Holiday Guest List—When the Uninvited Arrive: COVID-19 and Coinfections

Winter, riding in on the coattails of autumn, is just starting to make its appearance. The leaves have tumbled gracefully from the trees, and the bite in the air and the possibility of snow on the ground has forced some of us to don our insulated clothing and cozy up indoors with the fireplace crackling in the background. Despite the familiarity and comfort during this time of year, there is also uncertainty––a foreign, unknown, obscure landscape that we are still learning to navigate: coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has upended our lives this year. Despite the continued threat of this pandemic, there are large family gatherings, holiday traveling, and crowding together in celebration for sporting events (read: Chiefs or in Nebraska, Huskers). Although SARS-CoV-2 has become the elephant in the room during such gatherings, it isn’t alone at this party; there are also the frequent sniffles, sneezes, and coughs from the variety of seasonal respiratory viruses that arrive as unwanted party guests.

Typically, it is at this time of year that we tend to see many respiratory viruses surface. Influenza has been of most concern, historically, with its ability to cause life-threatening disease and its tendency to mutate and spread rapidly, which has resulted in past pandemics. But now we have a new guest––SARS-CoV-2––and we realize that we are unsure how it will play with the others. Will it start to peak in a similar fashion? What about its impact on coinfections that are known to occur with the other seasonal respiratory viruses? Let’s first take a look at how SARS-CoV-2 compares with our standard seasonal viruses.

SARS-CoV-2 vs Other Seasonal Viruses

COVID-19 and other respiratory viruses have similar clinical presentations, creating difficulty in differentiating them without a diagnostic test. Although asymptomatic infections do occur, these infections, including COVID-19, generally exhibit an overlapping influenza-like illness: cough, shortness of breath, muscle aches, fatigue, sore throat and runny nose, headaches, and fever are among the more common symptoms.^1-5 There are some less common, though notable symptoms, such as loss of taste and smell or gastrointestinal complaints such as nausea and diarrhea, that are more specific to COVID-19 and thus may help differentiate it.^4-6 However, this all becomes even more difficult to distinguish based on symptoms alone with coinfections of 2 or more pathogens.

Overall, most respiratory viruses cause a relatively mild illness, though there are several viruses (Respiratory syncytial virus (RSV) and influenza) that can have a more severe course. Whereas many people recover without complications, there are certain groups of people who are at higher risk for developing more severe disease or complications from infection, especially with SARS-CoV-2 and influenza: older adults and those with certain underlying medical conditions are among the highest-risk populations.^6-8

All the above can be summarized thusly: although there are some differences between COVID-19 and other common seasonal respiratory viruses, there are plenty of similarities with significant overlap, and the courses of such viruses are relatively well understood. But there is one aspect in which we still don’t have much experience and that we may start to encounter shortly: what happens when a person becomes infected with COVID-19 and another respiratory virus (especially influenza), a phenomenon we refer to as coinfection?

Respiratory Coinfections and COVID-19

We know that infection with different, yet simultaneous, respiratory viruses does occur.^9-10 Virus-specific interactions play a key role in the morbidity and mortality of respiratory viral coinfections, but our understanding of this concerning even our typical pathogens is limited; the introduction of SARS-CoV-2 raises even more questions.^11-12 Early in the COVID-19 pandemic, there were reports of coinfection in various parts of the world. One particular study in northern California revealed that of 116 patients with COVID-19, 21% exhibited coinfections, with the most common being rhinovirus, RSV, and other types of coronaviruses.¹³ Additionally, there were some reports of coinfection with influenza in particular that demonstrated a subset of patients progressing to severe disease.^1-2,14 Although the data are far from definitive due to the limited number of patients and the varying treatment modalities employed for them, there were suggestions in these cases that persons who were coinfected with SARS-CoV-2 and another respiratory virus had severe disease and poor outcomes.

Ultimately, it is unclear if influenza and COVID-19 will peak at the same time this season, nor do we fully understand the interactions between the 2 viruses within an individual. Yet reason for concern remains as both viruses cause life-threatening illness in certain populations and have very different ways in which clinicians approach their treatment, potentially impacting those who do develop coinfection with influenza and COVID-19. Due to the differences in treatment, rapid, easily accessible, and reliable testing for a broad variety of respiratory viruses has been a focus of diagnostics, leading to both the development of a combination SARS-CoV-2/influenza multiplex PCR assay and the inclusion of SARS-CoV-2 on a revised respiratory pathogen panel that detects nearly 2 dozen viral and bacterial pathogens.¹⁵

Prevention and Management of Coinfection with COVID-19

Most seasonal respiratory viruses are self-limited (that is, people tend to recover without the assistance of medication that targets the virus). Influenza and SARS-CoV-2 can be exceptions, as there are certain circumstances and specific populations in which treatment is recommended. For influenza, this is typically with the antiviral oseltamivir (Tamiflu), which is given to patients who require hospitalization, especially those with severe disease, or to high-risk populations. For COVID-19, on the other hand, although there are many ongoing trials to determine what works best, the most recent National Institutes of Health guidelines recommend the use of the antiviral remdesivir, often with dexamethasone, in hospitalized patients.¹⁶ The effects of administering oseltamavir and remdesivir to those who are simultaneously infected with both viruses are unknown, but clinicians have found that steroids, which have become important in the treatment of COVID-19, worsen outcomes with influenza. This makes treatment decisions in coinfection more convoluted, as the optimal treatment is currently unknown.

Most important, however, as we move into this season, will be our efforts to mitigate the spread of infection. Social distancing, hand hygiene, and wearing masks remain crucial to preventing the spread of COVID-19, with similar effects on seasonal respiratory viruses. Vaccinations, similarly, have an important role in mitigation efforts; we do have a safe and reasonably effective influenza vaccine, which will become that much more important to receive this year, particularly while we await the completion of COVID-19 vaccination trials.

Conclusions

We have witnessed the severity and intensity with which both influenza and COVID-19 can strike, and we are uncomfortably aware of how quickly and efficiently both can permeate a population.^6,17 Therefore, as we enter the season when influenza and other respiratory viruses are most prominent, while remaining very much in the midst of the COVID-19 pandemic, we must become more vigilant in our public health and research efforts to prepare for a rise in such coinfections.

Clayton Mowrer, DO, MBA, is a PGY2 ID fellow in internal medicine/pediatrics infectious diseases at the University of Nebraska Medical Center in Omaha.

Kelly Cawcutt, MD, MS, is Assistant Professor, Divisions of Infectious Diseases and Pulmonary and Critical Care Medicine, Associate Director of Infection Control and Hospital Epidemiology, Co-Director of Digital Innovation & Social Media Strategy for the Division of Infectious Diseases at the University of Nebraska Medical Center.

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