Unexpected detection of SARS-CoV-2 antibodies in the prepandemic period in Italy
Authors: Paola Suatoni
Ugo Pastorino
Donata Martinuzzi
Mattia Boeri
Livia Mazzini
Alfonso Marchianò
Gianluca Milanese
Federica Sabia
Stefano Sestini
Laura Cantone
Gabriella Sozzi
Emanuele Montomoli
Giovanni Apolone
Alessandro Manenti
Inesa Hyseni
Valentina Bollati
Journal: Tumori Journal (2020)
Discipline: CLINICAL MEDICINE
Keywords: COVID-19; SARS-CoV-2 antibodies; Screening.
Affiliations: Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy, Faculty of Medicine and Surgery, University of Siena, Siena, Italy, VisMederi Srl, Siena, Italy, VisMederi Research Srl, Siena, Italy, EPIGET–Epidemiology, Epigenetics and Toxicology Lab, University of Milan, Milan, Italy, Radiology, Department of Medicine and Surgery, University of Parma, Parma, Italy

Abstract:  There are no robust data on the real onset of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and spread in the prepandemic period worldwide. We investigated the presence of SARS-CoV-2 receptor-binding domain (RBD)-specific antibodies in blood samples of 959 asymptomatic individuals enrolled in a prospective lung cancer screening trial between September 2019 and March 2020 to track the date of onset, frequency, and temporal and geographic variations across the Italian regions. SARS-CoV-2 RBD-specific antibodies were detected in 111 of 959 (11.6%) individuals, starting from September 2019 (14%), with a cluster of positive cases (&gt;30%) in the second week of February 2020 and the highest number (53.2%) in Lombardy. This study shows an unexpected very early circulation of SARS-CoV-2 among asymptomatic individuals in Italy several months before the first patient was identified, and clarifies the onset and spread of the coronavirus disease 2019 (COVID-19) pandemic. Finding SARS-CoV-2 antibodies in asymptomatic people before the COVID-19 outbreak in Italy may reshape the history of pandemic. 

Retracted: No

PubPeer comments:
  This study shows an unexpected very early circulation of SARS-CoV-2 among asymptomatic individuals in Italy several months before the first patient was identified, and clarifies the onset and spread of the coronavirus disease 2019 (COVID-19) pandemic. If true, then will this finding  invalidate claims made by potentially dozens of papers on Covid-19 in Italy? For example, a paper by Santacroce et al. stated that the first two cases were in Chinese citizens and that Covid-19 had been detected in Rome on January 31, 2020: https: www.ejgm.co.uk download covid-19-in-italy-an-overview-from-the-first-case-to-date-7926.pdf , 
 The authors should add a second test for antibodies, such as the Roche test, which measures antibodies to Nucleocapsid. Too early to say that this is definitive , 
 The conclusions are based on the results obtained by means of RBD-based ELISA developed in-house. Authors state  In our preliminary study, an excellent correlation between the neutralization titer and the IgG, IgM, and immunoglobulin A ELISA response against the RBD of the S-protein was observed,4 confirming that the RBD-based ELISA can be used as a valid surrogate for neutralization . However, reference [4] is their non-peer review article published on bioRxiv. A cursory look at the preprinted manuscript reveals serious potential flaws. E.g. cross-reactivity with other coronaviruses has not been evaluated [?]. Furthermore, insufficient details related to the methodology are provided ( data not shown ). On top of that, even (most likely) unrealistic data related to the sensitivity and specificity of the assay, when used in the setting described in the original article (retrospective analysis of samples from before the pandemic) with prevalence not set to ~10% as shown in the article would yield erroneous results. Even a very unrealistic assumption of 1% disease prevalence gives the positive predictive value of 31,45% [CI 6,04 - 76,60%]. Although the idea of the manuscript is interesting, severe methodological flaws are evident, and the fact that authors based their conclusions on the presented data is unscientific at best, especially considering the consequences of communicating such highly uncertain findings with the wider audience. , 
 Can anyone confirm that this paper was peer reviewed? I asked the authors directly but they didn t reply. Moreover, it says:  Received: October 29, 2020; Accepted: October 29, 2020 which sounds quite fishy, considering that the journal editors are from the same institution of some of the authors. , 
 Any updates on this paper? by now, it should have been possible to do a confirmatory test? , 
 This paper is one of several discussed in this thread. https: twitter.com Ayjchan status 1349163446143746052 , 
 A month ago I wrote to the authors and asked them if they had done any confirmatory tests. No reply. I think that says it all. , 
 Genuine question, are there details on the expression of concern available anywhere? The extant description of the original EoC is vague, and the EoC itself was subsequently removed in June 2021. https: journals.sagepub.com doi 10.1177 0300891620987756 , 
 This article was independently re-reviewed following publication to ensure the data and findings were robust. Following this additional re-review, the Editor and the Tumori Institute, owner of the Tumori Journal, have determined that no changes will be made to the published article, and are satisfied that no further action is required. The Expression of Concern that was posted to the article has therefore been removed. ,