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Abstract
Background
A notable increase in severe cases of COVID-19, with significant hospitalizations due to the emergence and spread of JN.1 was observed worldwide in late 2023 and early 2024. However, no clinical data are available regarding critically-ill JN.1 COVID-19 infected patients.
Methods
The current study is a substudy of the SEVARVIR prospective multicenter observational cohort study. Patients admitted to any of the 40 participating ICUs between November 17, 2022, and January 22, 2024, were eligible for inclusion in the SEVARVIR cohort study (NCT05162508) if they met the following inclusion criteria: age ≥ 18 years, SARS-CoV-2 infection confirmed by a positive reverse transcriptase-polymerase chain reaction (RT-PCR) in nasopharyngeal swab samples, ICU admission for acute respiratory failure. The primary clinical endpoint of the study was day-28 mortality. Evaluation of the association between day-28 mortality and sublineage group was conducted by performing an exploratory multivariable logistic regression model, after systematically adjusting for predefined prognostic factors previously shown to be important confounders (i.e. obesity, immunosuppression, age and SOFA score) computing odds ratios (OR) along with their corresponding 95% confidence intervals (95% CI).
Results
During the study period (November 2022–January 2024) 56 JN.1- and 126 XBB-infected patients were prospectively enrolled in 40 French intensive care units. JN.1-infected patients were more likely to be obese (35.7% vs 20.8%; p = 0.033) and less frequently immunosuppressed than others (20.4% vs 41.4%; p = 0.010). JN.1-infected patients required invasive mechanical ventilation support in 29.1%, 87.5% of them received dexamethasone, 14.5% tocilizumab and none received monoclonal antibodies. Only one JN-1 infected patient (1.8%) required extracorporeal membrane oxygenation support during ICU stay (vs 0/126 in the XBB group; p = 0.30). Day-28 mortality of JN.1-infected patients was 14.6%, not significantly different from that of XBB-infected patients (22.0%; p = 0.28). In univariable logistic regression analysis and in multivariable analysis adjusting for confounders defined a priori, we found no statistically significant association between JN.1 infection and day-28 mortality (adjusted OR 1.06 95% CI (0.17;1.42); p = 0.19). There was no significant between group difference regarding duration of stay in the ICU (6.0 [3.5;11.0] vs 7.0 [4.0;14.0] days; p = 0.21).
Conclusions
Critically-ill patients with Omicron JN.1 infection showed a different clinical phenotype than patients infected with the earlier XBB sublineage, including more frequent obesity and less immunosuppression. Compared with XBB, JN.1 infection was not associated with higher day-28 mortality.
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1 Hôpitaux Universitaires Henri Mondor, Assistance Publique – Hôpitaux de Paris (AP-HP), Médecine Intensive Réanimation, Créteil, France (GRID:grid.412116.1) (ISNI:0000 0004 1799 3934); Université Paris-Est-Créteil (UPEC), Groupe de Recherche Clinique CARMAS, Créteil, France (GRID:grid.410511.0) (ISNI:0000 0004 9512 4013); Université Paris-Est-Créteil (UPEC), Créteil, France (GRID:grid.410511.0) (ISNI:0000 0004 9512 4013); INSERM U955, Team Viruses, Hepatology, Cancer, Créteil, France (GRID:grid.462410.5) (ISNI:0000 0004 0386 3258); Hôpital Henri Mondor, Service de Médecine Intensive Réanimation, Créteil, France (GRID:grid.412116.1) (ISNI:0000 0004 1799 3934)
2 Université Paris-Est-Créteil (UPEC), Créteil, France (GRID:grid.410511.0) (ISNI:0000 0004 9512 4013); Hôpitaux Universitaires Henri Mondor, Assistance Publique – Hôpitaux de Paris (AP-HP), Department of Public Health, Créteil, France (GRID:grid.412116.1) (ISNI:0000 0004 1799 3934); IMRB INSERM U955, Team CEpiA, Créteil, France (GRID:grid.462410.5) (ISNI:0000 0004 0386 3258)
3 Tours University Hospital, University of Tours, Intensive Care Unit, Research Center for Respiratory Diseases (CEPR), INSERM U1100, Tours, France (GRID:grid.12366.30) (ISNI:0000 0001 2182 6141)
4 INSERM U1259, Université de Tours, Tours, France (GRID:grid.12366.30); CHRU de Tours, National Reference Center for HIV-Associated Laboratory, , Tours, France (GRID:grid.411167.4) (ISNI:0000 0004 1765 1600)
5 University Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167 – RID-AGE Facteurs de Risque et Déterminants Moléculaires des Maladies Liées au Vieillissement, Lille, France (GRID:grid.523099.4) (ISNI:0000 0005 1237 6862)
6 CHU de Lille, Service de Virologie, Lille, France (GRID:grid.410463.4) (ISNI:0000 0004 0471 8845)
7 Université Paris Cité, APHP, Hôpital Louis Mourier, DMU ESPRIT, Service de Médecine Intensive Réanimation, Colombes, France (GRID:grid.414205.6) (ISNI:0000 0001 0273 556X); Université Paris Cité, INSERM UMR-S1151, CNRS UMR-S8253, Institut Necker-Enfants Malades (INEM), Paris, France (GRID:grid.508487.6) (ISNI:0000 0004 7885 7602)
8 Université Paris Cité, Hôpital Bichat-Claude Bernard, Assistance Publique – Hôpitaux de Paris, IAME INSERM UMR 1137, Service de Virologie, Paris, France (GRID:grid.508487.6)
9 CHU Rennes, Maladies Infectieuses et Réanimation Médicale, Rennes, France (GRID:grid.411154.4) (ISNI:0000 0001 2175 0984)
10 CHU Rennes, Laboratoire de Virologie, Rennes, France (GRID:grid.411154.4) (ISNI:0000 0001 2175 0984)
11 CHU De Rouen, Service de Médecine Intensive-Réanimation, Rouen, France (GRID:grid.41724.34) (ISNI:0000 0001 2296 5231)
12 Univ Rouen Normandie, Université de Caen Normandie, Normandie Univ, CHU Rouen, National Reference Center of HIV, INSERM DYNAMICURE UMR 1311 Department of Virology, Rouen, France (GRID:grid.41724.34) (ISNI:0000 0001 2296 5231)
13 Service de Réanimation Médico-Chirurgicale, Centre Hospitalier du Mans, Le Mans, France (GRID:grid.418061.a) (ISNI:0000 0004 1771 4456)
14 Laboratoire de Microbiologie, Centre Hospitalier du Mans, Le Mans, France (GRID:grid.418061.a) (ISNI:0000 0004 1771 4456)
15 Hôpital Victor Dupouy, Service de Réanimation, Argenteuil, France (GRID:grid.414474.6) (ISNI:0000 0004 0639 3263)
16 Hôpital Victor Dupouy, Service de Virologie, Argenteuil, France (GRID:grid.414474.6) (ISNI:0000 0004 0639 3263)
17 Réanimation Polyvalente, CHU Limoges, INSERM CIC 1435 and UMR 1092, Limoges, France (GRID:grid.411178.a) (ISNI:0000 0001 1486 4131)
18 French National Reference Center for Herpesviruses, CHU Limoges, Bacteriology, Virology, Hygiene Department, Limoges, France (GRID:grid.411178.a) (ISNI:0000 0001 1486 4131); INSERM, RESINFIT, U1092, Limoges, France (GRID:grid.7429.8) (ISNI:0000 0001 2186 6389)
19 Service de Réanimation Médicale, CHU de Nice, Nice, France (GRID:grid.410528.a) (ISNI:0000 0001 2322 4179)
20 Laboratoire de Virologie, CHU de Nice, Nice, France (GRID:grid.410528.a) (ISNI:0000 0001 2322 4179)
21 Université Paris-Est-Créteil (UPEC), Groupe de Recherche Clinique CARMAS, Créteil, France (GRID:grid.410511.0) (ISNI:0000 0004 9512 4013); Assistance Publique – Hôpitaux de Paris, Hôpital de Bicêtre, FHU Sepsis, Service de Médecine Intensive-Réanimation, DMU 4 CORREVE Maladies du Cœur Et Des Vaisseaux, Le Kremlin-Bicêtre, France (GRID:grid.50550.35) (ISNI:0000 0001 2175 4109); Equipe d’Epidémiologie Respiratoire Intégrative, CESP, Inserm U1018, Villejuif, France (GRID:grid.463845.8) (ISNI:0000 0004 0638 6872)
22 Hôpital Paul Brousse, Assistance Publique – Hôpitaux de Paris, Laboratoire de Virologie, Villejuif, France (GRID:grid.413133.7) (ISNI:0000 0001 0206 8146)
23 Hôpitaux Universitaires Henri Mondor, Assistance Publique – Hôpitaux de Paris (AP-HP), Médecine Intensive Réanimation, Créteil, France (GRID:grid.412116.1) (ISNI:0000 0004 1799 3934); Université Paris-Est-Créteil (UPEC), Groupe de Recherche Clinique CARMAS, Créteil, France (GRID:grid.410511.0) (ISNI:0000 0004 9512 4013); Université Paris-Est-Créteil (UPEC), Créteil, France (GRID:grid.410511.0) (ISNI:0000 0004 9512 4013); INSERM U955, Team Viruses, Hepatology, Cancer, Créteil, France (GRID:grid.462410.5) (ISNI:0000 0004 0386 3258)
24 Université Paris-Est-Créteil (UPEC), Créteil, France (GRID:grid.410511.0) (ISNI:0000 0004 9512 4013); INSERM U955, Team Viruses, Hepatology, Cancer, Créteil, France (GRID:grid.462410.5) (ISNI:0000 0004 0386 3258); Hôpitaux Universitaires Henri Mondor, Assistance Publique – Hôpitaux de Paris, Department of Virology, Créteil, France (GRID:grid.412116.1) (ISNI:0000 0004 1799 3934)