using RStudio. Results: A total of 9,443 ADR reports related to hydroxychloroquine; 6,160 (71.49) patients were female, and higher percentage of patients of both sexes were over the age of 65 years. QT prolongation (1.48%), pain (1.38%), and arthralgia (1.25%) were most frequently reported ADRs during the COVID-19 pandemic. The association of QT prolongation with use of hydroxychloroquine was statistically significant (ROR 47.28 [95% CI 35.95-62.18]; PRR 42.41 [95% CI 32.25-55.78]; EBGM 16.08; IC 4.95) compared with fluoroquinolone. The outcome was serious medical events in 48.01% of ADR reports; 27.42% required hospitalization and 8.61% resulted in death. Of 6,673 ADR reports related to remdesivir, 3,928 (61.13%) patients were male. During 2020, the top three ADR reports were elevated liver function tests (17.26%), acute kidney injury (5.95%) and death (2.84%). Additionally, 42.71% of ADR reports indicated serious medical events; 19.69% resulted in death and 11.71% indicated hospitalization. The ROR and PRR of hepatic and renal events associated with remdesivir were statistically significant, (4.81 [95% CI 4.46-5.19] and 2.96 [95% CI 2.66-3.29], respectively. Conclusion: Our study showed that several serious ADRs were reported with the use of hydroxychloroquine, which resulted in hospitalization and death. Trends with the use of remdesivir were similar, but to a lesser extent. Therefore, this study showed us that off-label use should be based on thorough evidence-based evaluation.

Contextualising adverse events of special interest to characterise the baseline incidence rates in 24 million patients with COVID-19 across 26 databases: a multinational retrospective cohort study.

Background: Adverse events of special interest (AESIs) were pre-specified to be monitored for the COVID-19 vaccines. Some AESIs are not only associated with the vaccines, but with COVID-19. Our aim was to characterise the incidence rates of AESIs following SARS-CoV-2 infection in patients and compare these to historical rates in the general population. Methods: A multi-national cohort study with data from primary care, electronic health records, and insurance claims mapped to a common data model. This study's evidence was collected between Jan 1, 2017 and the conclusion of each database (which ranged from Jul 2020 to May 2022). The 16 pre-specified prevalent AESIs were: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain- Barré syndrome, haemorrhagic stroke, non-haemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, transverse myelitis, and thrombosis with thrombocytopenia. Age-sex standardised incidence rate ratios (SIR) were estimated to compare post-COVID-19 to pre-pandemic rates in each of the databases. Findings: Substantial heterogeneity by age was seen for AESI rates, with some clearly increasing with age but others following the opposite trend. Similarly, differences were also observed across databases for same health outcome and age-sex strata. All studied AESIs appeared consistently more common in the post-COVID-19 compared to the historical cohorts, with related meta-analytic SIRs ranging from 1.32 (1.05 to 1.66) for narcolepsy to 11.70 (10.10 to 13.70) for pulmonary embolism. Interpretation: Our findings suggest all AESIs are more common after COVID-19 than in the general population. Thromboembolic events were particularly common, and over 10-fold more so. More research is needed to contextualise post-COVID-19 complications in the longer term. Funding: None.

Impact of risk communication on patient's safety during the pandemic.

More than 2 years has passed since the pandemic was declared in 2019 due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was later declared to be the pathogen causing coronavirus disease 2019 (COVID-19). During this time, many healthcare systems faced numerous challenges to control the high morbidity and mortality of the disease. Unlike previous pandemics, the actions against this pandemic started quickly on both the global and country levels. These actions were, scientifically, to study the virus as well as transmission process and to develop medications and vaccines against it. Also, we had to protect people from transmission by knowing how best to apply precautionary methods. However, there were some unexpected negative consequences of the pandemic and one of those the World Health Organization (WHO) called 'infodemic'. This term infodemic refers to the manipulation of a population's behavior in the assessment of information (or, more accurately, lack of assessment) related to the use of medications, particularly vaccines. Unfortunately, even with positive development in science, there was limited and often contradictory amount of information on the safety and efficacy profile of drugs and vaccines. Therefore, this made it harder for public health agencies to determine the impact of the incidence of adverse reactions and events associated with interventions such as vaccines. Hence, risk communication needs to be emphasized during any pandemic, as ignoring risk communications to different stakeholders could undermine all well-intended therapeutic interventions. Given this, it is important that the different stakeholders involved (health authorities, societies, healthcare professionals, etc.) assess the different behavioral patterns within their respective populations and propose appropriate strategies to act. Such an approach complement having risk management and communication plans for this and future pandemics. The aim of this article is to explore how information management, risk management, and risk communication during the pandemic can provide valuable lessons for the future. Plain language summary: Impact of risk communication on patient's safety during the pandemic More than 2 years have gone by since the pandemic was declared in 2019 due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Many challenges have been confronted by the healthcare system during this time to control the high impact of this disease. This pandemic, unlike others that humanity has faced, is characterized by a special feature: today, we have an enormous amount of information only a click away. This situation has been of great benefit to humanity and has allowed the development of science; nevertheless, misinformation (infodemics) has been a major problem, which has revealed the behavior of the population regarding the evaluation of information (or better, lack of assessment) related to the use of medications and particularly of vaccines. Given this, it is important that the different people involved (health authorities, societies, healthcare professionals, etc.) assess the behavior and propose appropriate strategies to act and have plans for this and future pandemics. This article intends to explore from the authors' perspective how information management, risk management, and risk communication during the pandemic can provide valuable lessons for the future.

Characteristics and outcomes of COVID-19 patients with COPD from the United States, South Korea, and Europe.

Background: Characterization studies of COVID-19 patients with chronic obstructive pulmonary disease (COPD) are limited in size and scope. The aim of the study is to provide a large-scale characterization of COVID-19 patients with COPD. Methods: We included thirteen databases contributing data from January-June 2020 from North America (US), Europe and Asia. We defined two cohorts of patients with COVID-19 namely a 'diagnosed' and 'hospitalized' cohort. We followed patients from COVID-19 index date to 30 days or death. We performed descriptive analysis and reported the frequency of characteristics and outcomes among COPD patients with COVID-19. Results: The study included 934,778 patients in the diagnosed COVID-19 cohort and 177,201 in the hospitalized COVID-19 cohort. Observed COPD prevalence in the diagnosed cohort ranged from 3.8% (95%CI 3.5-4.1%) in French data to 22.7% (95%CI 22.4-23.0) in US data, and from 1.9% (95%CI 1.6-2.2) in South Korean to 44.0% (95%CI 43.1-45.0) in US data, in the hospitalized cohorts. COPD patients in the hospitalized cohort had greater comorbidity than those in the diagnosed cohort, including hypertension, heart disease, diabetes and obesity. Mortality was higher in COPD patients in the hospitalized cohort and ranged from 7.6% (95%CI 6.9-8.4) to 32.2% (95%CI 28.0-36.7) across databases. ARDS, acute renal failure, cardiac arrhythmia and sepsis were the most common outcomes among hospitalized COPD patients.   Conclusion: COPD patients with COVID-19 have high levels of COVID-19-associated comorbidities and poor COVID-19 outcomes. Further research is required to identify patients with COPD at high risk of worse outcomes.

Pharmacovigilance regulatory actions by national pharmacovigilance centers in Arab countries following COVID-19 pandemic.

BACKGROUND: Pharmacovigilance (PV) activities were affected by COVID-19. Therefore, several health authorities around the world have issued guidelines and practices to ensure that PV activities are maintained and continued during the pandemic. This study aimed to assess the impact of COVID-19 on the preparedness and performance of national PV systems in 14 Arab countries. RESEARCH DESIGN AND METHODS: This was a cross-sectional study that was conducted between July and October 2020. National PV centers in 18 Arab countries were invited to participate in this study. Descriptive analysis was used to summarize and present the results of this study. RESULTS: Responses were obtained from 14 (77.8%) countries. Adverse events reporting was the main PV activity that was covered by PV guidelines and practices. National guidelines and practices covered other PV activities in 8 (57.14%) of the participating countries. Performance and practices of national PV centers vary considerably among participating countries during the pandemic. CONCLUSION: The findings highlight the differences in preparedness and performance of different national PV centers in participating Arab countries. Improving digital infrastructure among participating countries could serve as a useful tool to minimize the impact of the pandemic on PV activities.

Characteristics and Outcomes of Over 300,000 Patients with COVID-19 and History of Cancer in the United States and Spain.

BACKGROUND: We described the demographics, cancer subtypes, comorbidities, and outcomes of patients with a history of cancer and coronavirus disease 2019 (COVID-19). Second, we compared patients hospitalized with COVID-19 to patients diagnosed with COVID-19 and patients hospitalized with influenza. METHODS: We conducted a cohort study using eight routinely collected health care databases from Spain and the United States, standardized to the Observational Medical Outcome Partnership common data model. Three cohorts of patients with a history of cancer were included: (i) diagnosed with COVID-19, (ii) hospitalized with COVID-19, and (iii) hospitalized with influenza in 2017 to 2018. Patients were followed from index date to 30 days or death. We reported demographics, cancer subtypes, comorbidities, and 30-day outcomes. RESULTS: We included 366,050 and 119,597 patients diagnosed and hospitalized with COVID-19, respectively. Prostate and breast cancers were the most frequent cancers (range: 5%-18% and 1%-14% in the diagnosed cohort, respectively). Hematologic malignancies were also frequent, with non-Hodgkin's lymphoma being among the five most common cancer subtypes in the diagnosed cohort. Overall, patients were aged above 65 years and had multiple comorbidities. Occurrence of death ranged from 2% to 14% and from 6% to 26% in the diagnosed and hospitalized COVID-19 cohorts, respectively. Patients hospitalized with influenza (n = 67,743) had a similar distribution of cancer subtypes, sex, age, and comorbidities but lower occurrence of adverse events. CONCLUSIONS: Patients with a history of cancer and COVID-19 had multiple comorbidities and a high occurrence of COVID-19-related events. Hematologic malignancies were frequent. IMPACT: This study provides epidemiologic characteristics that can inform clinical care and etiologic studies.

Health economic burden of COVID-19 in Saudi Arabia.

Background: The coronavirus disease 2019 (COVID-19) pandemic has added a massive economic burden on health care systems worldwide. Saudi Arabia is one of the numerous countries that have been economically affected by this pandemic. The objective of this study was to provide real-world data on the health economic burden of COVID-19 on the Saudi health sector and assess the direct medical costs associated with the management of COVID-19. Methods: A retrospective cohort study was conducted based on data collected from patients hospitalized with COVID-19 across 10 institutions in eight different regions in Saudi Arabia. The study calculated the direct medical costs of all cases during the study period by using SAS statistical analysis software. These costs included costs directly related to medical services, such as the health care treatment, hospital stays, laboratory investigations, treatment, outcome, and other related care. Results: A total of 5,286 adult patients admitted with COVID-19 during the study period were included in the study. The average age of the patients was 54 years, and the majority were male (79%). Among the COVID-19 patients hospitalized in a general ward, the median hospital length of stay was 5.5 days (mean: 9.18 days), while the ICU stay was 4.2 days (mean: 7.94 days). The total medical costs for general ward and ICU patients were US$ 38,895 and US$ 24,207,296.9, respectively. The total laboratory investigations ranked as the highest-cost services US$ 588,975 followed by treatment US$ 3,886,509.8. Overall, the total cost of all medical services for patients hospitalized with COVID-19 was US$ 51,572,393.4. Conclusion: This national study found that COVID-19 was not only a serious concern for patients but also a serious economic burden on the health care system in Saudi Arabia.

Vaccine adverse event reporting system (VAERS): Evaluation of 31 years of reports and pandemics' impact.

Background: Vaccine adverse event reporting system (VAERS) was established in the United States (U.S.) as an early warning system with a main purpose of collecting post-marketing Adverse events following immunizations (AEFIs) reports to monitor the vaccine safety and to mitigate the risks from vaccines. During the coronavirus diseases 2019 (COVID-19) pandemic, VAERS got more attention as its important role in monitoring the safety of the vaccines. The aim of this study was to investigate VAERS patterns, reported AEFI, vaccines, and impact of different pandemics since its inception. Methods: This was an observational study using VARES data from 2/7/1990 to 12/11/2021. Patterns of reports over years were first described, followed by a comparison of reports statistics per year. Furthermore, a comparison of incidents (death, ER visits, etc.) statistics over years, in addition to statistics of each vaccine were calculated. Moreover, each incident's statistics for each vaccine were calculated and top vaccines were reported. All analyses were conducted using R (Version 1.4.1717) and Excel for Microsoft 365. Results: There were 1,396,280 domestic and 346,210 non-domestic reports during 1990-2021, including 228 vaccines. For both domestic and non-domestic reports, year of 2021 had the highest reporting rate (48.52 % and 70.33 %), in addition a notable change in AEFIs patterns were recorded during 1991, 1998, 2000, 2006, 2009, 2011, and 2017. AEFIs were as follow: deaths (1.00 % and 4.08 %), ER or doctor visits (13.37 % and 2.27 %), hospitalizations (5.84 % and 27.78 %), lethal threat (1.42 % and 4.38 %), and disabilities (1.4 % and 7.96 %). Pyrexia was the top reported symptom during the past 31 years, except for 2021 where headache was the top one. COVID-19 vaccines namely Moderna, Pfizer-Biontech, and Janssen were the top 3 reported vaccines with headache, pyrexia, and fatigue as the top associated AEFIs. Followed by Zoster, Seasonal Influenza, Pneumococcal, and Human papillomavirus vaccines. Conclusions: The large data available in VARES make it a useful tool for detecting and monitoring vaccine AEFIs. However, its usability relies on understating the limitations of this surveillance system, the impact of governmental regulations, availability of vaccines, and public health recommendations on the reporting rate.

Coronavirus disease 2019 in Saudi Arabia: A nationwide real-world characterization study

Background On March 11th, 2020, The World Health Organization (WHO) declared that the COVID-19 is a pandemic due to its worldwide spread. The COVID-19 pandemic has extended its impact to Saudi Arabia. By mid-February 2021, The Kingdom of Saudi Arabia has reported more than 373,000 COVID-19 cases impacting different population categories (i.e., male, female, different age groups, comorbidities status). The objective of this nationwide study was to describe and explore the characteristics of hospitalized patients diagnosed with COVID-19 in Saudi Arabia. Methods This study was an observational epidemiological study based on collected clinical data from ten health institutions across all regions in Saudi Arabia. The study was conducted during the period from March 2nd, 2020, to January 31st, 2021. The data were collected included demographics, medical information, medications, and laboratory and diagnostic. More detailed information on usually missing factors such as smoking status, comorbidities, length of hospital stay were also collected. Both descriptive and inferential analyses were conducted using the statistical analysis software “SAS®” version 9.4. Results During the study period, 5286 patients were included in this study. Of these, (79.15%) were male. Of all 5286 patients, quite a high number of the studied population 2010 (38.02%) were smokers. The majority of the patients 3436 (65%) were reported to have comorbidities, with hypertension being the most common disease 1725 (32.6%), followed by diabetes 1641(31.04%). A high proportion of the patients, 2220 patients (41.99%), were admitted to the intensive care unit;of these, (33.52%) were on mechanical ventilation. Most patients received anticoagulant prophylaxis medications (n = 4414, 83.5%). All patients were given more than one antibiotic prophylaxis. Overall, the median hospital stay was 5.5 days, and the median length in the intensive care unit was 4.26 days. Around (89.14%) of patients were discharged from the hospital, and (10.8%) died. Conclusion In this real-world study utilizing a large sample size, this study provides confirmatory results on the COVID-19 patients characteristics that are similar to other populations. Healthcare professionals need to give COVID-19 patients with specific characteristics including smoking, diabetes mellitus and cardiac disease more care to avoid losing these patients.

Phenotype Algorithms for the Identification and Characterization of Vaccine-Induced Thrombotic Thrombocytopenia in Real World Data: A Multinational Network Cohort Study.

INTRODUCTION: Vaccine-induced thrombotic thrombocytopenia (VITT) has been identified as a rare but serious adverse event associated with coronavirus disease 2019 (COVID-19) vaccines. OBJECTIVES: In this study, we explored the pre-pandemic co-occurrence of thrombosis with thrombocytopenia (TWT) using 17 observational health data sources across the world. We applied multiple TWT definitions, estimated the background rate of TWT, characterized TWT patients, and explored the makeup of thrombosis types among TWT patients. METHODS: We conducted an international network retrospective cohort study using electronic health records and insurance claims data, estimating background rates of TWT amongst persons observed from 2017 to 2019. Following the principles of existing VITT clinical definitions, TWT was defined as patients with a diagnosis of embolic or thrombotic arterial or venous events and a diagnosis or measurement of thrombocytopenia within 7 days. Six TWT phenotypes were considered, which varied in the approach taken in defining thrombosis and thrombocytopenia in real world data. RESULTS: Overall TWT incidence rates ranged from 1.62 to 150.65 per 100,000 person-years. Substantial heterogeneity exists across data sources and by age, sex, and alternative TWT phenotypes. TWT patients were likely to be men of older age with various comorbidities. Among the thrombosis types, arterial thrombotic events were the most common. CONCLUSION: Our findings suggest that identifying VITT in observational data presents a substantial challenge, as implementing VITT case definitions based on the co-occurrence of TWT results in large and heterogeneous incidence rate and in a cohort of patints with baseline characteristics that are inconsistent with the VITT cases reported to date.

Unraveling COVID-19: A Large-Scale Characterization of 4.5 Million COVID-19 Cases Using CHARYBDIS.

Purpose: Routinely collected real world data (RWD) have great utility in aiding the novel coronavirus disease (COVID-19) pandemic response. Here we present the international Observational Health Data Sciences and Informatics (OHDSI) Characterizing Health Associated Risks and Your Baseline Disease In SARS-COV-2 (CHARYBDIS) framework for standardisation and analysis of COVID-19 RWD. Patients and Methods: We conducted a descriptive retrospective database study using a federated network of data partners in the United States, Europe (the Netherlands, Spain, the UK, Germany, France and Italy) and Asia (South Korea and China). The study protocol and analytical package were released on 11th June 2020 and are iteratively updated via GitHub. We identified three non-mutually exclusive cohorts of 4,537,153 individuals with a clinical COVID-19 diagnosis or positive test, 886,193 hospitalized with COVID-19, and 113,627 hospitalized with COVID-19 requiring intensive services. Results: We aggregated over 22,000 unique characteristics describing patients with COVID-19. All comorbidities, symptoms, medications, and outcomes are described by cohort in aggregate counts and are readily available online. Globally, we observed similarities in the USA and Europe: more women diagnosed than men but more men hospitalized than women, most diagnosed cases between 25 and 60 years of age versus most hospitalized cases between 60 and 80 years of age. South Korea differed with more women than men hospitalized. Common comorbidities included type 2 diabetes, hypertension, chronic kidney disease and heart disease. Common presenting symptoms were dyspnea, cough and fever. Symptom data availability was more common in hospitalized cohorts than diagnosed. Conclusion: We constructed a global, multi-centre view to describe trends in COVID-19 progression, management and evolution over time. By characterising baseline variability in patients and geography, our work provides critical context that may otherwise be misconstrued as data quality issues. This is important as we perform studies on adverse events of special interest in COVID-19 vaccine surveillance.

Characteristics and outcomes of patients with COVID-19 with and without prevalent hypertension: a multinational cohort study.

OBJECTIVE: To characterise patients with and without prevalent hypertension and COVID-19 and to assess adverse outcomes in both inpatients and outpatients. DESIGN AND SETTING: This is a retrospective cohort study using 15 healthcare databases (primary and secondary electronic healthcare records, insurance and national claims data) from the USA, Europe and South Korea, standardised to the Observational Medical Outcomes Partnership common data model. Data were gathered from 1 March to 31 October 2020. PARTICIPANTS: Two non-mutually exclusive cohorts were defined: (1) individuals diagnosed with COVID-19 (diagnosed cohort) and (2) individuals hospitalised with COVID-19 (hospitalised cohort), and stratified by hypertension status. Follow-up was from COVID-19 diagnosis/hospitalisation to death, end of the study period or 30 days. OUTCOMES: Demographics, comorbidities and 30-day outcomes (hospitalisation and death for the 'diagnosed' cohort and adverse events and death for the 'hospitalised' cohort) were reported. RESULTS: We identified 2 851 035 diagnosed and 563 708 hospitalised patients with COVID-19. Hypertension was more prevalent in the latter (ranging across databases from 17.4% (95% CI 17.2 to 17.6) to 61.4% (95% CI 61.0 to 61.8) and from 25.6% (95% CI 24.6 to 26.6) to 85.9% (95% CI 85.2 to 86.6)). Patients in both cohorts with hypertension were predominantly >50 years old and female. Patients with hypertension were frequently diagnosed with obesity, heart disease, dyslipidaemia and diabetes. Compared with patients without hypertension, patients with hypertension in the COVID-19 diagnosed cohort had more hospitalisations (ranging from 1.3% (95% CI 0.4 to 2.2) to 41.1% (95% CI 39.5 to 42.7) vs from 1.4% (95% CI 0.9 to 1.9) to 15.9% (95% CI 14.9 to 16.9)) and increased mortality (ranging from 0.3% (95% CI 0.1 to 0.5) to 18.5% (95% CI 15.7 to 21.3) vs from 0.2% (95% CI 0.2 to 0.2) to 11.8% (95% CI 10.8 to 12.8)). Patients in the COVID-19 hospitalised cohort with hypertension were more likely to have acute respiratory distress syndrome (ranging from 0.1% (95% CI 0.0 to 0.2) to 65.6% (95% CI 62.5 to 68.7) vs from 0.1% (95% CI 0.0 to 0.2) to 54.7% (95% CI 50.5 to 58.9)), arrhythmia (ranging from 0.5% (95% CI 0.3 to 0.7) to 45.8% (95% CI 42.6 to 49.0) vs from 0.4% (95% CI 0.3 to 0.5) to 36.8% (95% CI 32.7 to 40.9)) and increased mortality (ranging from 1.8% (95% CI 0.4 to 3.2) to 25.1% (95% CI 23.0 to 27.2) vs from 0.7% (95% CI 0.5 to 0.9) to 10.9% (95% CI 10.4 to 11.4)) than patients without hypertension. CONCLUSIONS: COVID-19 patients with hypertension were more likely to suffer severe outcomes, hospitalisations and deaths compared with those without hypertension.

Analyzing the U.S. Post-marketing safety surveillance of COVID-19 vaccines.

INTRODUCTION: Since December 2020, three COVID-19 vaccines have been authorized in the United States (U.S.) and were proceeded by large immunization programs. The aim of this study was to characterize the U.S. post-marketing safety (PMS) profiles of these vaccines with an in-depth analysis of mortality data. METHODS: This was a retrospective database analysis study. Details of the U.S. PMS reports (15 December 2020 to 19 March 2021) of the three vaccines (Pfizer-BioNTech, Moderna, and Janssen Ad26.COV2.S) were retrieved from the U.S. Vaccine Adverse Event Reporting System (VAERS). A descriptive analysis was conducted to characterize the reported adverse events (AEs). A comparative (Pfizer-BioNTech vs. Moderna) analysis of mortality was conducted. The mean count ratio of death between the two vaccines was estimated using a negative binomial regression model adjusting for the measured confounders. RESULTS: A total of 44,451 AE reports were retrieved (corresponding to 0.05% of the U.S. population who received at least one dose). The most commonly reported AEs were injection site reactions (30.4% of the reports), pain (reported in 26.7% of the reports), and headache (18.6% of the reports). Serious AEs were reported in only 14.6% of the reports with 4,108 hospitalizations. The total number of deaths was 1,919 with a mean count ratio of Moderna (n = 997) vs. Pfizer-BioNTech (n = 899) of 1.07 (95% confidence interval 0.86 to 1.33). CONCLUSIONS: The vast majority of PMS AEs in the U.S. were non-serious, and the number of serious AEs is very low given the total number of vaccinated U.S. population.

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.

Thirty-Day Outcomes of Children and Adolescents With COVID-19: An International Experience.

OBJECTIVES: To characterize the demographics, comorbidities, symptoms, in-hospital treatments, and health outcomes among children and adolescents diagnosed or hospitalized with coronavirus disease 2019 (COVID-19) and to compare them in secondary analyses with patients diagnosed with previous seasonal influenza in 2017-2018. METHODS: International network cohort using real-world data from European primary care records (France, Germany, and Spain), South Korean claims and US claims, and hospital databases. We included children and adolescents diagnosed and/or hospitalized with COVID-19 at age <18 between January and June 2020. We described baseline demographics, comorbidities, symptoms, 30-day in-hospital treatments, and outcomes including hospitalization, pneumonia, acute respiratory distress syndrome, multisystem inflammatory syndrome in children, and death. RESULTS: A total of 242 158 children and adolescents diagnosed and 9769 hospitalized with COVID-19 and 2 084 180 diagnosed with influenza were studied. Comorbidities including neurodevelopmental disorders, heart disease, and cancer were more common among those hospitalized with versus diagnosed with COVID-19. Dyspnea, bronchiolitis, anosmia, and gastrointestinal symptoms were more common in COVID-19 than influenza. In-hospital prevalent treatments for COVID-19 included repurposed medications (<10%) and adjunctive therapies: systemic corticosteroids (6.8%-7.6%), famotidine (9.0%-28.1%), and antithrombotics such as aspirin (2.0%-21.4%), heparin (2.2%-18.1%), and enoxaparin (2.8%-14.8%). Hospitalization was observed in 0.3% to 1.3% of the cohort diagnosed with COVID-19, with undetectable (n < 5 per database) 30-day fatality. Thirty-day outcomes including pneumonia and hypoxemia were more frequent in COVID-19 than influenza. CONCLUSIONS: Despite negligible fatality, complications including hospitalization, hypoxemia, and pneumonia were more frequent in children and adolescents with COVID-19 than with influenza. Dyspnea, anosmia, and gastrointestinal symptoms could help differentiate diagnoses. A wide range of medications was used for the inpatient management of pediatric COVID-19.

Characteristics and outcomes of 627 044 COVID-19 patients living with and without obesity in the United States, Spain, and the United Kingdom.

BACKGROUND: A detailed characterization of patients with COVID-19 living with obesity has not yet been undertaken. We aimed to describe and compare the demographics, medical conditions, and outcomes of COVID-19 patients living with obesity (PLWO) to those of patients living without obesity. METHODS: We conducted a cohort study based on outpatient/inpatient care and claims data from January to June 2020 from Spain, the UK, and the US. We used six databases standardized to the OMOP common data model. We defined two non-mutually exclusive cohorts of patients diagnosed and/or hospitalized with COVID-19; patients were followed from index date to 30 days or death. We report the frequency of demographics, prior medical conditions, and 30-days outcomes (hospitalization, events, and death) by obesity status. RESULTS: We included 627 044 (Spain: 122 058, UK: 2336, and US: 502 650) diagnosed and 160 013 (Spain: 18 197, US: 141 816) hospitalized patients with COVID-19. The prevalence of obesity was higher among patients hospitalized (39.9%, 95%CI: 39.8-40.0) than among those diagnosed with COVID-19 (33.1%; 95%CI: 33.0-33.2). In both cohorts, PLWO were more often female. Hospitalized PLWO were younger than patients without obesity. Overall, COVID-19 PLWO were more likely to have prior medical conditions, present with cardiovascular and respiratory events during hospitalization, or require intensive services compared to COVID-19 patients without obesity. CONCLUSION: We show that PLWO differ from patients without obesity in a wide range of medical conditions and present with more severe forms of COVID-19, with higher hospitalization rates and intensive services requirements. These findings can help guiding preventive strategies of COVID-19 infection and complications and generating hypotheses for causal inference studies.

Are countries' precautionary actions against COVID-19 effective? An assessment study of 175 countries worldwide.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has affected many countries negatively, particularly in terms of their health care and financial systems. Numerous countries have attempted to employ precautions to address this pandemic. This study was aimed at exploring and assessing the early precautionary actions taken by 175 countries on six continents to prevent the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: An observational study utilizing available public data was conducted on the basis of data collected from December 31, 2019 until the end of April 2020 and then compared with data in January 2021. Several data were extracted, including information related to the date of the first reported case of SARS-CoV-2, total confirmed cases, total active cases and more. In addition, seven validated indicators were used to assess the countries' preparedness and precautionary actions. RESULTS: A total of 175 countries were included in the study. The total COVID-19 infection rate increased exponentially and rapidly in North America and Europe from March to April. The application of precautions (indicators) varied between countries. School closures, quarantines and curfews were the most-applied indicators among all countries. As for the relationship between the indicators and their effects on the infection rate, Italy and Spain were the top countries in Europe and adopted all the indicators. Nevertheless, they faced high infection rates: 239,639 and 205,463 COVID-19 cases in Spain and Italy, respectively. CONCLUSION: The precautionary actions might have played a role in limiting the spread of COVID-19 in several countries. However, many countries might not benefit from applying these indicators.

Use of repurposed and adjuvant drugs in hospital patients with covid-19: multinational network cohort study.

OBJECTIVE: To investigate the use of repurposed and adjuvant drugs in patients admitted to hospital with covid-19 across three continents. DESIGN: Multinational network cohort study. SETTING: Hospital electronic health records from the United States, Spain, and China, and nationwide claims data from South Korea. PARTICIPANTS: 303 264 patients admitted to hospital with covid-19 from January 2020 to December 2020. MAIN OUTCOME MEASURES: Prescriptions or dispensations of any drug on or 30 days after the date of hospital admission for covid-19. RESULTS: Of the 303 264 patients included, 290 131 were from the US, 7599 from South Korea, 5230 from Spain, and 304 from China. 3455 drugs were identified. Common repurposed drugs were hydroxychloroquine (used in from <5 (<2%) patients in China to 2165 (85.1%) in Spain), azithromycin (from 15 (4.9%) in China to 1473 (57.9%) in Spain), combined lopinavir and ritonavir (from 156 (<2%) in the VA-OMOP US to 2,652 (34.9%) in South Korea and 1285 (50.5%) in Spain), and umifenovir (0% in the US, South Korea, and Spain and 238 (78.3%) in China). Use of adjunctive drugs varied greatly, with the five most used treatments being enoxaparin, fluoroquinolones, ceftriaxone, vitamin D, and corticosteroids. Hydroxychloroquine use increased rapidly from March to April 2020 but declined steeply in May to June and remained low for the rest of the year. The use of dexamethasone and corticosteroids increased steadily during 2020. CONCLUSIONS: Multiple drugs were used in the first few months of the covid-19 pandemic, with substantial geographical and temporal variation. Hydroxychloroquine, azithromycin, lopinavir-ritonavir, and umifenovir (in China only) were the most prescribed repurposed drugs. Antithrombotics, antibiotics, H2 receptor antagonists, and corticosteroids were often used as adjunctive treatments. Research is needed on the comparative risk and benefit of these treatments in the management of covid-19.

COVID-19 in patients with autoimmune diseases: characteristics and outcomes in a multinational network of cohorts across three countries.

OBJECTIVE: Patients with autoimmune diseases were advised to shield to avoid coronavirus disease 2019 (COVID-19), but information on their prognosis is lacking. We characterized 30-day outcomes and mortality after hospitalization with COVID-19 among patients with prevalent autoimmune diseases, and compared outcomes after hospital admissions among similar patients with seasonal influenza. METHODS: A multinational network cohort study was conducted using electronic health records data from Columbia University Irving Medical Center [USA, Optum (USA), Department of Veterans Affairs (USA), Information System for Research in Primary Care-Hospitalization Linked Data (Spain) and claims data from IQVIA Open Claims (USA) and Health Insurance and Review Assessment (South Korea). All patients with prevalent autoimmune diseases, diagnosed and/or hospitalized between January and June 2020 with COVID-19, and similar patients hospitalized with influenza in 2017-18 were included. Outcomes were death and complications within 30 days of hospitalization. RESULTS: We studied 133 589 patients diagnosed and 48 418 hospitalized with COVID-19 with prevalent autoimmune diseases. Most patients were female, aged ≥50 years with previous comorbidities. The prevalence of hypertension (45.5-93.2%), chronic kidney disease (14.0-52.7%) and heart disease (29.0-83.8%) was higher in hospitalized vs diagnosed patients with COVID-19. Compared with 70 660 hospitalized with influenza, those admitted with COVID-19 had more respiratory complications including pneumonia and acute respiratory distress syndrome, and higher 30-day mortality (2.2-4.3% vs 6.32-24.6%). CONCLUSION: Compared with influenza, COVID-19 is a more severe disease, leading to more complications and higher mortality.

Renin-angiotensin system blockers and susceptibility to COVID-19: an international, open science, cohort analysis.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been postulated to affect susceptibility to COVID-19. Observational studies so far have lacked rigorous ascertainment adjustment and international generalisability. We aimed to determine whether use of ACEIs or ARBs is associated with an increased susceptibility to COVID-19 in patients with hypertension. METHODS: In this international, open science, cohort analysis, we used electronic health records from Spain (Information Systems for Research in Primary Care [SIDIAP]) and the USA (Columbia University Irving Medical Center data warehouse [CUIMC] and Department of Veterans Affairs Observational Medical Outcomes Partnership [VA-OMOP]) to identify patients aged 18 years or older with at least one prescription for ACEIs and ARBs (target cohort) or calcium channel blockers (CCBs) and thiazide or thiazide-like diuretics (THZs; comparator cohort) between Nov 1, 2019, and Jan 31, 2020. Users were defined separately as receiving either monotherapy with these four drug classes, or monotherapy or combination therapy (combination use) with other antihypertensive medications. We assessed four outcomes: COVID-19 diagnosis; hospital admission with COVID-19; hospital admission with pneumonia; and hospital admission with pneumonia, acute respiratory distress syndrome, acute kidney injury, or sepsis. We built large-scale propensity score methods derived through a data-driven approach and negative control experiments across ten pairwise comparisons, with results meta-analysed to generate 1280 study effects. For each study effect, we did negative control outcome experiments using a possible 123 controls identified through a data-rich algorithm. This process used a set of predefined baseline patient characteristics to provide the most accurate prediction of treatment and balance among patient cohorts across characteristics. The study is registered with the EU Post-Authorisation Studies register, EUPAS35296. FINDINGS: Among 1 355 349 antihypertensive users (363 785 ACEI or ARB monotherapy users, 248 915 CCB or THZ monotherapy users, 711 799 ACEI or ARB combination users, and 473 076 CCB or THZ combination users) included in analyses, no association was observed between COVID-19 diagnosis and exposure to ACEI or ARB monotherapy versus CCB or THZ monotherapy (calibrated hazard ratio [HR] 0·98, 95% CI 0·84-1·14) or combination use exposure (1·01, 0·90-1·15). ACEIs alone similarly showed no relative risk difference when compared with CCB or THZ monotherapy (HR 0·91, 95% CI 0·68-1·21; with heterogeneity of >40%) or combination use (0·95, 0·83-1·07). Directly comparing ACEIs with ARBs demonstrated a moderately lower risk with ACEIs, which was significant with combination use (HR 0·88, 95% CI 0·79-0·99) and non-significant for monotherapy (0·85, 0·69-1·05). We observed no significant difference between drug classes for risk of hospital admission with COVID-19, hospital admission with pneumonia, or hospital admission with pneumonia, acute respiratory distress syndrome, acute kidney injury, or sepsis across all comparisons. INTERPRETATION: No clinically significant increased risk of COVID-19 diagnosis or hospital admission-related outcomes associated with ACEI or ARB use was observed, suggesting users should not discontinue or change their treatment to decrease their risk of COVID-19. FUNDING: Wellcome Trust, UK National Institute for Health Research, US National Institutes of Health, US Department of Veterans Affairs, Janssen Research & Development, IQVIA, South Korean Ministry of Health and Welfare Republic, Australian National Health and Medical Research Council, and European Health Data and Evidence Network.