Wednesday, December 09, 2020

EID Journal: Evidence of SARS-CoV-2 RNA in an Oropharyngeal Swab Specimen, Milan, Italy, Early December 2019


#15,612

It is practically axiomatic that - by the time we recognize that an new emerging disease has jumped species to humans - that it has been circulating unnoticed (or misdiagnosed) for months, or even years. 

And the cases that are reported - even under the best of circumstances - are inevitably only a subset of the total number of cases in the community.

We see this with infections as common and ubiquitous as seasonal flu (see CDC: The Estimated Burden Of Last Year's Flu Season), and as rare and exotic as MERS-CoV (see EID Journal: Estimation of Severe MERS Cases in the Middle East, 2012–2016).

While the first recognized cases of what would be later identified as COVID-19 emerged in early December in Wuhan, China, it is likely that low-level transmission - perhaps inefficiently - had been occurring for some time in China.  

And if that is true, it isn't beyond the realm of possibility that a few cases were exported to other countries in the last half of 2019.  In fact, we've seen evidence - based on environmental sampling of sewage in Italy - that may well be the case. 

Adding to this evidence, we have a report in the CDC's EID Journal of a retrospective analysis of 39 swabs collected between Sept 2019 and February 2020 in Milan, Italy which has turned up one SARS-CoV-2 positive result form a 4-year-old child suspected of having measles. 

I've posted excerpts from the research letter below, but follow the link to read it in its entirety. 

Evidence of SARS-CoV-2 RNA in an Oropharyngeal Swab Specimen, Milan, Italy, Early December 2019
 
 
Antonella Amendola1, Silvia Bianchi1, Maria Gori, Daniela Colzani, Marta Canuti, Elisa Borghi, Mario C. Raviglione, Gian Vincenzo Zuccotti, and Elisabetta Tanzi 

Author affiliations: University of Milan, Milan, Italy (A. Amendola, S. Bianchi, M. Gori, D. Colzani, E. Borghi, M.C. Raviglione, G.V. Zuccotti, E. Tanzi); Memorial University of Newfoundland, St. John’s, Newfoundland, Canada (M. Canuti)

 
Abstract

We identified severe acute respiratory syndrome coronavirus 2 RNA in an oropharyngeal swab specimen collected from a child with suspected measles in early December 2019, ≈3 months before the first identified coronavirus disease case in Italy. This finding expands our knowledge on timing and mapping of novel coronavirus transmission pathways.


Coronavirus disease (COVID-19) symptoms can encompass a Kawasaki disease–like multisystem inflammatory syndrome and skin manifestations that accompany common viral infections such as chickenpox and measles (1,2). Some of the earliest reports of COVID-19 cutaneous manifestations came from dermatologists in Italy. In fact, Italy was the first Western country severely hit by the COVID-19 epidemic. The first known COVID-19 case in Italy was reported in the town of Codogno in the Lombardy region on February 21, 2020. However, some evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had been circulating unnoticed for several weeks in Lombardy before the first official detection (3). Phylogenetic studies highlighted an early circulation of SARS-CoV-2 in Italy and suggest multiple introductions of the virus from China and Germany, followed by an autochthonous transmission (4,5). Furthermore, environmental surveillance has unequivocally demonstrated the presence of the virus, at concentrations comparable to those obtained from samples collected at later stages of the pandemic, in the untreated wastewater of the Milan area as early as mid-December 2019 (6).

As participants in Italy’s Measles and Rubella Network, a sensitive case-based surveillance system, we observed in Milan during late autumn 2019 cases of suspected measles in patients who eventually tested negative for measles. We therefore retrospectively explored a possible etiologic involvement of SARS-CoV-2 in these non–measles-linked rash cases.

(SNIP)

We describe the earliest evidence of SARS-CoV-2 RNA in a patient in Italy, ≈3 months before Italy’s first reported COVID-19 case. These findings, in agreement with other evidence of early COVID-19 spread in Europe, advance the beginning of the outbreak to late autumn 2019 (6,810).
However, earlier strains also might have been occasionally imported to Italy and other countries in Europe during this period, manifesting with sporadic cases or small self-limiting clusters. These importations could have been different from the strain that became widespread in Italy during the first months of 2020. Unfortunately, the swab specimen, which was collected for measles diagnosis, was not optimal for SARS-CoV-2 detection because it was an oropharyngeal rather than a nasopharyngeal swab specimen and it was collected 14 days after the onset of symptoms, when viral shedding is reduced. In addition, thawing might have partially degraded the RNA, preventing the sequencing of longer genomic regions that could have been helpful in determining the origin of the strain.

This finding is of epidemiologic importance because it expands our knowledge on timing and mapping of the SARS-CoV-2 transmission pathways. Long-term, unrecognized spread of SARS-CoV-2 in northern Italy would help explain, at least in part, the devastating impact and rapid course of the first wave of COVID-19 in Lombardy. Full exploitation of existing virologic surveillance systems to promptly identify emerging pathogens is therefore a priority to more precisely clarify the course of outbreaks in a population. Further studies aimed at detecting SARS-CoV-2 RNA in archived samples suitable for whole-genome sequencing will be crucial at determining exactly the timeline of the COVID-19 epidemic in Italy and will be helpful for the preparedness against future epidemics.


Prof. Amendola and Dr. Bianchi are researchers at the Department of Biomedical Sciences for Health, University of Milan, Italy. Their primary research interests include the epidemiology and prevention of viral infectious diseases. Prof. Amendola heads the subnational laboratory MoRoNET (Measles and Rubella Surveillance Network).