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A wide variety of inflammatory mediators, mainly cytokines and chemokines, are induced during SARS CoV-2 infection. Among these proinflammatory mediators, chemokines tend to play a pivotal role in virus-mediated immunopathology. The C-C chemokine ligand 2 (CCL2), also known as monocyte chemoattractant protein-1 (MCP-1) is a potent proinflammatory cytokine and strong chemoattractant of monocytes, macrophages and CD4+ T cells bearing C-C chemokine receptor type-2 (CCR2). Besides controlling immune cell trafficking, CCL2 is also involved in multiple pathophysiological processes including systemic hyperinflammation associated cytokine release syndrome (CRS), organ fibrosis and blood coagulation. These pathological features are commonly manifested in severe and fatal cases of COVID-19. Given the crucial role of CCL2 in COVID-19 pathogenesis, the CCL2:CCR2 axis may constitute a potential therapeutic target to control virus-induced hyperinflammation and multi-organ dysfunction. Herein we describe recent advances on elucidating the role of CCL2 in COVID-19 pathogenesis, prognosis, and a potential target of anti-inflammatory interventions., (© 2024 The Author(s). Reviews in Medical Virology published by John Wiley & Sons Ltd.)

Pulmonary infections contribute substantially to emergency department (ED) visits, posing a considerable health burden. Lower respiratory tract infections are prevalent, particularly among the elderly, constituting a significant percentage of infectious disease-related ED visits. Timely recognition and treatment are crucial to mitigate morbidity and mortality. Imaging studies, primarily chest radiographs and less frequently CT chests, play a pivotal role in diagnosis. This article aims to elucidate the imaging patterns of both common and rare pulmonary infections (bacterial and viral) in the post COVID-19 era, emphasizing the importance of recognizing distinct radiological manifestations. The integration of clinical and microbiological evidence aids in achieving accurate diagnoses, and guiding optimal therapeutic interventions. Despite potential overlapping manifestations, a nuanced understanding of radiological patterns, coupled with comprehensive clinical and microbiological information, enhances diagnostic precision in majority cases., (© 2024. The Author(s), under exclusive licence to American Society of Emergency Radiology (ASER).)

Objective: This study investigated the association between Coronavirus Disease 2019 mRNA vaccination and stroke in Qatar., Methods: Between December 1, 2020, and April 11, 2023, a matched case-control study was conducted to investigate the association between 3036 acute stroke cases and 3036 controls drawn from the entire population of Qatar., Results: The adjusted odds ratio (aOR) for vaccination among cases compared to controls was 0.87 (95% CI: 0.75-1.00). The aOR was 0.74 (95% CI: 0.45-1.23) for a single vaccine dose, 0.87 (95% CI: 0.73-1.04) for primary-series vaccination (two doses), and 0.91 (95% CI: 0.66-1.25) for booster vaccination (three or more doses). The aOR was 0.87 (95% CI: 0.72-1.04) for BNT162b2 and 0.86 (95% CI: 0.67-1.11) for mRNA-1273. Subgroup analyses, considering different durations since vaccination, also demonstrated no association. Subgroup analyses based on nationality, age, number of coexisting conditions, or prior infection status yielded similar results. Subgroup analysis, stratified by stroke type, suggested an association between vaccination and cerebral venous sinus thrombosis (aOR of 2.50 [95% CI: 0.97-6.44]), but it did not reach statistical significance., Conclusion: There was no evidence of an increased risk of stroke following vaccination, both in the short term and in the long term, extending beyond a year after receiving the vaccine., Competing Interests: Declarations of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Dr. Butt has received institutional grant funding from Gilead Sciences unrelated to the work presented in this paper. Otherwise, we declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: To investigate the occurrence of chorioretinopathy post-COVID-19, emphasizing demographic characteristics, medication history, clinical presentation, diagnostic evaluation, and treatment approaches, with a specific focus on the role of corticosteroid use., Methods: Our protocol was registered prospectively on PROSPERO (CRD42023457712). A systematic search of databases (PubMed, Cochrane, WOS, Scopus) from November 2020 to August 2023 were performed to identify any original research reporting chorioretinopathy in COVID-19 patients. Data extraction included patient demographics, COVID-19 timeline, medication history, symptoms, diagnostic tests, and treatment outcomes. We used Joanna Briggs Institute (JBI) critical appraisal tool to assess the quality of our included studies., Results: We identified seven case reports and two case series including 10 patients, six females and four males (mean age 36.5 years), who exhibited chorioretinopathy after COVID-19. Onset varied from 6 days to three months post-infection (average = 24.3 days). Seven patients (70%) had a history of corticosteroid use during COVID-19 treatment. Symptoms included visual loss, blurred vision, and deterioration. Diagnostic assessments revealed central serous chorioretinopathy in seven patients (70%) and punctate inner choroidopathy in two (20%). Treatment approaches varied, with corticosteroid discontinuation leading to symptom improvement, while two patients were treated with corticosteroids. Five patients who discontinued corticosteroids were reported to have improvement in visual acuity, two of them changed to 20/25 after being 20/40, two changed to 6/6, and one changed to 20/20, while the visual acuity in the sixth patient was not reported. Regarding the two patients who were treated with corticosteroids, visual acuity was reported in one case only and it improved to 20/20., Conclusion: This systematic review states the prevalence and potential association between chorioretinopathy, and corticosteroid use in the context of COVID-19. This relation is still unclear because of the relief of symptoms in some cases after corticosteroid discontinuation, while two other cases were treated with corticosteroids and their symptoms improved.

Background: In randomized controlled trials, Nirmatrelvir/ritonavir (NMV/r) and Molnupiravir (MPV) reduced the risk of severe/fatal COVID-19 disease. Real-world data are limited, particularly studies directly comparing the two agents., Methods: Using the VA National COVID-19 database, we identified previously uninfected, non-hospitalized individuals with COVID-19 with ≥1 risk factor for disease progression who were prescribed either NMV/r or MPV within 3 days of a positive test. We used inverse probability of treatment weights (IPTW) to account for providers' preferences for a specific treatment. Absolute risk difference (ARD) with 95% confidence intervals were determined for those treated with NMV/r vs. MPV. The primary outcome was hospitalization or death within 30 days of treatment prescription using the IPTW approach. Analyses were repeated using propensity-score matched groups., Results: Between January 1 and November 30, 2022, 9,180 individuals were eligible for inclusion (6,592 prescribed NMV/r; 2,454 prescribed MPV). The ARD for hospitalization/death for NMV/r vs MPV was -0.25 (95% CI -0.79 to 0.28). There was no statistically significant difference in ARD among strata by age, race, comorbidities, or symptoms at baseline. Kaplan-Meier curves did not demonstrate a difference between the two groups (p-value = 0.6). Analysis of the propensity-score matched cohort yielded similar results (ARD for NMV/r vs. MPV -0.9, 95% CI -2.02 to 0.23). Additional analyses showed no difference for development of severe/critical/fatal disease by treatment group., Conclusion: We found no significant difference in short term risk of hospitalization or death among at-risk individuals with COVID-19 treated with either NMV/r or MPV., Competing Interests: Dr. Butt has received investigator initiated grant funding from Gilead Sciences and Merck and Company (to the institution, Veterans Health Foundation of Pittsburgh) which are unrelated to the work presented here., (Copyright: © 2024 Butt et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The COVID-19 pandemic has highlighted the need to use infection testing databases to rapidly estimate effectiveness of prior infection in preventing reinfection ($P{E}_S$) by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Mathematical modeling was used to demonstrate a theoretical foundation for applicability of the test-negative, case-control study design to derive $P{E}_S$. Apart from the very early phase of an epidemic, the difference between the test-negative estimate for $P{E}_S$ and true value of $P{E}_S$ was minimal and became negligible as the epidemic progressed. The test-negative design provided robust estimation of $P{E}_S$ and its waning. Assuming that only 25% of prior infections are documented, misclassification of prior infection status underestimated $P{E}_S$, but the underestimate was considerable only when > 50% of the population was ever infected. Misclassification of latent infection, misclassification of current active infection, and scale-up of vaccination all resulted in negligible bias in estimated $P{E}_S$. The test-negative design was applied to national-level testing data in Qatar to estimate $P{E}_S$ for SARS-CoV-2. $P{E}_S$ against SARS-CoV-2 Alpha and Beta variants was estimated at 97.0% (95% CI, 93.6-98.6) and 85.5% (95% CI, 82.4-88.1), respectively. These estimates were validated using a cohort study design. The test-negative design offers a feasible, robust method to estimate protection from prior infection in preventing reinfection., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Background: Vaccines were developed and deployed to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to characterize patterns in the protection provided by the BNT162b2 and mRNA-1273 mRNA vaccines against a spectrum of SARS-CoV-2 infection symptoms and severities., Methods: A national, matched, test-negative, case-control study was conducted in Qatar between January 1 and December 18, 2021, utilizing a sample of 238,896 PCR-positive tests and 6,533,739 PCR-negative tests. Vaccine effectiveness was estimated against asymptomatic, symptomatic, severe coronavirus disease 2019 (COVID-19), critical COVID-19, and fatal COVID-19 infections. Data sources included Qatar's national databases for COVID-19 laboratory testing, vaccination, hospitalization, and death., Results: Effectiveness of two-dose BNT162b2 vaccination was 75.6% (95% CI: 73.6-77.5) against asymptomatic infection and 76.5% (95% CI: 75.1-77.9) against symptomatic infection. Effectiveness against each of severe, critical, and fatal COVID-19 infections surpassed 90%. Immediately after the second dose, all categories-namely, asymptomatic, symptomatic, severe, critical, and fatal COVID-19-exhibited similarly high effectiveness. However, from 181 to 270 days post-second dose, effectiveness against asymptomatic and symptomatic infections declined to below 40%, while effectiveness against each of severe, critical, and fatal COVID-19 infections remained consistently high. However, estimates against fatal COVID-19 often had wide 95% confidence intervals. Analogous patterns were observed in three-dose BNT162b2 vaccination and two- and three-dose mRNA-1273 vaccination. Sensitivity analyses confirmed the results., Conclusion: A gradient in vaccine effectiveness exists and is linked to the symptoms and severity of infection, providing higher protection against more symptomatic and severe cases. This gradient intensifies over time as vaccine immunity wanes after the last vaccine dose. These patterns appear consistent irrespective of the vaccine type or whether the vaccination involves the primary series or a booster., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: The global healthcare burden of COVID-19 pandemic has been unprecedented with a high mortality. Metabolomics, a powerful technique, has been increasingly utilized to study the host response to infections and to understand the progression of multi-system disorders such as COVID-19. Analysis of the host metabolites in response to SARS-CoV-2 infection can provide a snapshot of the endogenous metabolic landscape of the host and its role in shaping the interaction with SARS-CoV-2. Disease severity and consequently the clinical outcomes may be associated with a metabolic imbalance related to amino acids, lipids, and energy-generating pathways. Hence, the host metabolome can help predict potential clinical risks and outcomes., Methods: In this prospective study, using a targeted metabolomics approach, we studied the metabolic signature in 154 COVID-19 patients (males=138, age range 48-69 yrs) and related it to disease severity and mortality. Blood plasma concentrations of metabolites were quantified through LC-MS using MxP Quant 500 kit, which has a coverage of 630 metabolites from 26 biochemical classes including distinct classes of lipids and small organic molecules. We then employed Kaplan-Meier survival analysis to investigate the correlation between various metabolic markers, disease severity and patient outcomes., Results: A comparison of survival outcomes between individuals with high levels of various metabolites (amino acids, tryptophan, kynurenine, serotonin, creatine, SDMA, ADMA, 1-MH and carnitine palmitoyltransferase 1 and 2 enzymes) and those with low levels revealed statistically significant differences in survival outcomes. We further used four key metabolic markers (tryptophan, kynurenine, asymmetric dimethylarginine, and 1-Methylhistidine) to develop a COVID-19 mortality risk model through the application of multiple machine-learning methods., Conclusions: Metabolomics analysis revealed distinct metabolic signatures among different severity groups, reflecting discernible alterations in amino acid levels and perturbations in tryptophan metabolism. Notably, critical patients exhibited higher levels of short chain acylcarnitines, concomitant with higher concentrations of SDMA, ADMA, and 1-MH in severe cases and non-survivors. Conversely, levels of 3-methylhistidine were lower in this context., Competing Interests: Authors TS, OJ, RA, and A-NE were employed by the Hamad Medical Corporation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Abdallah, Doudin, Sulaiman, Jamil, Arif, Sada, Yassine, Elrayess, Elzouki, Emara, Thillaiappan and Cyprian.)

This study evaluated the potential for antibody-dependent enhancement (ADE) in serum samples from patients exposed to Middle East respiratory syndrome coronavirus (MERS-CoV). Furthermore, we evaluated the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination on ADE in individuals with a MERS infection history. We performed ADE assay in sera from MERS recovered and SARS-CoV-2-vaccinated individuals using BHK cells expressing FcgRIIa, SARS-CoV-2, and MERS-CoV pseudoviruses (PVs). Further, we analyzed the association of ADE to serum IgG levels and neutralization. Out of 16 MERS patients, nine demonstrated ADE against SARS-CoV-2 PV, however, none of the samples demonstrated ADE against MERS-CoV PV. Furthermore, out of the seven patients exposed to SARS-CoV-2 vaccination after MERS-CoV infection, only one patient (acutely infected with MERS-CoV) showed ADE for SARS-CoV-2 PV. Further analysis indicated that IgG1, IgG2, and IgG3 against SARS-CoV-2 S1 and RBD subunits, IgG1 and IgG2 against the MERS-CoV S1 subunit, and serum neutralizing activity were low in ADE-positive samples. In summary, samples from MERS-CoV-infected patients exhibited ADE against SARS-CoV-2 and was significantly associated with low levels of neutralizing antibodies. Subsequent exposure to SARS-CoV-2 vaccination resulted in diminished ADE activity while the PV neutralization assay demonstrated a broadly reactive antibody response in some patient samples., (© 2024 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Background: Priming with ChAdOx1 followed by heterologous boosting is considered in several countries. Nevertheless, analyses comparing the immunogenicity of heterologous booster to homologous primary vaccination regimens and natural infection are lacking. In this study, we aimed to conduct a comparative assessment of the immunogenicity between homologous primary vaccination regimens and heterologous prime-boost vaccination using BNT162b2 or mRNA-1273., Methods: We matched vaccinated naïve (VN) individuals (n = 673) with partial vaccination (n = 64), primary vaccination (n = 590), and primary series plus mRNA vaccine heterologous booster (n = 19) with unvaccinated naturally infected (NI) individuals with a documented primary SARS-CoV-2 infection (n = 206). We measured the levels of neutralizing total antibodies (NTAbs), total antibodies (TAbs), anti-S-RBD IgG, and anti-S1 IgA titers., Results: Homologous primary vaccination with ChAdOx1 not only showed less potent NTAb, TAb, anti-S-RBD IgG, and anti-S1 IgA immune responses compared to primary BNT162b2 or mRNA-1273 vaccination regimens (p < 0.05) but also showed ~3-fold less anti-S1 IgA response compared to infection-induced immunity (p < 0.001). Nevertheless, a heterologous booster led to an increase of ~12 times in the immune response when compared to two consecutive homologous ChAdOx1 immunizations. Furthermore, correlation analyses revealed that both anti-S-RBD IgG and anti-S1 IgA significantly contributed to virus neutralization among NI individuals, particularly in symptomatic and pauci-symptomatic individuals, whereas among VN individuals, anti-S-RBD IgG was the main contributor to virus neutralization., Conclusion: The results emphasize the potential benefit of using heterologous mRNA boosters to increase antibody levels and neutralizing capacity particularly in patients who received primary vaccination with ChAdOx1., (© 2024 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Background: The world has witnessed one of the largest pandemics, dubbed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of December 2020, the USA alone reported 98,948 cases of coronavirus disease 2019 (COVID-19) infection during pregnancy, with 109 related maternal deaths. Current evidence suggests that unvaccinated pregnant women infected with SARS-CoV-2 are at a higher risk of experiencing complications related to COVID-19 compared to nonpregnant women. This review aimed to provide healthcare workers and non-healthcare workers with a comprehensive overview of the available information regarding the efficacy of vaccines in pregnant women., Summary: We performed a systematic review and meta-analysis following PRISMA guidelines. The search through the database for articles published between December 2019 and October 2021 was performed. A comprehensive search was performed in PubMed, Scopus, and EMBASE databases for research publications published between December 2019 and October 2021. We focused on original research, case reports, case series, and vaccination side effect by authoritative health institutions. Phrases used for the Medical Subject Heading [MeSH] search included ("COVID-19" [MeSH]) or ("Vaccine" [MeSH]) and ("mRNA" [MeSH]) and ("Pregnant" [MeSH]). Eleven studies were selected and included, with a total of 46,264 pregnancies that were vaccinated with mRNA-containing lipid nanoparticle vaccine from Pfizer/BioNTech and Moderna during pregnancy. There were no randomized trials, and all studies were observational (prospective, retrospective, and cross-sectional). The mean maternal age was 32.2 years, and 98.7% of pregnant women received the Pfizer COVID-19 vaccination. The local and systemic adverse effects of the vaccination in pregnant women were analyzed and reported. The local adverse effects of the vaccination (at least 1 dose) such as local pain, swelling, and redness were reported in 32%, 5%, and 1%, respectively. The systemic adverse effects such as fatigue, headaches, new onset or worsening of muscle pain, chills, fever, and joint pains were also reported in 25%, 19%, 18%, 12%, 11%, and 8%, respectively. The average birthweight was 3,452 g. Among these pregnancies, 0.03% were stillbirth and 3.68% preterm (&lt;37 weeks) births., Key Messages: The systemic side effect profile after administering the COVID-19 mRNA vaccine to pregnant women was similar to that in nonpregnant women. Maternal and fetal morbidity and mortality were lowered with the administration of either one or both the doses of the mRNA COVID-19 vaccination., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Objectives: We assessed short-, medium-, and long-term all-cause mortality risks after a primary SARS-CoV-2 infection., Methods: A national, matched, retrospective cohort study was conducted in Qatar to assess risk of all-cause mortality in the national SARS-CoV-2 primary infection cohort compared with the national infection-naïve cohort. Associations were estimated using Cox proportional-hazards regression models. Analyses were stratified by vaccination status and clinical vulnerability status., Results: Among unvaccinated persons, within 90 days after primary infection, the adjusted hazard ratio (aHR) comparing mortality incidence in the primary-infection cohort with the infection-naïve cohort was 1.19 (95% confidence interval 1.02-1.39). aHR was 1.34 (1.11-1.63) in persons more clinically vulnerable to severe COVID-19 and 0.94 (0.72-1.24) in those less clinically vulnerable. Beyond 90 days after primary infection, aHR was 0.50 (0.37-0.68); aHR was 0.41 (0.28-0.58) at 3-7 months and 0.76 (0.46-1.26) at ≥8 months. The aHR was 0.37 (0.25-0.54) in more clinically vulnerable persons and 0.77 (0.48-1.24) in less clinically vulnerable persons. Among vaccinated persons, mortality incidence was comparable in the primary-infection versus infection-naïve cohorts, regardless of clinical vulnerability status., Conclusions: COVID-19 mortality was primarily driven by an accelerated onset of death among individuals who were already vulnerable to all-cause mortality, but vaccination prevented these accelerated deaths., Competing Interests: Declaration of competing interests Dr. Butt has received institutional grant funding from Gilead Sciences unrelated to the work presented in this paper. The remaining authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: There is debate over whether physical attendance at school affects the spread of the SARS-CoV-2 pandemic., Methods: A cohort of personnel from several schools in Qatar provided nasopharyngeal swabs (NPS) for SARS-CoV-2 RT-PCR and rapid antigen testing. Each of them was monitored for infection until February 2022., Results: In total, 3,241 employees gave samples for analysis. Prior to the start of the 2020-2021 academic year (Group I), 3.49% of samples tested positive for SARS-CoV-2. Most of the positive PCR results were from male, senior, non-teaching staff members. Only 110 (3.39%) employees who had enrolled in face-to-face instruction before the B.1.1.7 variant's emergence (Group II), 238 (7.34%) after the B.1.1.7 variant's emergence (Group III), and 410 (12.65%) after the introduction of the Omicron variant (Group IV) had reported infection by PCR test. Most people who tested positive by PCR after enrolling in school were young, female teachers. In the Cox Proportional-Hazards Model, exposure to a confirmed case, the presence of symptoms in the two weeks prior to exposure in all groups-young age in Groups II and III, male gender in Groups I and IV, shared housing in Group III, and the presence of comorbidities in Groups II and III independently predicted SARS-CoV-2 infection in school staff., Conclusion: Critical information about the risk of SARS-CoV-2 infection in school workers during the whole pandemic is provided by our study. School operations in Qatar were made safer through initial and ongoing screenings, as well as widespread vaccination of school personnel., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Alishaq et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To estimate the real-world effectiveness of sotrovimab against severe, critical, or fatal COVID-19 in Qatar at a time in which most SARS-CoV-2 incidences occurred due to the BA.2 Omicron subvariant., Methods: We conducted a matched case-control study among all individuals eligible for sotrovimab treatment per United States Food and Drug Administration guidelines in the resident population of Qatar. The odds of progression to severe forms of COVID-19 were compared in cases (treatment group) versus controls (eligible patients who opted not to receive the treatment). Subgroup analyses were conducted., Results: A total of 3364 individuals were eligible for sotrovimab treatment during the study period, of whom 519 individuals received the treatment, whereas the remaining 2845 constituted the controls. The adjusted odds ratio of disease progression to severe, critical, or fatal COVID-19 comparing the treatment group to the control group was 2.67 (95% confidence interval 0.60-11.91). In the analysis including only the subgroup of patients at higher risk of severe forms of COVID-19, the adjusted odds ratio was 0.65 (95% confidence interval 0.17-2.48)., Conclusion: There was no evidence for a protective effect of sotrovimab in reducing COVID-19 severity in a setting dominated by the BA.2 subvariant., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In 2021, Qatar experienced considerable incidence of SARS-CoV-2 infection that was dominated sequentially by the Alpha, Beta, and Delta variants. Using the cycle threshold (Ct) value of an RT-qPCR-positive test to proxy the inverse of infectiousness, we investigated infectiousness of SARS-CoV-2 infections by variant, age, sex, vaccination status, prior infection status, and reason for testing in a random sample of 18,355 RT-qPCR-genotyped infections. Regression analyses were conducted to estimate associations with the Ct value of RT-qPCR-positive tests. Compared to Beta infections, Alpha and Delta infections demonstrated 2.56 higher Ct cycles (95% CI: 2.35-2.78), and 4.92 fewer cycles (95% CI: 4.67- 5.16), respectively. The Ct value declined gradually with age and was especially high for children <10 years of age, signifying lower infectiousness in small children. Children <10 years of age had 2.18 higher Ct cycles (95% CI: 1.88-2.48) than those 10-19 years of age. Compared to unvaccinated individuals, the Ct value was higher among individuals who had received one or two vaccine doses, but the Ct value decreased gradually with time since the second-dose vaccination. Ct value was 2.07 cycles higher (95% CI: 1.42-2.72) for those with a prior infection than those without prior infection. The Ct value was lowest among individuals tested because of symptoms and was highest among individuals tested as a travel requirement. Delta was substantially more infectious than Beta. Prior immunity, whether due to vaccination or prior infection, is associated with lower infectiousness of breakthrough infections, but infectiousness increases gradually with time since the second-dose vaccination., Competing Interests: AB has received institutional grant funding from Gilead Sciences unrelated to the work presented in this paper. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Qassim, Hasan, Tang, Chemaitelly, Ayoub, Yassine, Al-Khatib, Smatti, Abdul-Rahim, Nasrallah, Al-Kuwari, Al-Khal, Coyle, Gillani, Kaleeckal, Shaik, Latif, Al-Kuwari, Jeremijenko, Butt, Bertollini, Al-Romaihi, Al-Thani and Abu-Raddad.)

Background: Breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections after vaccination have been reported. Outcomes among persons with breakthrough infection are poorly understood., Methods: We identified all veterans with a confirmed SARS-CoV-2 infection >14 days after the second dose of an mRNA vaccine between 15 December 2020 and 30 June 2021 and propensity score-matched unvaccinated controls with SARS-CoV-2 infection. The primary outcome was severe/critical disease, defined as admission to an intensive care unit, need for mechanical ventilation, or death within 28 days of diagnosis or during index hospitalization., Results: Among 502 780 vaccinated and 599 974 unvaccinated persons, there were 2332 (0.5%) breakthrough infections in the vaccinated group and 40 540 (6.8%) infections in the unvaccinated group over a follow-up period of 69 083 person-days in each group. Among these groups, we identified 1728 vaccinated persons with breakthrough infection (cases) and 1728 propensity score-matched unvaccinated controls with infection. Among the former, 95 (5.5%) persons met the criteria for severe/critical disease, while 200 (11.6%) persons met the criteria among the latter group. The incidence rate for severe/critical disease per 1000 person-days (95% confidence interval [CI]) was .55 (.45-.68) among vaccinated persons with breakthrough infection and 1.22 (1.07-1.41) among the unvaccinated matched controls who developed infection (P < .0001). Risk was higher; the hazard ratio (95% CI) with increasing age per 10-year increase was 1.25 (1.11-1.41); for those with >4 comorbidities, it was 2.85 (1.49-5.43), while being vaccinated was associated with strong protection against severe/critical disease (HR, 0.41; 95% CI: .32-.52)., Conclusions: The rate of severe/critical disease is higher among older persons and those with >4 comorbidities but lower among fully vaccinated persons with breakthrough infection compared with unvaccinated controls who develop infection., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Beta (B.1.351)-variant coronavirus disease 2019 (COVID-19) disease was investigated in Qatar. Compared with the Alpha (B.1.1.7) variant, odds (95% confidence interval) of progressing to severe disease, critical disease, and COVID-19-related death were 1.24-fold (1.11-1.39), 1.49-fold (1.13-1.97), and 1.57-fold (1.03-2.43) higher, respectively, for the Beta variant., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

SARS-CoV-2 Omicron BA.1 and BA.2 subvariants are genetically divergent. We conducted a matched, test-negative, case-control study to estimate duration of protection of the second and third/booster doses of mRNA COVID-19 vaccines against BA.1 and BA.2 infections in Qatar. BNT162b2 effectiveness was highest at 46.6% (95% CI: 33.4-57.2%) against symptomatic BA.1 and at 51.7% (95% CI: 43.2-58.9%) against symptomatic BA.2 infections in the first three months after the second dose, but declined to ~10% or below thereafter. Effectiveness rebounded to 59.9% (95% CI: 51.2-67.0%) and 43.7% (95% CI: 36.5-50.0%), respectively, in the first month after the booster dose, before declining again. Effectiveness against COVID-19 hospitalization and death was 70-80% after the second dose and >90% after the booster dose. mRNA-1273 vaccine protection showed similar patterns. mRNA vaccines provide comparable, moderate, and short-lived protection against symptomatic BA.1 and BA.2 Omicron infections, but strong and durable protection against COVID-19 hospitalization and death., (© 2022. The Author(s).)

Numerous studies demonstrate parallels between CVD, type 2 diabetes mellitus (T2DM) and COVID-19 pathology, which accentuate pre-existing complications in patients infected with COVID-19 and potentially exacerbate the infection course. Antidiabetic drugs such as sodium-glucose transporter-2 (SGLT-2) inhibitors have garnered substantial attention recently due to their efficacy in reducing the severity of cardiorenal disease. The effect of SGLT-2 inhibitors in patients with COVID-19 remains unclear particularly since SGLT-2 inhibitors contribute to altering the RAAS cascade activity, which includes ACE-2, the major cell entry receptor for SARS-CoV2. A study, DARE-19, was carried out to unveil the effects of SGLT-2 inhibitor treatment on comorbid disease complications and concomitant COVID-19 outcomes and demonstrated no statistical significance. However, the need for further studies is essential to provide conclusive clinical findings., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: The effective reproduction number, R t , is a tool to track and understand pandemic dynamics. This investigation of R t estimations was conducted to guide the national COVID-19 response in Qatar, from the onset of the pandemic until August 18, 2021., Methods: Real-time "empirical" R t Empirical was estimated using five methods, including the Robert Koch Institute, Cislaghi, Systrom-Bettencourt and Ribeiro, Wallinga and Teunis, and Cori et al. methods. R t was also estimated using a transmission dynamics model ( R t Model-based ). Uncertainty and sensitivity analyses were conducted. Correlations between different R t estimates were assessed by calculating correlation coefficients, and agreements between these estimates were assessed through Bland-Altman plots., Results: R t Empirical captured the evolution of the pandemic through three waves, public health response landmarks, effects of major social events, transient fluctuations coinciding with significant clusters of infection, and introduction and expansion of the Alpha (B.1.1.7) variant. The various estimation methods produced consistent and overall comparable R t Empirical estimates with generally large correlation coefficients. The Wallinga and Teunis method was the fastest at detecting changes in pandemic dynamics. R t Empirical estimates were consistent whether using time series of symptomatic PCR-confirmed cases, all PCR-confirmed cases, acute-care hospital admissions, or ICU-care hospital admissions, to proxy trends in true infection incidence. R t Model-based correlated strongly with R t Empirical and provided an average R t Empirical ., Conclusions: R t estimations were robust and generated consistent results regardless of the data source or the method of estimation. Findings affirmed an influential role for R t estimations in guiding national responses to the COVID-19 pandemic, even in resource-limited settings., Competing Interests: Competing interests: Dr Butt has received institutional grant funding from Gilead Sciences unrelated to the work presented in this paper. The authors have completed the ICMJE Declaration of Interest Form (available upon request from the corresponding author), and declare no further conflicts of interest., (Copyright © 2022 by the Journal of Global Health. All rights reserved.)

Importance: The Delta variant is now the predominant circulating SARS-CoV-2 strain worldwide. Severity of illness in persons infected with the SARS-CoV-2 Delta variant compared with the Beta variant is not known., Objective: To directly compare clinical outcomes in persons infected with the SARS-CoV-2 Delta variant vs those infected with the Beta variant in Qatar., Design, Setting, and Participants: This retrospective cohort study used data from the national COVID-19 database in Qatar, which includes information on all individuals who were ever tested for SARS-CoV-2 using a reverse transcriptase-polymerase chain reaction test and all individuals who received any SARS-CoV-2 vaccine in Qatar. Among persons with confirmed SARS-CoV-2 infection between March 22 and July 7, 2021, those infected with the Delta variant were identified and were propensity score matched with control individuals infected with the Beta variant. The variants were ascertained by variant genotyping of the positive samples., Exposures: SARS-CoV-2 infection with the Delta or Beta variant., Main Outcomes and Measures: The main outcomes were admission to the hospital, admission to the intensive care unit, use of supplemental oxygen, use of high-flow oxygen, receipt of mechanical ventilation, or death among those infected with the Delta or Beta variant overall and stratified by vaccination status., Results: Among 1427 persons infected with the Delta variant (252 [55.9%] male; median age, 34 years [IQR, 17-43 years]) and 5353 persons infected with the Beta variant (233 [51.7%] male; median age, 34 years [IQR, 17-45 years]), 451 propensity score-matched pairs were identified. Persons infected with the Delta variant were more likely to be hospitalized (27.3% [95% CI, 23.2%-31.6%] vs 20.0% [95% CI, 16.4-24.0]; P = .01) or to have mild-moderate or severe-critical disease outcomes (27.9% [95% CI, 23.8%-32.3%] vs 20.2% [95% CI, 16.6%-24.2%]; P = .01) compared with persons infected with the Beta variant. Infection with the Delta variant was independently associated with higher odds of experiencing any adverse outcome (adjusted odds ratio [aOR], 2.53; 95% CI, 1.72-3.72). Compared with being unvaccinated, being vaccinated with a second dose more than 3 months before infection was associated with lower odds of any adverse outcome among persons infected with the Delta variant (aOR, 0.11; 95% CI, 0.04-0.26) and among those infected with the Beta variant (aOR, 0.22; 95% CI, 0.05-0.98). Protection was similar among those who received a second vaccine dose less than 3 months before infection, but having received only a single dose was not associated with a lower odds of any severe outcome among those infected with the Delta variant (aOR, 1.12; 95% CI, 0.41-3.06) or those infected with the Beta variant (aOR, 0.74; 95% CI, 0.20-2.72)., Conclusions and Relevance: In this cohort study of persons with COVID-19 in Qatar, infection with the SARS-CoV-2 Delta variant was associated with more severe disease than was infection with the Beta variant. Being unvaccinated was associated with greater odds of severe-critical disease.

This study investigated the performance of a rapid point-of-care antibody test, the BioMedomics COVID-19 IgM/IgG Rapid Test, in comparison with a high-quality, validated, laboratory-based platform, the Roche Elecsys Anti-SARS-CoV-2 assay. Serological testing was conducted on 709 individuals. Concordance metrics were estimated. Logistic regression was used to assess associations with seropositivity. SARS-CoV-2 seroprevalence was 63.5% (450/709; 95% CI 59.8%-67.0%) using the BioMedomics assay and 71.9% (510/709; 95% CI 68.5%-75.2%) using the Elecsys assay. There were 60 discordant results between the two assays, all of which were seropositive in the Elecsys assay, but seronegative in the BioMedomics assay. Overall, positive, and negative percent agreements between the two assays were 91.5% (95% CI 89.2%-93.5%), 88.2% (95% CI 85.1%-90.9%), and 100% (95% CI 98.2%-100%), respectively, with a Cohen's kappa of 0.81 (95% CI 0.78-0.84). Excluding specimens with lower (Elecsys) antibody titers, the agreement improved with overall, positive, and negative percent concordance of 94.4% (95% CI 92.3%-96.1%), 91.8% (95% CI 88.8%-94.3%), and 100% (95% CI 98.2%-100%), respectively, and a Cohen's kappa of 0.88 (95% CI 0.85-0.90). Logistic regression confirmed better agreement with higher antibody titers. The BioMedomics COVID-19 IgM/IgG Rapid Test demonstrated good performance in measuring detectable antibodies against SARS-CoV-2, supporting the utility of such rapid point-of-care serological testing to guide the public health responses and vaccine prioritization., Competing Interests: The authors have declared that no competing interests exist.

Background: The epidemiology of the SARS-CoV-2 B.1.1.7 (or Alpha) variant is insufficiently understood. This study's objective was to describe the introduction and expansion of this variant in Qatar and to estimate the efficacy of natural infection against reinfection with this variant., Methods and Findings: Reinfections with the B.1.1.7 variant and variants of unknown status were investigated in a national cohort of 158,608 individuals with prior PCR-confirmed infections and a national cohort of 42,848 antibody-positive individuals. Infections with B.1.1.7 and variants of unknown status were also investigated in a national comparator cohort of 132,701 antibody-negative individuals. B.1.1.7 was first identified in Qatar on 25 December 2020. Sudden, large B.1.1.7 epidemic expansion was observed starting on 18 January 2021, triggering the onset of epidemic's second wave, 7 months after the first wave. B.1.1.7 was about 60% more infectious than the original (wild-type) circulating variants. Among persons with a prior PCR-confirmed infection, the efficacy of natural infection against reinfection was estimated to be 97.5% (95% CI: 95.7% to 98.6%) for B.1.1.7 and 92.2% (95% CI: 90.6% to 93.5%) for variants of unknown status. Among antibody-positive persons, the efficacy of natural infection against reinfection was estimated to be 97.0% (95% CI: 92.5% to 98.7%) for B.1.1.7 and 94.2% (95% CI: 91.8% to 96.0%) for variants of unknown status. A main limitation of this study is assessment of reinfections based on documented PCR-confirmed reinfections, but other reinfections could have occurred and gone undocumented., Conclusions: In this study, we observed that introduction of B.1.1.7 into a naïve population can create a major epidemic wave, but natural immunity in those previously infected was strongly associated with limited incidence of reinfection by B.1.1.7 or other variants., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: A.A.B. has received institutional grant funding from Gilead Sciences unrelated to the work presented in this paper, otherwise, the authors declare no competing interests.

With the global expansion of the highly transmissible SARS-CoV-2 Delta (B.1.617.2) variant, we conducted a matched test-negative case-control study to assess the real-world effectiveness of COVID-19 messenger RNA vaccines against infection with Delta in Qatar's population. BNT162b2 effectiveness against any, symptomatic or asymptomatic, Delta infection was 45.3% (95% CI, 22.0-61.6%) ≥14 d after the first vaccine dose, but only 51.9% (95% CI, 47.0-56.4%) ≥14 d after the second dose, with 50% of fully vaccinated individuals receiving their second dose before 11 May 2021. Corresponding mRNA-1273 effectiveness ≥14 d after the first or second dose was 73.7% (95% CI, 58.1-83.5%) and 73.1% (95% CI, 67.5-77.8%), respectively. Notably, effectiveness against Delta-induced severe, critical or fatal disease was 93.4% (95% CI, 85.4-97.0%) for BNT162b2 and 96.1% (95% CI, 71.6-99.5%) for mRNA-1273 ≥ 14 d after the second dose. Our findings show robust effectiveness for both BNT162b2 and mRNA-1273 in preventing Delta hospitalization and death in Qatar's population, despite lower effectiveness in preventing infection, particularly for the BNT162b2 vaccine., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

BackgroundSARS-CoV-2 infection in pregnancy is associated with a higher risk of pregnancy-related complications and neonatal respiratory distress and hospitalization. Effectiveness of SARS-CoV-2 vaccines in pregnant women is not known.MethodsAll women with confirmed pregnancy who presented to the national referral hospital in Qatar between December 20, 2020, and May 30, 2021, with at least 1 SARS-CoV-2 test and not testing prior to pregnancy were included. We determined the vaccine effectiveness of mRNA vaccines in preventing confirmed SARS-CoV-2 infection during pregnancy using both cohort and test-negative case-control designs. Analyses were adjusted for age group, nationality, and gestational age.ResultsAmong 4534 pregnant women, there were 407 vaccinated and 407 unvaccinated women in the matched cohort analysis. Vaccine effectiveness was 87.6% (95%CI 44.1%-97.2%) at least 14 days after the second dose. There were 386 test-positive and 834 matched women in the test-negative case control analysis. Vaccine effectiveness was 86.8% (95%CI 47.5%-98.5%) at least 14 days after the second dose. Adjustment for age, nationality, and gestational age yielded similar results for both designs. In the test-negative analysis, vaccine effectiveness at least 14 days after the first dose but before the second dose was 40.8% (95% CI 0.0%-80.4%). Of the 386 test-positive pregnant women, 74 cases were Alpha variant, 163 cases were Beta variant, and 156 cases were variants of unknown status. There were 9 severe or critical disease cases and no deaths in the test-positive pregnant women, all of whom were unvaccinated.ConclusionThe mRNA vaccines provide a high level of protection against documented SARS-CoV-2 infection, which supports the inclusion of pregnant women in vaccination campaigns.FUNDINGHamad Medical Corporation, Weill Cornell Medicine Qatar, and the Ministry of Public Health Qatar.

Qatar, a country with a strong health system and a diverse population consisting mainly of expatriate residents, has experienced two large waves of COVID-19 outbreak. In this study, we report on 2634 SARS-CoV-2 whole-genome sequences from infected patients in Qatar between March-2020 and March-2021, representing 1.5% of all positive cases in this period. Despite the restrictions on international travel, the viruses sampled from the populace of Qatar mirrored nearly the entire global population's genomic diversity with nine predominant viral lineages that were sustained by local transmission chains and the emergence of mutations that are likely to have originated in Qatar. We reported an increased number of mutations and deletions in B.1.1.7 and B.1.351 lineages in a short period. These findings raise the imperative need to continue the ongoing genomic surveillance that has been an integral part of the national response to monitor the SARS-CoV-2 profile and re-emergence in Qatar., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Benslimane, Al Khatib, Al-Jamal, Albatesh, Boughattas, Ahmed, Bensaad, Younuskunju, Mohamoud, Al Badr, Mohamed, El-Kahlout, Al-Hamad, Elgakhlab, Al-Kuwari, Saad, Jeremijenko, Al-Khal, Al-Maslamani, Bertollini, Al-Kuwari, Al-Romaihi, Al-Marri, Al-Thani, Badji, Mbarek, Al-Sarraj, Malek, Ismail, Abu-Raddad, Coyle, Thani and Yassine.)

Complementing whole genome sequencing strategies with high-throughput multiplex RT-qPCR genotyping allows for more comprehensive and real-time tracking of SARS-CoV-2 variants of concern. During the second and third waves of COVID-19 in Qatar, PCR genotyping, combined with Sanger sequencing of un-typeable samples, was employed to describe the epidemiology of the Alpha, Beta and Delta variants. A total of 9792 nasopharyngeal PCR-positive samples collected between April-June 2021 were successfully genotyped, revealing the importation and transmission dynamics of these three variants in Qatar., Competing Interests: Conflict of Interest/Disclosure The authors have declared no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The current coronavirus disease (COVID-19) pandemic caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a male bias in severity and mortality. This is consistent with previous coronavirus pandemics such as SARS-CoV and MERS-CoV, and viral infections in general. Here, we discuss the sex-disaggregated epidemiological data for COVID-19 and highlight underlying differences that may explain the sexual dimorphism to help inform risk stratification strategies and therapeutic options., (© 2021 The Authors. Reviews in Medical Virology published by John Wiley & Sons Ltd.)

Background and Objective: The risk factors for breakthrough infections among healthcare workers (HCW) after completion of a full course of vaccination are poorly understood. Our objective was to determine the risk factors for breakthrough SARS-CoV-2 infection among HCWs at a national healthcare system in Qatar., Methods: We identified all HCWs at Hamad Medical Corporation in Qatar between December 20, 2020 and May 18, 2021 with confirmed SARS-CoV-2 RT-PCR infection >14 days after the second vaccine dose. For each case thus identified, we identified one control with a negative test after December 20, 2020, matched on age, sex, nationality, job family and date of SARS-CoV-2 testing. We excluded those with a prior positive test and temporary workers. We used Cox regression analysis to determine factors associated with breakthrough infection., Results: Among 22,247 fully vaccinated HCW, we identified 164 HCW who had breakthrough infection and matched them to 164 controls to determine the factors associated with SARS-CoV-2 breakthrough infection. In the breakthrough infection group the nursing and midwifery job family constituted the largest group, spouse was identified as the most common positive contact followed by a patient. Exposure to a confirmed case, presence of symptoms and all other job families except Allied Health Professionals when compared with nursing and Midwifery staff independently predicted infection., Conclusion: Presence of symptoms and contact with a confirmed case are major risk factors for breakthrough SARS-CoV-2 infection after vaccination, and these groups should be prioritized for screening even after full vaccination., Competing Interests: All authors declare no competing interest and have no financial disclosures relevant to this paper.

Background: Risk of reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. We assessed the risk and incidence rate of documented SARS-CoV-2 reinfection in a cohort of laboratory-confirmed cases in Qatar., Methods: All SARS-CoV-2 laboratory-confirmed cases with at least 1 polymerase chain reaction-positive swab that was ≥45 days after a first positive swab were individually investigated for evidence of reinfection. Viral genome sequencing of the paired first positive and reinfection viral specimens was conducted to confirm reinfection., Results: Out of 133 266 laboratory-confirmed SARS-CoV-2 cases, 243 persons (0.18%) had at least 1 subsequent positive swab ≥45 days after the first positive swab. Of these, 54 cases (22.2%) had strong or good evidence for reinfection. Median time between the first swab and reinfection swab was 64.5 days (range, 45-129). Twenty-three of the 54 cases (42.6%) were diagnosed at a health facility, suggesting presence of symptoms, while 31 (57.4%) were identified incidentally through random testing campaigns/surveys or contact tracing. Only 1 person was hospitalized at the time of reinfection but was discharged the next day. No deaths were recorded. Viral genome sequencing confirmed 4 reinfections of 12 cases with available genetic evidence. Reinfection risk was estimated at 0.02% (95% confidence interval [CI], .01%-.02%), and reinfection incidence rate was 0.36 (95% CI, .28-.47) per 10 000 person-weeks., Conclusions: SARS-CoV-2 reinfection can occur but is a rare phenomenon suggestive of protective immunity against reinfection that lasts for at least a few months post primary infection., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: While many studies have reported the rate and risk of SARS-CoV-2 infection among healthcare workers (HCWs), there are scant data regarding the impact of employment type and job grades upon such risk., Methods: We determined the rate of SARS-CoV-2 infection based on a positive nasopharyngeal swab (NPS) PCR among employees of a large national healthcare system. Antibody testing was performed on those who agreed to provide a blood sample. Using logistic regression analysis, we determined the risk of infection (PCR+) associated with demographic characteristics, job family and job grade., Results: We identified 35,075 staff (30,849 full-time, 4,226 outsourced) between March 1-October 31, 2020. Among full-time employees, 78.0% had a NPS (11.8% positive). Among outsourced staff, 94.4% had a NPS (31.1% positive). Antibody testing was performed on 33.9% full-time employees (13.0% reactive), and on 39.1% of the outsourced staff (47.0% reactive). PCR-positivity was higher among outsourced staff (31.0% vs. 18.3% in non-clinical and 9.0% in clinical full-time employees) and those in the low-grade vs. mid-grade and high-grade job categories. Male sex (OR 1.88), non-clinical job family (OR 1.21), low-grade job category (OR 3.71) and being an outsourced staff (OR 2.09) were associated with a higher risk of infection., Conclusion: HCWs are a diverse population with varying risk of infection. Clinical staff are at a lower risk likely due to increased awareness and infection prevention measures. Risk is higher for those in the lower socioeconomic strata. Infection is more likely to occur in non-healthcare setting than within the healthcare facilities., Competing Interests: Dr. Butt has received an investigator initiated research grant (to the institution, Veterans Health Foundation of Pittsburgh) form Gilead Sciences which is unrelated to this work. All other authors declare no competing interest and have no financial disclosures relevant to this paper.

Background: Breakthrough infections after SARS-CoV-2 vaccination have been reported. Clinical outcomes in these persons are not widely known., Methods: We evaluated all vaccinated persons with breakthrough infection ≥14 days after the second vaccine dose and unvaccinated controls matched on age, sex, nationality, and reason for testing between December 23, 2020 and March 28, 2021 in Qatar. Our primary outcome was severe disease defined as hospitalization, mechanical ventilation, or death., Results: Among 456 persons cases of breakthrough infection and 456 unvaccinated matched controls with confirmed infection, median age was 45 years, 60.7% were males, and ≥1 comorbid condition was present in 61.2% of the vaccinated and 47.8% of the unvaccinated persons (P=0.009). Severe disease was recorded in 48 (10.5%) of the vaccinated and 121 (26.5%) of the unvaccinated group (P<0.001). Factors associated with severe disease included increasing age (HR vs. <40 years old: >40-60 years, HR 2.32; >60-70 years, HR 4.34; >70 years, HR 5.43); presence of symptoms at baseline (HR 2.42, 95%CI 1.44-4.07); and being unvaccinated (HR 2.84, 95%CI 1.80-4.47)., Conclusions: In persons with breakthrough SARS-CoV-2 infection, increasing age is associated with a higher risk of severe disease or death, while vaccination is associated with a lower risk. Presence of comorbidities was not associated with severe disease or death among persons with breakthrough infection., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The SARS-CoV-2 pandemic continues to be a global health concern. The mRNA-1273 (Moderna) vaccine was reported to have an efficacy of 94.1% at preventing symptomatic COVID-19 due to infection with 'wild-type' variants in a randomized clinical trial. Here, we assess the real-world effectiveness of this vaccine against SARS-CoV-2 variants of concern, specifically B.1.1.7 (Alpha) and B.1.351 (Beta), in Qatar, a population that comprises mainly working-age adults, using a matched test-negative, case-control study design. We show that vaccine effectiveness was negligible for 2 weeks after the first dose, but increased rapidly in the third and fourth weeks immediately before administration of a second dose. Effectiveness against B.1.1.7 infection was 88.1% (95% confidence interval (CI): 83.7-91.5%) ≥14 days after the first dose but before the second dose, and was 100% (95% CI: 91.8-100.0%) ≥14 days after the second dose. Analogous effectiveness against B.1.351 infection was 61.3% after the first dose (95% CI: 56.5-65.5%) and 96.4% after the second dose (95% CI: 91.9-98.7%). Effectiveness against any severe, critical or fatal COVID-19 disease due to any SARS-CoV-2 infection (predominantly B.1.1.7 and B.1.351) was 81.6% (95% CI: 71.0-88.8%) and 95.7% (95% CI: 73.4-99.9%) after the first and second dose, respectively. The mRNA-1273 vaccine is highly effective against B.1.1.7 and B.1.351 infections, whether symptomatic or asymptomatic, and against any COVID-19 hospitalization and death, even after a single dose., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Coronavirus disease 2019 (COVID-19) increases the risk of coagulopathy. Although the presence of antiphospholipid antibodies (aPLs) has been proposed as a possible mechanism of COVID-19-induced coagulopathy, its clinical significance remains uncertain. Therefore, this study aimed to evaluate the prevalence and clinical significance of aPLs among critically ill patients with COVID-19. This prospective observational study included 60 patients with COVID-19 admitted to intensive care units (ICU). The study outcomes included prevalence of aPLs, and a primary composite outcome of all-cause mortality and arterial or venous thrombosis between antiphospholipid-positive and antiphospholipid-negative patients during their ICU stay. Multiple logistic regression was used to assess the influence of aPLs on the primary composite outcome of mortality and thrombosis. A total of 60 critically ill patients were enrolled. Among them, 57 (95%) were men, with a mean age of 52.8 ± 12.2 years, and the majority were from Asia (68%). Twenty-two patients (37%) were found be antiphospholipid-positive; 21 of them were positive for lupus anticoagulant, whereas one patient was positive for anti-β2-glycoprotein IgG/IgM. The composite outcome of mortality and thrombosis during their ICU stay did not differ between antiphospholipid-positive and antiphospholipid-negative patients (4 [18%] vs. 6 [16%], adjusted odds ratio 0.98, 95% confidence interval 0.1-6.7; p value = 0.986). The presence of aPLs does not seem to affect the outcomes of critically ill patients with COVID-19 in terms of all-cause mortality and thrombosis. Therefore, clinicians may not screen critically ill patients with COVID-19 for aPLs unless deemed clinically appropriate.

Raw municipal wastewater from five wastewater treatment plants representing the vast majority of the Qatar population was sampled between the third week of June 2020 and the end of August 2020, during the period of declining cases after the peak of the first wave of infection in May 2020. The N1 region of the SARS-CoV-2 genome was used to quantify the viral load in the wastewater using RT-qPCR. The trend in Ct values in the wastewater samples mirrored the number of new daily positive cases officially reported for the country, confirmed by RT-qPCR testing of naso-pharyngeal swabs. SARS-CoV-2 RNA was detected in 100% of the influent wastewater samples (7889 ± 1421 copy/L - 542,056 ± 25,775 copy/L, based on the N1 assay). A mathematical model for wastewater-based epidemiology was developed and used to estimate the number of people in the population infected with COVID-19 from the N1 Ct values in the wastewater samples. The estimated number of infected population on any given day using the wastewater-based epidemiology approach declined from 542,313 ± 51,159 to 31,181 ± 3081 over the course of the sampling period, which was significantly higher than the officially reported numbers. However, seroprevalence data from Qatar indicates that diagnosed infections represented only about 10% of actual cases. The model estimates were lower than the corrected numbers based on application of a static diagnosis ratio of 10% to the RT-qPCR identified cases, which is assumed to be due to the difficulty in quantifying RNA losses as a model term. However, these results indicate that the presented WBE modeling approach allows for a realistic assessment of incidence trend in a given population, with a more reliable estimation of the number of infected people at any given point in time than can be achieved using human biomonitoring alone., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Vaccine hesitancy is a global threat undermining control of preventable infections. Emerging evidence suggests that hesitancy to COVID-19 vaccination varies globally. Qatar has a unique population with around 90% of the population being economic migrants, and the degree and determinants of hesitancy are not known., Methods: This study was carried out to evaluate the degree of vaccine hesitancy and its socio-demographic and attitudinal determinants across a representative sample. A national cross-sectional study using validated hesitancy measurement tool was carried out from October 15, 2020, to November 15, 2020. A total of 7821 adults completed the survey. Relevant socio-demographic data along with attitudes and beliefs around COVID-19 vaccination were collected from the respondents., Results: 20.2% of the respondents stated they would not take the vaccine and 19.8% reported being unsure about taking the prospective COVID-19 vaccine. Citizens and females were more likely to be vaccine hesitators than immigrants and males, respectively. Concerns around the safety of COVID-19 vaccine and its longer-term side effects were the main concerns cited. Personal research around COVID-19 and vaccine were by far the most preferred methods that would increase confidence in accepting the vaccine across all demographic groups., Conclusions: This study reports an overall vaccine hesitancy of 20% toward the COVID-19 vaccine and the influence of social media on attitudes toward vaccination which is in keeping with emerging evidence. This finding comes at a time that is close to the start of mass immunization and reports from a migrant-majority population highlighting important socio-demographic determinants around vaccine hesitancy., (© 2021 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

We document two cases of viremic and prolonged active infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) where the viral genome was conserved for two months, but infection was with little or no symptoms. The first infection persisted for 80 days and the second for 62 days. Clearance of infection occurred 40 and 41 days, respectively, after development of detectable antibodies. Both cases were identified incidentally in an investigation of reinfection in a cohort of 133,266 laboratory-confirmed infected persons., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

COVID-19 has surfaced as a multi-organ disease predominantly affecting the respiratory system. Detection of the viral RNA through reverse transcriptase-PCR (RT-PCR) from a nasopharyngeal or throat sample is the preferred method of diagnosis. Recent evidence has suggested that COVID-19 patients can shed the SARS-CoV-2 for several weeks. Herein, we report six cases of COVID-19 who had persistently positive SARS-CoV-2 on repeat RT-PCR testing reaching up to 9 weeks. The spectrum of cases described ranges from asymptomatic infection to severe COVID-19 pneumonia. A full understanding of the virus's transmission dynamics needs further research. Prolonged viral shedding currently has unclear implications on the management and isolation decisions-the role of the cycle threshold (Ct) value in guiding therapeutic decisions is yet to be clarified. More data on the relationship between Ct values and viral cultivation are needed, especially in patients with prolonged viral shedding, to understand the virus's viability and infectivity.

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spurred a global health crisis. The safety and supply of blood during this pandemic has been a concern of blood banks and transfusion services as it is expected to adversely affect blood system activities. We aim to assess the situation in the Eastern Mediterranean Region (EMR) during the first months of the pandemic., Materials and Methods: A survey was designed to address blood supply, transfusion demand, and donor management during the coronavirus disease-19 (COVID-19) pandemic. Medical directors of different blood banks were invited to participate., Results: A total of 16 centers participated with representation from 15/19 countries in the region. In total, 75% were from national blood banks. Most centres had a decrease in the blood supply, ranging from 26-50%. Representatives from 14 countries (93.3%) believed that public fear has contributed to a decrease in donations. Most centres (n=12, 75%) had a reduction in transfusion demand, while those who did not, reported heavy involvement in treating patients with underlying haemoglobinopathies and haematological malignancies. Half of the centres activated their contingency plans. Four centres had to alter the blood donor eligibility criteria to meet demands. All centres implemented donor deferral criteria in relation to SARS-CoV-2, but were variable in measures to mitigate the risk of donor and staff exposure., Conclusion: Blood services in the region faced variable degrees of blood shortages. We summarize lessons learnt during this pandemic for the blood banks to consider to plan, assess, and respond proportionately to future similar pandemics., (Copyright © 2020 Société française de transfusion sanguine (SFTS). Published by Elsevier Masson SAS. All rights reserved.)

Pneumonia cases of unknown etiology in Wuhan, Hubei province, China were reported to the World Health Organization on 31st of December 2019. Later the pathogen was reported to be a novel coronavirus designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes Corona virus disease 2019 (COVID-19). The disease outspread was followed by WHO declaration of COVID-19 pandemic as a "Public Health Emergency of International Concern". SARS-CoV-2 is a novel pathogenic beta coronavirus that infects humans causing severe respiratory illness. However, multifarious factors can contribute to the susceptibility to COVID-19 related morbidity and mortality such as age, gender, and underlying comorbidities. Infection initiates when viral particles bind to the host cell surface receptors where SARS-CoV-2 spike glycoprotein subunit 1 binds to the Angiotensin Converting Enzyme 2 (ACE2). It is of importance to mention that SARS-CoV and SARS-CoV-2 viruses' mediate entry into the host cells via ACE2 receptor which might be correlated with the structural similarity of spike glycoprotein subunit 1 of both SARS viruses. However, the structural binding differs, whereas ACE2 receptor binding affinity with SARS-CoV-2 is 4 folds higher than that with SARS-CoV. Moreover, amino acids sequence divergence between the two S glycoproteins might be responsible for differential modulations of the specific immune response to both viruses. Identification of different aspects such as binding affinity, differential antigenic profiles of S-glycoproteins, and ACE2 mutations might influence the investigation of potential therapeutic strategies targeting SARS-CoV-2/ACE2 binding interface. In this review, we aim to elaborate on the expression of hACE2 receptor protein and its binding with SARS-CoV-2 S1 subunit, the possible immunogenic sequences of spike protein, effect of ACE 2 polymorphism on viral binding, and infectivity/susceptibility to disease. Furthermore, targeting of hACE2 receptor binding with SARS-CoV-2 S1 subunit via various mechanisms will be discussed to understand its role in therapeutics.