Coronavirus COVID-19 Update for April 11, 2021

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Clinical Reports

Efficacy and safety of azithromycin in Covid-19 patients: A systematic review and meta-analysis of randomized clinical trials
Azithromycin (AZM) is commonly used in Covid-19 patients based on low-quality evidence, increasing the risk of developing adverse events and antimicrobial resistance. The current systematic review and meta-analysis investigated the safety and efficacy of AZM in treating Covid-19 patients using published randomized controlled trials. Google Scholar, PubMed, Scopus, Cochrane Library, Clinical Trials.gov, MEDLINE, bioRxiv and medRxiv were searched for relevant studies. The random-effects model was used to pool estimates using the Paule-Mandel estimate for heterogeneity. The odds ratio and raw difference in medians were used for dichotomous and continuous outcomes, respectively. The analysis included seven studies with 8822 patients (median age, 55.8 years; 61% males). The risk of bias was assessed as 'low' for five of the seven mortality results and as 'some concerns' and 'high' in one trial each. There were 657/3100 (21.2%) and 1244/5654 (22%) deaths among patients randomized to AZM and standard of care, respectively. The use of AZM was not associated with mortality in Covid-19 patients (OR = 0.96, 95% CI 0.88-1.05, p = 0.317 based on the random-effect meta-analysis). The use of AZM was not associated with need for invasive mechanical ventilation (OR = 0.96, 95% CI 0.49-1.87, p = 0.85) and length of stay (Δ = 1.11, 95% CI -2.08 to 4.31, p = 0.49). The results show that using AZM as routine therapy in Covid-19 patients is not justified due to lack of efficacy and potential risk of bacterial resistance that is not met by an increased clinical benefit.
Characterization of Bacterial and Fungal Infections in Hospitalized Patients With Coronavirus Disease 2019 and Factors Associated With Health Care-Associated Infections
Patients hospitalized with coronavirus disease 2019 (COVID-19) are at increased risk of health care–associated infections (HAIs), especially with prolonged hospital stays. This study sought to identify incidence, antimicrobial susceptibilities, and outcomes associated with bacterial/fungal secondary infections in a large cohort of patients with COVID-19. Adult patients diagnosed with COVID-19 between 2 March and 31 May 2020 and hospitalized >24 hours were evaluated. Data extracted from medical records included diagnoses, vital signs, laboratory results, microbiological data, and antibiotic use. Microbiologically confirmed bacterial and fungal pathogens from clinical cultures were evaluated to characterize community- and health care–associated infections, including describing temporal changes in predominant organisms on presentation and throughout hospitalization. Univariable and multivariable logistic regression analyses were performed to investigate risk factors for HAIs. A total of 3028 patients were included and accounted for 899 positive clinical cultures. Overall, 516 (17%) patients with positive cultures met criteria for infection. Community-associated coinfections were identified in 183 (6%) patients, whereas HAIs occurred in 350 (12%) patients. Fifty-seven percent of HAIs were caused by gram-negative bacteria and 19% by fungi. Antibiotic resistance increased with longer hospital stays, with incremental increases in the proportion of vancomycin resistance among enterococci and ceftriaxone and carbapenem resistance among Enterobacterales. Intensive care unit stay, invasive mechanical ventilation, and steroids were associated with HAIs. HAIs occur in a small proportion of patients hospitalized with COVID-19 and are most often caused by gram-negative and fungal pathogens. Antibiotic resistance is more prevalent with prolonged hospital stays. Antimicrobial stewardship is imperative in this population to minimize unnecessary broad-spectrum antibiotic use.

Antiviral Therapeutics and Vaccines

Safety and Immunogenicity of a Third Dose of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: A Case Series Objective of this study was to describe antibody responses and vaccine reactions in recipients of solid organ transplants who had a suboptimal response to standard vaccination and subsequently received a third dose of vaccine between 20 March 2021 and 10 May 2021. Of the 6 patients with low-positive antibody titers before the third dose, all had high-positive antibody titers after the third dose. In contrast, of the 24 patients with negative antibody titers before the third dose, only 6 (25%) had high-positive antibody titers after the third dose. Two (8%) had low-positive antibody titers, and 16 (67%) remained negative. The observations support the use of clinical trials to determine whether booster doses to prevent COVID-19 in transplant patients can be incorporated into clinical practice, as they have been for hepatitis B and influenza vaccination
Effect of monoclonal antibody treatment on clinical outcomes in ambulatory patients with COVID-19
Rates of emergency department visits or hospitalizations among ambulatory COVID-19 patients treated with monoclonal antibody (mAb) therapy (n=305) versus untreated patients (n=6354) were compared. Treatment was associated with decreased encounters within 30 days (adjusted OR 0.23; 95%CI 0.15-0.36). These findings support treatment of acute COVID-19 with mAb.
Gilead’s Veklury® (Remdesivir) Associated With a Reduction in Mortality Rate in Hospitalized Patients With COVID-19 Across Three Analyses of Large Retrospective Real-World Data Sets
Gilead Sciences, Inc. today announced positive data from three retrospective studies of the real-world treatment of patients hospitalized with COVID-19, adding to the body of mortality and hospital discharge data for patients treated with Veklury® (remdesivir). The three real-world data analyses presented at WMF include 98,654 patients hospitalized with COVID-19. Two retrospective studies observed treatment trends and outcomes in the U.S. from the HealthVerity and Premier Healthcare databases. A third analysis compared clinical outcomes in patients receiving a 10-day treatment course of Veklury in the extension phase of the global, open-label SIMPLE-Severe study with patients receiving standard of care in a real-world retrospective longitudinal cohort study. All three analyses utilized pre-specified endpoints, best practice methodologies, including robust matching and weighting approaches, and sensitivity analyses, and were conducted in collaboration with independent experts in real-world comparative effectiveness research. Real-world evidence (RWE) analyses of Veklury from other sources are ongoing and may vary in their results or conclusions.

Epidemiology

Assessing the Association Between Social Gatherings and COVID-19 Risk Using Birthdays
This study determined if there is an association between household birthdays, which likely correspond to informal social gatherings, and COVID-19 infection. This cross-sectional study used administrative health care data on 2.9 million households from the first 45 weeks of 2020 and found that, among households in the top decile of county COVID-19 prevalence, those with birthdays had 8.6 more diagnoses per 10 000 individuals compared with households without a birthday, a relative increase of 31% of county-level prevalence, an increase in COVID-19 diagnoses of 15.8 per 10 000 persons after a child birthday, and an increase in COVID-19 diagnoses of 5.8 per 10 000 among households with an adult birthday. Results suggest that events that lead to small and informal social gatherings, such as birthdays, and in particular, children’s birthdays, are a potentially important source in SARS-CoV-2 transmission.
Re-infection with SARS-CoV-2 in Patients Undergoing Serial Laboratory Testing
A better understanding of re-infection after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become one of the healthcare priorities in the current pandemic. This study determined the rate of re-infection, associated factors and mortality during follow up in a cohort of patients with SARS-CoV-2 infection. 9,119 patients with SARS-CoV-2 infection who received serial tests in total of 62 healthcare facilities in United States were analyzed between December 1, 2019 to November 13, 2020. Re-infection was defined by two positive tests separated by interval of greater than 90 days two after resolution of first infection was confirmed by two or more consecutive negative tests. Logistic regression analysis was done to identify demographic and clinical characteristics associated with re-infection. Re-infection was identified in 0.7% (n=63, 95% confidence interval [CI] 0.5%-0.9%) during follow up of 9,119 patients with SARS-CoV-2 infection. The mean period (±standard deviation [SD]) between two positive tests was 116 ± 21 days. A logistic regression analysis identified that asthma (odds ratio [OR] 1.9, 95% CI 1.1-3.2) and nicotine dependence/tobacco use (OR 2.7, 95% CI 1.6-4.5) were associated with re-infection. There was a significantly lower rate of pneumonia, heart failure, and acute kidney injury observed with re-infection compared with primary infection among the 63 patients with re-infection There were two deaths (3.2%) associated with re-infection. A low rate of re-infection confirmed by laboratory tests was observed in a large cohort of patients with SARS-CoV-2 infection. Although re-infection appeared to be milder than primary infection, there was associated mortality.