key: cord-0704414-qvsgpbuz authors: Milani, Gregorio Paolo; Montomoli, Emanuele; Bollati, Valentina; Albetti, Benedetta; Bandi, Claudio; Bellini, Tommaso; Bonzini, Matteo; Buscaglia, Marco; Cantarella, Carlo; Cantone, Laura; Carugno, Michele; Casartelli, Sergio; Cavaletti, Guido; D'Alessandro, Sarah; De Chiara, Francesca; Delbue, Serena; Dioni, Laura; Eberini, Ivano; Favero, Chiara; Ferrari, Luca; Ferraroni, Monica; Galastri, Laura; Galli, Cristina; Hoxha, Mirjam; Iodice, Simona; La Vecchia, Carlo; Macchi, Chiara; Manini, Ilaria; Marchi, Serena; Mariani, Jacopo; Pariani, Elena; Pesatori, Angela Cecilia; Rota, Federica; Ruscica, Massimiliano; Schioppo, Tommaso; Tarantini, Letizia; Trombetta, Claudia Maria; Valsecchi, Maria Grazia; Vicenzi, Marco; Zanchetta, Giuliano title: SARS-CoV-2 infection among asymptomatic homebound subjects in Milan, Italy date: 2020-06-09 journal: Eur J Intern Med DOI: 10.1016/j.ejim.2020.06.010 sha: 15a9ea36489c7112f5fe6839ec901a41efa30745 doc_id: 704414 cord_uid: qvsgpbuz nan At the end of December 2019, the first cases of SARS-CoV-2 infection were identified in Wuhan, China. [1] In the following months, the outbreak of SARS-COV-2 infections spreads worldwide [1] As of May 1, 2020, more than 3 million of SARS-CoV-2 infections have been detected worldwide. These data were mainly collected from inpatients. On the other hand, asymptomatic or mildly symptomatic subjects are usually untested for SARS-CoV-2 although they are supposed to far outnumber the symptomatic patients. [2] Therefore, there is an urgent need to estimate as accurately as possible the real number of subjects who have been infected by the virus. The aim of this study was to assess the frequency of asymptomatic subjects with a SARS-CoV-2 positive nasal swab or presenting immunoglobulins against the virus in Milan (Italy). This study is the first part of the UNICORN ("UNIversity against CORoNavirus") project that is being conducted among the personnel of the University of Milan, the largest university in Lombardy (Italy). In this first part of the project, we aimed at investigating a sample of 200 asymptomatic subjects, enrolled during the lockdown period. Subjects with fever, any In this study conducted among a group of asymptomatic subjects in Milan, 11% presented a positive SARS-CoV-2 nasal swab and 10% had antibodies against SARS-CoV-2. The data on asymptomatic carriers of SARS-CoV-2 are of great interest, considering that the study was performed three weeks after the Italian Government had applied strict homebound measures to all citizens. The reasons underlying the infection of these subjects remain unknown. Milan is the capital of Lombardy, one of the regions with the highest SARS-CoV-2 local transmission in the world and it is possible that some subjects have been infected before the introduction of homebound measures. However, literature suggests that only a minority of asymptomatic cases are still positive for SARS-CoV-2 RNA in the nasal swab after 14 days. [6] Moreover, the large majority of positive subjects did not report any symptoms in the weeks preceding the enrolment, and some subjects never had symptoms in the previous 6 months. Approximately 10% of subjects presented with antibodies against SARS-CoV-2. The ability of antibodies against SARS-CoV-2 infection is still under debate. However, these data suggest that only a minority of asymptomatic subjects in Milan developed antibodies against this virus so far. Some considerations about the usefulness of antibodies testing for large-scale screening should be acknowledged. Data collected among inpatients affected by SARS-CoV-2 have shown that the seroconversion occurs in almost all cases within 2-3 weeks after symptoms onset. [7, 8] Testing for antibodies among asymptomatic subjects has been strongly emphasized as a promising strategy to guide societies to a gradual reopening, and many international authorities are addressing efforts to this goal. [9] The results of this study suggest that the use of antibodies for the general public should be cautious and new studies are needed to test their reliability in asymptomatic subjects. Our study has some limitations. First, the self-sampling strategy could have increased the number of false negatives. Second, the presence of viral RNA does not necessarily mean that the virus is present in a replicative state. [10] Third, we did not test plasma samples for virus neutralization. In conclusion, this study suggests that approximately 15% of homebound subjects in Milan has been infected by SARS-CoV-2. The reliability of antibodies tests this virus deserves further studies before its systematic use for screening in the general population. WHO Director-General's opening remarks at the media briefing on COVID-19: 11 Covid-19: four fifths of cases are asymptomatic, China figures indicate Centers for Diseases Control and Prevention Guideline for "Collecting, Handling, and Testing Clinical Specimens from Persons for Coronavirus Disease Towards the next phase: evaluation of serological assays for diagnostics and exposure assessment. medRxiv: 2020 Evaluation of nine commercial SARS-CoV-2 immunoassays. medRxiv: 2020 Clinical Features and Outcomes of Asymptomatic Cases of SARS-CoV-2 Infection Antibody responses to SARS-CoV-2 in patients with COVID-19 Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study The Promise and Peril of Antibody Testing for Coronaviruses post-SARS: update on replication and pathogenesis The figure describes the symptoms reported by subjects testing positive for one or more of the SARS-CoV-2 marker, including upper airways infections (red), lower airway infections (brown) and fever (blue). Right panel. The table specifies what marker resulted positive for each subject We thank all the AVIS-Milano volunteers for their support with blood collection, Patrizia Angiolillo for electronic questionnaire preparation, Nicla Diomede for informatics security, Elena del Giorgio for support during subject's enrolment, Angelo Casertano and all the University of Milan staff for their precious help. All authors declare no conflict of interest The study was approved by the ethics committee of the University of Milan (approval number 17/20, approval date March 6, 2020) and conducted in accordance with the Declaration of Helsinki. GM: Study design, literature search, data collection, data analysis, data interpretation, writing EM: Data collection, data analysis, data interpretation VB: Study design, figures, data collection, data analysis, data interpretation, writing UNICORN CONSORTIUM: Subject's enrolment, Laboratory analysis, data interpretation. GPM and VB received a grant from "Ricerche Emergenza coronavirus", University of Milan, 2020 to support the study (https://lastatalenews.unimi.it/statale-individuati-sette-progettiricerca-ad-alta-priorita-contro-covid-19). Funds have been used for purchasing reagents. The authors have nothing to disclose.