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3 key considerations for COVID-19 testing during flu season

By Sonia N. Rao, PharmD, BCIDP, BCPS
QIAGEN Medical Affairs – Infectious Diseases

SARS-CoV-2 is a novel beta coronavirus that has caused a global outbreak of respiratory disease – Coronavirus Disease 2019 (COVID-19) – with significant morbidity, mortality, and excess healthcare costs (1). As COVID-19 continues spreading around the world, an economic and healthcare crisis is left in its wake due to overwhelmed healthcare systems and resources. As the 2021–2022 Influenza and influenza-like illness (ILI) season begins, one topic drawing attention is co-infections.

No one can predict the course of COVID-19, but two things are clear:

  • The virus is likely to continue circulating until there is sufficient vaccine uptake 
  • The next flu season is here

The overlap of COVID-19 and influenza season is especially concerning as we may soon face two epidemics, or what some are calling a “twindemic”. The worst-case situation may be that both SARS-CoV-2 and influenza are spreading fast, causing severe disease, complicating diagnosis due to similar symptomology and simultaneously straining health care systems.


What can we expect as the COVID-19 pandemic continues into the flu season and how can we prepare?

1) We can expect additional dangers during flu season

Back in April 2020, the US Centers for Disease Control and Prevention (CDC) director warned the public about the risk of a second wave of COVID-19 in the fall, which would coincide with flu season. Unfortunately, differentiating causes of respiratory illnesses including SARS-CoV-2 and influenza is difficult due to overlapping symptoms including fever, cough, dyspnea and fatigue, as well as similar chest computed tomography scans showing ground-glass opacity and consolidation with bilateral lung involvement. Since SARS-CoV-2 and influenza bind to different receptors on cells to cause illness, co-infections are a distinct possibility and demonstrate a diagnostic challenge as diagnosis of one respiratory virus does not exclude another respiratory pathogen.

A study from early in the COVID-19 pandemic found that co-infection with another respiratory pathogen, including influenza, occurred in more than 20% of SARS-CoV-2 positive patients who presented with a respiratory viral syndrome (2). Although other studies have shown the co-infection rate to be lower, it may be higher when two viruses are heavily circulating in the same region during flu season. Historically in seasonal influenza epidemics, bacterial secondary infections or co-infections have been associated with more severe outcomes such as increased morbidity and mortality, especially among high-risk groups (3,4). Additionally, recent data published in Pediatrics found high rates of co-infection (51% of 34 COVID-19+ children) including 8/19 having ≥2 pathogens other than SARS-CoV-2 (5). Therefore, co-infections must be identified quickly as recommended by the CDC: “Clinicians are encouraged to consider testing for other causes of respiratory illness, for example influenza, in addition to testing for SARS-CoV-2 depending on patient age, season, or clinical setting; detection of one respiratory pathogen does not exclude the potential for co-infection with SARS-CoV-2” (6).

2) We can expect an urgent need for multiplex SARS-CoV-2 testing

The ongoing approach to COVID-19 management is identification of the source of infection, early diagnosis, quarantine and supportive treatments. However, the similar clinical presentations of influenza-like illnesses make it difficult for clinicians to differentiate SARS-CoV-2 from other respiratory pathogens without a laboratory diagnosis. Using multiplex PCR testing for influenza A&B, SARS-CoV-2 and other respiratory pathogens will be important to distinguish the cause of ILI and determine appropriate clinical management.

3) We can prepare by supporting public health measures with multiplex testing

Rapid and accurate diagnoses are critical not only for the patient and their family, but also for public health measures such as contact tracing, quarantine or isolation, and appropriate use of personal protective equipment. Although single-plex testing for influenza or SARS-CoV-2 may be more cost-effective and accessible, multiplex PCR testing for SARS-CoV-2, influenza and other respiratory pathogens may ultimately conserve resources by providing a thorough differential diagnosis in a relatively short time. Infection control programs may also benefit from the ability to track epidemiological trends.

Differentiating SARS-CoV-2 from other respiratory pathogens is critical because of the increased risk of transmission and actions needed for COVID-19 management. A patient diagnosed with COVID-19 must isolate themselves with resource-intensive public health measures needed to identify all individuals in contact with them. By contrast, a patient diagnosed with a bacterial pathogen such as Mycoplasma pneumoniae or Bordetella pertussis would warrant antimicrobial therapy or patients positive for influenza A or B may be prescribed an antiviral agent to help shorten the course of symptoms. During a pandemic when demand is high and resources are low, proper allocation of resources is crucial.

In summary, the potential advantages of multiplex PCR testing for SARS-CoV-2 plus other respiratory pathogens include:

  • Determining the cause of respiratory illness
  • Surveillance and monitoring of seasonal respiratory pathogens
  • Clinical management
  • Treatment decisions (antivirals vs. antibiotics vs. supportive care)
  • Quarantine recommendations (droplet or isolation measures)
  • Public health measures (infection control, epidemiology and hospital-acquired infections)

Concluding thoughts

The new reality of COVID-19 will only complicate the upcoming flu season. Experts from the World Health Organization have stated that the typical epidemiology of viruses such as influenza shows seasonal patterns in the absence of control measures. However, it remains uncertain whether COVID-19 will exhibit a seasonal pattern (8). Measures to reduce the overall burden of respiratory viral infection—including social distancing, wearing of masks, increased vaccination rates, and availability of diagnostics to detect co-infections such as multiplex PCR tests—will be paramount in planning for the months ahead.

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  1. Bchetnia, M., Girard, C., Duchaine, C., Laprise, C. (2020) The outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): A review of the current global status. Infect. Public Health.
  2. Kim, D. et al. (2020) Rates of co-infection between SARS-CoV-2 and other respiratory pathogens. JAMA 323, 2085–2086.
  3. Jain, S. et al. (2015) Community-acquired pneumonia requiring hospitalization among U.S. adults. Engl. J. Med. 3737, 415—427.
  4. Joseph, C., Togawa, Y., Shindo, N. (2013) Bacterial and viral infections associated with influenza. Influenza Other Respir Viruses 7, 105—113.
  5. Wu, Q. et al. (2020) Co-infection and other clinical characteristics of COVID-19 in children. Pediatrics 146, e20200961.
  6. (2020) Overview of Testing for SARS-CoV-2 July 17, 2020. https://www.cdc.gov/coronavirus/2019-ncov/hcp/testing-overview.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fhcp%2Fclinical-criteria.html
  7. Academy of Medical Sciences. (2020) Preparing for a challenging winter 2020/21 July 14, 2020. https://acmedsci.ac.uk/file-download/51353957
  8. Telenti, A., et al. (2021) Nature. After the pandemic: perspectives on the future trajectory of COVID-19. 596(7873), 495–504.