It is not yet fully understood whether coinfection with another pathogen may impact the severity of COVID-19. It has been reported in previous studies that coinfections between SARS-CoV-2 and other common respiratory viruses have occurred. Coinfection has been reported in patients with SARS and MERS and co-pathogens include bacteria, fungi and viruses, which lead to complications in the identification and treatment of respiratory syndrome and aggravate the state of illness. A recent meta-analysis of 30 studies, including 3834 patients with COVID-19, revealed that 7% had a bacterial coinfection and 3% had viral coinfections, with influenza A virus and RSV being the most common. In a study published in Nature, researchers from the Israel Institute of Biological Research delineated the interplay between influenza A and SARS-CoV-2 infections. To establish a SARS-CoV-2 susceptible mouse model, the authors employed transgenic mice expressing human hACE2 under control of human cytokeratin 18 promoter (K18-hACE2 mice).
Firstly, the authors tested the outcome of the coronavirus infection two days post influenza infection (dpli) during presymptomatic influenza. At these early stages, the viral titer of the virus in the lings was high, but the mice did not present with any disease manifestations. At five dpli, the infected mice began to lose weight, and at 9 to ten dpli, they exhibited maximal morbidity. The mice that were only infected with either influenza or SARS-CoV-2 displayed a mortality rate of 38%, while all the coinfected mice died five to seven days post SARS-CoV-2 infection (dpsi). At six to seven dpli, the influenza-infected and coinfected mice began to lose weight. However, the maximal weight loss of the influenza-infected mice was reached at 8 dpli, while the coinfected mice continued to lose weight until ten dpli. Finally, the authors assessed the effects of coinfection when the administration of SARS-CoV-2 occurred in the late symptomatic stage of influenza disease when maximal morbidity was detected.
The body weight and survival rate of the mice were not affected by SARS-CoV-2 infection at eight dpli. The authors achieved SARS-CoV-2 immunity in the mice by intramuscular immunization of coronavirus. That induced both cellular and humoral responses against SARS-CoV-2 and was sufficient to protect the mice from a viral challenge. However, while mortality caused by SARS-CoV-2 infection was completely prevented by pre-existing coronavirus immunity, no effect was observed regarding morbidity and mortality caused by the coinfection of SARS-CoV-2 and influenza. 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 employed by the authors, which also did not protect against coinfection. Mice were administered intramuscular immunization of influenza virus, 30 days before infection with SARS-CoV-2 and/or influenza.
The aim was to determine whether pre-existing immunity to influenza can protect against coinfection. The influenza virus pre-exposure induced specific cellular and humoral responses and appeared to reduce the observed morbidity against this virus The SARS-CoV-2 survival rate was not affected by the pre-exposure to influenza virus. Interestingly, the mortality and severe clinical manifestations associated with a coinfection were prevented by immunity to influenza. There was no increase in mortality and no weight loss detected in the coinfected mice immunized against influenza compared to the coinfected mice without pre-existing immunity. These results suggest that the severe manifestations associated with coinfection are not due to a more severe COVID, but one of influenza virus. These severe manifestations in coinfected mice were associated with robust induction of innate immunity, higher influenza viral load and intensified pathology of the respiratory system.
These data suggest that influenza immunity gained via vaccination may be a valuable tool for reducing the risk of severe coinfection of influenza and SARS-CoV-2. But apparently it is not the only type of vaccination able to reproduce this kind of scenario. Accordingto preliminary data, people who get the shingles vaccine may have a lower risk of being diagnosed and hospitalized with COVID-19. In about 150,000 people over the age of 50, vaccination for shingles was associated with a 32% reduced risk of severe COVID-19 infection. The researchers suggest the shingles vaccine may boost innate immunity — increasing the body’s cytokine levels and prepping an antiviral response against potential infections. In addition, innate immunity may help weaken coronavirus ability to replicate during early infection. Alternatively, people who are vaccinated for shingles may already be health-conscious and more proactive in getting vaccinated.
About 149,244 people were vaccinated with at least one dose of the recombinant adjuvanted zoster vaccine. A control group consisted of 298,488 unvaccinated individuals for comparison. About 16.2% of individuals were 50 to 59 years old, and 12.8% were over 80. Vaccinated individuals were more likely to have frequent outpatient medical visits before the pandemic and were associated with hypertension and having other vaccinations. Of the approximate 150,000 vaccinated individuals, there were 5,951 COVID-19 diagnoses and 1,066 COVID-19 related hospitalizations. Individuals not vaccinated with at least one shingles vaccine dose reported more COVID-19 diagnoses. As a result, there were 13,028 COVID-19 cases, and 2,765 individuals required hospitalization for severe COVID-19 infection.An additional analysis further confirmed lower incidences of COVID-19 and related hospitalization in vaccinated versus unvaccinated individuals.
One dose of the shingles vaccine correlated with a 16% reduced risk of a COVID-19 diagnosis. An association was also found between the shingles vaccine and a 32% lower rate for COVID-19 related hospitalization. Of the 94,895 individuals with two doses of the shingles vaccine, 3,403 were diagnosed with COVID-19 infection. Of those, 612 required hospitalization. A cohort of 189,790 unvaccinated individuals was matched to individuals who received two vaccine doses. This group had 7,689 COVID-19 diagnoses and 1,676 COVID-19 related hospitalizations. Results translated to a 19% reduced risk of COVID-19 infection in vaccinated individuals and a 36% reduced hospitalization rate. The study results are correlational, and more research is needed to identify whether it is the shingles vaccine itself or other factors driving the lowered risk of COVID-19. Up to now, COVID vaccines continue to be the best form of protection against the coronavirus.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Li H et al. Emerg Microb Infect. 2021; 10(1):1156-68.
Achdout, H. et al. Nature Commun 2021 Oct, 12(1).
Bruxvoort KJ et al. medRxiv 2021 Oct 1:21264400.