key: cord-0303785-kugaac8m authors: Meireles, P.; Costa, J. P.; Novais, M.; Miranda, D.; Mendes Lopes, M.; Severo, M.; Barros, H. title: The SARS-CoV-2 infection among students in the University of Porto: a cross-sectional study date: 2021-10-18 journal: nan DOI: 10.1101/2021.10.14.21264978 sha: 6b06cb13ea998f385f846fa1cd2a51d8bb03ac3f doc_id: 303785 cord_uid: kugaac8m Introduction: Incidence based on notified cases of SARS-CoV-2 infection underestimates the real extension of the infection. We aimed to quantify SARS-CoV-2 specific antibodies seroprevalence among University students in Porto. Methods: A rapid point of care testing for SARS-CoV-2 specific immunoglobulin (Ig) M and IgG antibodies was performed, and a questionnaire was applied to the 6512 voluntary students from September to December 2020. We computed the apparent IgM, IgG and IgM or IgG prevalence, and the true prevalence and 95% credible intervals (95% CI) using Bayesian inference. Results: We found an apparent prevalence (IgM or IgG) of 9.7%, the true prevalence being 7.9% (95% CI 4.9-11.1). Prevalence was significantly higher among males (10.9% vs 9.2%), international students (18.1% vs 10.4% local vs 8.8% nationally displaced) and increased with age. Those with a known risk contact, that experienced quarantine, had symptoms, or a previous negative molecular test had a higher seroprevalence. Of the 91 (1.4%) students who reported a molecular diagnosis, 86.7% were reactive for IgM or IgG. Conclusion: Based on immunological evidence infection was 5.6 times more frequent than if based on a molecular diagnosis. The higher seroprevalence among male, older, and international students emphasizes the importance of identifying particular groups. The infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can 37 follow many distinct courses, with ominous outcomes mostly in the elderly population and no 38 or few unspecific symptoms mainly among young and healthy individuals [1] [2] [3] . Real-time 39 Polymerase Chain Reaction (RT-PCR) is the diagnostic "reference standard", but testing 40 strategies changed over the course of the epidemic and varied according to local logistic 41 capacity. Thus, confirmed cases are a suboptimal indicator of the extent of SARS-CoV-2 42 infection, and the magnitude of undiagnosed infections can vary widely [4] . SARS-CoV-2 43 seroprevalence studies are critical to monitor the epidemic evolution in a population and to 44 inform public health measures, such as vaccine allocation [5] . Those studies estimate the 45 number of past infections higher than the number of RT-PCR confirmed cases [6, 7] . In the case 46 of an emergent agent, it is assumed that all population is initially susceptible; therefore, the 47 presence of specific antibodies provides good estimates of the cumulative incidence 48 particularly if the infection provides long-term serological immunity. 49 In Portugal, the first case of coronavirus disease 2019 (COVID-19) was diagnosed on March 2, 50 2020 and on March 16 a nationwide schools closure was decreed affecting all education levels 51 [8] -around 2 million students, more than 346 thousand from higher education [9] . Schools 52 and universities fully reopened in mid-September 2020, providing an excellent opportunity to 53 obtain data on the serum status of a large sample of university young adults exposed to highly 54 varied risk contexts. 55 students. The identifying information needed to schedule testing was kept only at the U.Porto 83 information systems' department. The linkage between datasets is impossible. 84 All participants presenting with symptoms or reporting high-risk contacts in the previous 14 95 days were recommended to contact the National Health Service Contact Center. All 96 participants were communicated their results orally and also in the form of a written leaflet 97 with the information that the serological test only indicates whether there is evidence of 98 previous contact with the SARS-CoV-2 and that it cannot be used to diagnose or rollout SARSintervals (95% CI) using Bayesian inference. We used a uniform prior distribution for sensitivity 105 ranging from 0.82 to 1 and specificity between 0.94 and 1. Estimates were obtained using the 106 'rjags' package in R. 107 is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint (5.8%) for IgG and 634 (9.7%) for IgM or IgG. The estimated true prevalence was 6.6 (95% CI 114 3.6-9.6) for IgM, 3.5 (95% CI 0.5-6.5) for IgG and 7.9 (95% CI 4.9-11.1) for IgM or IgG. 115 The prevalence of IgG was higher among males (7.1% vs 5.3% among females, p=0.006). The 116 prevalence of IgM or IgG antibodies was higher among the 30-34 years old and the 40 and 117 more years old, 13.5% and 16.1%, respectively (vs 7.9 % in students under 20, 9.7% in 20-24 118 years, 10.9% in 25-29 years and 8.7% in 35-39 years, p=0.001). A history of prior diagnosis was 119 also higher in those age groups, 2.5% among the 30-34 years old and 2.2% in those aged 40 120 years or over (vs 0.7% in students under 20, 1.5% in 20-24 years, 1.6% in 25-29 years and 1.6% 121 in 35-39 years, p=0.028). 122 The prevalence of antibodies was higher among international students (18.1% for IgM or IgG vs 123 10.4% among those living in their usual family home and 8.8% among nationally displaced, 124 p<0.001). The proportion of those who report a previous infection diagnosis was also higher 125 among international students (3.8% vs 1.2% among those living in their usual family home and 126 1.0% among nationally displaced, p<0.001). 127 Students who had contact with confirmed cases showed a prevalence of IgM or IgG of 20.5%, 128 higher than the prevalence of 8.0% among those without (p<0.001). Similar results were found 129 among those who were quarantined (21.3% vs 8.3%, p<0.001). IgM or IgG prevalence was also 130 higher whenever there was a history of symptoms since the beginning of 2020, being 7.5% 131 . CC-BY-NC 4.0 International license It is made available under a perpetuity. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint Among students without an infection diagnosis, the prevalence of antibodies increased with 142 the increased perception of having been infected; it varied from 39.3% among those who 143 considered this probability to be very high to 7.0% among those who thought it was low or 144 very low. 145 The 6512 students had a 9.7% prevalence of IgM or IgG antibodies. However, only 1. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint age this may not have been the case in U.Porto. Students whose usual residence was abroad 170 had a higher seroprevalence of infection. This might reflect a higher risk experience in their 171 own countries or sharing a more vulnerable context during their stay in U.Porto. 172 We found higher seroprevalence among students who reported previous negative molecular 173 test compared with those never tested, suggesting that some RT-PCR results might have been 174 false negatives [16] . In accordance with previous studies, the self-reported belief of having had immunological evidence of infection more than six months after diagnosis, indicating that 183 antibodies may last long in a substantial proportion of individuals, as previously reported [19] . 184 The national cumulative incidence of notified COVID-19 cases was 3.5% by the end of our data 185 collection. However, only 1.4% of students reported a positive RT-PCR test for SARS-CoV-2. 186 This lower incidence may be partially explained by the higher proportion of young people with 187 few or no symptoms and, therefore, unnoticed infections, students' higher socioeconomic 188 status, and an increased commitment to non-pharmacological preventive measures [1, 2] . It is 189 worth mentioning that the number of reported cases among U.Porto students from September 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 October 18, 2021. ; https://doi.org/10.1101/2021.10.14.21264978 doi: medRxiv preprint probably explained by the voluntary nature of this testing program and the fact that many 207 students remained on virtual learning. It is even possible that those who have had symptoms, 208 high-risk contacts, or a self-perception of a higher probability of having been infected might be 209 overrepresented. However, the dimension of infection in an educated, probably relatively low-210 risk community, is strong evidence of the increasing burden of COVID-19 in Portugal. 211 In the University of Porto, students had a 7.9% seroprevalence, which was five times higher 213 than the prevalence based on the reported molecular diagnoses and two times higher than the 214 notified national cumulative incidence by the end of the study. Being an international student, 215 reporting symptoms, self-perceiving high probability of infection, having had contact with a 216 case, experiencing quarantine, and having had a diagnostic test performed though negative 217 was associated with higher seroprevalence. Antibodies were present in 87% of those 218 previously diagnosed with a molecular test, though reactivity decreased with increased time 219 since the diagnosis. 220 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 October 18, 2021. ; https://doi.org/10.1101/2021.10.14.21264978 doi: medRxiv preprint SARS-CoV-2 infections in children and young people Prevalence of Asymptomatic SARS-CoV-2 Infection Risk factors for severity and mortality 245 in adult COVID-19 inpatients in Wuhan Antibodies to SARS-CoV-2 in 10 Sites in the United States Decreto-Lei n.º 10-A/2020: Diário da República n.º 52/2020, 1º Suplemento, Série I de COVID-19 Impact on Education: Global monitoring of school closures 262 caused by COVID-19 Assessment of Seroprevalence of SARS-CoV-2 and Risk Factors Associated With COVID-19 Infection Among Outpatients in Virginia Test, test, 268 test for COVID-19 antibodies: the importance of sensitivity Seroprevalence of SARS-CoV-2 Infection in Portugal in May-July 2020: Results of the First 272 National Serological Survey Cross-Sectional Study Examining the Seroprevalence of Severe Acute Respiratory Syndrome 277 Coronavirus 2 Antibodies in a University Student Population SARS-CoV-2 seroprevalence worldwide: a systematic review and meta-280 analysis False-negative results of initial RT-PCR assays for COVID-19 The authors have no conflicts of interest to declare that are relevant to