Nirmatrelvir-ritonavir chez les patients greffés rénaux infectés par le SARS-CoV-2 : l’expérience d’une cohorte belge

Introduction Le nirmatrelvir-ritonavir (NR) a démontré son efficacité et sa sécurité pour prévenir la survenue de formes sévères de COVID-19 chez les patients à risque de progression. Néanmoins, peu de données existent chez les greffés rénaux. De plus, le ritonavir interagit avec de nombreux médicaments, notamment avec les inhibiteurs de la calcineurine (IC). Description Nous avons inclus dans cette étude monocentrique rétrospective tous les patients traités par NR entre le 28/04/2022 et le 03/06/2022. Méthodes Le traitement par NR était de 5jours (jour 1 à jour 5) à la dose recommandée. Le traitement usuel (notamment immunosuppresseur) était adapté selon les recommandations de la Société Française de Pharmacologie et Thérapeutiques. Un suivi standardisé biologique et clinique a été réalisé. Résultats Quatorze patients ont été inclus (Tableau 1). Comparées à celles du jour 0 (veille de l’initiation du NR), les concentrations médianes de créatinine plasmatique et les charges virales de SARS-CoV-2 au jour 7 étaient respectivement similaires (p=0,866) et fortement diminuées (p=0,002). Deux patients ont eu une insuffisance rénale aigue rapidement résolutive dans un contexte de diarrhée et de sepsis urinaire. Les concentrations résiduelles d’IC sont restées relativement stables avec néanmoins 5 patients qui ont présenté des taux supra-thérapeutiques au premier dosage post reprise de l’IC. Après un suivi médian de 34jours, aucun patient n’est mort ni n’a présenté de pneumonie virale. Deux patients ont dû être hospitalisés pour sepsis urinaire (au jour 2 et 11). Nous avons néanmoins observé 2 cas de récidive précoce de symptômes associée à une réaugmentation de la charge virale après traitement par NR (au jour 10 et 21). Conclusion L’utilisation du NR est possible chez les greffés rénaux sous condition d’un respect strict des adaptations thérapeutiques recommandées. 14 % de la cohorte a présenté une récidive précoce en cours d’investigation.

A world apart: Levels and determinants of excess mortality due to COVID-19 in care homes: The case of the Belgian region of Wallonia during the spring 2020 wave

BACKGROUND In Western countries, COVID-19 has been particularly deadly for care home residents. OBJECTIVE To understand the role of age and sex structures, health frailty, and contamination dynamics in COVID-19 mortality in populations living inside and outside care homes. METHODS We compared COVID-19 death data recorded in March-June 2020 in Wallonia (southern Belgium) for populations living inside and outside care homes, using annual death data (all-cause mortality in 2017) to assess the health condition of each population. RESULTS Sixty-four percent of COVID-19 deaths were residents in care homes, where the outbreak started after that in the external population, but at a faster pace. The death rate varied between 0 parts per thousand and 340 parts per thousand (mean 43 parts per thousand) per care home, increasing with the number of both residents and staff. All-cause and COVID-19 mortality rates increased exponentially with age but were much higher in care homes. The ratio of male (M) to female (F) death rates was 1.6 for all-cause mortality and 2.0 for COVID-19 mortality (both confirmed and suspected). The COVID-19 mortality reached 24% (M) and 18% (F) of the all-cause mortality rate in care homes, compared to 5% (M) and 4% (F) outside care homes. CONCLUSIONS The COVID-19 mortality rate was 130x higher inside than outside care homes, due to the near multiplicative effects of differences in the residents' age and sex structure (11x), health frailty (3.8x), and infection risk (probably 3.5x). CONTRIBUTION Care homes should be treated as a very specific population in epidemiological studies due to their extreme vulnerability to COVID-19.

Safety of systemic anti-cancer treatment in oncology patients with non-severe COVID-19: a cohort study.

BACKGROUND: The viral pandemic coronavirus disease 2019 (COVID-19) has disrupted cancer patient management around the world. Most reported data relate to incidence, risk factors, and outcome of severe COVID-19. The safety of systemic anti-cancer therapy in oncology patients with non-severe COVID-19 is an important matter in daily practice. METHODS: ONCOSARS-1 was a single-center, academic observational study. Adult patients with solid tumors treated in the oncology day unit with systemic anti-cancer therapy during the initial phase of the COVID-19 pandemic in Belgium were prospectively included. All patients (n = 363) underwent severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) serological testing after the first peak of the pandemic in Belgium. Additionally, 141 of these patients also had a SARS-CoV-2 RT-PCR test during the pandemic. The main objective was to retrospectively determine the safety of systemic cancer treatment, measured by the rate of adverse events according to the Common Terminology Criteria for Adverse Events, in SARS-CoV-2-positive patients compared with SARS-CoV-2-negative patients. RESULTS: Twenty-two (6%) of the 363 eligible patients were positive for SARS-CoV-2 by RT-PCR and/or serology. Of these, three required transient oxygen supplementation, but none required admission to the intensive care unit. Hematotoxicity was the only adverse event more frequently observed in SARS-CoV-2 -positive patients than in SARS-CoV-2-negative patients: 73% vs 35% (P < 0.001). This association remained significant (odds ratio (OR) 4.1, P = 0.009) even after adjusting for performance status and type of systemic treatment. Hematological adverse events led to more treatment delays for the SARS-CoV-2-positive group: 55% vs 20% (P < 0.001). Median duration of treatment interruption was similar between the two groups: 14 and 11 days, respectively. Febrile neutropenia, infections unrelated to COVID-19, and bleeding events occurred at a low rate in the SARS-CoV-2-positive patients. CONCLUSION: Systemic anti-cancer therapy appeared safe in ambulatory oncology patients treated during the COVID-19 pandemic. There were, however, more treatment delays in the SARS-CoV-2-positive population, mainly due to a higher rate of hematological adverse events.

Do fully automated immunoassays for the evaluation of the immune response to SARS-CoV-2 are commutable?

On December 30, 2019, the city of Wuhan, China, experienced an outbreak of unexplained pneumonia. From January 7, 2020, a new betacoronavirus, severe acute respiratory syndrome coronavirus was identified (SARS-CoV-2). The World Health Organization (WHO) has since declared a pandemic with millions of confirmed cases worldwide. As part of the fight against the epidemic, laboratories have a critical role in assessing the reliability of new serological assays before taking part of diagnostic protocols or made available broader to the community and to evaluate commutability between assays. The aim of this study was to perform a comparison between two automated assays for SARS-CoV-2 IgG testing, the MAGLUMI ® 800 and the LIAISON ® XL. Among the patients confirmed positive for COVID-19, the two automated assays were significantly correlated (r = 0.811; p < 0.0001). The overall concordance made for MAGLUMI 2019-nCoV IgG positive/negative vs. LIAISON® SARS-CoV-2 IgG positive/negative results was 79% (Index Kappa of Cohen). We list the discrepancies between the two analyzers among the 44 tested patients. In conclusion, the overall agreement between the two automated assays for SARS-CoV-2 was good. However, the MAGLUMI assay might be more sensitive at the early stages of antibody development and there is a lack of specificity with LIAISON XL.

Clinical characteristics and humoral immune response in healthcare workers with COVID-19 in a teaching hospital in Belgium.

BACKGROUND: Healthcare workers (HCWs) are at high risk of acquiring COVID-19 and could play a role in nosocomial transmission. Since 4th February 2020, Belgian Health authorities reported more than 90,568 cases, of which 8.3% were HCWs. Data on clinical characteristics, sources of infection and humoral immune response of HCWs with COVID-19 remain scarce. AIM: To analyse the clinical characteristics, humoral immune response, sources of contamination, and outcomes among HCWs with COVID-19. METHODS: This retrospective study included 176 HCWs with laboratory-confirmed COVID-19 in a teaching hospital in Belgium. Between 1st March and 31st May 2020, all HCWs with symptoms suspected of COVID-19 were tested by reverse transcription polymerase chain reaction on a nasopharyngeal swab. Serological testing was performed between 55 and 137 days after the onset of symptoms. FINDINGS: Median age was 40.8 years and 75% were female. Median delay between onset of symptoms and diagnosis was 4.39 days. Most frequent symptoms were cough and headache (both 75%). Fever accounted for 68.7%. Most represented professions were nurses (42%). HCWs were mainly infected by patient contact (32.9%); 7.6% required hospitalization and 1.7% were admitted to the intensive care unit. Unfortunately, one HCW died (0.5%). Total antibodies were positive in 109/126 (86.5%). CONCLUSIONS: Clinical presentation of COVID-19 in HCWs does not differ from the general population. However, outcomes were more favourable with a mortality rate lower than that reported in Belgian COVID-19 patients in general (16%). The main source of infection was the hospital setting. Our positive antibodies rate was high but lower than previously reported.