Clinical phenotypes and outcomes associated with SARS-CoV-2 Omicron sublineage JN.1 in critically ill COVID-19 patients: a prospective, multicenter cohort study in France, November 2022 to January 2024
Authors: de Prost Nicolas , Audureau Etienne , Guillon Antoine , Handala Lynda , Préau Sébastien , Guigon Aurélie , Uhel Fabrice , Le Hingrat Quentin , Delamaire Flora , Grolhier Claire , Tamion Fabienne , Moisan Alice , Darreau Cédric , Thomin Jean , Contou Damien , Henry Amandine , Daix Thomas , Hantz Sébastien , Saccheri Clément , Giordanengo Valérie , Pham Tài , Chaghouri Amal , Bay Pierre , Pawlotsky Jean-Michel , Fourati Slim ,   the SEVARVIR investigators, Razazi Keyvan , Mekontso Dessap Armand , Bellaïche Raphaël , Picard Lucile , Soulier Alexandre , N’Debi Mélissa , Seng Sarah , Rodriguez Christophe , Pene Frédéric , L’Honneur Anne-Sophie , Joseph Adrien , Azoulay Elie , Salmona Maud , Chaix Marie-Laure , Luyt Charles-Edouard , Levy David , Mayaux Julien , Marot Stéphane , Bernier Juliette , Gasperment Maxime , Urbina Tomas , Ait-Oufella Hafid , Maury Eric , Morand-Joubert Laurence , Bocar Fofana Djeneba , Timsit Jean-François , Descamps Diane , Voiriot Guillaume , de Montmollin Nina , Turpin Mathieu , Gaudry Stéphane , Brichler Ségolène , Pham Tài Olivier , Gault Elyanne , Jochmans Sébastien , Pitsch Aurélia , Chevrel Guillaume , Clergue Céline , Sabah Kubab , Courdavault Vagh Weinmann Laurence , Garcia-Sanchez Claudio , Meziani Ferhat , Jandeaux Louis-Marie , Fafi-Kremer Samira , Laugel Elodie , Preau Sébastien , Guignon Aurélie , Kimmoun Antoine , Schvoerer Evelyne , Hartard Cédric , Damoisel Charles , Brechot Nicolas , Péré Helene , Beloncle François , Lunel Fabiani Francoise , Coudroy Rémi , Thille Arnaud W , Arrive François , le Pape Sylvain , Marchasson Laura , Deroche Luc , Leveque Nicolas , Thibaut Vincent , la Combe Béatrice , Haouisee Séverine , Boyer Alexandre , Burrel Sonia , Beduneau Gaetan , Girault Christophe , Grall Maximillien , Carpentier Dorothée , Plantier Jean-Christophe , Canet Emmanuel , Rodallec Audrey , Imbert Berthe Marie , Hraeich Sami , Fournier Pierre-Edouard , Colson Philippe , Dartevel Anaïs , Larrat Sylvie , Thiery Guillaume , Pillet Sylvie , Klouche Kada , Tuaillon Edouard , Aubron Cécile , Tran Adissa , Vallet Sophie , Charles Pierre-Emmanuel , le Rougemont Alexis , Souweine Bertrand , Henquell Cecile , Mirand Audrey , Mourvillier Bruno , Andreoletti Laurent , Lier Clément , du Cheyron Damien , Candace Dossou Nefert , Vabret Astrid , Piton Gaël , Lepiller Quentin , Roger Sylvie 
Published: June 2024

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.