key: cord-0290301-607r3gxg authors: Anne Gégout petit, Hélène Jeulin; Karine Legrand, Agathe Bochnakian; Pierre Vallois, Evelyne Schvoerer; Guillemin, Francis title: Seroprevalence of SARS-CoV-2, symptom profiles and seroneutralization during the first COVID-19 wave in a suburban area, France date: 2021-02-12 journal: nan DOI: 10.1101/2021.02.10.21250862 sha: 74d0960250e59add767556c2240f45b939b3cdf9 doc_id: 290301 cord_uid: 607r3gxg nan • IgT seroprevalence was 2.1% in the Grand Nancy Metropolitan area, France; was 48 highest for young adults; in socially deprived area, but this was not confirmed at the 49 individual level; and was associated with high intra-family viral transmission. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 12, 2021. ; https://doi.org/10.1101/2021.02.10.21250862 doi: medRxiv preprint BACKGROUND 57 The World Health Organisation (WHO) (1) recommends a good observation of the circulation 58 of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including local 59 seroprevalence surveys, to adapt the public health response to COVID-19 (2) . Indeed, 60 population containment, sanitary procedures and planning must be defined in terms of a 61 quantified health concern. To estimate the proportion of individuals who were or are infected 62 by the virus, serology assays for detecting anti-SARS-CoV-2 antibodies are useful in all 63 individuals with mild (or no) clinical signs, with or without a RT-PCR test. 64 Between January and July 2020, 13 general-population serology surveys of SARS-CoV-2 were 65 reported in Europe, 10 in the United States, 4 in Brazil, 1 in Pakistan and 1 in Japan (personal 66 communication). Most (n=20) estimated the seroprevalence between 0 and 5%; half under 67 2.5%. Six studies conducted in regions highly affected by the epidemic estimated the anti-68 SARS-CoV-2 antibody seroprevalence at more than 15% (2) (3) (4) (5) (6) (7) . Few studies investigated the 69 relation between seroprevalence and social precariousness, despite some evidence that health 70 inequalities are reflected in the pandemic (8, 9) . 71 Serology assays usually detect antibodies against the viral spike "S" and nucleocapsid "N" 72 protein, both being highly antigenic and widely expressed during SARS-CoV-2 infection (10). is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 12, 2021. ; https://doi.org/10.1101/2021.02.10.21250862 doi: medRxiv preprint antibodies directed at the RBD of the S protein are highly neutralizing (14-16). Thus, well-82 standardized, reproducible antibody assays are crucial to establish correlates of risk and 83 protection so that SARS-CoV-2 neutralization assays can be used for antibody monitoring in 84 natural infection and vaccine trials (17). The first COVID-19 cases were reported in France in January 2020 (18) The COVAL Nancy cross-sectional study was conducted between 26 June and 24 July 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint All invited individuals were informed of the objectives and the workflow of the study by using 117 comprehensive messaging adapted to age. All individuals gave their signed consent. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint Blood samples were centrifuged to collect serum, which was stored at +4°C and then -20°C. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 12, 2021. ; https://doi.org/10.1101/2021.02.10.21250862 doi: medRxiv preprint suspension. Each dilution was tested five times in the same experiment and each sample in two 156 independent experiments. The cytopathic effect was read on day +6. Negative controls were uninfected cells; positive controls were the virus incubated without sera 158 and the virus incubated with SARS-CoV-2-negative sera at a 1/10 ratio. The samples were classified according to neutralization activity at the 1:40 dilution: The raw seroprevalence estimate was adjusted for age, sex, and EDI quintile, then standardized 167 to the metropolitan and national population (24) . For comparing seroprevalence or 168 characteristics between groups, we used chi-square or Fisher exact test and logistic regression, 169 estimating odds ratios (ORs) and 95% confidence intervals (CIs). We used the R package is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The Grand Nancy Metropolitan area comprises 110 IRIS zones; 108 were represented. People 184 in neighbourhoods with a high socio-economic level (measured by the EDI) and high socio-185 professional category responded better than others. According to the EPICES score, 388 of the 186 1816 (21%) participants with this score were considered to live in social precariousness. Social precariousness was also linked to the IRIS EDI quintile: less than 16% in the first three 188 quintiles, up to 23% in the fourth quintile and 40% in the last quintile (p<10 -5 ); it also increased 189 with age: 16% in the 5-44 age group, 18% in the 45-64 age group and 28% in those over 65 190 (p<10 -6 ). Among the 2006 participants, 16% were smokers, 2% used nicotine substitutes, and 29% were 192 former smokers. Moreover, 294 (14.6%) reported at least one comorbidity (among: 193 hypertension, cancer, diabetes, kidney failure, liver problems, immune deficiency, 194 immunosuppressive therapy, severe obesity). The presence of a comorbidity was not related to 195 EDI score but was strongly related to social precariousness: 26% of those in precarious 196 situations had at least one comorbidity as compared with 13% of others (p<10 -9 ). In total, 252 (12.6%) participants thought they were infected with COVID-19 because they 198 experienced symptoms (86%) and/or had been in contact with a sick person (44%). Among 199 contacts with COVID-19, 42% were from work areas, 28% were family and 22% were friends. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 12, 2021. ; https://doi.org/10.1101/2021.02.10.21250862 doi: medRxiv preprint According to the results of anti-SARS-CoV-2 IgT detection and complementary analyses 202 performed as described in Figure 1 , 43 of the 2006 participants were found to be seropositive. the probability of precariousness estimated with adjusted or random-effects models (P=0.07 to 216 0.11) (see Table 2 for one of the models). is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 12, 2021. In the overall sample, 25% (95% CI 23 to 27) showed symptoms that would indicate they had 232 COVID-19. This criterion was related to seroprevalence (6.5% vs 0.7% with and without 233 COVID-19 symptoms, p<10 -13 ). Nearly half of the individuals (47%) reported experiencing at 234 least one of the 18 collected symptoms (14% one "intense" symptom). Seroprevalence was 235 higher with than without at least one symptom (3.8% vs 0.7%, p<10 -5 ) and when at least one of 236 the symptoms was qualified as "intense" (9.4% vs 0.7%, p<10 -17 ). For each of the identified 237 symptoms (except irritated eyes and rash), seroprevalence was higher when the symptom was 238 expressed (see Table 3 is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 12, 2021. ; https://doi.org/10.1101/2021.02.10.21250862 doi: medRxiv preprint Among those with at least one symptom, many (72%) reported this symptom as "intense". A is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 12, 2021. to the spike S1 C-terminal domain in recovered patients might be associated with efficient 285 immune protection in COVID-19 patients (32) . A recent work reported that standard commercially available SARS-CoV-2 IgG results could 287 be a useful surrogate for neutralizing antibody testing (32) . However, in the present study, is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint This study has strengths. First, in this relatively small geographical area, we were able to 293 stratify sampling based on homogenous population zones (IRIS zones) and tag the level of 294 social deprivation by using the corresponding ecological EDI index, to better represent the 295 target population in terms of this variable that has been considered an important risk factor for Second, the estimated response rate was relatively low in a period immediately following the 306 lockdown, with many people already gone away for July summer holidays. Third, all data were 307 self-reported, which may lead to some measurement (declaration) bias. Moreover, even if the 308 number of individuals was sufficient to satisfy the main objective, the study lacked statistical 309 power for the study of risk factors. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 12, 2021. ; https://doi.org/10.1101/2021.02.10.21250862 doi: medRxiv preprint 2 seroneutralization among IgT-positive patients. IgT seroprevalence was higher for young 316 adults and was associated with intra-family SARS-CoV-2 transmission. The data for this article will be shared on reasonable request to the corresponding author. The authors warmly acknowledge the inhabitants of the Grand Nancy metropolitan who 326 participated in COVAL Nancy Study. COVAL is funded by the Grand Nancy metropolitan. The sponsor was CHRU de Nancy (Direction de la Recherche Clinique et de l'Innovation). Many people worked together enthusiastically to make the COVAL Nancy study a success. For is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 12, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 12, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 12, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 12, 2021. ; is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 12, 2021. ; https://doi.org/10.1101/2021.02.10.21250862 doi: medRxiv preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 12, 2021. ; https://doi.org/10.1101/2021.02.10.21250862 doi: medRxiv preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 12, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 12, 2021. ; https://doi.org/10.1101/2021.02.10.21250862 doi: medRxiv preprint Population-based age-stratified seroepidemiological investigation protocol 370 for coronavirus 2019 (COVID-19) infection Seroprevalence of SARS-CoV-2 373 antibodies among healthy blood donors in Karachi High Community SARS-CoV-2 Antibody 376 Seroprevalence in a Ski Resort Community Prevalence of SARS-CoV-2 specific neutralising 379 antibodies in blood donors from the Lodi Red Zone Seroprevalence of SARS-CoV-2 significantly varies with 383 age: Preliminary results from a mass population screening High Seroprevalence of Anti-SARS-CoV-2 Antibodies 385 in Chelsea, Massachusetts Seroprevalence of SARS-CoV-2 IgM and IgG 387 antibodies in an asymptomatic population in Sergipe, Brazil. 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