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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.

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.

Objectives: Accurate determination of the immediate causes of death in patients with COVID-19 is important for optimal care and mitigation strategies. Methods: All deaths in Qatar between March 01, 2020, and August 31, 2022, flagged for likely relationship to COVID-19 were reviewed by two independent, trained reviewers using a standardized methodology to determine the immediate and contributory causes of death. Results: Among 749 flagged deaths, the most common admitting diagnoses were respiratory tract infection (91%) and major adverse cardiac event (MACE, 2.3%). The most common immediate causes of death were COVID-19 pneumonia (66.2%), MACE (7.1%), hospital-associated pneumonia (HAP, 6.8%), bacteremia (6.3%), disseminated fungal infection (DFI, 5.2%), and thromboembolism (4.5%). After COVID-19 pneumonia, MACE was the predominant cause of death in the first 2 weeks but declined thereafter. No death occurred due to bacteremia, HAP, or DFI in the first week after hospitalization, but became increasingly common with increased length of stay in the hospital accounting for 9%, 12%, and 10% of all deaths after 4 weeks in the hospital, respectively. Conclusion: Nearly one-third of patients with COVID-19 infection die of non-COVID-19 causes, some of which are preventable. Mitigation strategies should be instituted to reduce the risk of such deaths.

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.

Summary: Background: Protection against SARS-CoV-2 symptomatic infection and severe COVID-19 of previous infection, mRNA two-dose vaccination, mRNA three-dose vaccination, and hybrid immunity of previous infection and vaccination were investigated in Qatar for the Alpha, Beta, and Delta variants. Methods: Six national, matched, test-negative, case-control studies were conducted between January 18 and December 18, 2021 on a sample of 239,120 PCR-positive tests and 6,103,365 PCR-negative tests. Findings: Effectiveness of previous infection against Alpha, Beta, and Delta reinfection was 89.5% (95% CI: 85.5–92.3%), 87.9% (95% CI: 85.4–89.9%), and 90.0% (95% CI: 86.7–92.5%), respectively. Effectiveness of two-dose BNT162b2 vaccination against Alpha, Beta, and Delta infection was 90.5% (95% CI, 83.9–94.4%), 80.5% (95% CI: 79.0–82.0%), and 58.1% (95% CI: 54.6–61.3%), respectively. Effectiveness of three-dose BNT162b2 vaccination against Delta infection was 91.7% (95% CI: 87.1–94.7%). Effectiveness of hybrid immunity of previous infection and two-dose BNT162b2 vaccination was 97.4% (95% CI: 95.4–98.5%) against Beta infection and 94.5% (95% CI: 92.8–95.8%) against Delta infection. Effectiveness of previous infection and three-dose BNT162b2 vaccination was 98.1% (95% CI: 85.7–99.7%) against Delta infection. All five forms of immunity had >90% protection against severe, critical, or fatal COVID-19 regardless of variant. Similar effectiveness estimates were observed for mRNA-1273. A mathematical model accurately predicted hybrid immunity protection by assuming that the individual effects of previous infection and vaccination acted independently. Interpretation: Hybrid immunity, offering the strongest protection, was mathematically predicted by assuming that the immunities obtained from previous infection and vaccination act independently, without synergy or redundancy. Funding: The Biomedical Research Program and the Biostatistics, Epidemiology, and the Biomathematics Research Core, both at Weill Cornell Medicine-Qatar, Ministry of Public Health, Hamad Medical Corporation, Sidra Medicine, Qatar Genome Programme, Qatar University Biomedical Research Center, and Qatar University Internal Grant ID QUCG-CAS-23/24-114.

Summary: Background: Waning of natural infection protection and vaccine protection highlight the need to evaluate changes in population immunity over time. Population immunity of previous SARS-CoV-2 infection or of COVID-19 vaccination are defined, respectively, as the overall protection against reinfection or against breakthrough infection at a given point in time in a given population. Methods: We estimated these population immunities in Qatar's population between July 1, 2020 and November 30, 2022, to discern generic features of the epidemiology of SARS-CoV-2. Effectiveness of previous infection, mRNA primary-series vaccination, and mRNA booster (third-dose) vaccination in preventing infection were estimated, month by month, using matched, test-negative, case–control studies. Findings: Previous-infection effectiveness against reinfection was strong before emergence of Omicron, but declined with time after a wave and rebounded after a new wave. Effectiveness dropped after Omicron emergence from 88.3% (95% CI: 84.8–91.0%) in November 2021 to 51.0% (95% CI: 48.3–53.6%) in December 2021. Primary-series effectiveness against infection was 84.0% (95% CI: 83.0–85.0%) in April 2021, soon after introduction of vaccination, before waning gradually to 52.7% (95% CI: 46.5–58.2%) by November 2021. Effectiveness declined linearly by ∼1 percentage point every 5 days. After Omicron emergence, effectiveness dropped from 52.7% (95% CI: 46.5–58.2%) in November 2021 to negligible levels in December 2021. Booster effectiveness dropped after Omicron emergence from 83.0% (95% CI: 65.6–91.6%) in November 2021 to 32.9% (95% CI: 26.7–38.5%) in December 2021, and continued to decline thereafter. Effectiveness of previous infection and vaccination against severe, critical, or fatal COVID-19 were generally >80% throughout the study duration. Interpretation: High population immunity against infection may not be sustained beyond a year, but population immunity against severe COVID-19 is durable with slow waning even after Omicron emergence. Funding: The Biomedical Research Program and the Biostatistics, Epidemiology, and the Biomathematics Research Core, both at Weill Cornell Medicine-Qatar, Ministry of Public Health, Hamad Medical Corporation, Sidra Medicine, Qatar Genome Programme, Qatar University Biomedical Research Center, and Qatar University Internal Grant ID QUCG-CAS-23/24-114.

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 (P40–60 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.

Background: Mortuary and cemetery workers may be exposed to the bodies of people with SARS-CoV-2 infection; however, prevalence of infection among these groups is unknown. Methods: Nasopharyngeal swabs (NPS) for RT-PCR and serologic testing for SARS-CoV-2 were performed on mortuary and cemetery workers in Qatar. Data on specific job duties, living conditions, contact history, and clinical course were gathered. Environmental sampling was carried out to explore any association with infection. Logistic regression analysis was used to determine the factors associated with infection. Results: Forty-seven mortuary workers provided an NPS and seven (14.9%) were PCR positive; 32 provided a blood sample and eight (25%) were antibody positive, six (75%) who were seropositive were also PCR positive. Among the 81 cemetery workers, 76 provided an NPS and five (6.6%) were PCR positive; 64 provided a blood sample and 22 (34.4%) were antibody positive, three (13.6%) who were seropositive were also PCR positive. Three (22.2%) and 20 (83.3%) of the infected mortuary and cemetery workers were asymptomatic, respectively. Age 35. Conclusion: A substantial proportion of mortuary and cemetery workers had evidence of SARS-CoV-2 infection, which was incidentally detected upon serologic testing. These data are most consistent with community acquisition rather than occupational acquisition.

Background: COVID-19 pandemic has exposed the lack of adequate and appropriate quarantine capacity globally. Most countries lack the knowledge and/or capacity to set up and manage quarantine facilities at a national scale. Methods: The State of Qatar developed a systematic plan to create and manage quarantine facilities for persons with confirmed or suspected COVID-19 infection or returning travelers and residents. A checklist was developed to streamline the process and to help other institutions requiring such guidance. Results: Three distinct stages were identified: acquisition, commissioning and active operations. Steps required for each stage were identified and added to the checklist. Conclusion: We share our experience and a checklist for setting up new quarantine capacity at a national level. Such checklists can serve as a critical tool to quickly and efficiently ramp up capacity in this setting.

Background: Breakthrough infections after SARS-CoV-2 infection have been reported. Clinical outcomes among persons with breakthrough infection are not known. Methods: We retrospectively identified all Veterans with a confirmed SARS-CoV-2 infection >14 days after the second dose of either Pfizer-BNT-162b2 or Moderna-mRNA-1273 vaccine between December 15, 2020 and March 30, 2021, and age, race, sex, body mass index, Charlson comorbidity index, geographical location, and date of positive test matched unvaccinated controls with SARS-CoV-2 infection. Our primary endpoint was the rate or severe disease defined as hospitalization, mechanical ventilation, or death in both groups. Findings: Among 258,716 persons with both doses of vaccines and 756,150 without any vaccination, we identified 271 (0.1%) vaccinated persons with breakthrough infection and 48,114 (6.4%) unvaccinated matched controls with infection between December 15, 2020 and March 30, 2021. Among 213 matched pairs, symptoms were present in 33.3% of those with breakthrough infection and 42.2% of the controls. A total of 79 persons met the definition of severe disease or death (42 in the breakthrough infection group and 37 in the control group). Rate of severe disease or death per 1,000 person-days (95% CI) was 4.08 (2.64,5.31) among those with breakthrough infection and 3.6 (2.53,4.73) among the controls (P = 0.58). Rate was similar among both groups regardless of age-group, race, BMI or presence of comorbidities. Among persons with breakthrough infection and matched controls with infection, vaccination was not associated with a lower risk of severe disease or death in the main analyses but was associated with a lower risk when matching did not include geographic location (HR 0.62, 95% CI 0.43,0.91). Interpretation: Demographic or clinical factors are not associated with a lower risk of severe disease or death in persons with breakthrough SARS-CoV-2 infection. Funding: None

Summary: The study objective was to the assess level of detectable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in the urban population of Qatar. Antibody testing was performed on residual blood specimens for 112,941 individuals (∼10% of Qatar's urban population) attending for routine/other clinical care between May 12 and September 9, 2020. Seropositivity was 13.3% (95% confidence interval [CI] = 13.1–13.6%) and was independently associated with sex, age, nationality, clinical care encounter type, and testing date. Median optical density (antibody titer) among antibody-positive persons was 27.0 (range = 1.0–150.0), with higher values associated with age, nationality, clinical care encounter type, and testing date. Seropositivity by nationality was positively correlated with the likelihood of having higher antibody titers (Pearson correlation coefficient = 0.85; 95% CI = 0.47–0.96). Less than two in every 10 individuals in Qatar's urban population had detectable antibodies against SARS-CoV-2, suggesting this population is still far from herd immunity and at risk of subsequent infection waves. Higher antibody titer appears to be a biomarker of repeated exposures to the infection.

Background: Reinfection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been documented, raising public health concerns. SARS-CoV-2 reinfections were assessed in a cohort of antibody-positive persons in Qatar. Methods: All SARS-CoV-2 antibody-positive persons from April 16 to December 31, 2020 with a PCR-positive swab ≥14 days after the first-positive antibody test were investigated for evidence of reinfection. Viral genome sequencing was conducted for paired viral specimens to confirm reinfection. Incidence of reinfection was compared to incidence of infection in the complement cohort of those who were antibody-negative. Findings: Among 43,044 antibody-positive persons who were followed for a median of 16.3 weeks (range: 0–34.6), 314 individuals (0.7%) had at least one PCR positive swab ≥14 days after the first-positive antibody test. Of these individuals, 129 (41.1%) had supporting epidemiological evidence for reinfection. Reinfection was next investigated using viral genome sequencing. Applying the viral-genome-sequencing confirmation rate, the incidence rate of reinfection was estimated at 0.66 per 10,000 person-weeks (95% CI: 0.56–0.78). Incidence rate of reinfection versus month of follow-up did not show any evidence of waning of immunity for over seven months of follow-up. Meanwhile, in the complement cohort of 149,923 antibody-negative persons followed for a median of 17.0 weeks (range: 0–45.6), incidence rate of infection was estimated at 13.69 per 10,000 person-weeks (95% CI: 13.22–14.14). Efficacy of natural infection against reinfection was estimated at 95.2% (95% CI: 94.1–96.0%). Reinfections were less severe than primary infections. Only one reinfection was severe, two were moderate, and none were critical or fatal. Most reinfections (66.7%) were diagnosed incidentally through random or routine testing, or through contact tracing. Interpretation: Reinfection is rare in the young and international population of Qatar. Natural infection appears to elicit strong protection against reinfection with an efficacy ~95% for at least seven months. Funding: Biomedical Research Program, the Biostatistics, Epidemiology, and Biomathematics Research Core, and the Genomics Core, all at Weill Cornell Medicine-Qatar, the Ministry of Public Health, Hamad Medical Corporation, and the Qatar Genome Programme.

Invasive Candida infections contribute to significant morbidity and mortality in patients with healthcare-associated infections. They represent a major burden on the public health system, and are challenging to diagnose and treat.A multidisciplinary expert panel critically reviewed available evidence to provide consensus recommendations for the management of invasive Candida infections in the Middle East.Based on diagnosis, recommendations were provided for the management of Candida infections in non-neutropenic and neutropenic patients. Polyenes (amphotericin B-deoxycholate [AmB-d] and lipid formulations amphotericin B [LFAmB]), triazoles (fluconazole, itraconazole and voriconazole), echinocandins (caspofungin, anidulafungin, and micafungin) and flucytosine are the recommended categories of antifungal agents for treatment of Candida infections. Echinocandins are preferred for treatment of proven and suspected Candida infections, especially in critically ill patients or those with previous exposure to azoles. Recommendations were also provided for infections caused by specific Candida species as well as management of different disease conditions.The experts highlighted that the guidelines should be used along with clinical judgment. Given the paucity of published data from the region, research in the form of randomized clinical trials should be given priority. Keywords: Candida, Treatment, Guidelines, Candidiasis, Middle East

Summary: The incidence of invasive Aspergillus infections in the Middle East continues to rise with the increase in the number of immunocompromised patients, and carries significant morbidity and mortality. A panel of experts analysed the evidence from the most recent international guidelines and relevant published literature to reach consensus and develop clear clinical practice guidelines to aid diagnosis and treatment of invasive Aspergillus infections in the Middle East. Disease-specific recommendations were provided for the management of invasive aspergillosis. The expert panel acknowledged that these guidelines should be followed as closely as possible but used alongside clinical judgement. Keywords: Aspergillus, Treatment, Guidelines, Aspergillosis, Middle East

OXA-48-producing isolates were identified in approximately 4% and less than 1% of ESBL-producing and non-ESBL-producing E. coli and K. pneumoniae causing bacteremia at the largest tertiary hospital in Abu Dhabi.

This study focused on the encapsulation of vancomycin (VAN) into liposomes coated with a red blood cell membrane with a targeting ligand, daptomycin–polyethylene glycol–1,2-distearoyl-sn-glycero-3-phosphoethanolamine, formed by conjugation of DAPT and N-hydroxysuccinimidyl-polyethylene glycol-1,2-distearoyl-sn-glycero-3-phosphoethanolamine. This formulation is capable of providing controlled and targeted drug delivery to the bacterial cytoplasm. We performed MALDI-TOF, NMR and FTIR analyses to confirm the conjugation of the targeting ligand via the formation of amide bonds. Approximately 45% of VAN could be loaded into the aqueous cores, whereas 90% DAPT was detected using UV–vis spectrophotometry. In comparison to free drugs, the formulations controlled the release of drugs for > 72 h. Additionally, as demonstrated using CLSM and flow cytometry, the resulting formulation was capable of evading detection by macrophage cells. In comparison to free drugs, red blood cell membrane–DAPT–VAN liposomes, DAPT liposomes, and VAN liposomes reduced the MIC and significantly increased bacterial permeability, resulting in > 80% bacterial death within 4 h. Cytotoxicity tests were performed in vitro and in vivo on mammalian cells, in addition to hemolytic activity tests in human erythrocytes, wherein drugs loaded into the liposomes and RBCDVL exhibited low toxicity. Thus, the findings of this study provide insight about a dual antibiotic targeting strategy that utilizes liposomes and red blood cell membranes to deliver targeted drugs against MRSA.

Background: Our aim was to determine the prevalence of COVID-19 infection in healthcare workers (HCWs) in a national healthcare system and to understand the risk factors for infection. Methods: The study was conducted at Hamad Medical Corporation (HMC) in Qatar, a national healthcare system with 14 hospitals and >28,000 employees, between March 10 and June 24, 2020. Data on COVID-19+ HCWs were retrieved from the electronic health records and employment records, followed by an email survey and a focused telephone interview. Results: Among 16,912 HCWs tested, 10.6% tested positive. Hospitalization rate was 11.6%, 1.3% required supplemental oxygen, 0.6% needed intensive care unit admission, and 0.3% required mechanical ventilation. There were no deaths. In a follow-up survey of 393 HCWs, 5% reported acquiring infection at a COVID-19-designated facility and 95% at a non-COVID-19 facility having acquired the infection through accidental exposure to a colleague (45%) or a patient (29%). Full personal protective equipment (PPE) adherence was 82% at COVID-19-designated facilities but only 68% at non-COVID-19 facilities. Conclusions: COVID- 19 infection among HCWs often occurs among those not directly working with COVID-19 patients. PPE use is less stringent in such settings. Risk of exposure and need for strict PPE must be stressed upon all HCWs in all settings.

Background: Antibiotics are often inappropriately prescribed for upper respiratory tract infections (URTIs) in developed countries. Data on the proportion of inappropriate prescriptions are lacking from the Middle East and other developing countries. Methods: Health insurance claims for all antibiotics prescribed for URTIs in the private sector in the State of Qatar between May 2014 and December 2015 were retrieved. During the study period, health insurance was limited to Qatari nationals. Topical antibiotics were excluded. Data on the prescriber's specialty, as listed with the licensing authority, were also retrieved. Diagnoses were classified as appropriate or inappropriate based on the likelihood of a bacterial etiology that may warrant antibiotic use. Results: A total of 75 733 claims were made during the study period. Of these, 41 556 (55%) were for an appropriate indication, while 34 177 (45%) were for an inappropriate indication. The most common antibiotic classes prescribed were cephalosporins (43% of claims; 44% inappropriate), penicillins (28% of claims; 44% inappropriate), macrolides (19% of claims; 52% inappropriate), and fluoroquinolones (9% of claims; 40% inappropriate). Nearly 5% of antibiotics were prescribed in intravenous formulations. The most common prescribers were General/Family Practice physicians (53% of claims; 50% inappropriate), followed by Pediatrics (18.6% of claims; 36% inappropriate) and Internal Medicine (14.1% of claims; 44% inappropriate). Conclusions: There is a high rate of inappropriate antibiotic prescription for acute URTIs in the private health care sector in the State of Qatar. Further studies are needed to determine the population-based rates across the country. Interventions to decrease inappropriate use in such settings are urgently needed.