It is not yet clear whether co-infection with another pathogen can impact the severity of coronavirus disease 2019 (COVID-19). It has been reported in previous studies that co-infections between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and other common respiratory viruses have occurred. A recent meta-analysis of 30 studies, including 3,834 patients with COVID-19, found that 7% had bacterial co-infection and 3% had viral co-infections, influenza A virus (IAV) and the respiratory syncytial virus being the most common.
Study: The increased lethality of influenza and SARS-CoV-2 co-infection is prevented by influenza immunity but not by SARS-CoV-2 immunity. Image Credit: Kateryna Kon / Shutterstock
In a study published in Nature, researchers at the Israel Institute for Biological Research have delineated the interaction between IAV infections and SARS CoV-2. To establish a SARS-CoV-2 sensitive mouse model, the authors used transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) under the control of the human cytokeratin 18 promoter (K18- mice). hACE2).
First, the authors tested the outcome of SARS-CoV-2 infection two days after influenza infection (dpli) during presymptomatic influenza. At these early stages, the viral titer of IAV in the ling was high, but the mice showed no manifestation of the disease. At five dpli, the mice infected with the IAV began to lose weight, and at 9 to ten dpli, they had maximum morbidity.
Mice that were only infected with influenza or SARS-CoV-2 had a 38% mortality rate, while all co-infected mice died five to seven days after infection with SARS- CoV-2 (dpsi). At six to seven dpli, the mice infected and co-infected with the IAV began to lose weight. However, the maximum weight loss of the mice infected with IAV was achieved at 8 dpli, while the coinfected mice continued to lose weight up to ten dpli.
Finally, the authors evaluated the effects of co-infection when the administration of SARS-CoV-2 occurred in the late symptomatic stage of influenza, when maximum morbidity was detected. The body weight and survival rate of the mice were unaffected by the eight-fold SARS-CoV-2 infection.
The authors obtained immunity against SARS-CoV-2 in mice by intramuscular immunization of SARS-CoV-2. Immunization by this route induced both cellular and humoral responses against SARS-CoV-2 and was sufficient to protect mice from SARS-CoV-2 challenge. However, while the mortality caused by SARS-CoV-2 infection was completely avoided by pre-existing immunity to SARS-CoV-2, no effect was observed regarding morbidity and mortality caused by SARS-CoV-2. co-infection of SARS-CoV-2 and IAV.
The authors also examined an alternative route of immunization to rule out the possibility that inadequate protection against coinfection was due to intramuscular immunization. The intranasal route of immunization was used by the authors, which also did not protect against co-infection.
Mice were immunized intramuscularly with IAV, 30 days prior to infection with SARS-CoV-2 and / or IAV, to determine if pre-existing immunity to IAV can protect against co-infection. . Pre-exposure to IAV induced cellular and humoral responses against IAV and appeared to reduce the morbidity observed during infection with IAV.
The survival rate of SARS-CoV-2 was not affected by pre-exposure to IAV. Interestingly, the mortality and severe clinical manifestations associated with co-infection with IAV and SARS-CoV-2 have been prevented by immunity to IAV. No increased mortality and no weight loss were detected in co-infected mice immunized against IAV compared to co-infected mice without pre-existing immunity. These results suggest that the severe manifestations associated with co-infection are not due to more severe SARS-CoV-2 disease but to IAV.
This study shows that co-infection with IAV and SARS-CoV-2 causes severe and fatal disease in mice. The severe manifestations presented by co-infected mice were associated with a robust induction of innate immunity, a high IAV viral load, and an intensified pathology of the respiratory system.
Previous humoral immunity to influenza, but not SARS-CoV-2, halted progression to severe disease and mortality, suggesting that immunity to influenza acquired through vaccination may be a valuable tool for reduce the risk of severe co-infection with influenza and SARS-CoV-2.
- Achdout, H. et al. (2021) “Increased lethality in influenza and SARS-CoV-2 co-infection is prevented by influenza immunity but not by SARS-CoV-2 immunity”, Nature Communication, 12 (1). do I: 10.1038 / s41467-021-26113-1.