Epidemiology, microbiological, clinical characteristics, and outcome of Burkholderia cepacia complex infections in non-cystic fibrosis adult patients from Qatar.

Objectives: Burkholderia species infections are associated with diverse and challenging clinical presentations because of distinct virulence and antimicrobial resistance factors. The study aims to evaluate the epidemiology, microbiological, and clinical outcomes of Burkholderia cepacia complex (Bcc) infections in non-cystic fibrosis (CF) patients from Qatar. Methods: A retrospective study was conducted on adult patients across all hospitals at Hamad Medical Corporation between January 2012 and December 2018 to evaluate clinically relevant Bcc in non-CF adult patients. Results: Over 7 years, 72 episodes of Burkholderia species infections were recorded, 64 were secondary to Bcc primarily affecting males (78.12%) with a mean age of 53 years, from the Middle and Southeastern region (92.2%) affected predominantly by diabetes mellitus (34.4%), chronic kidney (23.4%), coronary heart (20.3%), and hypertensive diseases (17.2%) while recent hospitalization and admission to critical care were evident in 45.3% and 93.8% of cases, respectively. Main infection sites were urinary (43.8%) and respiratory (29.7%) with associated bacteremia recorded in 26.6% of cases. Microbiological characteristics demonstrated high-level resistance profiles leading to delayed microbiological clearance in case of bacteremia (61%) and management with multiple therapeutic agents (range 4-6) resulting in disease resolution in 90.6% of cases with observed 30-day mortality of 7.8%. Conclusions: B. cepacia infections are infrequent, recorded mainly in middle-aged males with chronic comorbidities presenting as urinary, respiratory, and bacteremia associated with hospitalization, admission to critical care, and invasive procedures. High-level antimicrobial resistance is observed necessitating multiple therapeutic agents and suboptimal bacteriological clearance.

Evaluation of Hospital Antimicrobial Stewardship Programs: Implementation, Process, Impact, and Outcomes, Review of Systematic Reviews.

Antimicrobial Stewardship Programs (ASP) were introduced in healthcare as a public health priority to promote appropriate prescribing of antimicrobials, to reduce adverse events related to antimicrobials, as well as to control the escalating challenges of antimicrobial resistance. To deliver aimed outcome objectives, ASPs involve multiple connected implementation process measures. A systematic review was conducted to evaluate both concepts of ASPs. Guided by PRISMA frames, published systematic reviews (SR) focusing on ASPs restricted to secondary and tertiary healthcare were evaluated over the past 10 years involving all age groups. Out of 265 identified SR studies, 63 met the inclusion criteria. The majority were conducted in Europe and North America, with limited studies from other regions. In the reviewed studies, all age groups were examined, although they were conducted mainly on adults when compared to children and infants. Both process and outcomes measures of ASPs were examined equally and simultaneously through 25 different concepts, dominated by efficacy, antimicrobial resistance, and economic impact, while information technology as well as role of pharmacy and behavioral factors were equally examined. The main broad conclusions from the review were that, across the globe, ASPs demonstrated effectiveness, proved efficacy, and confirmed efficiency, while focused evaluation advocated that developed countries should target medium- and small-sized hospitals while developing countries should continue rolling ASPs across healthcare facilities. Additionally, the future of ASPs should focus on embracing evolving information technology to bridge the gaps in knowledge, skills, and attitude, as well as to enhance appropriate decision making.

HIV case reporting and HIV treatment outcomes in Qatar.

Aim: The aim of the paper is to provide an overview of available HIV case reporting and treatment data for in Qatar for the period 2015-2020. Methods: HIV case reporting data were analyzed by sex and mode of transmission. To construct HIV care continuum from the data available, we obtained information on the total number of HIV diagnosed patients on antiretroviral treatment (ART) between January 1st 2015 and December 31st 2020, number of patients on ART who had an HIV viral load test and the number who were virally suppressed (defined as having the viral load of less than 1,000 copies/mL). Results: A total of 515 HIV cases were reported to the Ministry of Public Health since beginning of reporting in 1986, and that included Qatari nationals and expatriate residents diagnosed in Qatar. There was an increase in the annual number of newly reported HIV cases from 16 cases in 2015 (of these, 14 were males) to 58 cases in 2020 (of these, 54 were males). The total number of HIV diagnosed people on ART increased from 99 in 2015 to 213 in 2020. During 2020 the overall viral load testing coverage and viral load suppression among those tested for viral load in men were 72.5% and 93.1%, respectively, while in women these values were 60.4% and 84.4%, respectively. Conclusion: Due to increase in newly reported HIV cases, there is a need to develop an effective HIV strategic information system in Qatar and data-driven and targeted national HIV response.

Clinical manifestations and outcome of Mpox infection in Qatar: An observational study during the 2022 outbreak.

Mpox emerged in May 2022 as a global outbreak, mostly in hitherto non-endemic countries. To describe the epidemiological and clinical characteristics of mpox in Qatar, data were retrospectively retrieved for all laboratory-confirmed mpox cases diagnosed in Qatar between May and November 2022. Twelve cases were identified; of which 10 were males, and the median age was 33.5 years (IQR 24.5-37.5). Recent sexual exposure was reported in 9 patients, 6 of which were outside Qatar. Seven individuals reported exclusive heterosexual contact. Pleomorphic skin lesions were present in all cases, with anogenital involvement in 11. Fever (7/12) and lymphadenopathy (4/12) were relatively common. All cases were HIV-negative. The majority of cases had an uncomplicated and self-limiting clinical illness. In conclusion, the majority of early mpox infections in Qatar were purportedly acquired through heterosexual contact, primarily among middle-aged men. The clinical course was mostly uneventful. In the absence of active case finding and the mild and self-limiting nature of the clinical illness, undetected community transmission cannot be ruled out.

Seroprevalence and clinical outcome of hepatitis D infection in Qatar.

Background: Worldwide, 5-10% of people with chronic hepatitis B virus infection are co-infected with hepatitis D virus. In Qatar, there are no data on hepatitis D virus infection among patients positive for hepatitis B surface antigen (HBsAg). Aims: To determine the seroprevalence of hepatitis D virus infection among patients with chronic hepatitis B virus infection in Qatar and assess the characteristics of these patients. Methods: This was a retrospective cohort study of all HBsAg-positive individuals tested for hepatitis D virus between 1 January 2010 and 29 December 2019 within the Hamad Medical Corporation. Data were retrieved from electronic records and included demographic and clinical information of the patients. Results: Of the 2348 HBsAg-positive patients, 125 were positive for hepatitis D virus (seroprevalence 5.3%). The median age of hepatitis D positive patients was significantly higher than for hepatitis D negative patients (P = 0.001). Most of the patients with hepatitis D had a hepatitis B viral load < 2000 IU/mL (53.6%) and were negative for hepatitis B e antigen (93.6%). A significantly greater proportion of hepatitis D positive patients than hepatitis D negative patients were infected with hepatitis C virus (P < 0.001), and had liver cirrhosis (P < 0.001) and hepatocellular carcinoma (P = 0.006). Conclusions: Hepatitis D virus infection is associated with lower hepatitis B virus viraemia and more advanced liver disease in the study population.

Microbiological and clinical characteristics of invasive Group B Streptococcal blood stream infections in children and adults from Qatar.

INTRODUCTION: Group B Streptococci (GBS) colonize almost one third of human gastrointestinal and genitourinary tracts, particularly in females. The aim of this study is to evaluate the epidemiology, microbiological characteristics, and clinical outcomes of invasive GBS disease in Qatar from all age groups. METHODS: A retrospective study was conducted on patients with confirmed GBS blood stream infections during the period between January 2015 and March 2019. Microbiological identification was performed using automated BD PhoenixTM system, while additional antimicrobial susceptibility tests were performed using E test and disc diffusion methods. RESULT: During the four years period, the incidence steadily rose from 1.48 to 2.09 cases per 100.000 population. Out of 196 confirmed cases of invasive GBS infections, the majority were females (63.7%, 125/196) of which 44.8% were pregnant and 53.6% were colonized. Three distinct affected age groups were identified: children ≤ 4 years of age (35.7%), young adults 25-34 (20.9%) and the elderly ≥ 65 year (17.4%). Presenting symptoms were mild with fever in 53% of cases while 89% of cases had Pitt bacteraemia score of ≤ 2. Isolates were universally sensitive to penicillin, ceftriaxone, and vancomycin at 100% but with significant resistance to erythromycin (49%) and clindamycin (28.6%) while 16.8% had inducible clindamycin resistance. Clinical outcomes showed cure rate of 87.25% with complications in (8.76%) and 4% mortality. CONCLUSION: There is a rising trend of Group B Streptococcal blood stream infections in Qatar with significantly high clindamycin and erythromycin resistance rates. Universal susceptibility rates were demonstrated for penicillin, ceftriaxone, and vancomycin.

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.

Evaluation of in Vitro Activity of Ceftazidime/Avibactam and Ceftolozane/Tazobactam against ESBL-producing Enterobacterales Isolated from Intensive Care Units from Qatar.

Objectives: Extended-spectrum -lactamases (ESBLs) mechanism of resistance in Enterobacterales leads to poor clinical outcomes. Ceftazidime/avibactam and ceftolozane/tazobactam are two broad-spectrum antimicrobial combinations that are effective against multidrug-resistant organisms with regional variations. This study aims to evaluate the antimicrobial susceptibility test (AST) for both combinations against ESBL-producing Enterobacterales isolated from intensive care units (ICUs) in tertiary hospitals from November 2012 to October 2013 in Qatar. Methods: A total of 629 Enterobacterales isolates from ICUs were screened for ESBL production using BD-PhoenixTM confirmed by double-disk potentiation, while ESBL-genes were detected by polymerase chain reaction. The ASTs for ceftazidime/avibactam and ceftolozane/tazobactam were assessed by minimum inhibitory concentration (MIC) test strips. A single isolate that was resistant to both combinations was subjected to whole-genome sequencing. Results: The prevalence of ESBL-producing Enterobacterales isolated from ICUs was 17.3% (109/629) with predominance of Klebsiella pneumoniae (56/109; 51.4%) and Escherichia coli (38/109; 34.9%). The susceptibility of ceftazidime/avibactam and ceftolozane/tazobactam against ESBL-producers was 99.1% (108/109) and most (81/109; 74.3%) had MICs < 0.5 for both combinations. The predominant ESBL-gene was blaCTX-M (72/109; 66.1%). A single isolate that was resistant to both combinations harbored multiple ESBL resistant-genes including blaVEB-5 and blaVIM-2. Conclusions: ESBL-producing Enterobacterales isolated from ICUs were predominantly K. pneumoniae and E. coli, mainly harboring blaCTX-M gene. They were highly susceptible to ceftazidime/avibactam and ceftolozane/tazobactam suggesting potential alternatives to currently available therapeutic options.

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.

Epidemiology, microbiological and clinical characteristics of Enterococcus species bloodstream infections: A 10-year retrospective cohort study from Qatar.

Background and objective: Enterococcus species is one of the leading causes of community and healthcare-associated infections resulting in significant morbidity and mortality. In this study, we aim to evaluate the epidemiology, microbiological and clinical characteristics of Enterococcus Blood Stream Infections (BSIs) over 10 years period in a national secondary care setting. Methods: A retrospective cohort study was conducted on verified cases of enterococcal BSIs in adults from January 2009-December 2018 from specialized care hospitals at Hamad Medical Corporation, Qatar. Epidemiological, microbiological and clinical data were reported and analyzed. Results: A total of 263 enterococcus BSIs cases were identified, predominant were males (65%) with a median age of 63 (IQR 48-74). E. faecalis and E. faecium were predominate at 93.5% (73.38% and 20.15% respectively). Diabetes was the commonest premorbid condition (54.3%) followed by chronic kidney disease (36.5%). Central lines and genitourinary were the most common sources (18.25%, 14.83% respectively) while no identified source was reported in 45.25% of cases. Ampicillin susceptibility was 82.51% while vancomycin resistance was reported in 10.6% of isolates. Successful bacteremia clearance was achieved in 81.37% of cases at a mean of 4 days (Range 2-5 days) while metastatic complications occurred in 5.3% of cases. Univariate mortality risk analysis was associated with ICU admission, low level of consciousness, high bacteremia scores, and presence of catheters. The 30 days mortality was high at 66.54% with CKD and cancer patients at the highest mortality risks (OR 16.334 (CI 4.2-62.4) and 16 (CI 3-84) respectively. Conclusion: Significant mortality was associated with enterococcus BSI despite low rates for ampicillin and vancomycin resistance necessitating early identification of susceptible patients to instigate suitable preventive measures.

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.

Clinical characteristics and outcomes of care in patients hospitalized with diabetic ketoacidosis.

AIMS: To assess the clinical characteristics and outcomes of patients hospitalized with DKA. METHODS: We examined the hospital database for patients admitted with DKA to all government hospitals in Qatar over 6 years. RESULTS: We evaluated a total of 1330 patients [(37.3 % with type 1 diabetes (T1DM) and 62.7 % with type 2 diabetes (T2DM)] with 1613 episodes of DKA. Patients with T2DM were older than those with T1DM [48.0 (38.0-60.0), 26.0 (21.0-31.0) years] while there was no difference in DKA severity and laboratory values on admission or time to resolution of DKA. Admission to the intensive care unit was higher (38.9 % vs. 26.6 %; P < 0.001) with a longer hospital stay [5 (2.0-9.0) vs. 2 (2.0-4.0) days, P < 0.001] and markedly higher mortality (7.4 % vs. 1 %; P < 0.001) in patients with T2DM compared to T1DM. On multivariable logistic regression analysis, significant predictors of mortality were older age (odds ratio, 1.11; 95 % CI, 1.07-1.15; P = 0.0001), and admission to the intensive care unit (odds ratio, 3.61; 95 % CI, 1.69-7.72;P = 0.001). CONCLUSION: In this national cohort of patients hospitalized with DKA, those with T2DM had a 7-fold increase in inpatient mortality associated with older age and admission to the intensive care unit.

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 Role of Post-Bronchoscopy Sputum Examination in Screening for Active Tuberculosis.

Early diagnosis is a fundamental component of global tuberculosis control. The objective of this study was to evaluate the diagnostic yield of post-bronchoscopy sputum (PBS) testing as part of a tuberculosis diagnostic work-up. All new residents in the State of Qatar undergo a tuberculosis (TB) screening program. Those with abnormal chest radiology, negative sputum acid-fast bacilli (AFB) smears, and nucleic acid amplification testing (NAAT) for M. tuberculosis, undergo an additional bronchoscopic evaluation for TB. We prospectively enrolled individuals who were going to undergo bronchoscopy to provide two PBS samples for AFB smears and mycobacterial cultures between 18 September 2018 and 12 March 2021. A total of 495 individuals, with a median age of 31 years, were included. The majority of the patients were males (329, 66.5%). The most frequent country of origin was India (131, 26.5%) followed by the Philippines (123, 24.8%). The addition of PBS to bronchoalveolar lavage (BAL) testing allowed microbiological confirmation of tuberculosis in an additional 13 patients (3.9%), resulting in improved sensitivity (from 77.9% to 81.9%), negative predictive value (from 69.2% to 73.2%), and negative likelihood ratio (from 0.22 to 0.18). Where resources are available, the incorporation of routine PBS examination as part of tuberculosis diagnostic work-up can enhance the diagnostic yield.

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.