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Molecular Evidence for SARS-CoV-2 in Samples Collected From Patients With Morbilliform Eruptions Since Late Summer 2019 in Lombardy, Northern Italy

27 Pages Posted: 6 Aug 2021

See all articles by Antonella Amendola

Antonella Amendola

University of Milan - Department of Biomedical Sciences for Health

Marta Canuti

Memorial University of Newfoundland - Biology Department

Silvia Bianchi

University of Milan - Department of Health Sciences

Sudhir Kumar

Temple University - Institute for Genomics and Evolutionary Medicine

Clara Fappani

University of Milan - Department of Biomedical Sciences for Health

Maria Gori

University of Milan - Coordinate Research Centre EpiSoMI

Daniela Colzani

University of Milan - Department of Biomedical Sciences for Health

Sergei LK Pond

Temple University - Institute for Genomics and Evolutionary Medicine

Sayaka Miura

Temple University - Institute for Genomics and Evolutionary Medicine

Melissa Baggieri

Istituto Superiore di Sanità - Department of Infectious Diseases

Antonella Marchi

Istituto Superiore di Sanità - Department of Infectious Diseases

Elisa Borghi

University of Milan - Department of Health Sciences

Gian Vincenzo Zuccotti

University of Milan - Department of Clinical and Biological Sciences; University of Milan - Department of Pediatrics

Mario C. Raviglione

University of Milan - Centre for Multidisciplinary Research in Health Science

Fabio Magurano

Istituto Superiore di Sanità - Department of Infectious Diseases

Elisabetta Tanzi

University of Milan - Department of Biomedical Sciences for Health

More...

Abstract

Background: Skin manifestations have been reported in patients with SARS-CoV-2 infection. As a reference laboratory for measles and rubella surveillance in Lombardy, we evaluated the association between SARS-CoV-2 infection and measles-like symptomatology while providing evidence for undetected early circulation of SARS-CoV-2.

Methods: Overall, 435 samples from 156 cases were investigated. RNA isolated from oropharyngeal swabs (N=148) and urine (N=141) was screened by hemi-nested PCRs targeting key sites for viral typing. After Sanger sequencing, detected mutations were used to estimate the time of emergence of the progenitor SARS-CoV-2 using a previously calibrated molecular clock. Sera (N=146) were tested for anti-SARS-CoV-2 IgG, IgM, and IgA, and the titre of neutralizing antibodies was assessed.

Findings: Molecular evidence for SARS-CoV-2 infection was found in 13 subjects. Two patients were from the pandemic period (2/12, 16·7%, March 2020-March 2021) and 11 were from the pre-pandemic period (11/44, 25%, August 2019-February 2020). Five of the positive individuals showed the simultaneous presence of anti-SARS-CoV-2 antibodies. No clear evidence of infection was found in 281 samples collected between August 2018 and July 2019 from 100 patients. The first positivity for SARS-CoV-2 RNA was found in a sample collected on September 12, 2019. Mutations typical of B.1 (PANGOLIN classification) strains, previously reported to have emerged in January 2020, had already been circulating in October 2019. Hence, we estimate SARS-CoV-2 progenitor of known human infections to have emerged in late June-late August 2019.

Interpretations: We find evidence that SARS-CoV-2 was circulating in Lombardy during the late summer of 2019. This finding highlights the importance of retrospective surveillance studies to understand the early dynamics of COVID-19 spread and improve national-level preparedness.

Funding Information: Research support from: Romeo and Enrica Invernizzi Pediatric Research Center, University of Milan, Milan, Italy; U.S. National Science Foundation to S.K. and S.M. (DEB‐2034228) and S.P. (DBI‐2027196); U.S. National Institutes of Health to S.K. (GM‐139504) and S.P. (AI‐134384

Declaration of Interests: The authors declare no conflict of interest.

Ethics Approval Statement: This work was carried out as part of the Integrated Measles-Rubella Surveillance, performed by law in accordance with the Prime Minister's Decree of 3 March 2017
(https://www.gazzettaufficiale.it/eli/id/2017/05/12/17A03142/sg). The retrospective study was conducted in the absence of consent following the declaration of state of emergency caused by the SARS-CoV-2 pandemic, in accordance with letter i, article 9 of the GDPR (https://eurlex.europa.eu/legal-content/IT/TXT/HTML/?uri=OJ:L:2016:119:FULL&from=FI).

Suggested Citation

Amendola, Antonella and Canuti, Marta and Bianchi, Silvia and Kumar, Sudhir and Fappani, Clara and Gori, Maria and Colzani, Daniela and Pond, Sergei LK and Miura, Sayaka and Baggieri, Melissa and Marchi, Antonella and Borghi, Elisa and Zuccotti, Gian Vincenzo and Zuccotti, Gian Vincenzo and Raviglione, Mario C. and Magurano, Fabio and Tanzi, Elisabetta, Molecular Evidence for SARS-CoV-2 in Samples Collected From Patients With Morbilliform Eruptions Since Late Summer 2019 in Lombardy, Northern Italy. Available at SSRN: https://ssrn.com/abstract=3883274 or http://dx.doi.org/10.2139/ssrn.3883274

Antonella Amendola

University of Milan - Department of Biomedical Sciences for Health ( email )

Milan
Italy

Marta Canuti

Memorial University of Newfoundland - Biology Department ( email )

Faculty of Education
St. John's, Newfoundland A1B 3X5 A1C 5V3
Canada

Silvia Bianchi

University of Milan - Department of Health Sciences ( email )

Milano
Italy

Sudhir Kumar

Temple University - Institute for Genomics and Evolutionary Medicine ( email )

Medicine Education & Research Building
3500 N. Broad St.
Philadelphia, PA 19122
United States

Clara Fappani

University of Milan - Department of Biomedical Sciences for Health ( email )

Milan
Italy

Maria Gori

University of Milan - Coordinate Research Centre EpiSoMI

Via Festa del Perdono, 7
Milan, 20122
Italy

Daniela Colzani

University of Milan - Department of Biomedical Sciences for Health ( email )

Milan
Italy

Sergei LK Pond

Temple University - Institute for Genomics and Evolutionary Medicine

Philadelphia, PA 19122
United States

Sayaka Miura

Temple University - Institute for Genomics and Evolutionary Medicine ( email )

Medicine Education & Research Building
3500 N. Broad St.
Philadelphia, PA 19122
United States

Melissa Baggieri

Istituto Superiore di Sanità - Department of Infectious Diseases

Viale Regina Elena 299
Roma, 00161
Italy

Antonella Marchi

Istituto Superiore di Sanità - Department of Infectious Diseases

Viale Regina Elena 299
Roma, 00161
Italy

Elisa Borghi

University of Milan - Department of Health Sciences ( email )

Milano
Italy

Gian Vincenzo Zuccotti

University of Milan - Department of Clinical and Biological Sciences ( email )

Milan
Italy

University of Milan - Department of Pediatrics ( email )

Via Lodovico Castelvetro, 32
Milan, 20154
Italy

Mario C. Raviglione

University of Milan - Centre for Multidisciplinary Research in Health Science

Fabio Magurano

Istituto Superiore di Sanità - Department of Infectious Diseases

Viale Regina Elena 299
Roma, 00161
Italy

Elisabetta Tanzi (Contact Author)

University of Milan - Department of Biomedical Sciences for Health ( email )

Milan
Italy

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