ABSTRACT
Background. The impact of the COVID-19 pandemic on hospitalization for cardiac infections is not well known. We aimed to evaluate the nationwide trends in hospital stays for myocarditis and endocarditis cases before, during and after the nationwide lockdown for the COVID-19 pandemic in France. We then aimed to describe the proportion of myocarditis and endocarditis patients with and without COVID-19 and their clinical characteristics. Methods. Hospitalized cases of cardiac infection were extracted from the French National Discharge database, which collects the medical records of all patients discharged from all public and private hospitals in France. Age, sex, and available cardiovascular risk factors were compared between stays with and without COVID-19 during the lockdown. Results. The number of myocarditis cases was 11% higher in 2020, compared to the average of the three prior years. In 2020, 439 of 3727 cases of myocarditis were associated with COVID-19. For endocarditis, there was an increase in cases by 7% in 2020 versus prior years. For endocarditis, 3% (240 of 8128 cases) of patients with endocarditis had COVID-19. For myocarditis, older age, hypertension, diabetes, obesity, and atrial fibrillation were more frequent in patients with COVID-19 than in those without. For endocarditis, only hypertension was more frequent in patients with COVID-19 than in those without. Conclusion. Our study reports an increase in hospitalizations for both myocarditis and endocarditis in 2020, possibly related to the COVID-19 pandemic. Interestingly, the trends differ according to the COVID-19 status. Knowledge of the factors associating myocarditis or endocarditis and COVID-19 may improve the quality and the type of monitoring for people with COVID-19, the identification of patients at risk of cardiac infections, and the treatment of COVID-19 patients.
ABSTRACT
Genome-wide CRISPR/Cas9 knock-out genetic screens are powerful approaches to unravel new regulators of viral infections. With the aim of identifying new cellular inhibitors of HIV-1, we have developed a strategy in which we took advantage of the ability of type 1 interferon (IFN) to potently inhibit HIV-1 infection, in order to create a cellular environment hostile to viral replication. This approach led to the identification of the DEAD-box RNA helicase DDX42 as an intrinsic inhibitor of HIV-1. Depletion of endogenous DDX42 using siRNA or CRISPR/Cas9 knock-out increased HIV-1 infection, both in model cell lines and in physiological targets of HIV-1, primary CD4+ T cells and monocyte-derived macrophages (MDMs), and irrespectively of the IFN treatment. Similarly, the overexpression of a dominant-negative mutant of DDX42 positively impacted HIV-1 infection, whereas wild-type DDX42 overexpression potently inhibited HIV-1 infection. The positive impact of endogenous DDX42 depletion on HIV-1 infection was directly correlated to an increase in viral DNA accumulation. Interestingly, proximity ligation assays showed that DDX42, which can be mainly found in the nucleus but is also present in the cytoplasm, was in the close vicinity of HIV-1 Capsid during infection of primary monocyte-derived macrophages. Moreover, we show that DDX42 is also able to substantially decrease infection with other retroviruses and retrotransposition of long interspersed elements-1 (LINE-1). Finally, we reveal that DDX42 potently inhibits other pathogenic viruses, including Chikungunya virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).