A Narrative Review of the Coronavirus Disease 2019 Response in the Kingdom of Bahrain.

Background: The Kingdom of Bahrain has reported more than 696,000 cases of coronavirus disease 2019 (COVID-19) and 1548 associated deaths as of December 26, 2022. Objectives: To better inform responses to future public health threats, this narrative review documents the challenges and responses to the COVID-19 pandemic in the Kingdom of Bahrain. Methods: A PubMed search was conducted focusing on severe acute respiratory syndrome or COVID-19 in Bahrain. Additional relevant references were also included from the authors' personal reference collections. Results: The search indicated that Bahrain achieved well-established control of the pandemic through robust public health measures, including an early, comprehensive vaccination program. Bahrain was among the first countries to grant emergency authorization for COVID-19 vaccines; as of December 2022, nearly 73% of the eligible population has been fully vaccinated, and approximately 60% has been boosted. Low case rates in recent months highlight Bahrain's successful response to the COVID-19 pandemic. Conclusions: Early organization, robust and systematic protective measures, and a comprehensive vaccination program were key components of the Kingdom's response to the pandemic; traveler quarantines and attempts to combat misinformation were of little or no benefit. These lessons provide guidance for future preparedness to minimize the public health impacts of another pandemic. (Curr Ther Res Clin Exp. 2024; XX:XXX-XXX).

Diversity of carbapenem-resistant Klebsiella pneumoniae ST14 and emergence of a subgroup with KL64 capsular locus in the Arabian Peninsula.

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.

COVID-19 and mucormycosis superinfection: the perfect storm.

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.

COVID-19 viral load not associated with disease severity: findings from a retrospective cohort study.

BACKGROUND: Being able to use COVID-19 RT-PCR Ct values as simple clinical markers of disease outcome or prognosis would allow for the easy and proactive identification and triaging of high-risk cases. This study's objective was thus to explore whether a correlation exists between COVID-19 viral loads, as indicated by RT-PCR Ct values, and disease severity, as indicated by respiratory indices. RESULTS: A multi-centre cross-sectional retrospective study was conducted, using data obtained from Bahrain's National COVID-19 Task force's centralised database. The study period ranged from May 2, 2020 to July 31, 2020. A multivariable logistic regression was used to assess for a correlation using data from a total of 1057 admitted COVID-19 cases. The covariates adjusted for included sex, age, presentation, and comorbidities. In our cohort, Ct value showed no statistical significance for an association with requirement for oxygenation on admission (Odds ratio 1.046; 95%CI 0.999 to 1.096, p = 0.054). CONCLUSION: Viral load, as indicated by Ct values, did not seem to be associated with requirement for oxygenation on admission in our cohort. We postulate however that time since onset of symptom may have acted as an unaccounted-for confounder. As such, RT-PCR Ct values may not be a useful prognostic clinical tool in isolation.

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

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.

Real world effectiveness of sotrovimab in preventing COVID-19-related hospitalisation or death in patients infected with Omicron BA.2.

BACKGROUND: Laboratory-based evidence indicates that neutralization of the BA.2 (Omicron) variant by sotrovimab is reduced versus previous SARS-CoV-2 variants. Since there is a lack of real-world data, we investigated whether sotrovimab has reduced clinical efficacy against the BA.2 variant. METHODS: We performed a prospective cohort study using real-world data from 1180 randomly-selected BA.2 variant-infected patients. Follow-up to study endpoints averaged 29 days. For mild cases (not requiring oxygen-supplementation), primary outcomes were requiring O2-supplementation, intensive care unit (ICU) admission or death. For moderate-to-severe COVID-19 cases (requiring oxygen-supplementation other than mechanical ventilation), the primary outcome was ICU admission or death. RESULTS: Patients in the sotrovimab group (n = 569) and control patients (n = 611) were included. Sotrovimab-treated patients versus controls had reduced risk of death (0.4% vs 6.4%, p < 0.001), need for oxygen supplementation (3.5% vs 12.8%, p < 0.001) and ICU admission (0.2% vs 4.9%, p < 0.001). The adjusted-odds ratio for developing any of these outcomes was 0.090 (95% CI 0.049-0.165, p < 0.001). Subgroup analysis of moderate-to-severe sotrovimab-treated patients versus controls revealed reduced mortality (17.7% vs 37.2%, p = 0.006) and ICU admission (0.0% vs 37.2%, p < 0.001). Adjusted-hazards ratio for death or ICU admission was 0.256 (95% CI 0.111-0.593, p < 0.001). CONCLUSION: Sotrovimab was effective in reducing COVID-19 progression risk in high-risk BA.2 variant-infected patients. This finding may alleviate concerns about its clinical efficacy.

Safety and efficacy of COVID-19 prime-boost vaccinations: Homologous BBIBP-CorV versus heterologous BNT162b2 boosters in BBIBP-CorV-primed individuals.

BACKGROUND: Booster vaccine doses against SARS-CoV-2 have been advocated to address evidence of waning immunity, breakthrough infection, and the emergence of immune-evasive variants. A heterologous prime-boost vaccine strategy may offer advantages over a homologous approach, but the safety and efficacy of this approach with the mRNA vaccine BNT162b2 (BNT: Pfizer) and inactivated BBIBP-CorV (BBIBT: Sinopharm) vaccines have not been studied. METHODS: We conducted a non-randomized, non-blinded phase II observational community trial acrossBahrain, investigating the reactogenic and immunogenic responseof participants who had previously received two doses of BBIBP, followed by a third booster dose of either BBIBP (homologous booster) or BNT (heterologous booster). Immunogenicity through serological statuswas determined at baseline and on the following 8thweek. Reactogenicity data (safety and adverse events) were collected throughout study period, in addition to participant-led electronic journaling. RESULTS: 305 participants (152 BBIBP and 153 BNT booster) were enrolled in the study,with 246 (127 BBIBP and 119 BNT booster) included in the final analysis. There was a significant increase in anti-SARS-CoV-2 antibody levels post booster administration in both groups; however, the heterologous BNT arm demonstrated a significantly larger mean increase in the level of spike (S) antigen-specific antibodies (32.7-fold increase versus 2.6, p < 0.0001) and sVNT neutralising antibodies (3.4-fold increase versus 1.8, p < 0.0001), whereas the homologous arm demonstrated a significant increase in the levels of nucleocapsid (N) antigen-specific antibodies (3.8-fold increase versus none). Non-serious adverse events (injection site pain, fever, and fatigue) were more commonly reported in the heterologous arm, but no serious adverse events occurred. CONCLUSION: Heterologous prime-boost vaccination with the mRNA BNT162b2 (Pfizer) vaccine in those who had received two doses of inactivated virus BBIBP-CorV (Sinopharm) vaccine demonstrated a more robust immune response against SARS-CoV-2 than the homologous BBIBP booster and appears safe and well tolerated. Clinical Trial Registry Number (ClinicalTrials.gov): NCT04993560.

COVID-19 Recovery Patterns Across Alpha (B.1.1.7) and Delta (B.1.617.2) Variants of SARS-CoV-2.

Background: B.1.1.7 (alpha) and B.1.617.2 (delta) variants of concern for SARS-CoV-2 have been reported to have differential infectivity and pathogenicity. Difference in recovery patterns across these variants and the interaction with vaccination status has not been reported in population-based studies. Objective: The objective of this research was to study the length of stay and temporal trends in RT-PCR cycle times (Ct) across alpha and delta variants of SARS-CoV-2 between vaccinated and unvaccinated individuals. Methods: Participants consisted of patients admitted to national COVID-19 treatment facilities if they had a positive RT-PCR test for SARS-CoV-2, and analysis of variants was performed (using whole genome sequencing). Information on vaccination status, age, sex, cycle times (Ct) for four consecutive RT-PCR tests conducted during hospital stay, and total length of hospital stay for each participant were ascertained from electronic medical records. Results: Patients infected with the delta variant were younger (mean age = 35years vs 39 years for alpha, p<0.001) and had lesser vaccination coverage (54% vs 72% for alpha, p<0.001). RT-PCR Ct values were similar for both variants at the baseline test; however by the fourth test, delta variant patients had significantly lower Ct values (27 vs 29, p=0.05). Length of hospital stay was higher in delta variant patients in vaccinated (3 days vs 2.9 days for alpha variant) as well as in unvaccinated patients (5.2 days vs 4.4 days for alpha variant, p<0.001). Hazards of hospital discharge after adjusting for vaccination status, age, and sex was higher for alpha variant infections (HR=1.2, 95% CI: 1.01-1.41, p=0.029). Conclusion: Patients infected with the delta variant of SARS-CoV-2 were found to have a slower recovery as indicated by longer length of stay and higher shedding of the virus compared to alpha variant infections, and this trend was consistent in both vaccinated and unvaccinated patients.

Epidemiological assessment of SARS-CoV-2 reinfection.

OBJECTIVES: SARS-CoV-2 vaccination has been shown to reduce infection severity; however, the reinfection frequency among unvaccinated, partially vaccinated, and fully vaccinated individuals remains unclear. This study aims to elucidate the rates of and factors associated with such occurrences. METHODS: This retrospective epidemiological report included 1362 COVID-19 reinfection cases in Bahrain between April 2020 and July 2021. We analyzed differences in disease severity and reinfection characteristics among various vaccination statuses: fully vaccinated, interrupted vaccination, one-dose vaccination, postreinfection vaccination, and unvaccinated. RESULTS: Reinfection cases increased from zero per month in April-June 2020 to a sharp peak of 579 in May 2021. A significantly larger proportion of reinfected individuals were male (60.3%, P <0.0001). Reinfection episodes were highest among those 30-39 years of age (29.7%). The fewest reinfection episodes occurred at 3-6 months after the first infection (20.6%) and most occurred ≥9 months after the initial infection (46.4%). Most individuals were asymptomatic during both episodes (35.7%). Reinfection disease severity was mild, with vaccinated patients less likely to have symptomatic reinfection (odds ratio 0.71, P = 0.004). Only 6.6% of reinfected patients required hospitalization. One death was recorded; the patient belonged to the unvaccinated group. CONCLUSION: Vaccine-induced immunity and previous infection with or without vaccination were effective in reducing reinfection disease severity.

Post-vaccination outcomes in association with four COVID-19 vaccines in the Kingdom of Bahrain.

With the emergence of new SARS-Cov2 variants, critical questions have arisen about: (1) the effectiveness of the available COVID-19 vaccines developed to protect against the original Wuhan (wild type) variant and (2) the magnitude and clinical consequences of post-vaccination infections in the context of the Delta variant of SARS-Cov2. While some "real world" experiences with various vaccines have been reported, to our knowledge, few have examined comparative outcomes of various vaccines in one country as new SARS-CoV-2 variants have emerged. Here we present an analysis of COVID-19 related outcomes from a national database in Bahrain, a country with a total population of 1.51 million, where four vaccines were deployed (total vaccinated = 1,003,960 adults): AstraZeneca (AZ/Covishield), Pfizer/BioNtech, Sinopharm and Sputnik V. We compare the four vaccines, based on the following post-vaccination outcomes: SARS-CoV-2 infections, hospitalisations, ICU admissions and deaths, compared to unvaccinated individuals. We conclude that the four vaccines used in Bahrain were effective in significantly reducing all four COVID-19 related outcomes compared to unvaccinated individuals, prior to, and during the period when the Delta variant predominated in the country. However, compared to the three other vaccines, individuals vaccinated with Sinopharm vaccine had a higher risk of post-vaccination infections, hospitalisations and ICU admissions (e.g., 6.94%, 2.24%, 1.99% and 1.52% of COVID-19 cases of Sinopharm, Sputnik V, Pfizer and Covishield recipients, respectively, required hospitalisation versus 13.66% of COVID-19 cases among unvaccinated individuals); however, given the confounding factors, this needs to be confirmed by further studies. We find no evidence of biased selection for any vaccine, but note waning protection of the Pfizer/BioNtech vaccine during the January to June 2021 period in the age > 60 y cohort; however, this cannot be distinguished from the overall fall in hospitalisations overall. Our findings support the value of vaccination in preventing COVID-19 related outcomes, provide real world estimates on the outcomes and frequencies of post-vaccination infections for the four vaccines, which may inform vaccine selection in the context of the Delta variant across the globe.

Randomized controlled trial of favipiravir, hydroxychloroquine, and standard care in patients with mild/moderate COVID-19 disease.

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.

Is glucose-6-phosphatase dehydrogenase deficiency associated with severe outcomes in hospitalized COVID-19 patients?

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.

First Report of Acute Myocarditis Post-Pfizer-BioNTech COVID-19 Vaccination in the Kingdom of Bahrain.

We present a case of a 24-year-old male patient who presented to our institution five days after receiving his first dose of Pfizer-BioNTech vaccine to rule out acute coronary syndrome due to chest pain along with troponin increase and ECG changes. Acute coronavirus disease 2019 (COVID-19) infection was excluded based on a negative real-time reverse transcription-polymerase chain reaction (RT-PCR) test of specimens acquired using nasopharyngeal swabs for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and all other viral serologies were found to be negative. Coronary angiogram showed normal coronaries, and the presence of late gadolinium enhancement, which is indicative of myocarditis, was identified using cardiac magnetic resonance imaging (MRI). Our case report raises concern that the COVID-19 vaccine may cause myocarditis as a rare side effect.

Vaccine trials during a pandemic: potential approaches to ethical dilemmas.

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.

Time Till Viral Clearance of Severe Acute Respiratory Syndrome Coronavirus 2 Is Similar for Asymptomatic and Non-critically Symptomatic Individuals.

Despite the modeled estimations of the burden of asymptomatic spread, the duration of viral positivity and infectiousness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains understudied. The objective of the present study was to estimate and compare the time till viral clearance of SARS-CoV-2 in asymptomatic and non-critical symptomatic individuals. We studied 184 SARS-CoV-2-positive participants, of whom 145 were asymptomatic. Our analysis uncovered that time till viral negativity is similar for subclinical [median time till viral clearance: 11 days, interquartile range (IQR): 8, 14] and overt infections (median: 11 days, IQR: 9, 14) after controlling for age and sex. This has implications in understanding the period of infectivity for SARS-CoV-2 in order to plan adequate public health measures to control the community spread.

Evaluation of Rapid Antigen Tests Using Nasal Samples to Diagnose SARS-CoV-2 in Symptomatic Patients.

INTRODUCTION: The best way to mitigate an outbreak besides mass vaccination is via early detection and isolation of infected cases. As such, a rapid, cost-effective test for the early detection of COVID-19 is required. METHODS: The study included 4,183 mildly symptomatic patients. A nasal and nasopharyngeal sample obtained from each patient was analyzed to determine the diagnostic ability of the rapid antigen detection test (RADT, nasal swab) in comparison with the current gold-standard (RT-PCR, nasopharyngeal swab). RESULTS: The calculated sensitivity and specificity of the RADT was 82.1 and 99.1%, respectively. Kappa's coefficient of agreement between the RADT and RT-PCR was 0.859 (p < 0.001). Stratified analysis showed that the sensitivity of the RADT improved significantly when lowering the cut-off RT-PCR Ct value to 24. CONCLUSION: Our study's results support the potential use of nasal swab RADT as a screening tool in mildly symptomatic patients, especially in patients with higher viral loads.

Association between RT-PCR Ct values and COVID-19 new daily cases: a multicenter cross-sectional study.

Proactive prediction of the epidemiologic dynamics of viral diseases and outbreaks of the type of COVID-19 has remained a difficult pursuit for scientists, public health researchers, and policymakers. It is unclear whether RT-PCR Cycle Threshold (Ct) values of COVID-19 - or any other virus - as indicator of viral load, could represent a possible predictor for underlying epidemiologic changes on a population level. The study objective is thus to investigate whether population-wide changes in SARS-CoV-2 RT-PCR Ct values over time are associated with the daily fraction of positive COVID-19 tests. In addition, this study analyses the factors that could influence RT-PCR Ct values. A retrospective cross-sectional study was conducted on 63,879 patients from May 4, 2020 to September 30, 2020, in all COVID-19 facilities in the Kingdom of Bahrain. Data collected included number of tests and newly diagnosed cases, as well as Ct values, age, sex nationality, and symptomatic status. Ct values were found to be negatively and very weakly correlated with the fraction of daily positive tests in the population r = -0.06 (CI 95%: -0.06; -0.05; p=0.001). The R-squared for the regression model (adjusting for age and number of daily tests) showed an accuracy of 45.3%. Ct Values showed an association with nationality (p=0.012). After the stratification, the association between Ct values and the fraction of daily positive cases was only maintained for the female sex and Bahraini-nationality. Symptomatic presentation was significantly associated with lower Ct values (higher viral loads). Ct values do not show any correlation with age (p=0.333) or sex (p=0.522). We report one of the first and largest studies to investigate the epidemiologic associations of Ct values with COVID-19. Although changes in Ct values showed a moderate association with daily cases, our results indicate that it may not be as predictive within a simple model. More population studies and models from global cohorts are necessary.

The effect of ABO blood group and antibody class on the risk of COVID-19 infection and severity of clinical outcomes.

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.

The Efficacy and Safety of Hydroxychloroquine in Patients with COVID-19: A Multicenter National Retrospective Cohort.

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.

Quarantining arriving travelers in the era of COVID-19: balancing the risk and benefits a learning experience from Bahrain.

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.