ABSTRACT
Infection with SARS-CoV-2 variant Omicron is considered to be less severe than infection with variant Delta, with a rarer occurrence of severe disease requiring intensive care. However, a substantial number of patients infected with variant Omicron still experienced severe COVID-19. Little information is available on comorbid factors, clinical conditions and specific viral mutational patterns associated with the severity of variant Omicron infection. In this multicenter prospective cohort study, patients consecutively admitted for severe COVID-19 in 20 participating intensive care units in France between December 7th 2021 and May 1st 2022 were included. Among 259 patients for whom SARS-CoV-2 variant lineage was determined, we show that the clinical phenotype of patients infected with variant Omicron (n = 148) was different from that in those infected with variant Delta (n = 111). We observed no significant relationship between Delta and Omicron variant lineages/sublineages and 28-day mortality (adjusted odds ratio [95% confidence interval] = 0.68 [0.35–1.32]; p = 0.253). Among Omicron-infected patients, 43.2% were immunocompromised, most of whom had received two doses of vaccine or more (85.9%) but displayed a poor humoral response to vaccination (mean difference in serum anti-spike IgG antibody titers between vaccinated and non-vaccinated immunocompromised patients: 1078 BAU/mL [-319.4; 2475.0]; p = 0.160). The mortality rate of immunocompromised patients infected with variant Omicron was significantly higher than that of non-immunocompromised patients (46.9% vs 26.2%; p = 0.009). In patients infected with variant Omicron, there was no association between specific sublineages (BA.1/BA.1.1 (n = 109) and BA.2 (n = 21)) or any viral genome polymorphisms or mutational profile and the 28-day mortality.
Subject(s)
COVID-19ABSTRACT
Background: SARS-CoV-2 variant of concern (VOC) α spread worldwide, including in France, at the beginning of 2021. This variant was suggested to be associated with a higher risk of mortality than other variants. Little information is available in the subset of patients with severe disease admitted in the intensive care unit (ICU). We aimed to characterize the genetic diversity of SARS-CoV-2 variants isolated from patients with severe COVID-19 in order to unravel the relationships between specific viral mutations/mutational patterns and clinical outcomes. Methods: : Prospective multicentre observational cohort study. Patients aged ≥18 years admitted in 11 ICUs from Great Paris area hospitals between October 1, 2020, and May 30, 2021 (before the introduction of VOC δ (B.617.2) in France) for acute respiratory failure (SpO2≤90% and need for supplemental oxygen or ventilator support) were included. SARS-CoV-2 infection, determined by RT-PCR testing. The primary clinical endpoint was day-28 mortality. Full-length SARS-CoV-2 genomes were sequenced by means of next-generation sequencing (Illumina COVIDSeq). Results: : 413 patients were included, 183 (44.3%) had been infected with pre-existing variants, 197 (47.7%) with variant α (B.1.1.7), and 33 (8.0%) with other variants. Patients infected with pre-existing variants were significantly older (64.9±11.9 vs 60.5±11.8 years; p=0.0005); they had significantly more frequent COPD (11.5% (n=21/183) vs 4.1% (n=8/197); p=0.009), and higher SOFA score (4 [3-8] vs 3 [2-4]; 0.0002). Day-28 mortality was not different between patients infected with pre-existing, α (B.1.1.7) or other variants (31.1% (n=57/183) vs 26.2% (n=51/197) vs 30.3% (n=10/33), respectively; p=0.550). There was no association between day-28 mortality with a specific variant or the presence of specific mutations in SARS CoV-2 genome, including 17 mutations selected in the spike protein and all 1017 non-synonymous mutations detected throughout the entire viral genome. Conclusions: : At ICU admission, patients infected with pre-existing variants had a different clinical presentation from those infected with variant α (B.1.1.7) and other variants later in the course of the pandemic, but mortality did not differ between these groups. There was no association between a specific variant or SARS CoV-2 genome mutational pattern and day-28 mortality.
Subject(s)
COVID-19 , Respiratory InsufficiencyABSTRACT
BackgroundRT-PCR testing is crucial in the diagnostic of SARS-CoV-2 infection. The use of reliable and comparable PCR assays is a cornerstone to allow use of different PCR assays depending on the local equipment. In this work, we provide a comparison of the Cobas(R) (Roche) and the RealStar(R) assay (Altona). MethodsAssessment of the two assays was performed prospectively in three reference Parisians hospitals, using 170 clinical samples. They were tested with the Cobas(R) assay, selected to obtain a distribution of cycle threshold (Ct) as large as possible, and tested with the RealStar assay with three largely available extraction platforms: QIAsymphony (Qiagen), MagNAPure (Roche) and NucliSENS-easyMag (BioMerieux). ResultsOverall, the agreement (positive for at least one gene) was 76%. This rate differed considerably depending on the Cobas Ct values for gene E: below 35 (n = 91), the concordance was 99%. Regarding the positive Ct values, linear regression analysis showed a determination correlation (R2) of 0.88 and the Deming regression line revealed a strong correlation with a slope of 1.023 and an intercept of -3.9. Bland-Altman analysis showed that the mean difference (Cobas(R) minus RealStar(R)) was + 3.3 Ct, with a SD of + 2.3 Ct. ConclusionsIn this comparison, both RealStar(R) and Cobas(R) assays provided comparable qualitative results and a high correlation when both tests were positive. Discrepancies exist after 35 Ct and varied depending on the extraction system used for the RealStar(R) assay, probably due to a low viral load close to the detection limit of both assays.