Temporal, age, and geographical variation in vaccine efficacy against infection by the Delta and Omicron variants in the community in France, December 2021 to March 2022.

OBJECTIVES: We aimed to quantify how the vaccine efficacy of BNT162b2, messenger RNA-1273, AD26.COV2-S, and ChAdOx1 nCoV-19 against detected infection by the SARS-CoV-2 Delta and Omicron variants varied by time since the last dose, vaccine scheme, age, and geographic areas. METHODS: We analyzed 3,261,749 community polymerase chain reaction tests conducted by private laboratories in France from December 2021 to March 2022 with a test-negative design comparing vaccinated to unvaccinated individuals. RESULTS: Efficacy against detected infection by Delta was 89% (95% confidence interval, 86-91%) at 2 weeks, down to 59% (56-61%) at 26 weeks and more after the second dose. Efficacy against Omicron was 48% (45-51%) at 2 weeks, down to 4% (2-5%) at 16 weeks after the second dose. A third dose temporarily restored efficacy. Efficacy against Omicron was lower in children and the elderly. Geographical variability in efficacy may reflect variability in the ratio of the number of contacts of vaccinated vs unvaccinated individuals. This ratio ranged from 0 to +50% across departments and correlated with the number of restaurants and bars per inhabitant (beta = 15.0 [0.75-29], P-value = 0.04), places that only vaccinated individuals could access in the study period. CONCLUSION: SARS-CoV-2 vaccines conferred low and transient protection against Omicron infection.

Dynamics of viral shedding during ancestral or Omicron BA.1 SARS-CoV-2 infection and enhancement of pre-existing immunity during breakthrough infections.

Omicron variant is circulating in the presence of a globally acquired immunity unlike the ancestral SARS-CoV-2 isolate. Herein, we investigated the normalized viral load dynamics and viral culture status in 44 fully vaccinated healthcare workers (HCWs) infected with the Omicron BA.1 variant. Viral load dynamics of 38 unvaccinated HCWs infected with the 20A variant during the first pandemic wave was also studied. We then explored the impact of Omicron infection on pre-existing immunity assessing anti-RBD IgG levels, neutralizing antibody titres against 19A, Delta and Omicron isolates, as well as IFN-γ release following cell stimulation with SARS-CoV-2 peptides. We reported that two weeks after diagnosis a greater proportion of HCWs infected with 20A (78.9%, 15/19) than with Omicron BA.1 (44.7%, 17/38; p = 0.02) were still positive by RT-qPCR. We found that Omicron breakthrough infections led to an overall enhancement of vaccine-induced humoral and cellular immunity as soon as a median [interquartile range] of 8 [7-9] days post symptom onset. Among samples with similar high viral loads, non-culturable samples exhibited higher neutralizing antibody titres and anti-RBD IgG levels than culturable samples. Additionally, Omicron infection led to an enhancement of antibodies neutralization capacity against other SARS-CoV-2 isolates. Taken together, the results suggest that Omicron BA.1 vaccine breakthrough infection is associated with a faster viral clearance than that of the ancestral SARS-CoV-2, in addition this new variant leads to a rapid enhancement of the humoral response against multiple SARS-CoV-2 variants, and of the cellular response.

Epidemiological and clinical insights from SARS-CoV-2 RT-PCR crossing threshold values, France, January to November 2020.

BackgroundThe COVID-19 pandemic has led to an unprecedented daily use of RT-PCR tests. These tests are interpreted qualitatively for diagnosis, and the relevance of the test result intensity, i.e. the number of quantification cycles (Cq), is debated because of strong potential biases.AimWe explored the possibility to use Cq values from SARS-CoV-2 screening tests to better understand the spread of an epidemic and to better understand the biology of the infection.MethodsWe used linear regression models to analyse a large database of 793,479 Cq values from tests performed on more than 2 million samples between 21 January and 30 November 2020, i.e. the first two pandemic waves. We performed time series analysis using autoregressive integrated moving average (ARIMA) models to estimate whether Cq data information improves short-term predictions of epidemiological dynamics.ResultsAlthough we found that the Cq values varied depending on the testing laboratory or the assay used, we detected strong significant trends associated with patient age, number of days after symptoms onset or the state of the epidemic (the temporal reproduction number) at the time of the test. Furthermore, knowing the quartiles of the Cq distribution greatly reduced the error in predicting the temporal reproduction number of the COVID-19 epidemic.ConclusionOur results suggest that Cq values of screening tests performed in the general population generate testable hypotheses and help improve short-term predictions for epidemic surveillance.

Characterisation of vaccine breakthrough infections of SARS-CoV-2 Delta and Alpha variants and within-host viral load dynamics in the community, France, June to July 2021.

We compared PCR results from SARS-CoV-2-positive patients tested in the community in France from 14 June to 30 July 2021. In asymptomatic individuals, Cq values were significantly higher in fully vaccinated than non-fully vaccinated individuals (effect size: 1.7; 95% CI: 1-2.3; p < 10-6). In symptomatic individuals and controlling for time since symptoms, the difference vanished (p = 0.26). Infections with the Delta variant had lower Cq values at symptom onset than with Alpha (effect size: -3.32; 95% CI: -4.38 to -2.25; p < 10-6).

[Retrospective analysis of the performance of the SARS-CoV-2 rapid antigen detection test compared to the reference RT-PCR test]. / Analyse rétrospective des performances du test de détection rapide antigénique du SARS-CoV-2 comparé au test de référence RT-PCR.

BACKGROUND: Discovered in 2019 in the region of Wuhan, China, the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) rapidly established itself as a major pathogenic agent of morbidity and mortality. France has implemented a strategy to fight this virus which relies essentially on widespread RT-PCR virological testing in order to isolate positive patients. Antigenic tests have recently been made available to help the diagnostics. We have conducted a retrospective study to determine the sensitivity of these antigenic tests, comparing them to the reference RT-PCR method. METHOD: Between December 7, 2020 and January 31, 2021, each patient we received in our laboratories for an RT-PCR test was enrolled. Out of 271,649 patients, 4,881 had been submitted to an antigenic test (TDR) in the preceding 24 hours. Comparing the data resulting from both tests, we established the sensitivity and the specificity of the antigenic tests. For our analysis we included the parameter of symptom and/or the value of Cycles threshold (Ct) in our parameters. RESULTS: The sensitivity of the TDRs compared to all the positive RT-PCR tests is 56%. We further demonstrate the correlation between the symptom duration and the reduction of the nasopharyngeal viral load. Based on this data, we have established that the sensitivity of the TDRs decreases very rapidly after symptom onset, contrary to the estimated viral load in the RT-PCR. Indeed, less the 24 hours after clinical symptom onset, the sensitivity of the TDRs decreases from 74% to 60%. By including the Ct value in our parameters, we have established that, despite a high viral load and clinical symptoms since 7 days or less, the sensitivity of the TDRs is 66%. Although, a high number of asymptomatic patients among carriers of SARS-CoV-2, we have estimated a specificity of 93% for our test. CONCLUSIONS: Performance in terms of sensitivity and specificity of the TDR, as assessed in practice, are inferior to those given by the manufacturer, which raises several questions. What is the impact of falsely negative results for patients carrying a high viral load? Are the implemented measures sufficient to prevent the epidemic?