Influenza A(H1N1)pdm09 Virus but Not Respiratory Syncytial Virus Interferes with SARS-CoV-2 Replication during Sequential Infections in Human Nasal Epithelial Cells

Abstract

The types of interactions between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory viruses are not well-characterized due to the low number of co-infection cases described since the onset of the pandemic. We have evaluated the interactions between SARS-CoV-2 (D614G mutant) and influenza A(H1N1)pdm09 or respiratory syncytial virus (RSV) in the nasal human airway epithelium (HAE) infected simultaneously or sequentially (24 h apart) with virus combinations. The replication kinetics of each virus were determined by RT-qPCR at different post-infection times. Our results showed that during simultaneous infection, SARS-CoV-2 interferes with RSV-A2 but not with A(H1N1)pdm09 replication. The prior infection of nasal HAE with SARS-CoV-2 reduces the replication kinetics of both respiratory viruses. SARS-CoV-2 replication is decreased by a prior infection with A(H1N1)pdm09 but not with RSV-A2. The pretreatment of nasal HAE with BX795, a TANK-binding kinase 1 inhibitor, partially alleviates the reduced replication of SARS-CoV-2 or influenza A(H1N1)pdm09 during sequential infection with both virus combinations. Thus, a prior infection of nasal HAE with SARS-CoV-2 interferes with the replication kinetics of A(H1N1)pdm09 and RSV-A2, whereas only A(H1N1)pdm09 reduces the subsequent infection with SARS-CoV-2. The mechanism involved in the viral interference between SARS-CoV-2 and A(H1N1)pdm09 is mediated by the production of interferon.

Epidemiological Interactions of Influenza and SARS-CoV-2 within a University Population During Omicron B.1.1.529 Outbreak

“…Our observation supports possible SARS-CoV-2 dominance via unique host interactions as well as the potential occurrence of priming the immune system to limit co-infection [4]. Symptomatic testing demand was higher during the first year of the pandemic with weekly averages of 38.5, 95% CI [35.8, 41.2], daily orders, yet the weekly average SARS-CoV-2 positive cases of 1.6, 95%CI [1.4, 1.7] may further indicate the activity of another pathogen during that time.…”

“…Our observation supports possible SARS-CoV-2 dominance via unique host interactions as well as the potential occurrence of priming the immune system to limit co-infection [4]. Symptomatic testing demand was higher during the first year of the pandemic with weekly averages of 38.…”

An Italian Multicenter Study on the Epidemiology of Respiratory Syncytial Virus During SARS-CoV-2 Pandemic in Hospitalized Children

“…Recently, it has been demonstrated that hRV triggers an interferon response that blocks SARS-CoV-2 replication ( 28 ). Influenza Virus, but not RSV, reduced SARS-CoV-2 replication and in turn, SARS-CoV-2 interfered with RSV-A replication in Nasal Epithelial Cells in vitro ( 29 ). Accordingly, it is possible to hypothesize that RSV circulation this year was halted by the ongoing spread of the SARS-CoV-2 Omicron variant surge that was particularly contagious and abundant in unvaccinated children ( 30 ).…”

Suppression of influenza virus infection by rhinovirus interference – at the population, individual and cellular levels

“…and Fage et al. studied the interference between RV, RSV, influenza and SARS-CoV-2 by simultaneous or sequential infection in the human ALI culture system ( Essaidi-Laziosi et al., 2022 ; Fage et al., 2022 ). While both studies indicated the effect of influenza in suppressing the subsequent SARS-CoV-2 replication and both of them suggested that the viral interference was dependent on interferon pathways but not related to blockage of viral entry, the effect of SARS-CoV-2 in inhibiting the subsequent infection of influenza virus diverged in these two studies.…”