Protection against symptomatic SARS-CoV-2 BA.5 infection conferred by the Pfizer-BioNTech Original/BA.4-5 bivalent vaccine compared to the mRNA Original (ancestral) monovalent vaccines - a matched cohort study in France (preprint)

This cohort study aimed to evaluate the protection against symptomatic SARS-CoV-2 infection conferred by the Pfizer-BioNTech Original/BA.4-5 bivalent vaccine compared to mRNA Original (ancestral) monovalent vaccines. Individuals of [≥]60 years old who received a booster dose between 03/10/2022 and 06/11/2022, when both the bivalent and monovalent vaccines were used in France, were included. Individuals who received a booster dose with (1) a monovalent Original mRNA vaccine (Pfizer- BioNTech or Moderna) or (2) the bivalent Pfizer-BioNTech Original/BA.4-5 vaccine were matched. The outcome of interest was a positive SARS-CoV-2 RT-PCR or antigenic test associated to self-reported symptoms, at least seven days after receiving the booster dose. Data were analysed with a Cox Proportional-Hazards model adjusted for the presence of previous infection, age, sex, and the presence of medium risk comorbidities. A total of 136852 individuals were included and followed for a median period of 77days. The bivalent vaccine conferred an additional protection of 8% [95% CI: 0% - 16%, p=0.045] against symptomatic SARS-CoV-2 infection compared to the monovalent vaccines.

Effectiveness of second booster compared to first booster and protection conferred by previous SARS CoV-2 infection against symptomatic Omicron BA.2 and BA.4/5 in France (preprint)

In face of evidence of rapid waning of vaccine effectiveness against Omicron and its sub-lineages, a second booster with mRNA vaccines was recommended for the most vulnerable in France. We used a test negative design to estimate the effectiveness of the second booster relative to the first booster and the protection conferred by a previous SARS-CoV-2 infection, against symptomatic Omicron BA.2 or BA.4/5. We included symptomatic ≥60 years old individuals tested for SARS-CoV-2 in March 21-October 30, 2022. Compared to a 181-210 days old first booster, a second booster restored protection with an effectiveness of 39% [95%CI: 38% - 41%], 7-30 days post-vaccination This gain in protection was lower than the one observed with the first booster, at equal time points since vaccination. High levels of protection were associated to previous SARS-CoV-2 infection, especially if the infection was recent and occurred when an antigenic-related variant was dominant.

COVID-19 testing, infection and places of contamination in France, a national cross- sectional study, December 2021 (preprint)

Background: This study aimed to describe the use of diagnostic testing for COVID-19 in France until December 2021, the characteristics of people infected, and places of contamination. Methods: Data were collected from the national 2021 Health Barometer cross-sectional study, which was conducted between February and December 2021 and included French-speaking individuals aged 18-85 years old selected through randomly generated landline and mobile phone numbers. Participants were interviewed about COVID-19-like symptoms in the previous 12 months, diagnostic testing for the disease, positive diagnosis for SARS-CoV-2, and the place(s) of contamination. Determinants of diagnostic testing and of infection were studied using univariate and multivariate Poisson regressions. Results: A total of 24,514 persons participated in the study. We estimated that 66.4% [65.0-67.7] of persons had been tested for COVID-19 the last time they experienced COVID-19-like symptoms, and that 9.8% [9.3-10.3] of the population in France - with or without symptoms - had been tested positive. Diagnostic testing was less frequent in men, unemployed persons, and people living alone; it was also less frequent during the first months of the pandemic. The estimated proportion of the population infected was higher in healthcare professionals (PRa: 1.5 [1.3-1.7]), those living in large cities (>=200 000 inhabitants, and Paris area) (1.4 [1.2-1.6]), and in households comprising >3 persons (1.7[1.5-2.0]). It was lower in retired persons (0.8 [0.6-0.97]) and those over 65 years old (0.6 [0.4-0.9]). Almost two-thirds (65.7%) of infected persons declared they knew where they were contaminated; 5.8% [4.5-7.4] reported being contaminated outdoors, 47.9% [44.8-51.0] in unventilated indoor environments, and 43.4% [40.3-46.6] in ventilated indoor environments. Specifically, 51.1% [48.0-54.2] declared they were contaminated at home or in a family of friend’s house, 29.1% [26.4-31.9] at their workplace, 13.9% [11.9-16.1] in a healthcare structure,  and 9.0% [7.4-10.8] in a public eating place (e.g., cafeteria, bar, restaurant). Conclusions: To limit viral spread, preventive actions should preferentially target persons tested least frequently and those at a higher risk of infection. They should also target contamination in households, healthcare structures, and public eating places. Importantly, contamination is most frequent in places where prevention measures are most difficult to implement.

Acceptability of mandatory vaccination against influenza, measles, pertussis and varicella by workers in healthcare facilities: a national cross-sectional study, France, 2019. (preprint)

Background: Vaccination of healthcare workers (HCW) aims to protect them and to reduce transmission to susceptible patients. Influenza, measles, pertussis, and varicella vaccinations are recommended but not mandatory for HCW in France. Insufficient vaccine coverage for these diseases in HCW has raised the question of introducing mandatory vaccination. We conducted a survey to estimate acceptability of mandatory vaccination for these four vaccines by HCW working in healthcare facilities (HCF) in France, and to identify associated determinants.Methods: In 2019, we performed a cross-sectional survey of physicians, nurses, midwives and nursing assistants working in HCF in France using a randomised stratified three-stage sampling design (HCF type, ward category, HCW category). Data were collected in face-to-face interviews using a tablet computer. We investigated the possible determinants of acceptability of mandatory vaccination using univariate and multivariate Poisson regressions, and estimated prevalence ratios (PR).Results: A total of 8594 HCW in 167 HCF were included. For measles, pertussis, and varicella, self-reported acceptability of mandatory vaccination (very or quite favourable) was 73.1% [CI95%: 70.9–75.1], 72.1% [69.8–74.3], and 57.5% [54.5–57.7], respectively. Acceptability varied according to i) HCW and ward category for these three vaccinations, ii) age group for measles and pertussis, and iii) sex for varicella. For mandatory influenza vaccination, acceptability was lower (42.7% [40.6–44.9]), and varied greatly between HCW categories (from 77.2% for physicians to 32.0% for nursing assistants).Conclusion: HCW acceptability of mandatory vaccination was high for measles, pertussis and varicella but not as high for influenza. Vaccination for COVID-19 is mandatory for HCW in France. Replication of this study after the end of the COVID-19 crisis would help assess whether the pandemic had an impact on their acceptability of mandatory vaccination, in particular for influenza.

Serious hospital events following symptomatic infection with Sars-CoV-2 Omicron and Delta variants: an exposed-unexposed cohort study in December 2021 from the COVID-19 surveillance databases in France (preprint)

Background: A rapid increase in incidence of the SARS-CoV-2 Omicron variant in France in December 2021, while the Delta variant was prevailing since July 2021. Aim: To determine whether the risk of occurrence of a serious hospital event in adults following symptomatic SARS-CoV-2 infection differs for Omicron versus Delta. Methods: A retrospective cohort study from 06/12/2021 to 07/01/2022. The outcome was a serious hospital event (admission to intensive care unit OR admission to critical care unit OR death). Omicron and Delta symptomatic cases were matched on the week of virological diagnosis and on age. Risk was adjusted for age, sex, vaccination status, presence of comorbidity and region of residence using Cox proportional-hazards model. Results: 149,064 cases were included of which 497 had a serious hospital event (447 in the Delta arm, 50 in the Omicron arm). The risk of serious event was lower among Omicron versus Delta cases (adjusted Hazard Ratio, aHR=0.13 CI95 0.09-0.18 in 18 to 79 yo, aHR=0.30 CI95 0.17-0.54 in 80+ yo). The risk increased sharply with age and was lower in vaccinated compared to unvaccinated, without interaction between variant and vaccination status (aHR=0.15 CI95 0.11-0.19 for 18-79 yo with primary vaccination versus unvaccinated), was higher in cases with comorbidities (aHR = 3.70 CI95 2.66-5.13 fort 18-79 yo with very-high-risk comorbidity versus no comorbidity) and in males. Conclusion: This study confirms the lower severity of Omicron. The vaccine protection is essential in the elderly as they have a high risk of severe hospital events following infection with Omicron, even if much this risk is lower than with Delta.

Underdetection of COVID-19 cases in France in the exit phase following lockdown (preprint)

A novel testing policy was implemented in May in France to systematically screen potential COVID-19 infections and suppress local outbreaks while lifting lockdown restrictions. 20,736 virologically-confirmed cases were reported in mainland France from May 13, 2020 (week 20, end of lockdown) to June 28 (week 26). Accounting for missing data and the delay from symptom onset to confirmation test, this corresponds to 7,258 [95% CI 7,160-7,336] cases with symptom onset during this period, a likely underestimation of the real number. Using age-stratified transmission models parameterized to behavioral data and calibrated to regional hospital admissions, we estimated that 69,115 [58,072-77,449] COVID-19 symptomatic cases occurred, suggesting that 9 out of 10 cases with symptoms were not ascertained. Median detection rate increased from 7% [6-9]% to 31% [28-35]% over time, with regional estimates varying from 11% (Grand Est) to 78% (Normandy) by the end of June. Healthcare-seeking behavior in COVID-19 suspect cases remained low (31%) throughout the period. Model projections for the incidence of symptomatic cases (4.5 [3.9-5.0] per 100,000) were compatible with estimates integrating participatory and virological surveillance data, assuming all suspect cases consulted. Encouraging healthcare-seeking behavior and awareness in suspect cases is critical to improve detection. Substantially more aggressive and efficient testing with easier access is required to act as a pandemic-fighting tool. These elements should be considered in light of the currently observed resurgence of cases in France and other European countries.