Clinical phenotypes and outcomes associated with SARS-CoV-2 Omicron variants BA.2, BA.5 and BQ.1.1 in critically ill patients with COVID-19: a prospective, multicenter cohort study
Authors: de Prost Nicolas , Audureau Etienne , Préau Sébastien , Favory Raphaël , Guigon Aurélie , Bay Pierre , Heming Nicholas , Gault Elyanne , Pham Tài , Chaghouri Amal , Voiriot Guillaume , Morand-Joubert Laurence , Jochmans Sébastien , Pitsch Aurélia , Meireles Sylvie , Contou Damien , Henry Amandine , Joseph Adrien , Chaix Marie-Laure , Uhel Fabrice , Descamps Diane , Emery Malo , Garcia-Sanchez Claudio , Luyt Charles-Edouard , Marot Stéphane , Pène Frédéric , Lhonneur Anne-Sophie , Gaudry Stéphane , Brichler Ségolène , Picard Lucile , Mekontso Dessap Armand , Rodriguez Christophe , Pawlotsky Jean-Michel , Fourati Slim ,   the SEVARVIR investigators, Razazi Keyvan , Bellaïche Raphaël , Azoulay Elie , Timsit Jean-François , Turpin Matthieu , de Montmollin Nina , Mayaux Julien , Roux Damien , Annane Djillali , Hartard Cédric , Kimmoun Antoine , Meziani Ferhat , Jandeaux Louis-Marie , Fafi-Kremer Samira 
Published: August 2023

Abstract
Background
Despite current broad natural and vaccine-induced protection, a substantial number of patients infected with emerging SARS-CoV-2 variants (e.g., BF.7 and BQ.1.1) still experience severe COVID-19. Real-life studies investigating the impact of these variants on clinical outcomes of severe cases are currently not available. We performed a prospective multicenter observational cohort study. Adult patients with acute respiratory failure admitted between December 7, 2021 and December 15, 2022, in one of the 20 participating intensive care units (17 from the Greater Paris area and 3 from the North of France) were eligible for inclusion if they had SARS-CoV-2 infection confirmed by a positive reverse transcriptase-polymerase chain reaction (RT-PCR). Full-length SARS-CoV-2 genomes from all included patients were sequenced by means of next-generation sequencing. The primary endpoint of the study was day-28 mortality.

Results
The study included 158 patients infected with three groups of Omicron sublineages, including (i) BA.2 variants and their early sublineages referred as “BA.2” (n = 50), (ii) early BA.4 and BA.5 sublineages (including BA.5.1 and BA.5.2, n = 61) referred as “BA.4/BA.5”, and (iii) recent emerging BA.5 sublineages (including BQ.1, BQ.1.1, BF.7, BE.1 and CE.1, n = 47) referred as “BQ.1.1”. The clinical phenotype of BQ1.1-infected patients compared to earlier BA.2 and BA.4/BA.5 sublineages, showed more frequent obesity and less frequent immunosuppression. There was no significant difference between Omicron sublineage groups regarding the severity of the disease at ICU admission, need for organ failure support during ICU stay, nor day 28 mortality (21.7%, n = 10/47 in BQ.1.1 group vs 26.7%, n = 16/61 in BA.4/BA.5 vs 22.0%, n = 11/50 in BA.2, p = 0.791). No significant relationship was found between any SARS-CoV-2 substitution and/or deletion on the one hand and survival on the other hand over hospital follow-up.

Conclusions
Critically-ill patients with Omicron BQ.1.1 infection showed a different clinical phenotype than other patients infected with earlier Omicron sublineage but no day-28 mortality difference.