ABSTRACT
Résumé Nous rapportons deux cas de réactivation tuberculeuse après COVID-19 sous corticostéroïdes et tocilizumab. Ils ont présenté une lymphopénie, des signes cliniques limités, une présentation radiologique inhabituelle mais des prélèvements microbiologiques positifs. Le dépistage de l'infection tuberculeuse latente (ITL) étant inapproprié dans ce contexte, il faudrait discuter de la traiter systématiquement chez des patients les plus à risque en cas de traitement immunomodulateur.
ABSTRACT
Résumé Nous rapportons deux cas de réactivation tuberculeuse après COVID-19 sous corticostéroïdes et tocilizumab. Ils ont présenté une lymphopénie, des signes cliniques limités, une présentation radiologique inhabituelle mais des prélèvements microbiologiques positifs. Le dépistage de l'infection tuberculeuse latente (ITL) étant inapproprié dans ce contexte, il faudrait discuter de la traiter systématiquement chez des patients les plus à risque en cas de traitement immunomodulateur. We report cases of tuberculosis reactivation after COVID-19 treated with corticosteroids and tocilizumab. Both patients had lymphopenia and limited clinical signs. Radiological findings were unusual but microbiological samples were positive. As screening for latent tuberculosis with IGRA seems unappropriate in this context, latent tuberculosis treatment should be discussed while introducing immunomodulatory treatment for patients at risk.
ABSTRACT
Monoclonal antibodies (MAbs) targeting the Spike glycoprotein of SARS-CoV-2 is a key strategy to prevent severe COVID-19. Here, the efficacy of two monoclonal antibody bitherapies against SARS-CoV-2 was assessed on 92 patients at high risk of severe COVID-19 between March and October 2021 (Bichat-Claude Bernard Hospital, Paris, France). Nine patients died despite appropriate management. From 14 days following treatment initiation, we observed a slower viral load decay for patients treated with the bitherapy Bamlanivimab/Etsevimab compared to the Casirivimab/Imdevimab association therapy (P = 0.045). The emergence of several mutations on the Spike protein known to diminish antiviral efficacy was observed from 1 to 3 weeks after infusion. The Q493R mutation was frequently selected, located in a region of joint structural overlap by Bamlanivimab/Etsevimab antibodies. Despite that this study was done on former SARS-CoV-2 variants (Alpha and Delta), the results provide new insights into resistance mechanisms in SARS-CoV-2 antibodies neutralization escape and should be considered for current and novel variants. IMPORTANCE Monoclonal antibody bitherapies (MAbs) are commonly prescribed to treat severe SARS-CoV-2-positive patients, and the rapid growth of resistance mutation emergence is alarming globally. To explore this issue, we conducted both clinical and genomic analyses of SARS-CoV-2 in a series of patients treated in 2021. We first noticed that the two dual therapies prescribed during the study had different kinetics of viral load decay. Rapidly after initiation of the treatments, resistance mutations emerged in the interface between the MAbs and the target Spike glycoprotein, demonstrating the importance to continuously screen the viral genome during treatment course. Taken together, the results highlight that viral mutations may emerge under selective pressure, conferring a putative competitive advantage, and could rapidly spread, as observed for the Omicron variant.
Subject(s)
COVID-19 Drug Treatment , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus , Antibodies, Monoclonal/therapeutic use , Neutralization Tests , Antibodies, Viral , Antiviral Agents/therapeutic use , Antibodies, NeutralizingABSTRACT
BACKGROUND: The impact of the variant of concern (VOC) Alpha on the severity of COVID-19 has been debated. We report our analysis in France. METHODS: We conducted an exposed/unexposed cohort study with retrospective data collection, comparing patients infected by VOC Alpha to contemporaneous patients infected by historical lineages. Participants were matched on age (± 2.5 years), sex and region of hospitalization. The primary endpoint was the proportion of hospitalized participants with severe COVID-19, defined as a WHO-scale > 5 or by the need of a non-rebreather mask, occurring up to day 29 after admission. We used a logistic regression model stratified on each matched pair and accounting for factors known to be associated with the severity of the disease. RESULTS: We included 650 pairs of patients hospitalized between Jan 1, 2021, and Feb 28, 2021, in 47 hospitals. Median age was 70 years and 61.3% of participants were male. The proportion of participants with comorbidities was high in both groups (85.0% vs 90%, p = 0.004). Infection by VOC Alpha was associated with a higher odds of severe COVID-19 (41.7% vs 38.5%-aOR = 1.33 95% CI [1.03-1.72]). CONCLUSION: Infection by the VOC Alpha was associated with a higher odds of severe COVID-19.
Subject(s)
COVID-19 , SARS-CoV-2 , Aged , Cohort Studies , Female , Hospitalization , Humans , Male , Retrospective StudiesABSTRACT
Coronavirus disease 2019 (CoVID-19) is a viral disease. Although the predominant presentation is respiratory disease, other manifestations such as gastrointestinal manifestations are commonly reported. Nevertheless, it has not been associated with chronic cholangitis or hepatic injury. In this study, we report three cases of severe CoVID-19 infection that required ICU admission, intubation, and sedation with ketamine. All three patients had abnormal liver function despite recovery and were diagnosed with cholangitis in the context of CoVID-19.
ABSTRACT
There is an urgent need to identify optimal antiviral therapies for COVID-19 caused by SARS-CoV-2. We have conducted a rapid and comprehensive review of relevant pharmacological evidence, focusing on (1) the pharmacokinetics (PK) of potential antiviral therapies; (2) coronavirus-specific pharmacodynamics (PD); (3) PK and PD interactions between proposed combination therapies; (4) pharmacology of major supportive therapies; and (5) anticipated drug-drug interactions (DDIs). We found promising in vitro evidence for remdesivir, (hydroxy)chloroquine and favipiravir against SARS-CoV-2; potential clinical benefit in SARS-CoV-2 with remdesivir, the combination of lopinavir/ritonavir (LPV/r) plus ribavirin; and strong evidence for LPV/r plus ribavirin against Middle East Respiratory Syndrome (MERS) for post-exposure prophylaxis in healthcare workers. Despite these emerging data, robust controlled clinical trials assessing patient-centred outcomes remain imperative and clinical data have already reduced expectations with regard to some drugs. Any therapy should be used with caution in the light of potential drug interactions and the uncertainty of optimal doses for treating mild versus serious infections.