Effectiveness of the neutralizing antibody sotrovimab among high-risk patients with mild-to-moderate SARS-CoV-2 in Qatar.

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.

Favipiravir for the treatment of coronavirus disease 2019 pneumonia; a propensity score-matched cohort study.

We retrospectively investigated the clinical outcomes of favipiravir in patients with COVID-19 pneumonia. Patients who between 23 May 2020 and 18 July 2020 received ≥ 24 h of favipiravir were assigned to the favipiravir group, while those who did not formed the non-favipiravir group. The primary outcome was 28-day clinical improvement, defined as two-category improvement from baseline on an 8-point ordinal scale. Propensity scores (PS) for favipiravir therapy were used for 1:1 matching. The unmatched cohort included 1493 patients, of which 51.7% were in the favipiravir group, and 48.3% were not receiving supplemental oxygen at baseline. Significant baseline differences between the two unmatched groups existed, but not between the PS-matched groups (N = 774). After PS-matching, there were no significant differences between the two groups in the proportion with 28-day clinical improvement (93.3% versus 92.8%, P 0.780), or 28-day all-cause mortality (2.1% versus 3.1%, P 0.360). Favipiravir was associated with more viral clearance by day 28 (79.8% versus 64.1%, P < 0.001). Adverse events were common in both groups, but the 93.9% were Grades 1-3. Favipiravir therapy for COVID-19 pneumonia is well tolerated but is not associated with an increased likelihood of clinical improvement or reduced all-cause mortality by 28 days.

Remdesivir for patients with Coronavirus disease 2019 pneumonia requiring high oxygen support.

BACKGROUND: Treatment options for patients with critical Coronavirus Disease 2019 (COVID-19) are limited. This study aimed to describe the clinical characteristics and outcomes associated with remdesivir therapy in patients with COVID-19 who require non-invasive (NIV) ventilation or invasive mechanical ventilation (IMV). METHODS: Data were retrospectively extracted for adults with COVID-19 confirmed using polymerase chain reaction (PCR) between August 1, 2020 and January 28, 2021 who received ≥ 48 hours of remdesivir therapy while on NIV or IMV. Clinical improvement was defined as two-category improvement on an eight-point ordinal severity scale. RESULTS: A total of 133 individuals were included, of which 114 (85.7%) were on NIV and 19 (14.3%) were on IMV at the time of remdesivir initiation. The majority of the patients were males (62.4%), and the median age was 56 years. All the patients received concomitant dexamethasone therapy. Remdesivir treatment was commenced after a median of 7 days from onset of symptoms and was continued for a median of 5 days. Clinical improvement within 28 days was achieved in 101 patients (75.9%); among which, 78.1% and 63.2% were subjected to baseline NIV and IMV, respectively. Among the 11 (8.3%) patients who died of any cause by day 28, 9 (7.9%) and 2 (10.5%) were subjected to baseline NIV and IMV, respectively. The most frequent adverse events were sinus bradycardia (21, 13.1%) and alanine transaminase increase (18, 11.3%). Almost all adverse events were classified as Grades 1-3. CONCLUSION: The use of remdesivir in combination with systemic corticosteroids is associated with high recovery rates and low all-cause mortality in patients with COVID-19 pneumonia who require NIV or IMV. The results need confirmation from clinical trials of appropriate design and size.

The association between tobacco use and COVID-19 in Qatar.

The effects of smoking on COVID-19 are controversial. Some studies show no link between smoking and severe COVID-19, whereas others demonstrate a significant link. This cross-sectional study aims to determine the prevalence of tobacco use among COVID-19 patients, examine the relationship between tobacco use and hospitalized COVID-19 (non-severe and severe), and quantify its risk factors. A random sample of 7430 COVID-19 patients diagnosed between 27 February-30 May 2020 in Qatar were recruited over the telephone to complete an interviewer-administered questionnaire. The prevalence of tobacco smoking in the total sample was 11.0%, with 12.6% among those quarantined, 5.7% among hospitalized patients, and 2.5% among patients with severe COVID-19. Smokeless tobacco and e-cigarette use were reported by 3.2% and 0.6% of the total sample, respectively. We found a significant lower risk for hospitalization and severity of COVID-19 among current tobacco smokers (p < 0.001) relative to non-smokers (never and ex-smokers). Risk factors significantly related to an increased risk of being hospitalized with COVID-19 were older age (aged 55 + ), being male, non-Qatari, and those with heart disease, hypertension, diabetes, asthma, cancer, and chronic renal disease. Smokeless tobacco use, older age (aged 55 + ), being male, non-Qatari, previously diagnosed with heart disease and diabetes were significant risk factors for severe COVID-19. Our data suggests that only smokeless tobacco users may be at an increased risk for severe disease, yet this requires further investigation as other studies have reported smoking to be associated with an increased risk of greater disease severity.

The initial impact of a national BNT162b2 mRNA COVID-19 vaccine rollout.

OBJECTIVE: This study examined the initial impact of a national BNT162b2 vaccine rollout on SARS-CoV-2 infections in Qatar. METHODS: All individuals who had completed ≥14 days of follow-up by 16 March 2021 after receiving the BNT162b2 vaccine were included. This study calculated incidence rates (IR) and their 95% confidence intervals (CI) during days 1-7, 8-14, 15-21, 22-28, and >28 days post-vaccination. Poisson regression was used to calculate incidence rate ratios (IRR) relative to the first 7-day post-vaccination period. RESULTS: A total of 199,219 individuals with 6,521,124 person-days of follow-up were included. SARS-CoV-2 infection was confirmed in 1877 (0.9%), of which 489 (26.1%) were asymptomatic and 123 (6.6%) required oxygen support. The median time from first vaccination to SARS-CoV-2 confirmation was 11.9 days (IQR 7.7-18.2). Compared with the first 7-day post-vaccination period, SARS-CoV-2 infections were lower by 65.8-84.7% during 15-21, 22-28, and >28 days (P < 0.001 for each). For severe COVID-19, the incidence rates were 75.7-93.3% lower during the corresponding time periods (P < 0.001 for each). CONCLUSION: The results were consistent with an early protective effect of BNT162b2 vaccine against all degrees of SARS-CoV-2 severity.

Convalescent plasma for the treatment of patients with severe coronavirus disease 2019: A preliminary report.

BACKGROUND: The role of convalescent plasma therapy for patients with coronavirus disease 2019 (COVID-19) is unclear. METHODS: We retrospectively compared outcomes in a cohort of critical COVID-19 patients who received standard care (SC Group) and those who, in addition, received convalescent plasma (CP Group). RESULTS: In total, 40 patients were included in each group. The median patient age was 53.5 years (interquartile range [IQR] 42-60.5), and the majority of patients required invasive ventilation (69, 86.2%). Plasma was harvested from donors after a median of 37 days (IQR 31-46) from the first positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) result and 26 days (IQR 21-32) after documented viral clearance; it was administered after a median of 10 days (IQR 9-10) from the onset of symptoms and 2.5 days (IQR 2-4) from admission to intensive care unit. The primary endpoint of improvement in respiratory support status within 28 days was achieved in 26 patients (65%) in the SC Group and 31 patients (77.5%) in the CP Group (p = .32). The 28-day all-cause mortality (12.5% vs. 2.5%; p = .22) and viral clearance (65% vs. 55%; p = .49) were not significantly different between the two groups. Convalescent plasma was not significantly associated with the primary endpoint (adjusted hazard ratio 0.87; 95% confidence interval 0.51-1.49; p = .62). Adverse events were balanced between the two study groups. CONCLUSION: In severe COVID-19, convalescent plasma therapy was not associated with clinical benefits. Randomized trials are required to confirm our findings.

Randomized double-blinded placebo-controlled trial of hydroxychloroquine with or without azithromycin for virologic cure of non-severe Covid-19.

BACKGROUND: Hydroxychloroquine (HC) ± azithromycin (AZ) is widely used for Covid-19. The Qatar Prospective RCT of Expediting Coronavirus Tapering (Q-PROTECT) aimed to assess virologic cure rates of HC±AZ in cases of low-acuity Covid-19. METHODS: Q-PROTECT employed a prospective, placebo-controlled design with blinded randomization to three parallel arms: placebo, oral HC (600 mg daily for one week), or oral HC plus oral AZ (500 mg day one, 250 mg daily on days two through five). At enrollment, non-hospitalized participants had mild or no symptoms and were within a day of Covid-19 positivity by polymerase chain reaction (PCR). After six days, intent-to-treat (ITT) analysis of the primary endpoint of virologic cure was assessed using binomial exact 95% confidence intervals (CIs) and χ2 testing. (ClinicalTrials.gov NCT04349592, trial status closed to new participants.). FINDINGS: The study enrolled 456 participants (152 in each of three groups: HC+AZ, HC, placebo) between 13 April and 1 August 2020. HC+AZ, HC, and placebo groups had 6 (3·9%), 7 (4·6%), and 9 (5·9%) participants go off study medications before completing the medication course (p = 0·716). Day six PCR results were available for all 152 HC+AZ participants, 149/152 (98·0%) HC participants, and 147/152 (96·7%) placebo participants. Day six ITT analysis found no difference (p = 0·821) in groups' proportions achieving virologic cure: HC+AZ 16/152 (10·5%), HC 19/149 (12·8%), placebo 18/147 (12·2%). Day 14 assessment also showed no association (p = 0·072) between study group and viral cure: HC+AZ 30/149 (20·1%,), HC 42/146 (28·8%), placebo 45/143 (31·5%). There were no serious adverse events. INTERPRETATION: HC±AZ does not facilitate virologic cure in patients with mild or asymptomatic Covid-19. FUNDING: The study was supported by internal institutional funds of the Hamad Medical Corporation (government health service of the State of Qatar).

The first consecutive 5000 patients with Coronavirus Disease 2019 from Qatar; a nation-wide cohort study.

BACKGROUND: There are limited data on Coronavirus Disease 2019 (COVID-19) outcomes at a national level, and none after 60 days of follow up. The aim of this study was to describe national, 60-day all-cause mortality associated with COVID-19, and to identify risk factors associated with admission to an intensive care unit (ICU). METHODS: This was a retrospective cohort study including the first consecutive 5000 patients with COVID-19 in Qatar who completed 60 days of follow up by June 17, 2020. The primary outcome was all-cause mortality at 60 days after COVID-19 diagnosis. In addition, we explored risk factors for admission to ICU. RESULTS: Included patients were diagnosed with COVID-19 between February 28 and April 17, 2020. The majority (4436, 88.7%) were males and the median age was 35 years [interquartile range (IQR) 28-43]. By 60 days after COVID-19 diagnosis, 14 patients (0.28%) had died, 10 (0.2%) were still in hospital, and two (0.04%) were still in ICU. Fatal COVID-19 cases had a median age of 59.5 years (IQR 55.8-68), and were mostly males (13, 92.9%). All included pregnant women (26, 0.5%), children (131, 2.6%), and healthcare workers (135, 2.7%) were alive and not hospitalized at the end of follow up. A total of 1424 patients (28.5%) required hospitalization, out of which 108 (7.6%) were admitted to ICU. Most frequent co-morbidities in hospitalized adults were diabetes (23.2%), and hypertension (20.7%). Multivariable logistic regression showed that older age [adjusted odds ratio (aOR) 1.041, 95% confidence interval (CI) 1.022-1.061 per year increase; P < 0.001], male sex (aOR 4.375, 95% CI 1.964-9.744; P < 0.001), diabetes (aOR 1.698, 95% CI 1.050-2.746; P 0.031), chronic kidney disease (aOR 3.590, 95% CI 1.596-8.079, P 0.002), and higher BMI (aOR 1.067, 95% CI 1.027-1.108 per unit increase; P 0.001), were all independently associated with increased risk of ICU admission. CONCLUSIONS: In a relatively younger national cohort with a low co-morbidity burden, COVID-19 was associated with low all-cause mortality. Independent risk factors for ICU admission included older age, male sex, higher BMI, and co-existing diabetes or chronic kidney disease.

Tocilizumab for the treatment of severe coronavirus disease 2019.

Tocilizumab, an interleukin-6 inhibitor, may ameliorate the inflammatory manifestations associated with severe coronavirus disease 2019 (COVID-19) and thus improve clinical outcomes. This was a retrospective review of patients with laboratory-confirmed severe COVID-19 who received tocilizumab and completed 14 days of follow up. Twenty-five patients were included, median age was 58 years (interquartile range, 50-63) and the majority were males (92%). Co-morbidities included diabetes mellitus (48%), chronic kidney disease (16%), and cardiovascular disease (12%). Fever (92%), cough (84%), and dyspnea (72%) were the commonest presenting symptoms. All patients received at least two concomitant investigational antiviral agents. Median oral temperature was on day 1, 3, and 7 was 38.0°C, 37.3°C (P = .043), and 37.0°C (P = .064), respectively. Corresponding median C-reactive protein was 193 and 7.9 mg/L (P < .0001) and <6 mg/L (P = .0001). Radiological improvement was noted in 44% of patients by day 7% and 68% by day 14. Nine patients (36%) were discharged alive from intensive care unit and three (12%) died. The proportion of patients on invasive ventilation declined from (84%) at the time of tocilizumab initiation to 60% on day 7 (P = .031) and 28% on day 14 (P = .001). The majority (92%) of patients experienced at least one adverse event. However, it is not possible to ascertain which adverse events were directly related to tocilizumab therapy. In patients with severe COVID-19, tocilizumab was associated with dramatic decline in inflammatory markers, radiological improvement and reduced ventilatory support requirements. Given the study's limitations, the results require assessment in adequately powered randomized controlled trials.