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. 2023 Aug 7;11(1):48.
doi: 10.1186/s40635-023-00536-0.

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

Nicolas de Prost  1   2   3 , Etienne Audureau  4   5   6 , Sébastien Préau  7 , Raphaël Favory  7 , Aurélie Guigon  8 , Pierre Bay  9   10 , Nicholas Heming  11 , Elyanne Gault  12 , Tài Pham  10   13   14 , Amal Chaghouri  15 , Guillaume Voiriot  16 , Laurence Morand-Joubert  17   18 , Sébastien Jochmans  19 , Aurélia Pitsch  20 , Sylvie Meireles  21 , Damien Contou  22 , Amandine Henry  23 , Adrien Joseph  24 , Marie-Laure Chaix  25   26 , Fabrice Uhel  27   28 , Diane Descamps  29 , Malo Emery  30 , Claudio Garcia-Sanchez  31 , Charles-Edouard Luyt  32   33 , Stéphane Marot  34 , Frédéric Pène  35 , Anne-Sophie Lhonneur  36 , Stéphane Gaudry  37 , Ségolène Brichler  38 , Lucile Picard  39 , Armand Mekontso Dessap  9   10   4 , Christophe Rodriguez  4   40   41 , Jean-Michel Pawlotsky  4   40   41 , Slim Fourati  4   40   41 ; SEVARVIR investigators
Collaborators, Affiliations

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

Nicolas de Prost et al. Intensive Care Med Exp. .

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.

Keywords: Acute respiratory failure; COVID-19; Omicron; SARS-CoV-2; Sublineage.

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Conflict of interest statement

S.F. has served as a speaker for GlaxoSmithKline, Cepheid and Astrazeneca. J.-M.P. has served as an advisor or speaker for Abbvie, Arbutus, Assembly Biosciences, Gilead, GSK, and Merck. E.A. has received fees for lectures from Alexion, Sanofi, Gilead and Pfizer. His hospital has received research grant from Pfizer, MSD and Alexion. D.D. served as an advisor for Gilead-Sciences, ViiV Health care, Janssen-Cilag and MSD. F.P. served as an advisor for Gilead; he also received research grant from Alexion. C.-E.L. received lecture fees from MSD, Aerogen, Advanzpharma, and BioMérieux, outside the submitted work. Other authors have no conflict of interest to disclose.

Figures

Fig. 1
Fig. 1
A Diagram representing all SARS-CoV-2 Omicron lineages included in the study (starting from BA.2 and their descendant sublineages), as designated by PANGOLIN (https://cov-lineages.org/). B Study flow chart. A total of 486 patients were included in the SEVARVIR study between December, 7 2021 and December, 15 2022, with 158 patients infected with BA.2, BA.4, and BA.5 Omicron sublineages, who were included in this substudy
Fig. 2
Fig. 2
Dynamics of infecting SARS-CoV-2 variants during the 40-week study period. Patient-related samples (n = 158) corresponding to BA.2, BA.4, BA.5 and emerging sublineages are displayed over time. BA.2 sublineages are in blue, BA.4/BA.5 sublineages are in orange, brown, green and yellow and BQ.1.1 and other sublineages are in red, burgundy and black. The x-axis displays the study time period in weeks (w) from week 12, 2021 to week 51, 2022; The y-axis displays the percentage of each variant/sublineage at each time-point
Fig. 3
Fig. 3
Prevalence of amino acid substitutions and deletions in Spike RBD in BA.2, BA.4/BA.5, and BQ.1.1-related group viral sequences; The percentage of detected mutations (amino acid substitutions and deletions) per group is displayed on the y-axis, relative to the original Omicron BA.2 reference sequence (SARS-CoV-2/human/USA/FL-CDC-STM-77CPCCUR3/2022). Other individual NTD (N-terminal domain) mutations include H49Y, W64R, M153I, M177L, I197T, Del211, L212I, A222S, T250I, P251H, V289I and S316F; other S1/RBD mutations include N354K, I358L, T376S, T547K, T572I and N568S; other S2 mutations include T547K, T572I, H625R, A642G, A647V, E654K, N658S, N856S, V963F, A1020S, T1117I, P1143L, E1144Q and S1249P
See this image and copyright information in PMC

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