Silent Transmission of SARS-CoV-2 Among Ambulatory Influenza Like Illness (ILI) Patients

Abstract

Background: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China in December 2019 has led to a pandemic. Influenza and coronaviruses are known to show cross-reactive immunity. Therefore, we hypothesized that influenza vaccination may provide a protective effect against SARS-CoV-2.Methods: We investigated the presence of SARS-CoV-2 in flu vaccinated and unvaccinated ILI cases by real time PCR, followed by confirmation of evolutionary and spatial relationships using next generation sequencing (NGS).Results: Out of 739 nasopharyngeal specimens collected from November 2019 to March 2020, we found 37 samples were positive for SARS-CoV-2 RNA mostly during February 2020. We observed that the overall incidence of ILI cases during 2019-2020 influenza season was considerably higher than previous years and was gradually replaced with SARS-CoV-2 which indicated a slow transmission among ambulatory patients. NGS data confirmed independent introductions and transmission earlier than previously thought. Phylogenetic reconstruction of representative isolates showed clustering in the GH clade which is characterized by two amino acid changes in spike gene (D614G) and NS3 (Q57H). Shortness of breath was significantly lower (p = 0.04) in the ILI cases with the history of influenza vaccination suggesting a protective effect of the influenza vaccine, at least in part, on COVID-19 disease outcomes.Conclusions: The detection of SARS-CoV-2 among ILI patients shows the importance of flu vaccination and ILI surveillance system and warrants their further strengthening to mitigate the ongoing transmission of SARS-CoV-2 and to guide policy makers to optimize public health interventions.Funding Statement: This work was supported by the Research Center at King Fahad Medical city (Grant No 20- 066).Declaration of Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.Ethics Approval Statement: The study was approved by the Institutional Review Board at King Fahad Medical City (IRB Log No. 19-477 approved on 25 September 2019) for influenza vaccine effectiveness study, started from 7 November 2019. When COVID-19 pandemic started, the collection of samples stopped on the 2nd of March 2020. To screen those samples for SARS-CoV-2, we applied for another IRB (Log No. 20-161 approved on 23 March 2020).