Antibiotic prescribing in patients with COVID-19: rapid review and meta-analysis

BackgroundThe proportion of patients infected with SARS-CoV-2 that are prescribed antibiotics is uncertain, and may contribute to patient harm and global antibiotic resistance.ObjectiveThe aim was to estimate the prevalence and associated factors of antibiotic prescribing in patients with COVID-19.Data SourcesWe searched MEDLINE, OVID Epub and EMBASE for published literature on human subjects in English up to June 9 2020.Study Eligibility CriteriaWe included randomized controlled trials; cohort studies; case series with ≥10 patients; and experimental or observational design that evaluated antibiotic prescribing.ParticipantsThe study participants were patients with laboratory-confirmed SARS-CoV-2 infection, across all healthcare settings (hospital and community) and age groups (paediatric and adult).MethodsThe main outcome of interest was proportion of COVID-19 patients prescribed an antibiotic, stratified by geographical region, severity of illness and age. We pooled proportion data using random effects meta-analysis.ResultsWe screened 7469 studies, from which 154 were included in the final analysis. Antibiotic data were available from 30 623 patients. The prevalence of antibiotic prescribing was 74.6% (95% CI 68.3–80.0%). On univariable meta-regression, antibiotic prescribing was lower in children (prescribing prevalence odds ratio (OR) 0.10, 95% CI 0.03–0.33) compared with adults. Antibiotic prescribing was higher with increasing patient age (OR 1.45 per 10 year increase, 95% CI 1.18–1.77) and higher with increasing proportion of patients requiring mechanical ventilation (OR 1.33 per 10% increase, 95% CI 1.15–1.54). Estimated bacterial co-infection was 8.6% (95% CI 4.7–15.2%) from 31 studies.ConclusionsThree-quarters of patients with COVID-19 receive antibiotics, prescribing is significantly higher than the estimated prevalence of bacterial co-infection. Unnecessary antibiotic use is likely to be high in patients with COVID-19.     

Bacterial co-infection and secondary infection in patients with COVID-19: a living rapid review and meta-analysis

BackgroundBacterial co-pathogens are commonly identified in viral respiratory infections and are important causes of morbidity and mortality. The prevalence of bacterial infection in patients infected with SARS-CoV-2 is not well understood.AimsTo determine the prevalence of bacterial co-infection (at presentation) and secondary infection (after presentation) in patients with COVID-19.SourcesWe performed a systematic search of MEDLINE, OVID Epub and EMBASE databases for English language literature from 2019 to April 16, 2020. Studies were included if they (a) evaluated patients with confirmed COVID-19 and (b) reported the prevalence of acute bacterial infection.ContentData were extracted by a single reviewer and cross-checked by a second reviewer. The main outcome was the proportion of COVID-19 patients with an acute bacterial infection. Any bacteria detected from non-respiratory-tract or non-bloodstream sources were excluded. Of 1308 studies screened, 24 were eligible and included in the rapid review representing 3338 patients with COVID-19 evaluated for acute bacterial infection. In the meta-analysis, bacterial co-infection (estimated on presentation) was identified in 3.5% of patients (95%CI 0.4–6.7%) and secondary bacterial infection in 14.3% of patients (95%CI 9.6–18.9%). The overall proportion of COVID-19 patients with bacterial infection was 6.9% (95%CI 4.3–9.5%). Bacterial infection was more common in critically ill patients (8.1%, 95%CI 2.3–13.8%). The majority of patients with COVID-19 received antibiotics (71.9%, 95%CI 56.1 to 87.7%).ImplicationsBacterial co-infection is relatively infrequent in hospitalized patients with COVID-19. The majority of these patients may not require empirical antibacterial treatment.     

A prospective multicentre study of the epidemiology and outcomes of bloodstream infection in cirrhotic patients

ObjectivesTo describe the current epidemiology of bloodstream infection (BSI) in patients with cirrhosis; and to analyse predictors of 30-day mortality and risk factors for antibiotic resistance.MethodsCirrhotic patients developing a BSI episode were prospectively included at 19 centres in five countries from September 2014 to December 2015. The discrimination of mortality risk scores for 30-day mortality were compared by area under the receiver operator risk and Cox regression models. Risk factors for multidrug-resistant organisms (MDRO) were assessed with a logistic regression model.ResultsWe enrolled 312 patients. Gram-negative bacteria, Gram-positive bacteria and Candida spp. were the cause of BSI episodes in 53%, 47% and 7% of cases, respectively. The 30-day mortality rate was 25% and was best predicted by the Sequential Organ Failure Assessment (SOFA) and Chronic Liver Failure–SOFA (CLIF-SOFA) score. In a Cox regression model, delayed (>24 hours) antibiotic treatment (hazard ratio (HR) 7.58; 95% confidence interval (CI) 3.29–18.67; p < 0.001), inadequate empirical therapy (HR 3.14; 95% CI 1.93–5.12; p < 0.001) and CLIF-SOFA score (HR 1.35; 95% CI 1.28–1.43; p < 0.001) were independently associated with 30-day mortality. Independent risk factors for MDRO (31% of BSIs) were previous antimicrobial exposure (odds ratio (OR) 2.91; 95% CI 1.73–4.88; p < 0.001) and previous invasive procedures (OR 2.51; 95% CI 1.48–4.24; p 0.001), whereas spontaneous bacterial peritonitis as BSI source was associated with a lower odds of MDRO (OR 0.30; 95% CI 0.12–0.73; p 0.008).ConclusionsMDRO account for nearly one-third of BSI in cirrhotic patients, often resulting in delayed or inadequate empirical antimicrobial therapy and increased mortality rates. Our data suggest that improved prevention and treatment strategies for MDRO are urgently needed in the liver cirrhosis patients.     

National surveillance of bacterial and fungal coinfection and secondary infection in COVID-19 patients in England: lessons from the first wave

ObjectivesThe impact of bacterial/fungal infections on the morbidity and mortality of persons with coronavirus disease 2019 (COVID-19) remains unclear. We have investigated the incidence and impact of key bacterial/fungal infections in persons with COVID-19 in England.MethodsWe extracted laboratory-confirmed cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (1st January 2020 to 2nd June 2020) and blood and lower-respiratory specimens positive for 24 genera/species of clinical relevance (1st January 2020 to 30th June 2020) from Public Health England's national laboratory surveillance system. We defined coinfection and secondary infection as a culture-positive key organism isolated within 1 day or 2–27 days, respectively, of the SARS-CoV-2-positive date. We described the incidence and timing of bacterial/fungal infections and compared characteristics of COVID-19 patients with and without bacterial/fungal infection.Results1% of persons with COVID-19 (2279/223413) in England had coinfection/secondary infection, of which >65% were bloodstream infections. The most common causative organisms were Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae. Cases with coinfection/secondary infections were older than those without (median 70 years (IQR 58–81) versus 55 years (IQR 38–77)), and a higher percentage of cases with secondary infection were of Black or Asian ethnicity than cases without (6.7% versus 4.1%, and 9.9% versus 8.2%, respectively, p < 0.001). Age-sex-adjusted case fatality rates were higher in COVID-19 cases with a coinfection (23.0% (95%CI 18.8–27.6%)) or secondary infection (26.5% (95%CI 14.5–39.4%)) than in those without (7.6% (95%CI 7.5–7.7%)) (p < 0.005).ConclusionsCoinfection/secondary bacterial/fungal infections were rare in non-hospitalized and hospitalized persons with COVID-19, varied by ethnicity and age, and were associated with higher mortality. However, the inclusion of non-hospitalized persons with asymptomatic/mild COVID-19 likely underestimated the rate of secondary bacterial/fungal infections. This should inform diagnostic testing and antibiotic prescribing strategy.     

Recommendations for antibacterial therapy in adults with COVID-19 – an evidence based guideline

ScopeThe Dutch Working Party on Antibiotic Policy constituted a multidisciplinary expert committee to provide evidence-based recommendation for the use of antibacterial therapy in hospitalized adults with a respiratory infection and suspected or proven 2019 Coronavirus disease (COVID-19).MethodsWe performed a literature search to answer four key questions. The committee graded the evidence and developed recommendations by using Grading of Recommendations Assessment, Development, and Evaluation methodology.Questions addressed by the guideline and RecommendationsWe assessed evidence on the risk of bacterial infections in hospitalized COVID-19 patients, the associated bacterial pathogens, how to diagnose bacterial infections and how to treat bacterial infections. Bacterial co-infection upon admission was reported in 3.5% of COVID-19 patients, while bacterial secondary infections during hospitalization occurred up to 15%. No or very low quality evidence was found to answer the other key clinical questions. Although the evidence base on bacterial infections in COVID-19 is currently limited, available evidence supports restrictive antibiotic use from an antibiotic stewardship perspective, especially upon admission. To support restrictive antibiotic use, maximum efforts should be undertaken to obtain sputum and blood culture samples as well as pneumococcal urinary antigen testing. We suggest to stop antibiotics in patients who started antibiotic treatment upon admission when representative cultures as well as urinary antigen tests show no signs of involvement of bacterial pathogens after 48 hours. For patients with secondary bacterial respiratory infection we recommend to follow other guideline recommendations on antibacterial treatment for patients with hospital-acquired and ventilator-associated pneumonia. An antibiotic treatment duration of five days in patients with COVID-19 and suspected bacterial respiratory infection is recommended upon improvement of signs, symptoms and inflammatory markers. Larger, prospective studies about the epidemiology of bacterial infections in COVID-19 are urgently needed to confirm our conclusions and ultimately prevent unnecessary antibiotic use during the COVID-19 pandemic.     

Clinical outcomes of COVID-19 in patients with rheumatic diseases: A systematic review and meta-analysis of global data

ObjectivesThe impact of rheumatic diseases on COVID-19 infection remains poorly investigated. Here we performed a systematic review and meta-analysis to evaluate the outcomes of COVID-19 in patients with rheumatic diseases.MethodsWe systematically searched PubMed, Embase, Cochrane Library, Scopus and preprint database up to 29th August 2020, for publications with confirmed COVID-19 infection in patients with rheumatic diseases. The primary outcomes were the rates of hospitalization, oxygen support, intensive care unit (ICU) admission and death. A meta-analysis of effect sizes using the random-effects models was performed, and meta-regression analyses were performed to explore heterogeneity. The data from the COVID-19 Global Rheumatology Alliance physician registry (the COVID-19 GRA) was used as a reference.ResultsA total of 31 articles involving 1138 patients were included in this systematic review and meta-analysis. The publications were from Europe, Asia and North America, but none from other continents. The overall rates of hospitalization, oxygen support, ICU admission and fatality among COVID-19 infected patients with rheumatic diseases were 0.58 (95% confidence interval (CI) 0.48–0.67), 0.33 (95% CI 0.21–0.47), 0.09 (95% CI 0.05–0.15) and 0.07 (95% CI 0.03–0.11), respectively. The rate of oxygen support in Europe (0.48, 95% CI 0.4–0.57) was higher than that in other continents. Among all hospitalized patients, the rates of oxygen support, ICU admission and fatality were 0.61 (95% CI 0.48–0.73), 0.13 (95% CI 0.07–0.21) and 0.13 (95% CI 0.09–0.18), respectively. The fatality rate was highest in Europe (0.19, 95% CI 0.15–0.24). The fatality rate was higher both in this meta-analysis and the COVID-19 GRA (7.0% and 6.7%, respectively) than that (3.4%) in WHO database, although the age, gender and comorbidity were not matched.ConclusionPatients with rheumatic diseases remain vulnerable with substantial rates of severe outcomes and a geographic variation. More studies were urgently needed to elucidate the risk factors of severe outcomes in this population.     

Predictors of multidrug-resistant Pseudomonas aeruginosa in neutropenic patients with bloodstream infection

ObjectivesTo assess risk factors for multidrug-resistant Pseudomonas aeruginosa (MDR-PA) infection in neutropenic patients.MethodsSingle-centre retrospective analysis of consecutive bloodstream infection (BSI) episodes (2004–2017, Barcelona). Two multivariate regression models were used at BSI diagnosis and P. aeruginosa detection. Significant predictors were used to establish rules for stratifying patients according to MDR-PA BSI risk.ResultsOf 661 Gram-negative BSI episodes, 190 (28.7%) were caused by P. aeruginosa (70 MDR-PA). Independent factors associated with MDR-PA among Gram-negative organisms were haematological malignancy (OR 3.30; 95% CI 1.15–9.50), pulmonary source of infection (OR 7.85; 95% CI 3.32–18.56), nosocomial-acquired BSI (OR 3.52; 95% CI 1.74–7.09), previous antipseudomonal cephalosporin (OR 13.66; 95% CI 6.64–28.10) and piperacillin/tazobactam (OR 2.42; 95% CI 1.04–5.63), and BSI occurring during ceftriaxone (OR 4.27; 95% CI 1.15–15.83). Once P. aeruginosa was identified as the BSI aetiological pathogen, nosocomial acquisition (OR 7.13; 95% CI 2.87–17.67), haematological malignancy (OR 3.44; 95% CI 1.07–10.98), previous antipseudomonal cephalosporin (OR 3.82; 95% CI 1.42–10.22) and quinolones (OR 3.97; 95% CI 1.37–11.48), corticosteroids (OR 2.92; 95% CI 1.15–7.40), and BSI occurring during quinolone (OR 4.88; 95% CI 1.58–15.05) and β-lactam other than ertapenem (OR 4.51; 95% CI 1.45–14.04) were independently associated with MDR-PA. Per regression coefficients, 1 point was assigned to each parameter, except for nosocomial-acquired BSI (3 points). In the second analysis, a score >3 points identified 60 (86.3%) out of 70 individuals with MDR-PA BSI and discarded 100 (84.2%) out of 120 with non-MDR-PA BSI.ConclusionsA simple score based on demographic and clinical factors allows stratification of individuals with bacteraemia according to their risk of MDR-PA BSI, and may help facilitate the use of rapid MDR-detection tools and improve early antibiotic appropriateness.     

Assessing the impact of coronavirus disease 2019 on mortality: a population-based,matched case-control study

ObjectivesEstimating the isolated effect of coronavirus disease 2019 (COVID-19) on the risk of mortality is challenging. We aimed to determine whether COVID-19 was associated with high rates of mortality independently of age, sex and underlying disorders.MethodsA population-based, matched, case-control study of adults insured by Clalit Health Services was performed. Cases were defined as patients who died of all causes between July and December 2020. Each case was matched in a ratio of 1:1 with a living control based on age, sex and co-morbidities. An unconditional logistic regression analysis was performed to identify independent risk factors for mortality.ResultsA total of 2874 patients who died were successfully matched with 2874 living controls. The prevalence of COVID-19 was higher among the patients who died than among the controls (13.5% [387/2874] vs. 4% [115/2874], respectively; OR, 3.73; 95% CI, 3.01–4.63; p < 0.001). A significantly increased odds of mortality was also observed in patients with COVID-19 without underlying diseases (OR, 3.67; 95% CI, 2.58–5.23) and in patients with COVID-19 and underlying diseases (OR, 3.77; 95% CI, 2.87–4.94). A multi-variate logistic analysis showed that COVID-19 (OR, 2.01; 95% CI, 1.07–3.77), low socio-economic status (OR, 1.36; 95% CI, 1.02–1.82), dementia (OR, 2.50; 95% CI, 2.10–3.01), smoking (OR, 1.35; 95% CI, 1.13–1.63) and an interaction variable of age >80 years and COVID-19 (OR, 2.27; 95% CI, 1.14–4.54) were independent risk factors for mortality, whereas influenza vaccination and high body mass index were associated with lower rates of mortality.ConclusionTesting positive for COVID-19 increased the risk of death three folds, regardless of underlying disorders. These results emphasize the effect of COVID-19 on mortality during the early period of the COVID-19 outbreak, when no vaccines or effective therapeutics were available.     

Non-occupational and occupational factors associated with specific SARS-CoV-2 antibodies among hospital workers – A multicentre cross-sectional study

ObjectivesProtecting healthcare workers (HCWs) from coronavirus disease-19 (COVID-19) is critical to preserve the functioning of healthcare systems. We therefore assessed seroprevalence and identified risk factors for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) seropositivity in this population.MethodsBetween 22 June 22 and 15 August 2020, HCWs from institutions in northern/eastern Switzerland were screened for SARS-CoV-2 antibodies. We recorded baseline characteristics, non-occupational and occupational risk factors. We used pairwise tests of associations and multivariable logistic regression to identify factors associated with seropositivity.ResultsAmong 4664 HCWs from 23 healthcare facilities, 139 (3%) were seropositive. Non-occupational exposures independently associated with seropositivity were contact with a COVID-19-positive household (adjusted OR 59, 95% CI 33–106), stay in a COVID-19 hotspot (aOR 2.3, 95% CI 1.2–4.2) and male sex (aOR 1.9, 95% CI 1.1–3.1). Blood group 0 vs. non-0 (aOR 0.5, 95% CI 0.3–0.8), active smoking (aOR 0.4, 95% CI 0.2–0.7), living with children <12 years (aOR 0.3, 95% CI 0.2–0.6) and being a physician (aOR 0.2, 95% CI 0.1–0.5) were associated with decreased risk. Other occupational risk factors were close contact to COVID-19 patients (aOR 2.7, 95% CI 1.4–5.4), exposure to COVID-19-positive co-workers (aOR 1.9, 95% CI 1.1–2.9), poor knowledge of standard hygiene precautions (aOR 1.9, 95% CI 1.2–2.9) and frequent visits to the hospital canteen (aOR 2.3, 95% CI 1.4–3.8).DiscussionLiving with COVID-19-positive households showed the strongest association with SARS-CoV-2 seropositivity. We identified several potentially modifiable work-related risk factors, which might allow mitigation of the COVID-19 risk among HCWs. The lower risk among those living with children, even after correction for multiple confounders, is remarkable and merits further study.     

Prevalence of Cardiac Diastolic Dysfunction in HIV-Infected Patients: Results of the HIV-HEART Study

Abstract

Purpose: Antiretroviral therapy has improved the prognosis for many individuals with HIV infection. Consequently, HIV infection has become a chronic and manageable disease with increased risk of cardiovascular disease. Isolated diastolic dysfunction (DD) may be the first indication of underlying cardiac disease and an early marker of coronary artery disease. Our aim was to assess the prevalence of DD in HIV-infected patients. Methods: In this cross-sectional cohort study, 698 unselected patients were included. All subjects underwent two-dimensional transthoracic echocardiography with tissue Doppler imaging. Results: The prevalence of DD among the HIV-infected patients was 48%. Patients with DD were characterized by older age, higher body mass index, higher total cholesterol, arterial hypertension, and diabetes mellitus. Diabetes mellitus and arterial hypertension were associated with approximately four times the risk for DD (odds ratio [OR] 3.9, 95% CI 1.65–9.17; OR 3.8, 95% CI 2.49–5.71, respectively). Persons with hyperlipidemia were approximately one and a half times more likely to have DD than those without hyperlipidemia (OR 1.5, 95% CI 1.12–2.07). Conclusions: In our study, an impressive high prevalence of DD in HIV-infected patients was demonstrated. Traditional cardiovascular risk factors substantially contributed to the development of DD in the HIV-infected cohort.     

The effect of preoperative oral antibiotic use on the risk of periprosthetic joint infection after primary knee or hip replacement: a retrospective study with a 1-year follow-up

ObjectivesAntibiotics are used for various reasons before elective joint replacement surgery. The aim of this study was to investigate patients' use of oral antibiotics before joint replacement surgery and how this affects the risk for periprosthetic joint infection (PJI).MethodsPatients having a primary hip or knee replacement in a tertiary care hospital between September 2002 and December 2013 were identified (n = 23 171). Information on oral antibiotic courses purchased 90 days preoperatively and patients' chronic diseases was gathered. Patients with a PJI in a 1-year follow-up period were identified. The association between antibiotic use and PJI was examined using a multivariable logistic regression model and propensity score matching.ResultsOne hundred and fifty-eight (0.68%) cases of PJI were identified. In total, 4106 (18%) joint replacement operations were preceded by at least one course of antibiotics. The incidence of PJI for patients with preoperative use of oral antibiotics was 0.29% (12/4106), whereas for patients without antibiotic use it was 0.77% (146/19 065). A preoperative antibiotic course was associated with a reduced risk for subsequent PJI in the multivariable model (OR 0.40, 95% CI 0.22–0.73). Similar results were found in the propensity score matched material (OR 0.34, 95% CI 0.18–0.65).ConclusionsThe use of oral antibiotics before elective joint replacement surgery is common and has a potential effect on the subsequent risk for PJI. Nevertheless, indiscriminate use of antibiotics before elective joint replacement surgery cannot be recommended, even though treatment of active infections remains an important way to prevent surgical site infections.     

SARS-CoV-2 exposures of healthcare workers from primary care,long-term care facilities and hospitals: a nationwide matched case-control study

ObjectivesThis study assessed the roles of various exposures and personal protective equipment (PPE) use on healthcare workers' (HCWs) risk of COVID-19 working in primary care, long-term-care facilities or hospitals.MethodsWe conducted a matched case-control (1:1) study (10 April through 9 July 2021). Cases (HCWs with confirmed COVID-19) and controls (HCWs without any COVID-19-positive test or symptoms) were invited by E-mail to complete an online questionnaire on their exposures and PPE use over the 10-day period preceding inclusion. Risk factors were analysed using multivariable conditional logistic regression.ResultsA total of 2076 cases and 2076 matched controls were included. The analysis retained exposure to an infected person outside work (adjusted OR 19.9 (95% CI, 12.4–31.9)), an infected colleague (OR 2.26 (95% CI, 1.53–3.33)) or COVID-19 patients (OR 2.37 (95% CI, 1.66–3.40)), as independent predictors of COVID-19 in HCWs, while partial (OR 0.30 (95% CI, 0.22–0.40)) or complete (OR 0.19 (95% CI, 0.14–0.27)) immunisation was protective. Eye protection (OR 0.57 (95% CI, 0.37–0.87)) and wearing a gown (OR 0.58 (95% CI, 0.34–0.97)) for COVID-19 patient care were protective, while wearing an apron slightly increased the risk of infection (OR 1.47 (95% CI, 1.00–2.18)). Protection of N95 respirators and surgical face masks did not differ. Compared to medical professions, being a nurse (OR 3.79 (95% CI, 2.50–5.76)) or a nurse's aide (OR 9.08 (95% CI, 5.30–15.5)) was associated with COVID-19. Results were consistent across all healthcare settings.DiscussionHCWs were more likely to get COVID-19 in their personal sphere than during occupational activities. Our results suggest that eye protection for HCWs during patient care should be actively promoted.     

Utility of prior cultures in predicting antibiotic resistance of bloodstream infections due to Gram-negative pathogens: a multicentre observational cohort study

ObjectivesAppropriate empiric antibiotic therapy in patients with bloodstream infections due to Gram-negative pathogens can improve outcomes. We evaluated the utility of prior microbiologic results for guiding empiric treatment in Gram-negative bloodstream infections.MethodsWe conducted a multicentre observational cohort study in two large health systems in Canada and the United States, including 1832 hospitalized patients with Gram-negative bloodstream infection (community, hospital and intensive care unit acquired) from April 2010 to March 2015.ResultsAmong 1832 patients with Gram-negative bloodstream infection, 28% (n = 504) of patients had a documented prior Gram-negative organism from a nonscreening culture within the previous 12 months. A most recent prior Gram-negative organism resistant to a given antibiotic was strongly predictive of the current organism's resistance to the same antibiotic. The overall specificity was 0.92 (95% confidence interval (CI) 0.91–0.93), and positive predictive value was 0.66 (95% CI 0.61–0.70) for predicting antibiotic resistance. Specificities and positive predictive values ranged from 0.77 to 0.98 and 0.43 to 0.78, respectively, across different antibiotics, organisms and patient subgroups. Increasing time between cultures was associated with a decrease in positive predictive value but not specificity. An heuristic based on a prior resistant Gram-negative pathogen could have been applied to one in four patients and in these patients would have changed therapy in one in five.ConclusionsIn patients with a bloodstream infection with a Gram-negative organism, identification of a most recent prior Gram-negative organism resistant to a drug of interest (within the last 12 months) is highly specific for resistance and should preclude use of that antibiotic.     

Nationwide effectiveness of five SARS-CoV-2 vaccines in Hungary—the HUN-VE study

ObjectivesThe Hungarian vaccination campaign was conducted with five different vaccines during the third wave of the coronavirus disease 2019 (COVID-19) pandemic in 2021. This observational study (HUN-VE: Hungarian Vaccine Effectiveness) estimated vaccine effectiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19-related mortality in 3.7 million vaccinated individuals.MethodsIncidence rates of SARS-CoV-2 infection and COVID-19-related mortality were calculated using data from the National Public Health Centre surveillance database. Estimated vaccine effectiveness was calculated as 1 – incidence rate ratio ≥7 days after the second dose for each available vaccine versus an unvaccinated control group using mixed-effect negative binomial regression controlling for age, sex and calendar day.ResultsBetween 22 January 2021 and 10 June 2021, 3 740 066 Hungarian individuals received two doses of the BNT162b2 (Pfizer-BioNTech), HB02 (Sinopharm), Gam-COVID-Vac (Sputnik-V), AZD1222 (AstraZeneca), or mRNA-1273 (Moderna) vaccines. Incidence rates of SARS-CoV-2 infection and COVID-19-related death were 1.73–9.3/100 000 person-days and 0.04–0.65/100 000 person-days in the fully vaccinated population, respectively. Estimated adjusted effectiveness varied between 68.7% (95% CI 67.2%–70.1%) and 88.7% (95% CI 86.6%–90.4%) against SARS-CoV-2 infection, and between 87.8% (95% CI 86.1%–89.4%) and 97.5% (95% CI 95.6%–98.6%) against COVID-19-related death, with 100% effectiveness in individuals aged 16–44 years for all vaccines.ConclusionsOur observational study demonstrated the high or very high effectiveness of five different vaccines in the prevention SARS-CoV-2 infection and COVID-19-related death.     

Length of hospital stay and risk of intensive care admission and in-hospital death among COVID-19 patients in Norway: a register-based cohort study comparing patients fully vaccinated with an mRNA vaccine to unvaccinated patients

ObjectivesWe estimated the length of stay (LoS) in hospital and the intensive care unit (ICU) and risk of admission to ICU and in-hospital death among COVID-19 patients ≥18 years in Norway who had been fully vaccinated with an mRNA vaccine (at least two doses or one dose and previous SARS-CoV-2 infection), compared to unvaccinated patients.MethodsUsing national registry data, we analyzed SARS-CoV-2–positive patients hospitalized in Norway between 1 February and 30 November 2021, with COVID-19 as the main cause of hospitalization. We ran Cox proportional hazards models adjusting for vaccination status, age, sex, county of residence, regional health authority, date of admission, country of birth, virus variant, and underlying risk factors.ResultsWe included 716 fully vaccinated patients (crude overall median LoS: 5.2 days; admitted to ICU: 103 (14%); in-hospital death: 86 (13%)) and 2487 unvaccinated patients (crude overall median LoS: 5.0 days; admitted to ICU: 480 (19%); in-hospital death: 102 (4%)). In adjusted models, fully vaccinated patients had a shorter overall LoS in hospital (adjusted log hazard ratios (aHR) for discharge: 1.61, 95% CI: 1.24–2.08), shorter LoS without ICU (aHR: 1.27, 95% CI: 1.07–1.52), and lower risk of ICU admission (aHR: 0.50, 95% CI: 0.37–0.69) compared to unvaccinated patients. We observed no difference in the LoS in ICU or in risk of in-hospital death between fully vaccinated and unvaccinated patients.DiscussionFully vaccinated patients hospitalized with COVID-19 in Norway have a shorter LoS and lower risk of ICU admission than unvaccinated patients. These findings can support patient management and ongoing capacity planning in hospitals.     

Vaccine effectiveness of ChAdOx1 nCoV-19 against COVID-19 in a socially vulnerable community in Rio de Janeiro,Brazil: a test-negative design study

ObjectivesTo estimate vaccine effectiveness after the first and second dose of ChAdOx1 nCoV-19 against symptomatic COVID-19 and infection in a socially vulnerable community in Brazil when Gamma and Delta were the predominant variants circulating.MethodsWe conducted a test-negative study in the community Complexo da Maré, the largest group of slums (n = 16) in Rio de Janeiro, Brazil, from January 17, 2021 to November 27, 2021. We selected RT-qPCR positive and negative tests from a broad community testing program. The primary outcome was symptomatic COVID-19 (positive RT-qPCR test with at least one symptom) and the secondary outcome was infection (any positive RT-qPCR test). Vaccine effectiveness was estimated as 1 – OR, which was obtained from adjusted logistic regression models.ResultsWe included 10 077 RT-qPCR tests (6,394, 64% from symptomatic and 3,683, 36% from asymptomatic individuals). The mean age was 40 (SD: 14) years, and the median time between vaccination and RT-qPCR testing among vaccinated was 41 (25–75 percentile: 21–62) days for the first dose and 36 (25–75 percentile: 17–59) days for the second dose. Adjusted vaccine effectiveness against symptomatic COVID-19 was 31.6% (95% CI, 12.0–46.8) 21 days after the first dose and 65.1% (95% CI, 40.9–79.4) 14 days after the second dose. Adjusted vaccine effectiveness against COVID-19 infection was 31.0% (95% CI, 12.7–45.5) 21 days after the first dose and 59.0% (95% CI, 33.1–74.8) 14 days after the second dose.DiscussionChAdOx1 nCoV-19 was effective in reducing symptomatic COVID-19 in a socially vulnerable community in Brazil when Gamma and Delta were the predominant variants circulating.     

Predictors of survival in elderly patients with coronavirus disease 2019 admitted to the hospital: derivation and validation of the FLAMINCOV score

ObjectiveTo identify predictors of 30-day survival in elderly patients with coronavirus disease 2019 (COVID-19).MethodsRetrospective cohort study including patients with COVID-19 aged ≥65 years hospitalized in six European sites (January 2020 to May 2021). Data on demographics, comorbidities, clinical characteristics, and outcomes were collected. A predictive score (FLAMINCOV) was developed using logistic regression. Regression coefficients were used to calculate the score. External validation was performed in a cohort including elderly patients from a major COVID-19 centre in Israel. Discrimination was evaluated using the area under the receiver operating characteristic curve (AUC) in the derivation and validation cohorts. Survival risk groups based on the score were derived and applied to the validation cohort.ResultsAmong 3010 patients included in the derivation cohort, 30-day survival was 74.5% (2242/3010). The intensive care unit admission rate was 7.6% (228/3010). The model predicting survival included independent functional status (OR, 4.87; 95% CI, 3.93–6.03), a oxygen saturation to fraction of inspired oxygen (SpO₂/FiO₂₎ ratio of >235 (OR, 3.75; 95% CI, 3.04–4.63), a C-reactive protein level of <14 mg/dL (OR, 2.41; 95% CI, 1.91–3.04), a creatinine level of <1.3 (OR, 2.02; 95% CI, 1.62–2.52) mg/dL, and absence of fever (OR, 1.34; 95% CI, 1.09–1.66). The score was validated in 1174 patients. The FLAMINCOV score ranges from 0 to 15 and showed good discrimination in the derivation (AUC, 0.79; 95% CI, 0.77–0.81; p < 0.001) and validation cohorts (AUC, 0.79; 95% CI, 0.76–0.81; p < 0.001). Thirty-day survival ranged from 39.4% (203/515) to 95.3% (634/665) across four risk groups according to score quartiles in the derivation cohort. Similar proportions were observed in the validation set.DiscussionThe FLAMINCOV score identifying elderly with higher or lower chances of survival may allow better triage and management, including intensive care unit admission/exclusion.     

Development and validation of a prediction model for severe respiratory failure in hospitalized patients with SARS-CoV-2 infection: a multicentre cohort study (PREDI-CO study)

ObjectivesWe aimed to develop and validate a risk score to predict severe respiratory failure (SRF) among patients hospitalized with coronavirus disease-2019 (COVID-19).MethodsWe performed a multicentre cohort study among hospitalized (>24 hours) patients diagnosed with COVID-19 from 22 February to 3 April 2020, at 11 Italian hospitals. Patients were divided into derivation and validation cohorts according to random sorting of hospitals. SRF was assessed from admission to hospital discharge and was defined as: Spo₂ <93% with 100% Fio₂, respiratory rate >30 breaths/min or respiratory distress. Multivariable logistic regression models were built to identify predictors of SRF, β-coefficients were used to develop a risk score. Trial Registration NCT04316949.ResultsWe analysed 1113 patients (644 derivation, 469 validation cohort). Mean (±SD) age was 65.7 (±15) years, 704 (63.3%) were male. SRF occurred in 189/644 (29%) and 187/469 (40%) patients in the derivation and validation cohorts, respectively. At multivariate analysis, risk factors for SRF in the derivation cohort assessed at hospitalization were age ≥70 years (OR 2.74; 95% CI 1.66–4.50), obesity (OR 4.62; 95% CI 2.78–7.70), body temperature ≥38°C (OR 1.73; 95% CI 1.30–2.29), respiratory rate ≥22 breaths/min (OR 3.75; 95% CI 2.01–7.01), lymphocytes ≤900 cells/mm³ (OR 2.69; 95% CI 1.60–4.51), creatinine ≥1 mg/dL (OR 2.38; 95% CI 1.59–3.56), C-reactive protein ≥10 mg/dL (OR 5.91; 95% CI 4.88–7.17) and lactate dehydrogenase ≥350 IU/L (OR 2.39; 95% CI 1.11–5.11). Assigning points to each variable, an individual risk score (PREDI-CO score) was obtained. Area under the receiver-operator curve was 0.89 (0.86–0.92). At a score of >3, sensitivity, specificity, and positive and negative predictive values were 71.6% (65%–79%), 89.1% (86%–92%), 74% (67%–80%) and 89% (85%–91%), respectively. PREDI-CO score showed similar prognostic ability in the validation cohort: area under the receiver-operator curve 0.85 (0.81–0.88). At a score of >3, sensitivity, specificity, and positive and negative predictive values were 80% (73%–85%), 76% (70%–81%), 69% (60%–74%) and 85% (80%–89%), respectively.ConclusionPREDI-CO score can be useful to allocate resources and prioritize treatments during the COVID-19 pandemic.     

Right ventricular dysfunction and pulmonary hypertension in COVID-19: a meta-analysis of prevalence and its association with clinical outcome

IntroductionRapid spread of COVID-19 has caused detrimental effects globally. Involvement of the ACE2 receptor has identified COVID-19 as a multi-organ disease. Preliminary studies have provided evidence that cardiac involvement, including right ventricular dysfunction (RVD) and pulmonary hypertension (PH), were found in COVID-19 cases, even in the non-advanced stage. This meta-analysis aims to analyze the prevalence of RVD and PH, and their association with COVID-19 clinical outcome.Material and methodsA systematic data search was conducted through PubMed, medRxiv, ProQuest, Science Direct, and Scopus databases using constructed keywords based on MeSH terms. Any outcomes regarding mortality, severity, ICU admission, and mechanical ventilation usage were analyzed using RevMan v.5.4 and Stata v.16.ResultsA total of 16 eligible studies (1,728 patients) were included. Pooled prevalence of RVD in COVID-19 was 19% (95% CI: 13–25%), and PH was 22% (95% CI: 14–31%). RVD was associated with increased mortality (OR = 2.98 (95% CI: 1.50–5.89), p = 0.002), severity (OR = 3.61 (95% CI: 2.05–6.35), p < 0.001), ICU admission (OR = 1.70 (95% CI: 1.12–2.56), p = 0.01), and mechanical ventilation (MV) usage (OR = 1.60 (95% CI: 1.14–2.25), p = 0.007). PH was also associated with increased mortality (OR = 5.42 (95% CI: 2.66–11.060, p < 0.001), severity (OR = 5.74 (95% CI: 2.28–14.49), p < 0.001), and ICU admission (OR = 12.83 (95% CI: 3.55–46.41), p < 0.001).ConclusionsRVD and PH were prevalent in COVID-19 and associated with mortality, severity, ICU admission, and MV usage in COVID-19 patients. Bedside echocardiography examination could be considered as a novel risk stratification tool in COVID-19.     

Association of the COVID-19 Pandemic and Low-rescue Suicide Attempts in Patients Visiting the Emergency Department after Attempting Suicide

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic may increase the total number of suicide attempts and the proportion of low-rescue attempts. We investigated the factors affecting low-rescue suicide attempts using the risk-rescue rating scale (RRRS) among patients who visited the emergency department (ED) after attempting suicide before or during the COVID-19 pandemic.MethodsWe retrospectively investigated suicide attempts made by patients who visited our ED from March 2019 to September 2020. Patients were classified into two groups based on whether they attempted suicide before or during the COVID-19 pandemic. Data on demographic variables, psychiatric factors, suicide risk factors and rescue factors were collected and compared.ResultsA total of 518 patients were included in the study, 275 (53.1%) of whom attempted suicide during the COVID-19 pandemic. The proportion of patients who made low-rescue suicide attempts differed before and during the COVID-19 pandemic (37.1% vs. 28.8%) (P = 0.046). However, the proportions of patients who made high-risk suicide attempts and high-lethality suicide attempts did not significantly differ between the two periods. The independent risk factors for low-rescue suicide attempts were age and the COVID-19 pandemic (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.00–1.03; P = 0.006) (OR, 1.52; 95% CI, 1.03–2.25; P = 0.034).ConclusionThe COVID-19 pandemic was associated with low-rescue suicide attempts in patients visiting the ED after attempting suicide. Thus, we need to consider the implementation of measures to prevent low-rescue suicide attempts during similar infectious disease crises.