key: cord-0975146-6tcj0r01
authors: Colson, Philippe; Esteves-Vieira, Vera; Giraud-Gatineau, Audrey; Zandotti, Christine; Filosa, Véronique; Chaudet, Hervé; Lagier, Jean-Christophe; Raoult, Didier
title: Temporal and age distributions of SARS-CoV-2 and other coronaviruses, Southeastern France
date: 2020-09-23
journal: Int J Infect Dis
DOI: 10.1016/j.ijid.2020.09.1417
sha: 333d76dcca202b472e8b79b814bb801d74a472de
doc_id: 975146
cord_uid: 6tcj0r01

OBJECTIVES: The SARS-CoV-2 epidemic presents a poorly understood epidemiological cycle. We aimed to compare the age and weekly distribution of the five human coronaviruses, including SARS-CoV-2 that circulated in southeastern France. METHODS: We analyzed all available diagnoses of respiratory viruses including SARS-CoV-2 performed between 09/2013 and 05/2020 at University Hospital Institute Méditerranée Infection in Marseille, Southeastern France. RESULTS: For SARS-CoV-2, positive children <15 years of age represented 3.4% (228/6,735) of all positive cases, which is significantly less than for endemic coronaviruses (46.1%; 533/1,156; p < 0.001). Among 10,026 patients tested for SARS-CoV-2 and endemic coronaviruses in 2020, children <15 years represented a significantly lower proportion of all positive cases for SARS-CoV-2 than for endemic coronaviruses [2.2% (24/1,067) vs 33.5% (149/445), respectively; p < 0.001]. Epidemic curves for endemic coronaviruses and SARS-CoV-2 in 91,722 patients showed comparable bell-shaped distributions with a slight time lag. In contrast, age distribution of endemic coronaviruses and 14 other respiratory viruses differed very significantly compared to that of SARS-CoV2, which was the only virus to spare children. CONCLUSIONS: Thus, we observed for SARS-CoV-2 a temporal distribution resembling that of endemic coronaviruses and an age distribution that spares the youngest subjects who are those the most exposed to endemic coronaviruses.

The SARS-CoV-2 epidemic, which apparently started in December in China (Wu and McGoogan, 2020) , currently presents a poorly understood epidemiological cycle. It seems to J o u r n a l P r e -p r o o f have had in China, Korea and now in Europe a bell-shaped distribution (https://coronavirus.jhu.edu/data/new-cases; https://www.mediterranee-infection.com/covid-19/) as is common for viral respiratory infections. Furthermore, we and others have shown that detection of SARS-CoV-2 in children is rare, as are clinical cases (Colson et al., 2020; Gudbjartsson et al., 2020; Jones et al., 2020; Li et al., 2020; Wu and McGoogan, 2020) . Thus, in three large studies, children under 10 years of age accounted for <1%, 0% and 1.3% of SARS-CoV-2 cases in China (Wu and McGoogan, 2020) , Iceland (Gudbjartsson et al., 2020) and

Germany (Jones et al., 2020) , respectively. The fate of this epidemic remains unknown, but we found it interesting to compare the age and weekly distribution of the five human coronaviruses, including SARS-CoV-2 that circulated in south-eastern France in order to compare the temporal and age distribution of these different viruses.

We analyzed all available diagnoses of respiratory viruses including SARS-CoV-2 performed between September 2013 and May 2020 at the clinical microbiology and virology laboratory of University Hospital Institute Méditerranée Infection (https://www.mediterraneeinfection.com/) and University hospitals of Marseille, the second largest French city, Southeastern France. Testing of respiratory samples were performed using the FTD Respiratory pathogens 21 (Fast Track Diagnosis, Luxembourg), the Biofire FilmArray Respiratory panel 2 plus (Biomérieux, Marcy-l'Etoile, France), the Respiratory Multi Well System r-gene (Argene, BioMérieux), or the GeneXpert Xpert Flu/RSV (Cepheid, Sunnyvale, CA) assays, or by onestep simplex real-time quantitative RT-PCR amplifications as previously reported (Hoang et al., 2019) . Diagnosis by reverse transcription-PCR of SARS-CoV-2 infection was performed as previously described (Amrane et al., 2020) . This study retrospectively analyzed patients' data issued from the hospital information system (RGPD/APHM 2019-73). Statistics were (Table 1) . Compared to SARS-CoV-2-positive patients, those infected with endemic coronaviruses or other respiratory viruses were significantly more likely to be <10 years of age ( Figure 1 ). Therefore, this age group accounted for 1.8% of SARS-CoV-2 cases compared to 25.0% (for HCoV-229E) and 87.0% 

In this large study, two elements are particularly noteworthy. First, the temporal distributions in our geographical area of infections by all coronaviruses are comparable. Thus, all five viruses have a bell-shaped incidence curve and their circulation stopped in the spring, suggesting that J o u r n a l P r e -p r o o f this is the natural SARS-CoV-2 epidemic pattern. Hence, we can speculate for temperate countries including Europe that SARS-CoV-2 could reappear seasonally during winter and circulate epidemically until spring. Alternatively, SARS-CoV-2 might disappear in the absence of asymptomatic human chronic carriage, like SARS-CoV-1 (Raoult et al., 2020) . Second, the age distribution of SARS-CoV-2 cases spares children considerably, which is radically different from other coronavirus and respiratory virus infections. Thus, SARS-CoV-2 is the only one we analyzed that does not significantly affect children. Therefore, its epidemiology could not be predicted based on previous knowledge of viral respiratory diseases. The simplest explanation for this difference is that a substantial proportion of children, and particularly those under 5 years of age, may have acquired immunity to endemic coronaviruses that infect young children with high frequencies (Raoult et al., 2020; Zhou et al., 2013) . Indeed, there is evidence that part of the population exhibited immune responses against SARS-CoV-2 before the epidemic, supporting the hypothesis of cross-immunity between endemic coronaviruses and the new coronavirus. Thus, in the US, circulating SARS-CoV-2-specific CD4+ and CD8+ T cells were detected in ≈20-60% of unexposed individuals sampled in 2015-2018 (Grifoni et al., 2020) . In the UK, IgG to SARS-CoV-2 were detected in 15% of SARS-CoV-2-uninfected patients with recent HCoV infection and in 10% of SARS-CoV-2-uninfected pregnant women (Ng et al., 2020) . In addition, we detected IgM to SARS-CoV-2 at titers 1:100 in 9/50 patients with endemic coronaviruses (Edouard et al., 2020) . It is also worth noting that the coinfection rate observed here with SARS-CoV-2 and another coronavirus was very low (0.1%) and that SARS-CoV-2-positivity was significantly lower among patients positive than negative for an endemic coronavirus, which supports the hypothesis of a protective cross-immunity.

Overall, we believe that this work contributes to the understanding of the epidemiology of SARS-CoV-2, which has a temporal distribution resembling that of endemic coronaviruses and an age distribution that spares the youngest subjects who are precisely those the most J o u r n a l P r e -p r o o f frequently exposed to endemic coronaviruses and may have consequently acquired protective immunity. Susceptibility to SARS-CoV-2 in elderly perhaps reflects the loss of immunity acquired during childhood, or changes in social organization that occurred during recent decades. Indeed, a small proportion of people over the age of 50 lived in communities with very young children, whereas women's work development has led to a much earlier socialization of children. Finally, the fact that age distributions for infections by SARS-CoV-2 and other respiratory viruses differ underscores that real data collection and real-time analysis are critical in the event of an outbreak to decipher the epidemiology of emerging pathogens.

collection, management, analysis and interpretation of the data; and preparation, review, or approval of the manuscript. J o u r n a l P r e -p r o o f 

Rapid viral diagnosis and ambulatory management of suspected COVID-19 cases presenting at the infectious diseases referral hospital

Children account for a small proportion of diagnoses of SARS-CoV-2 infection and do not exhibit greater viral loads than adults

Evaluating the serological status of COVID-19 patients using an indirect immunofluorescent assay

Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals

Spread of SARS-CoV-2 in the Icelandic Population

Respiratory and gastrointestinal infections at the 2017 Grand Magal de Touba, Senegal: A prospective cohort survey

An analysis of SARS-CoV-2 viral load by patient age. medRxiv preprint 2020

The role of children in transmission of SARS-CoV-2: A rapid review

Pre-existing and de novo humoral immunity to SARS-CoV-2 in humans

Coronavirus infections: Epidemiological, clinical and immunological features and hypotheses

Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72314 Cases From the Chinese Center for Disease Control and Prevention

First infection by all four non-severe acute respiratory syndrome human coronaviruses takes place during childhood

Acknowledgments. This work was supported by the French Government under the "Investments for the Future" program managed by the National Agency for Research (ANR), The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.