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Background Currently there is no systematic review and meta-analysis of the global incidence rates of anaphylactic and nonanaphylactic reactions to SARS-CoV-2 vaccines in the general adult population. Objectives To estimate the incidence rates of anaphylactic and nonanaphylactic reactions after COVID-19 vaccines and describe the demographic and clinical characteristics, triggers, presenting signs and symptoms, treatment and clinical course of confirmed cases. Design A systematic review and meta-analysis. Preferred Reporting Items for Systematic Reviews and Meta-Analyses [PRISMA] statement was followed. Methods Electronic databases (Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, and Nature) were searched from 1 December 2020 to 31 May 2021 in the English language using the following keywords alone or in combination: anaphylaxis, non-anaphylaxis, anaphylactic reaction, nonanaphylactic reaction, anaphylactic/anaphylactoid shock, hypersensitivity, allergy reaction, allergic reaction, immunology reaction, immunologic reaction, angioedema, loss of consciousness, generalized erythema, urticaria, urticarial rash, cyanosis, grunting, stridor, tachypnoea, wheezing, tachycardia, abdominal pain, diarrhea, nausea, vomiting and tryptase. We included studies in adults of all ages in all healthcare settings. Effect sizes of prevalence were pooled with 95% confidence intervals (CIs). To minimize heterogeneity, we performed sub-group analyses. Results Of the 1,734 papers that were identified, 26 articles were included in the systematic review (8 case report, 5 cohort, 4 case series, 2 randomized controlled trial and 1 randomized cross-sectional studies) and 14 articles (1 cohort, 2 case series, 1 randomized controlled trial and 1 randomized cross-sectional studies) were included in meta-analysis. Studies involving 26,337,421 vaccine recipients [Pfizer-BioNTech (n = 14,505,399) and Moderna (n = 11,831,488)] were analyzed. The overall pooled prevalence estimate of anaphylaxis to both vaccines was 5.0 (95% CI 2.9 to 7.2, I2 = 81%, p = I2 = 99%, p = I2 = 85% versus 2.8, 95% CI 0.0 to 5.7, I2 = 59%). However, lower incidence of nonanaphylactic reactions was associated with Pfizer-BioNTech compared to Moderna (43.9, 95% CI 0.0 to 131.9, I2 = 99% versus 63.8, 95% CI 0.0 to 151.8, I2 = 98%). The funnel plots for possible publication bias for the pooled effect sizes to determine the incidence of anaphylaxis and nonanaphylactic reactions associated with mRNA COVID-19 immunization based on mRNA vaccine type appeared asymmetrical on visual inspection, and Egger’s tests confirmed asymmetry by producing p values Conclusion The prevalence of COVID-19 mRNA vaccine-associated anaphylaxis is very low; and nonanaphylactic reactions occur at higher rate, however, cutaneous reactions are largely self-limited. Both anaphylactic and nonanaphylactic reactions should not discourage vaccination.

Glucose-6-phosphate dehydrogenase deficiency (G6PDd) is known to suppress the antioxidant system and is likely to aggravate severity of COVID-19, which results in a pro-oxidant response. This possible association has not been explored adequately in human studies. In this research, we report that the occurrence of non-invasive ventilation, intubation or death—all of which are indicative of severe COVID-19, are not significantly different in hospitalized COVID-19 patients with and without G6PDd (4.6 vs. 6.4%, p = 0.33). The likelihood of developing any of these severe outcomes were slightly lower in patients with G6PDd after accounting for age, nationality, presence of comorbidities and drug interventions (Odds ratio 0.40, 95% confidence intervals 0.142, 1.148). Further investigation that extends to both, hospitalized and non-hospitalized COVID-19 patients, is warranted to study this potential association.

Background The recent emergence of the Coronavirus Disease (COVID-19) disease had been associated with reports of fungal infections such as aspergillosis and mucormycosis especially among critically ill patients treated with steroids. The recent surge in cases of COVID-19 in India during the second wave of the pandemic had been associated with increased reporting of invasive mucormycosis post COVID-19. There are multiple case reports and case series describing mucormycosis in COVID-19. Purpose In this review, we included most recent reported case reports and case-series of mucormycosis among patients with COVID-19 and describe the clinical features and outcome. Results Many of the mucormycosis reports were eported from India, especially in COVID-19 patients who were treated and recovered patients. The most commonly reported infection sites were rhino-orbital/rhino-cerebral mucormycosis. Those patients were diabetic and had corticosteroids therapy for controlling the severity of COVID-19, leading to a higher fatality in such cases and complicating the pandemic scenario. The triad of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), corticosteroid use and uncontrolled diabetes mellitus have been evident for significant increase in the incidence of angioinvasive maxillofacial mucormycosis. In addition, the presence of spores and other factors might play a role as well. Conclusion With the ongoing COVID-19 pandemic and increasing number of critically ill patients infected with SARS-CoV-2, it is important to develop a risk-based approach for patients at risk of mucormycosis based on the epidemiological burden of mucormycosis, prevalence of diabetes mellitus, COVID-19 disease severity and use of immune modulating agents including the combined use of corticosteroids and immunosuppressive agents in patients with cancer and transplants.

Studies have shown increased immunogenicity from heterologous boosting. This study specifically assessed boosting with Pfizer-BioNTech in Sputnik V vaccination regimens. Reactogenicity was assessed through adverse events. Immunogenicity was assessed by comparing serum anti-Spike (Anti-S) protein antibody and neutralizing antibody titers before booster administration and after 30 days. A total of 428 participants were recruited in the heterologous arm and 351 in the homologous arm. Adverse events were more frequent in the heterologous arm (pARTICLE SUMMARY LINEBoth homologous and heterologous boosting are effective in eliciting an immunological response, however heterologous boosting with Pfizer-BioNTech elicited a higher immunological response, with more adverse effects.

The COVID-19 pandemic caused by SARS-CoV-2 has resulted in millions of cases and hundreds of thousands of deaths. Beyond there being no available antiviral therapy, stimulating protective immunity by vaccines is the best option for managing future infections. Development of a vaccine for a novel virus is a challenging effort that may take several years to accomplish. This mini-review summarizes the immunopathological responses to SARS-CoV-2 infection and discusses advances in the development of vaccines and immunotherapeutics for COVID-19.

Objectives: This study evaluated VivaDiag IgM/IgG Rapid Test (VDtest) for covid-19 screening, during disease progression and following recovery. Methods: Prospectively, 969 patients RT-PCR positive for SARS-CoV-2 virus were compared to VDtest in 166 individuals upon airport arrival; 62 active inpatient COVID-19 cases ranging 2-23 days; 741 recovered COVID-19 patients from diagnosis date (median 24-days). Findings: Screening; VDtest assay sensitivity 7.6% (95% CI 2.8–15.8%), specificity 94.3% (95% CI 87.1–98.1%). Active disease patients, positive IgG rate 27.4% and IgM positivity 0 of 62 patients. Recovery phase patients: positive rates of IgM and IgG were 0.7% and 1.2%, respectively, within 14-days of diagnosis date, increasing to 25.9% and 43.4%, respectively 14-days after diagnosis. Novelty: VDtest kit showed poor sensitivity and identification of COVID-19 infection for screening, moreover,need for larger sample study to confirm our findings. Keywords: COVID19; SARSCoV2; RTPCR; serological testing; rapid test

To understand the reasons of successful spread of carbapenem-resistant Klebsiella pneumoniae ST14 (CRKP-ST14) in countries of the Arabian Peninsula, the resistome, capsular locus, carbapenemase carrying plasmid types, and core genome of isolates from the region were compared to global isolates. Thirty-nine CRKP-ST14 strains isolated from 13 hospitals in the United Arab Emirates, Bahrain, and Saudi Arabia were selected for whole genome sequencing on Illumina MiSeq platform based on the variety of carbapenemase genes carried and plasmids bearing these genes. Their resistome, capsular locus, and core genome MLST were compared to 173 CRKP-ST14 genomes available in public databases. The selected 39 CRKP-ST14 produced either NDM-1, OXA-48, OXA-162, OXA-232, KPC-2, or co-produced NDM-1 and an OXA-48-like carbapenemase. cgMLST revealed three clusters: 16 isolates from five UAE cities (C1), 11 isolates from three UAE cities and Bahrain (C2), and 5 isolates from Saudi Arabia (C3), respectively, and seven singletons. Resistance gene profile, carbapenemase genes, and their plasmid types were variable in both C1 and C2 clusters. The majority of CRKP-ST14 had KL2, but members of the C2 cluster and two further singletons possessed KL64 capsular locus. Based on cgMLST comparison of regional and global isolates, CRKP-ST14 with KL64 from four continents formed a distinct cluster, suggesting a recent emergence and spread of this variant. Our findings confirmed clonal transmission coupled with likely horizontal gene transfer in carbapenem-resistant Klebsiella pneumoniae ST14. Dissemination of this genetically flexible, highly resistant clone warrants further monitoring.

This collaborative meta-analysis was supported by the Swiss National Science Foundation and the Laura and John Arnold Foundation (grant supporting the post-doctoral fellowship at the Meta-Research Innovation Center at Stanford (METRICS), Stanford University). The funders had no role in the design of this collaborative meta-analysis; in the collection, analysis, and interpretation of data; or in the report writing., We would like to express our warm gratitude to all participating patients and convalescent plasma donors. We thank Katja Suter and Sina Ullrich, University of Basel, for their administrative assistance. For their helpful contribution to individual trials, we thank Erica Wood, Iain Gosbell, Richard Charlewood, Thomas Hills, Veronica Hoad, Kristina Kairaitis, Aikaj Jindal, John Gerrard, Hong Foo, Adam Stewart, and Nanette Trask (ASCOT trial); Amalia Bravo-Lindoro, Ral Carrillo-Esper, Karla Maldonado-Silva, Catalina Casillas-Suárez, Orlando Carrillo-Torres, Sandra Murrieta, Elizabeth Diaz-Padilla, Eli Omar Zavaleta, Yadira Bejar-Ramirez, and Evelyn Cortina-de la Rosa (CPC-SARS trial); Sheri Renaud, Roel Rolando-Almario, and Jacqueline Day (NCT04385199 trial); Sandra Tingsgrd, MD, Karen Brorup Heje Pedersen, MD, Michaela Tinggaard, MD, Louise Thorlacius-Ussing, MD, Clara Lundetoft Clausen, MD, Nichlas Hovmand, MD, Simone Bastrup Israelsen, MD, Cecilie Leding, MD, Katrine Iversen, MD, Maria Engel Miller, MD, Hkon Sandholdt, MSc biostatistician (CCAP-2 trial). On behalf of the IRCT20200310046736N1 trial, we thank the Khuzestan Blood Transfusion Organization for specialized assistance in the preparation and maintenance of plasma samples. On behalf of the NCT04332835 trial, we thank all the members of the "PC-COVID-19 Group" at the Clinica del Occidente and Hospital Universitario Mayor Mederi in Bogota, and Clinica CES in Medellin. On behalf of the NCT04403477 trial, we thank Miles Carroll for his support regarding the antibody testing in Bangladesh. The Co-CLARITY team would like to extend their gratitude to the Department of Science and Technology Philippine Council for Health Research and Development and the UP-Philippine General Hospital for all their support in the setting up and conduct of the trial. For helpfully communicating details of their trial, we thank members of the PlasmAr trial, NCT04359810 trial (Max O´Donnell), NCT04468009 trial, and CTRI/2020/05/025299 trial. Support for title page creation and format was provided by AuthorArranger, a tool developed at the National Cancer Institute (https://www.cancer.gov/)., During the conduct of the study, the following is reported: Dr. Berry reports being employee with ownership role at Berry Consultants (receives payments for statistical modeling and design of REMAP-CAP). Dr. Castillo reports grants from DOST PCHRD. Dr. Daly reports grants from Medical Research Future Fund (Australian Govt) and RBWH. Dr. Denkinger reports grants from German Ministry for Education and Research. Dr. Dumagay reports grants from Philippine Council for Health Research and Development. Dr. Dunachie reports grants from UK Department of Health and Social Care, grants from UK National Institute of Health Research. Dr. Gauiran reports grants from Department of Science and Technology—Philippine Council for Health Research and Development. Dr. Gordon reports grants from NIHR, grants from NIHR Research Professorship (RP-2015-06-18), and non-financial support from NIHR Clinical Research Network. Dr. Higgins reports grants from NHMRC and from the Minderoo Foundation. Dr. Hills reports grants from Health Research Council of New Zealand. Dr. Holm reports grants from Swedish Government Funds for Clinical Research (ALF). Dr. Janssen and Dr. Müller-Tidow report grants from the Federal Ministry of Education and Research in Germany (BMBF) to the RECOVER clinical trial. Dr. Krapp reports grants from Department of Foreign Affairs, Trade, and Development of Canada, grants from Fundación Telefónica del Perú. Dr. J. Lim reports grants from the Department of Science and Technology, Philippine Council for Health Research and Development. Dr. Lucero reports grants from Philippine Council for Health Research and Development. Dr Manrique reports economic support from Grupo ISA Intercolombia for the project development of trial NCT04332835. Drs. McQuilten and Wood report grants from Medical Research Future Fund. Dr. McVerry reports grants from The Pittsburgh Foundation, Translational Breast Cancer Research Consortium, and from UPMC Learning While Doing Program. Mr. Mouncey reports grants from National Institute for Health Research and from the European Union FP7: PREPARE. Dr. Najdovski reports payment from KUL Leuven to Belgian Red Cross for supply of convalescent plasma. Dr. Nichol reports grants from Health Research Board of Ireland. Dr. D. Roberts reports grants from the National Institute for Health (UKRIDHSC COVID-19 Rapid Response Rolling Call—Grant Reference Number COV19-RECPLAS) and the European Commission (SUPPORT-E #101015756). Dr. Rowan reports grants from the European Commission and from the UK National Institute for Health Research. Dr. Shankar-Hari reports grants from National Institute for Health Research UK, grants from UKRI-National Institute for Health Research UK. Dr. Turgeon reports grants from Canadian Institutes of Health Research. Dr. Venkatesh reports grants from Baxter. Dr. Webb reports grants from National Health and Medical Research Council, grants from Minderoo Foundation. Dr. Zacharowski reports grants from EU Horizon 2020. The ASCOT trial team (Drs Bowen, Daly, Davis, Denholm, Hammond, Jha, L. Lim, McQuilten, Molton, Morpeth, O’Sullivan, Paterson, Perry, Price, Rees, Roberts, Rogers, Sasadeusz, Snelling, Tong, Venkatesh, Wood) is funded by grants from from Royal Brisbane and Women’s Hospital Foundation, Pratt Foundation, Minderoo Foundation, BHP Foundation, Hospital Research Foundation, Macquarie Group Foundation, Health Research Council of New Zealand, Australian Partnership for Preparedness Research on Infectious Disease Emergencies (APPRISE), and the collection and supply of convalescent plasma was conducted within Lifeblood’s funding arrangements. The CONFIDENT trial is funded by the Belgian KCE (blood establishments received payment for the convalescent plasma supplied in the clinical trial). REMAP-CAP was supported in part by funding from UKRIDHSC COVID-19 Rapid Response Rolling Call (Grant Reference Number COV19-RECPLAS). Collection of convalescent plasma for REMAP-CAP was funded by the Department of Health and Social Care, UK. The IRCT20200310046736N1 trial was supported by the Ahvaz Jundishapur University of Medical Sciences (Grant No. R.AJUMS.REC.1399.003, Dr. Pouladzadeh). The PC-COVID-19 Group is supported by the Universidad del Rosario, IDCBIS, ISA Group and Suramericana (Colombia). Outside the submitted work, the following is reported: Dr. Axfors reports postdoctoral grants from the Knut and Alice Wallenberg Foundation, Uppsala University, the Swedish Society of Medicine, the Blanceflor Foundation, and the Sweden-America Foundation. Dr. Aomar reports personal fees from SOBI, GEDEON RICHTER, and GSK. Dr. Benfield reports grants from Novo Nordisk Foundation, Simonsen Foundation, Lundbeck Foundation, Kai Hansen Foundation, Erik and Susanna Olesen’s Charitable Fund; grants and personal fees from GSK, Pfizer, Gilead; and personal fees from Boehringer Ingelheim, MSD, and Pentabase ApS. Dr. Estcourt reports being an investigator on the RECOVERY trial. Dr. Gordon reports personal fees from GlaxoSmithKline, Bristol Myers Squibb, and 30 Respiratory. Dr. Jha reports grants and personal fees from Baxter Healthcare, personal fees from Astra Zeneca, grants from NephroPlus. Dr. Laterre reports personal fees from Adrenomed. Dr. McVerry reports grants from NIH/NHLBI and Bayer Pharmaceuticals, Inc. Dr. Mondragon reports financial activities outside the submitted work (employment at Johnson & Johnson). Dr. Perry reports partner being employed at CSL and owning shares in CSL. Dr. Paterson reports involvement with ALLIANCE trial of COVID-19 treatments. Dr. J. Roberts reports other COVID-19 related trials (in different patient groups): tocilizumab in ICU patients; hydroxychloroquine dosing in ICU patients; planned study of remdesivir pharmacokinetics in patients during expanded access program; and in silico evaluation of ivermectin dosing. Dr Sasadeusz reports grants from various Pharma companies including Gilead Sciences, Abvvie, Merck, and Takeda. Dr. Zacharowski reports personal fees from Biotest AG, CSL Behring, GE Heathcare, and is President of the ESAIC., Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung–Knapp–Sidik–Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care., Amalia Bravo-Lindoro, BHP Foundation, Blanceflor Foundation, Department of Foreign Affairs, Trade, and Development of Canada, Eli Omar Zavaleta, Erik and Susanna Olesen’s Charitable Fund, Federal Ministry of Education and Research in Germany, Fundación Telefónica del Perú, IDCBIS, ISA Group and Suramericana, Kai Hansen Foundation, Katja Suter and Sina Ullrich, Khuzestan Blood Transfusion Organization, Macquarie Group Foundation, Medical Research Future Fund, NephroPlus, RBWH, Roel Rolando-Almario NCT04385199, Royal Brisbane, Sheri Renaud, Simonsen Foundation, UKRI-National Institute for Health Research UK, UKRIDHSC COV19-RECPLAS, UP-Philippine General Hospital CTRI/2020/05/025299, NCT04359810, NCT04468009, Women’s Hospital Foundation, National Institutes of Health, National Heart, Lung, and Blood Institute, Pittsburgh Foundation, Pfizer, Baxter International, Stanford University, Gilead Sciences, National Institute on Handicapped Research RP-2015-06-18, Meso Scale Diagnostics, Universität Basel, Laura and John Arnold Foundation, Health Research Board, Pratt Foundation, Canadian Institutes of Health Research, National Institute for Health Research, Department of Health and Social Care, European Commission 101015756, National Health and Medical Research Council, Department of Science and Technology, Ministry of Science and Technology, India, Health Research Council of New Zealand, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Sweden-America Foundation, Bundesministerium für Bildung und Forschung, Lundbeckfonden, Knut och Alice Wallenbergs Stiftelse, Seventh Framework Programme, Ahvaz Jundishapur University of Medical Sciences, Université Pierre et Marie Curie, Uppsala Universitet, Horizon 2020, Svenska Läkaresällskapet, Universidad del Rosario, Pharmaceuticals Bayer, Novo Nordisk Fonden, Department of Science and Technology, Philippines, Philippine Council for Health Research and Development, Minderoo Foundation

Ever since the emergence of the coronavirus disease 2019 (COVID-19), global public health infrastructures and systems, along with community-wide collaboration and service, have risen to an unprecedented challenge. Vaccine development was immediately propelled to the centre of all our scientific, public health and community efforts. Despite the development of SARS-CoV-2 vaccines arguably being the greatest and most palpable achievements of the past 12 months, they have also been one of the most contentious and debated issues during the pandemic. However, what uniquely differentiates vaccine development is its intimate relationship with the community it seeks to serve; both in its clinical trial testing as an efficacious and safe prophylactic, and its post-developmental ‘roll-out’ success, as an effective public health tool. These relationships have birthed a myriad of complexities, from community-based mistrust, to academically contended ethical dilemmas. Indeed, the accelerated advances in the COVID-19 vaccine race have further exacerbated this phenomenon, bringing with it new ethical dilemmas that need to be examined to ensure the continued clinical success of these therapeutics and a renewed societal trust in clinical medicine.In this paper, we discuss two major ethical dilemmas: (1) the equipoise of continuing new vaccine trials in the advent of successful candidates and (2) the maleficence of blinded placebo arms. Accordingly, we discuss six different potential approaches to these ethical dilemmas: (1) continuing with placebo-controlled trials, (2) transitioning from placebo-controlled to open-label, (3) unblinding at-risk priority groups only, (4) transitioning to a blinded stepped-wedge cross-over design, (5) progressing to a blinded active-controlled stepped-wedge cross-over trial, and (6) conducting randomised stepped-wedge community trials. We also propose a decision-making algorithm for relevant stakeholders in advanced stages of vaccine trials.It is important to remember that the emergent nature of the COVID-19 situation does not justify a compromise on core ethical values. In fact, the discourse surrounding this topic and the decisions made will remain a potent case study and a continuously referenced example for all such future scenarios.

The quarantine period imposed to travelers in many countries due to COVID19 is a major obstacle for any traveler. Lifting the quarantine period could lead to significant improvement in people’s quality of life and any country’s economy. Bahrain have used two quarantine models from arriving passengers. We report data about the incidence of COVID19 on arriving passengers at Bahrain International airport. Infection rates were reported on arrival, during quarantine and after leaving quarantine. Results showed that travelers had low incidence of COVID19 on arriving and during the quarantine period, while becoming at higher risk after leaving quarantine. We concluded that quarantine requirement maybe lifted for arriving travelers. Testing upon arrival with implementation of the public health preventative measures can minimize the risk of transmission.

The emergence of new SARS-CoV-2 variants across the world has raised concerns about the effectiveness of available COVID-19 vaccines that were designed against the original Wuhan (wild type) variant. Critical questions have arisen regarding: (a) the effectiveness of various vaccines in preventing infection, symptomatic disease, hospitalization, intensive care unit (ICU) admission and death and (b) the magnitude and clinical consequences of post-vaccination infections in the context of emerging variants, especially the Delta variant of SARS-Cov2. While “real world” experiences with various vaccines have been reported, few have examined comparative effectiveness of various vaccines in one population, as new SARS-CoV-2 variants have emerged. Here we present an analysis of COVID-19 related outcomes from Bahrain, a country with a total population of 1.501 million, where four vaccines were deployed (total vaccinated =1,003,960), including Astra-Zeneca (AZ/Covishield), Pfizer/BioNtech, Sinopharm and Sputnik V. By analyzing individual histories of vaccinated versus unvaccinated cases, we provide a granular description of the effectiveness of the four vaccines, disease burden in unvaccinated versus vaccinated individuals over time, and the risk of four outcomes (infections, hospitalizations, ICU admissions and deaths) due to breakthrough infections among vaccinated individuals. We conclude that the four vaccines were effective in reducing all four outcomes in vaccinated compared to unvaccinated individuals, prior to, and during the period when the Delta variant became dominant in the country (May 2021 to the present). However, after censoring early vaccine recipients of Sinopharm vaccine, compared to Pfizer/BionTech recipients, individuals vaccinated with Sinopharm had a higher risk of post-vaccination infections, hospitalizations, ICU admissions and deaths, especially in those > 50 years old. Our overall findings support the value of vaccination in preventing COVID-19 related events even with the advent of the Delta variant. These data support the urgent need to expand vaccination access around the world, and may serve to guide the choice of vaccines in the context of the Delta variant.

Favipiravir has antiviral activity against influenza, West Nile virus, and yellow fever virus and against flaviviruses. The objective of this pilot study was to compare three arms: favipiravir; hydroxychloroquine; standard care (no specific SARS-CoV-2 treatment) only, in symptomatic patients infected by SARS-CoV-2 in an open-labelled randomized clinical trial. The trial was registered with Bahrain National Taskforce for Combatting COVID-19 on the 7th of May 2020 (registration code: NCT04387760). 150 symptomatic patients with COVID-19 disease were randomized into one of three arms: favipiravir, hydroxychloroquine, or standard care only. The primary outcome was the clinical scale at the end of study follow up (day 14 or on discharge/death) based on a points scale. The secondary outcomes were viral clearance, biochemical parameter changes and mortality at 30-days. Baseline characteristics did not differ between groups. The proportion of patients who achieved a clinical scale 2 did not differ between groups. The favipiravir-treated and hydroxychloroquine-treated group showed increased viral clearance (OR, 95%CI 2.38, 0.83-6.78, OR, 95%CI 2.15, 0.78-5.92, respectively) compared to standard care, but this was not significant. The biochemical profile did not differ between groups, except for the platelet count (P 0.03) and uric acid (P 0.004) that were higher with favipiravir-treatment. Primary or secondary outcome measures did not differ between favipiravir, hydroxychloroquine, and standard therapy for mild to moderate COVID-19 disease; therefore, whilst favipiravir therapy appeared safe with a trend to increased viral clearance, there was no superior therapeutic utility.Clinical trials registration. NCT04387760. Registration date: 07/05/2020.

Background/objectiveThe novel coronavirus disease 2019 (COVID-19) pandemic poses a global threat to the public health. There is a challenge in measuring the patient’s length of hospital stay and managing the healthcare resources to handle the situation successfully. Our objective is to use the qPCR cycle of threshold (Ct) as a tool in evaluating the severity of the infection and hence the length of hospital stay to better utilize and manage the healthcare resources.MethodsThis cross sectional study was carried out on 306 patients who admitted to COVID-19 care centers in Kingdom of Bahrain from 20th March 2020 to 5th April 2020. Standard qPCR was used to estimate the viral load and data were analyzed to investigate the relationship between Ct values and various variables.ResultsOut of 306 patients, 2 deaths, 1 active stable case and 303 recovered cases were reported. Ct value was significantly and negatively associated (P value ConclusionCt value was inversely associated with hospital stay duration (and time to viral clearance), higher the Ct value is indicative of faster time to viral clearance. This association could help to better manage the infection and resources allocation.

Highlights • Sickle cell disease results from a mutation in the hemoglobin beta chain. • SARS-CoV-2 may decrease the heme oxygen-carrying capacity. • Reduced oxygen carrying capacity may lead to sickle cell crisis. • No increased disease severity was seen in Covid-19-infected sickle cell patients. • No patient underwent a sickle cell crisis with concurrent SARS-Cov-2 infection. • SARS-Cov-2 clearance rate did not differ between those with and without sickle cell disease., Introduction Coronavirus disease 2019 (COVID-19) is caused by a newly identified strain of the coronavirus family that has been shown to affect the hemoglobin beta chain, the same chain that has sickle cell disease (SCD) mutation. This study was undertaken to see if COVID-19 infection increased disease severity in patients with SCD. Methods Mass screening of the Bahraini population was undertaken between February and April 2020. Results A total of 38,092 Bahraini people were tested for COVID-19 during this period; 378 (1%) were SCD patients. Six patients with SCD had COVID-19 (1.6%): three remained asymptomatic, two had mild symptoms and one required oxygen therapy. The SCD patients had a similar average length of stay when compared with non-SCD COVID-19 patients (10.7 days). Conclusion The infection rate, clinical course and viral clearance seen for the SCD patients with COVID-19 were no different to those without SCD.

Catheter-associated urinary tract infections (CAUTIs) are the common hospital-associated infections (HAIs), which can be prevented by practicing necessary precautions and by using antimicrobial urinary catheters (UCs). The efficacy of antimicrobial UCs against standard catheters for averting CAUTIs is poorly studied. The objective of the review is to analyze the efficacy of various types of antimicrobial UCs used in hospitalized patients in preventing CAUTIs. The major antimicrobial UCs are silver and antibiotic catheters, in contrast, few antimicrobial catheters include antimicrobial peptides, bactericidal enzymes, bacteriophages, and many are under clinical evaluation. The review concludes that even though many antimicrobial methods are available to prevent CAUTIs, the incidence rate is still high. Antibiotic resistance, leaching of catheter materials which may cause side effects and additional costs are the major challenges for the UCs. Further research is warranted and should focus on cost-effective and ideal antimicrobial UCs, in which the microorganisms cannot form biofilms or develop resistance. Keywords: Anti-microbial urinary catheter, Catheter, Silver-Coated, Urinary tract infection

Coronavirus disease 2019 (COVID-19) is the second pandemic of the twenty-first century, with over one-hundred million infections and over two million deaths to date. It is a novel strain from the Coronaviridae family, named Severe Acute Respiratory Distress Syndrome Coronavirus-2 (SARS-CoV-2); the 7th known member of the coronavirus family to cause disease in humans, notably following the Middle East Respiratory syndrome (MERS), and Severe Acute Respiratory Distress Syndrome (SARS). The most characteristic feature of this single-stranded RNA molecule includes the spike glycoprotein on its surface. Most patients with COVID-19, of which the elderly and immunocompromised are most at risk, complain of flu-like symptoms, including dry cough and headache. The most common complications include pneumonia, acute respiratory distress syndrome, septic shock, and cardiovascular manifestations. Transmission of SARS-CoV-2 is mainly via respiratory droplets, either directly from the air when an infected patient coughs or sneezes, or in the form of fomites on surfaces. Maintaining hand-hygiene, social distancing, and personal protective equipment (i.e., masks) remain the most effective precautions. Patient management includes supportive care and anticoagulative measures, with a focus on maintaining respiratory function. Therapy with dexamethasone, remdesivir, and tocilizumab appear to be most promising to date, with hydroxychloroquine, lopinavir, ritonavir, and interferons falling out of favour. Additionally, accelerated vaccination efforts have taken place internationally, with several promising vaccinations being mass deployed. In response to the COVID-19 pandemic, countries and stakeholders have taken varying precautions to combat and contain the spread of the virus and dampen its collateral economic damage. This review paper aims to synthesize the impact of the virus on a global, micro to macro scale.

The COVID-19 pandemic has affected more than 100 million cases and caused immense burdens on governments and healthcare systems worldwide. Since its emergence in December 2019, research has been focused on treating the infected, identifying those at risk and preventing spread. There is currently no known biological biomarker that predicts the risk of infection. Several studies emerged suggesting an association between ABO blood group and the risk of COVID-19 infection. In this study, we used retrospective observational data in Bahrain to investigate the association between ABO blood group and risk of infection, as well as susceptibility to severe ICU-requiring infection. We found a higher risk associated with blood group B, and a lower risk with blood group AB. No association was observed between blood group and the risk of a severe ICU-requiring infection. We extended the analysis to study the association by antibodies; anti-a (blood groups B and O) and anti-b (blood groups A and O). No association between antibodies and both risk of infection or susceptibility to severe infection was found. The current study, along with the variation in blood group association results, indicates that blood group may not be an ideal biomarker to predict risk of COVID-19 infection.

Introduction Hydroxychloroquine (HCQ) is an antimalarial drug that received worldwide news and media attention in the treatment of patients with coronavirus disease 2019 (COVID-19). This drug was used on the basis of its antimicrobial and antiviral properties despite lack of definite evidence of clinical efficacy. In this study, we aim to assess the efficacy and safety of using HCQ in treatment of patients with COVID-19 who were admitted in acute care hospitals in Bahrain. Methods We conducted a retrospective cohort study on a random sample of patients admitted with COVID-19 between 24 February and 31 July 2020. The study was conducted in four acute care COVID-19 hospitals in Bahrain. Data was extracted from the medical records. The primary endpoint was the requirement of non-invasive ventilation, intubation, or death. Secondary endpoint was length of hospitalization for survivors. Three methods of analysis were used to control for confounding factors: logistic multivariate regression, propensity score adjusted regression, and matched propensity score analysis. Results A random sample of 1571 patients were included, 440 of whom received HCQ (treatment group) and 1131 did not receive it (control group). Our results showed that HCQ did not have a significant effect on primary outcomes due to COVID-19 infection when compared to controls after adjusting for confounders (OR 1.43, 95% CI 0.85–2.37, P = 0.17). Co-administration of azithromycin had no effect on primary outcomes (OR 2.7, 95% CI 0.82–8.85, P = 0.10). HCQ was associated with increased risk of hypoglycemia (OR 10.9, 95% CI 1.72—69.49, P = 0.011) and diarrhea (OR 2.8, 95% CI 1.4–5.5, P = 0.003), but not QT prolongation (OR 1.92, 95% CI 0.95–3.9, P = 0.06) or cardiac arrhythmia (OR 1.06, 95% CI 0.55–2.05, P = 0.85). Conclusion Our results showed no significant beneficial effect of using hydroxychloroquine on the outcome of patients with COVID-19. Moreover, the risk of hypoglycemia due to hydroxychloroquine would possess a significant risk for out-of-hospital use. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00397-8.

Purpose: The COVID-19 pandemic has led to over 92 million cases and 1.9 million deaths worldwide since its outbreak. Public health responses have focused on identifying symptomatic individuals to halt spread. However, evidence is accruing that asymptomatic individuals are infectious and contributing to this global pandemic. Methods: Observational data of 320 index cases and their 1289 positive contacts from the National COVID-19 Database in Bahrain were used to analyze symptoms, infectivity rate and PCR Cycle threshold (Ct) values. Results: No significant difference (p = 1.0) in proportions of symptomatic (n = 160; 50.0%) and asymptomatic index cases (n = 160; 50.0%) were seen; however, SARS-CoV-2 positive contact cases were predominantly asymptomatic (n = 1127, 87.4%). Individuals aged 0−19 years constituted a larger proportion of positive contact cases (20.8%) than index cases (4.7%; p

Introduction Studies that examine the association between sickle cell disease (SCD) and COVID‐19 outcomes are lacking. This study aims to determine whether SCD is a risk factor for severe COVID‐19 infection in regard to the requirement of noninvasive ventilation/high flow nasal cannula (NIV/HFNC), mechanical ventilation (MV), or death in hospitalized patients. Methods Retrospective cohort study included COVID‐19 patients admitted to four COVID‐19 treatment facilities in Bahrain between February 24, 2020 and July 31, 2020. All SCD patients with COVID‐19 were included and compared to a randomly selected sample of non‐SCD patients with COVID‐19. Data were collected from the medical records. Multivariate logistic regression models were used to control for confounders and estimate the effect of SCD on the outcomes. Results 1792 patients with COVID‐19 were included; 38 of whom were diagnosed with SCD as well. In the SCD group, one (2.6%) patient required NIV/HFNC, one (2.6%) required MV, and one (2.6%) death occurred. In comparison, 56 (3.2%) of the non‐SCD patients required NIV/HFNC, 47 (2.7%) required MV, and death occurred in 58 (3.3%) patients. Upon adjusting for confounders, SCD had an odds ratio of 1.847 (95% CI: 0.39–8.83; p = 0.442). Conclusion Our results indicate that SCD is not a risk factor for worse COVID‐19 outcomes in hospitalized patients.

IntroductionCoronavirus disease (COVID-19) caused by the novel coronavirus SARS-CoV-2 is an infectious disease which has evolved into a worldwide pandemic. Growing evidence suggests that individuals with pre-existing comorbidities are at higher risk of a more serious COVID-19 illness. Sickle cell disease (SCD) is an inherited hemoglobinopathy which increases the susceptibility to infections and as a consequent has higher risks of morbidity and mortality.The impact of COVID-19 on SCD patients could lead to further increase in disease severity and mortality. Studies that examine the effect of SCD on COVID-19 outcomes are lacking. This study aims to determine whether SCD is a risk factor for severe COVID-19 infection in regards to the requirement of non-invasive ventilation/high flow nasal cannula (NIV/HFNC), mechanical intubation (MV) or death.MethodsRetrospective cohort study which included COVID-19 patients admitted to four Ministry of Health COVID-19 treatment facilities in Bahrain during the period of 24, February 2020, to 31, July 2020. All SCD patients with COVID-19 were included and compared to randomly selected non-SCD patients with COVID-19. Data for the selected patients were collected from the medical records. Multivariate logistic regression models were used to control for confounders and estimate the effect of SCD on the outcomes.ResultsA total of 1,792 patients with COVID-19 were included; 38 of whom were diagnosed with SCD as well. In the SCD group, one (2.6%) patient required NIV/HFNC, one (2.6%) required MV and one (2.6%) death occurred. In comparison, 56 (3.2%) of the non-SCD patients required NIV/HFNC, 47 (2.7%) required MV and death occurred in 58 (3.3%) patients. Upon adjusting for confounders, SCD had an odds ratio of 1.847 (95% CI: 0.39 – 8.83; p=0.442).ConclusionOur results indicate that SCD is not a risk factor for worse disease outcomes in COVID-19 patients.

IntroductionNasopharyngeal (NP) swab is an invasive procedure that is difficult to perform in pediatric cases and those with special needs. On the other hand, saliva has been a proposed sample given the ease of collection, comfort and the ability to self-collect. The research project aims to study the presence of SARS-CoV-2 in the saliva of suspected COVID-19 patients in comparison to its presence in NP swabs.MethodologyA cross-sectional study was conducted in October 2020 in COVID19 clinic in the Bahrain Defense Force Hospital. The study compared the presence of SARS-CoV2 by PCR in saliva samples to nasopharyngeal samples. COVID-19 Clinic tests symptomatic, staff, close contacts and pre-operation patients.ResultsThe saliva PCR has shown a sensitivity of 72.9% (95% CI: 58.2% - 84.7%) and a specificity of 98.8% (95% CI: 97.8% - 99.4%). The PPV was 74.5% (95% CI 59.7% to 86.1%) and the NPV was 98.6% (95% CI 97.7% to 99.3%). Kappa coefficient of agreement between saliva and NP was 0.723 (95% CI 0.62 to 0.82, pConclusionThe findings of the study suggest that saliva samples have the potential to be used as a screening tool for SARS-CoV-2, especially in symptomatic individuals. This is especially important when it is difficult to collect NP samples. Saliva samples are however at risk of producing more false negative tests.

BackgroundHydroxychloroquine is an antimalarial drug that received worldwide news and media attention in the treatment of COVID-19 patients. This drug was used based on its antimicrobial and antiviral properties despite lack of definite evidence of clinical efficacy. In this study, we aim to assess the efficacy and safety of using Hydroxychloroquine in treatment of COVID-19 patients who are admitted in acute care hospitals in Bahrain.MethodologyWe conducted retrospective cohort study on a random sample of admitted COVID19 patients between 24 February and 31 July 2020. The study was conducted in four acute care COVID19 hospitals in Bahrain. Data was extracted from the medical records. The primary endpoint was the requirement of non-invasive ventilation, intubation or death. Secondary endpoint was length of hospitalization for survivors. Three methods of analysis were used to control for confounding factors: logistic multivariate regression, propensity score adjusted regression and matched propensity score analysis.ResultsA random sample of 1571 patients were included, 440 of which received HCQ (treatment group) and 1131 did not receive it (control group). Our results showed that HCQ did not have a significant effect on primary outcomes due to COVID-19 infection when compared to controls after adjusting for confounders (OR 1.43 95% CI 0.85 to 2.37, P value=0.17). Co-administration of azithromycin had no effect on primary outcomes (OR 2.7 95% CI 0.82 to 8.85 P value =0.10). HCQ was found to be associated with increased risk of hypoglycemia (OR 10.9 95% CI 1.72 - 69.49, P value =0.011) and diarrhea(OR 2.8, 95% CI 1.4-5.5, P value =0.003), but not QT prolongation(OR=1.92, 95% CI 0.95-3.9, P value =0.06) or cardiac arrhythmia.(OR=1.06, 95% CI 0.55-2.05, P value =0.85).ConclusionOur results showed no significant beneficial effect of using hydroxychloroquine on the outcome of COVID-19 patients. Moreover, the risk of hypoglycemia due to hydroxychloroquine would possess a significant risk for out of hospital use.

IntroductionCOVID 19 has been vastly spreading since December 2019 and the medical teams worldwide are doing their best to limit its spread. In the absence of a vaccine the best way to fight it is by detecting infected cases early and isolate them to prevent its spread. Therefore, a readily available, rapid, and cost-effective test with high specificity and sensitivity for early detection of COVID 19 is required. In this study, we are testing the diagnostic performance of a rapid antigen detection test in mildly symptomatic cases. (RADT).MethodsThe study included 4183 patients who were mildly symptomatic. A nasal sample for the rapid antigen test and a nasopharyngeal sample was taken from each patient. Statistical analysis was conducted to calculate the sensitivity, specificity, positive predictive value, negative predictive value and kappa coefficient of agreement.ResultsThe prevalence of COVID 19 in the study population was 17.5% (733/4183). The calculated sensitivity and specificity were 82.1% and 99.1% respectively. Kappa’s coefficient of agreement between the rapid antigen test and RT-PCR was 0.859 (p < 0.001). A stratified analysis was performed and it showed that the sensitivity of the test improved significantly with lowering the cutoff Ct value to 24.ConclusionThe results of the diagnostic assessment of nasal swabs in the RADT used in our study are promising regarding the potential benefit of using them as a screening tool in mildly symptomatic patients. The diagnostic ability was especially high in cases with high viral load. The rapid antigen test is intended to be used alongside RT-PCR and not replace it. RADT can be of benefit in reducing the use of PCR.

BackgroundConvalescent plasma (CP) therapy in COVID-19 disease has been suggested to improve clinical outcome in severe disease. This pilot study was designed to inform the design of a definitive phase 3 clinical trial.MethodsThis was a prospective, interventional and randomized open label pilot trial involving 40 patients with COVID-19 who were requiring oxygen therapy and who had radiological evidence of pneumonia. Twenty COVID-19 patients received two 200ml transfusions of convalescent patient CP over 24 hours were compared with 20 patients who received routine care alone. The primary outcome was the requirement for ventilation. The secondary outcomes were white blood cell count, lactate dehydrogenase (LDH), C-reactive protein (CRP), Troponin, Ferritin, D-Dimer, procalcitonin, mortality rate at 28 days.ResultsThe CP group were a higher risk group with higher ferritin levels (pConclusionThere were no significant differences in the primary or secondary outcome measures between CP and standard therapy though fewer patients required ventilation and for a shorter period of time. The study showed that CP therapy appears to be safe and it is feasible to perform a definitive phase 3 clinical trial using this study protocol.

Highlights • 2714 individuals underwent mandatory quarantine. • 136 individuals were SARS-CoV-2 positive on arrival of whom the majority (92) were asymptomatic. • A further 52 individuals became SARS-CoV-2 positive over a 14 day period. • 24 subjects found to be SARS-CoV-2 positive at day 14 remained asymptomatic until viral clearance. • Asymptomatic patients with COVID-19 were more prevalent than those exhibiting symptoms and are an infection reservoir., Background The frequency of asymptomatic SARS-CoV-2 infection with viral spread is unclear. Here, we investigated asymptomatic SARS-CoV-2 infection development and progression in subjects undergoing mandatory quarantine on airport arrival. Methods 2714 subjects were tested for SARS-CoV-2 and all were quarantined for 2 weeks. Viral retesting was undertaken on symptom development and routinely at 14 days if asymptomatic. Asymptomatic positive patients underwent viral testing every 2 days to determine viral clearance. Results 188/2714(6.9%) patients became SARS-CoV-2 positive. On arrival, 44/188(23.4%) testing positive were symptomatic and 92/188(48.9%) were asymptomatic (136/188 positive on arrival); all 92 patients remained asymptomatic and were retested every 2-days until viral clearance. 2526 quarantined subjects remained virus free at 14-days. Viral clearance did not differ between these symptomatic and asymptomatic patients (12.6 ± 1.0days and 12.1 ± 0.4days, respectively). Of the 52/188(27.7%) testing negative on arrival, 27/52 became positive and developed symptoms from day 2 to day 13 following arrival. 25/188(13.3%) subjects remained asymptomatic and tested positive at day 14; viral testing was undertaken every 2 days in these subjects, 24/188(12.8%) remained asymptomatic with viral clearance (9.4 ± 0.7days) less than those asymptomatic on arrival(p

IntroductionThe risk factors for transmission of SARS-CoV2 have been widely studied and it was evident that a population’s behavior has a direct effect on the risk of transmission. Public health measures and regulation are largely kept to control and direct these behaviors. In this study, we describe the change in transmission in SARS-CoV2 in relation to demographics before and after two major religious events: “Eid Alfitr” and “Ashura”MethodsThis is a national observational study conducted in Bahrain in September 2020 to compare the number and demographics of all newly diagnosed cases before and after Eid Alfitr (religious holiday) and Ashura religious event. A 10 day period before the event was compared to a 10 day period after the event by ten days. Data on the number of tests, number of new cases, their demographics (age, gender, nationality) and presence of symptoms were collected and analyzed.ResultsThere was significant increase in the number of COVID-19 cases after both Eid Alfitr (1997 more cases, with a 67% increase) and Ashura (4232 more cases with 2.19 times more cases). The majority of new cases after the religious events were found in local Bahrainis, from 472 cases to 2169 cases after Eid, and from 2201 to 6639 cases after Ashura. The rise was most notable in females (increased by 4.89 times after Eid and by 2.69 times after Ashura), children (increased by 4.69 times after Eid and by 5 times after Ashura) and elderly above the age of 60 years (increased by 5.7 times after Eid and by 3.23 times after Ashura).ConclusionIt is evident that religious events and holidays have important implications on the transmission of SARS-CoV2. This increased in transmission is related mainly to the behavior of the population in those days. Children, female, and elderly were the most affected categories due to these events. A thorough public health plan to limit the spread of the infection at these events should be planned and implemented ahead of time.