Retrospective screening of routine respiratory samples revealed undetected community transmission and missed intervention opportunities for SARS-CoV-2 in the United Kingdom

Abstract

In the early phases of the SARS coronavirus type 2 (SARS-CoV-2) pandemic, testing focused on individuals fitting a strict case definition involving a limited set of symptoms together with an identified epidemiological risk, such as contact with an infected individual or travel to a high-risk area. To assess whether this impaired our ability to detect and control early introductions of the virus into the UK, we PCR-tested archival specimens collected on admission to a large UK teaching hospital who retrospectively were identified as having a clinical presentation compatible with COVID-19. In addition, we screened available archival specimens submitted for respiratory virus diagnosis, and dating back to early January 2020, for the presence of SARS-CoV-2 RNA. Our data provides evidence for widespread community circulation of SARS-CoV-2 in early February 2020 and into March that was undetected at the time due to restrictive case definitions informing testing policy. Genome sequence data showed that many of these early cases were infected with a distinct lineage of the virus. Sequences obtained from the first officially recorded case in Nottinghamshire - a traveller returning from Daegu, South Korea – also clustered with these early UK sequences suggesting acquisition of the virus occurred in the UK and not Daegu. Analysis of a larger sample of sequences obtained in the Nottinghamshire area revealed multiple viral introductions, mainly in late February and through March. These data highlight the importance of timely and extensive community testing to prevent future widespread transmission of the virus.

Two doses of the SARS-CoV-2 BNT162b2 vaccine enhance antibody responses to variants in individuals with prior SARS-CoV-2 infection

“…Our study has several limitations. Prior exposure in our cohort involves only exposure to the lineage A or B variants (28,29), and natural infection by more antigenically diverse strains may skew the resultant immune potency and breadth. Unfortunately, we had too few positive PCR samples to try to elucidate any link between immunity and infecting lineage.…”

Performance analysis of English hospitals during the first and second waves of the coronavirus pandemic

“…The first confirmed cases of COVID-19 in the UK were on the 29 th January 2020, when two Chinese nationals fell ill in York. The earliest known person to contract COVID-19 within the UK is believed to be a 75-year-old woman from Nottinghamshire, who tested positive on the 21 st February 2020 [ 22 ]. She is also understood to be the first victim of COVID-19 in the UK.…”

Coronavirus Disease Case Definitions, Diagnostic Testing Criteria, and Surveillance in 25 Countries with Highest Reported Case Counts

“…The authors estimated that if the fifth version of the case definition had been applied throughout the outbreak, 4.2 times more confirmed cases would have been identified in China by February 20, 2020 (232,000 vs. 55,508). A more recent study benefitting from the availability of the complete genome sequence for SARS-CoV-2 and access to respiratory specimens collected early for retrospective analysis perhaps best demonstrates the effect of a restrictive case definition ( 23 ). Those authors identified multiple early cases of SARS-CoV-2 infection in Nottingham, UK, that, despite demonstrating symptoms consistent with COVID-19, did not meet case definition criteria used for diagnostic testing referral in place at the time because of lack of travel history or contact with an infected person.…”