Adults in hospital who have COVID-19 and the flu at the same time are at much greater risk of severe disease and death


Adults in hospital who have COVID-19 and the flu at the same time are at much greater risk of severe disease and death compared with patients who have COVID-19 alone or with other viruses, research shows.

Patients with co-infection of SARS-CoV-2, which causes COVID-19, and influenza viruses were over four times more likely to require ventilation support and 2.4 times more likely to die than if they only had COVID-19, experts found.

Researchers say the findings show the need for greater flu testing of COVID-19 patients in hospital and highlight the importance of full vaccination against both COVID-19 and the flu.

The team from the University of Edinburgh, University of Liverpool, Leiden University and Imperial College London, made the findings in a study of more than 305,000 hospitalized patients with COVID-19.

The research—delivered as part of the International Severe Acute Respiratory and emerging Infection Consortium’s (ISARIC) Coronavirus Clinical Characterisation Consortium—is the largest ever study of people with COVID-19 and other endemic respiratory viruses.

ISARIC’s study was set up in 2013 in readiness for a pandemic such as this.

The team looked at the data of adults who had been hospitalized with COVID-19 in the UK between 6 February 2020 and 8 December 2021.

Test results for respiratory viral co-infections were recorded for 6965 patients with COVID-19. Some 227 of these also had the influenza virus, and they experienced significantly more severe outcomes.

Dr. Maaike Swets, Ph.D. student at the University of Edinburgh and Leiden University, said: “In the last two years we have frequently witnessed patients with COVID-19 become severely ill, at times leading to an ICU admission and the employment of an artificial ventilator to help with breathing.

That an influenza infection could give rise to a similar situation was already known, but less was understood about the outcomes of a double infection of SARS-CoV-2 and other respiratory viruses.”

Professor Kenneth Baillie, Professor of Experimental Medicine at the University of Edinburgh, said: “We found that the combination of COVID-19 and flu viruses is particularly dangerous.

This will be important as many countries decrease the use of social distancing and containment measures. We expect that COVID-19 will circulate with flu, increasing the chance of co-infections. That is why we should change our testing strategy for COVID-19 patients in hospital and test for flu much more widely.”

Professor Calum Semple, Professor of Outbreak Medicine and Child Health at the University of Liverpool, said: “We are seeing a rise in the usual seasonal respiratory viruses as people return to normal mixing. So, we can expect flu to be circulating alongside COVID-19 this winter. We were surprised that the risk of death more than doubled when people were infected by both flu and COVID-19 viruses. It is now very important that people get fully vaccinated and boosted against both viruses, and not leave it until it is too late.”

Dr. Geert Groeneveld, doctor at Leiden University Medical Center’s infectious diseases department, said: “Understanding the consequences of double infections of SARS-CoV-2 and other respiratory viruses is crucial as they have implications for patients, hospitals and ICU capacity during seasons that SARS-CoV-2 and influenza circulate together.”

Professor Peter Openshaw, Professor of Experimental Medicine at Imperial College London, said: “Being infected with more than one virus is not very common but it’s important to be aware that co-infections do happen. The vaccines that protect against COVID-19 and flu are different, and people need both.

The way that these two infections are treated is also different so it’s important to test for other viruses even when you have a diagnosis in someone who is hospitalized with a respiratory infection. This latest discovery by the ISARIC consortium again adds significantly to improving the way we manage patients.”

The findings have been published in The Lancet.

COVID-19 as a highly transmissible viral infection which led to thousands of deaths worldwide has challenged the world’s healthcare systems (34). Therefore, several studies have been performed to identify how the infection occurs, its symptoms and complications, as well as the factors involved in increasing its severity and mortality, and it is still the subject of studies.

Co-occurrence of infections can be one of the causes of exacerbation of this disease. Lansbury et al. in their recent meta-analysis of 30 studies reports the pooled proportions of bacterial and viral co-infections in patients with COVID-19 were 7 and 3%, respectively (35).

In some viral infections, simultaneous infections with other bacterial and viral agents can exacerbate complications and increase disease mortality. The same can be said for SARS-CoV2 infection; however, there is not enough evidence to suggest that such concurrent infections increase disease morbidity or mortality.

COVID-19 often presents with nonspecific flu like respiratory symptoms. Influenza virus infection is thought to be similar to COVID-19 in clinical presentation, transmission mechanism, and seasonal coincidence. Simultaneous infection with influenza and SARS-CoV2 can interfere with the diagnosis and treatment of patients. In addition, this co-infection, especially in high-risk groups of patients, may aggravate the symptoms and complications of the disease (35).

SARS-CoV-2 and influenza virus are both airborne pathogens that affect the respiratory tract. Furthermore, SARS-CoV-2 appears to preferentially infect alveolar type II cells (AT2 pneumocytes), which are also the primary site of influenza virus replication. This can exacerbate the side effects of COVID-19 if there is a concomitant flu infection (36, 37).

As a result, the COVID-19 pandemic and seasonal influenza could put a large population at risk of contracting both viruses at the same time. To confirm the role of seasonal flu in the severity of the COVID-19 pandemic, Bai et al. in their research provide the first experimental evidence and reported that the preinfection with influenza virus strongly promotes SARS-CoV-2 virus entry and infectivity in cells and animals.

They demonstrated that among the viruses tested; only IAV enhanced SARS-CoV-2 infection (38). This underscores the importance of the risk of influenza infection in patients with COVID-19. Especially in people with underlying factors, the occurrence of such a concomitant infection can aggravate the complications caused by COVID-19.

Due to the onset of influenza infection in the cold seasons of the year, scattered reports have been published about the influenza co-infection in patients with COVID-19 from the countries of the Northern Hemisphere that were in the cold seasons at the time of performing this study. Since there are no accurate statistics on the rate of such concurrent infections, herein, we evaluated the results of prevalence studies as well as case reports and case series in this field in the form of meta-analysis and systematic review.

According to a study recently published from China, concurrent infection of SARS-CoV-2 and influenza virus was common during the initial COVID-19 outbreak in Wuhan, and patients who had co-infection encounter a higher risk of poor health outcomes (39).

Our meta-analysis indicated that overall 1.2% of COVID-19 patients had influenza co-infection. Reports of the frequency of co-infection between COVID-19 and influenza vary from different parts of the world. Lansbury et al. estimated that 3% of patients hospitalized with COVID-19 were also co-infected with another respiratory virus. Based on their analysis, respiratory syncytial virus and influenza-A being the most common viral pathogens in co-infected patients (35).

It should be noted that all studies reviewed in the present study used the molecular method to confirm the presence of SARS-CoV-2 as well as influenza viruses, except for one study in which the presence of infection was diagnosed serologically through detection of IgM. Since serological test is not highly specific and may result in overestimation of infections the overall rate of co-infection reported in that study was higher than others (12).

Overall, the rate of co-infection with COVID-19 and influenza has been reported between 0.24 and 44% in the reviewed studied. This dispersion and difference can be due to the study population, the underlying conditions of the patients, the method of confirming the infection as well as the time and place of the investigation in terms of the prevalence of influenza.

Influenza co-infection among patients with COVID-19 was more reported from Asia and China country. Given the high population of Asia, as well as China, it is reasonable to be likely that patients with COVID-19, as well as influenza in the region be more prevalent, other studies have reported similar statistics too (40, 41).

Based on the results of prevalence studies that reported the influenza virus type involved in the development of infection in patients with COVID-19, it was found that the prevalence of type A virus was higher than type B. This was to be expected due to the higher overall prevalence of influenza virus type A than type B (42).

Finally we should mention the limitations of our study. Since there is not enough information from many countries, we were not able to fully demonstrate the prevalence of influenza infection in COVID-19 patients worldwide. Many COVID-19 patients with influenza may not have been hospitalized and most of them could have been treated at home. Also, some articles lacked the necessary information to be added to the present study, and we had to exclude them.

In addition, only studies published in English were included, which may have caused important studies to be missed. Finally, the heterogeneity exists among the included publications. Despite the random effects model allows for the presence of heterogeneity, there may still be some controversy about combining study estimates in its presence.

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