How to Prepare For Possible “Tripledemic” of RSV, Influenza, and SARS-CoV-2

Infection Control TodayInfection Control Today, September/October 2023 (Vol. 27 No. 7)
Volume 27
Issue 7

The interaction between the respiratory viruses SARS-CoV-2, influenza, and RSV, poses ongoing challenges. Personal protective measures, testing, and vaccination are critical components of our strategy to mitigate the impact of these viruses.

COVID-19, RSV, and Influenza = Tripledemic

Now that autumn is here, there is renewed concern about a resurgence of respiratory syncytial virus (RSV), influenza, and SARS-CoV-2. These are not solitary pathogens but appear to have significant interactions by collectively weakening the host. The keystone in this deadly trio is SARS-CoV-2. Unfortunately, it is not disappearing but mutating and adapting.

Many viruses attack the immune system as one of their survival mechanisms. For example, influenza can cause transitory lymphopenia in up to 90% of patients and has led to lymphopenia being proposed as a diagnostic screening tool.1 Coinfections from these viruses can occur, which stresses the immune system’s ability to respond to the disease.2 However, in the case of SARS-CoV-2, coinfection is not a requirement because its induced immune dysfunction can last long after the acute infection has resolved.

SARS-CoV-2, which causes COVID-19, is a dangerous pathogen, much more so than influenza.3 (Figure) Between 2021 and 2022, COVID-19 was the leading cause of death in children4 and young persons. The US Department of Veterans Affairs has reported5 a 30-day mortality rate of 5.97% for COVID-19 and 3.75% for influenza. We may be seeing just the beginning regarding long-term conditions caused by COVID-19. Let’s not
forget that the immunodysfunction caused by HIV causes clinical symptoms years later, and the varicella-zoster virus can reemerge as herpes zoster decades after the initial infection.

Infection Control Today® has warned in several review articles6-8 that the immune dysfunction caused by SARS-CoV-2 is of significant clinical concern. Last year’s resurgence of influenza and RSV, both in numbers and severity of cases, was significantly augmented by a preceding infection of SARS-CoV-2. Sweden, a country with few public health interventions compared with the United States, has experienced unusually severe cases of influenza9 in children and large waves of influenza10 and RSV infections.11 A recent study12 in the US observed that rates of RSV infections in children aged 0 to 5 years were 40% higher if a previous SARS-CoV-2 infection had occurred. Pfizer has listed immune dysfunction13 as the second of 7 causes of post–COVID-19 condition (long COVID), stating, “Studies…in individuals with long COVID have found T-cell alterations, including exhausted T cells and reduced CD4+ central memory cells.”14 Studies have also reported “highly activated innate immune cells” but a lack of naive T and B cells.”15

Figure: Pneumonia, Influenza, and COVID-19 mortality from the National Center of Health.

Figure: Pneumonia, Influenza, and COVID-19 mortality from the National Center of Health.

Statistics Mortality Surveillance System. Data as of July 20, 2023.3

Materials developed by CDC. Reference to specific commercial products, manufacturers, companies, or trademarks does not constitute its endorsement or recommendation by the U.S. Government, Department of Health and Human Services, or CDC.

All 3 are respiratory viruses, and the mitigation and prevention of these pathogens are similar. As public health is declining in the United States, each person must increase personal health and protection efforts. This means wearing a well-fitted N95 or comparable mask, avoiding indoor settings, using real-time air quality testing in venues you visit.

The public health strategy of 2-way masking16 is the most effective, but only some in our society are willing to adhere. For personal protection, a well-fitted N95 mask is recommended. However, a respirator will not wholly stop transmission because the virus can enter through one’s eyes. Thus, ventilation and air quality are of utmost importance.

As with 2-way masking, all brick-and-mortar establishments have yet to adopt the public health strategy of maintaining adequate indoor air quality, despite an almost universal agreement in the scientific literature that SARS-CoV-2 is an airborne disease. Portable carbon dioxide monitors are an excellent screening tool for air quality. When asked whether carbon dioxide levels are a good indicator of air quality, renowned17 aerosol scientist Lidia Morawska, PhD, said, “[Carbon dioxide] monitors are very good devices for checking indoor air quality,” and she carries one with her.

New research focuses on real-time SARS-CoV-2, RSV, and influenza detection. A proof-of-concept portable monitor has been developed to detect SARS-CoV-2 within 5 minutes.18 This technology could also be applied to RSV and influenza.

Testing is still key in preventing the spread of these pathogens. Despite the curtailing of funds and testing centers in the United States, the White House continues to screen19 all of President Joe Biden’s visitors for
SARS-CoV-2. Supplementing masking and vaccinations, the American College of Surgeons also recommends COVID-19 testing before travel and attendance at its Clinical Congress 2023.

Measie, a company based in the Netherlands, has developed a handheld rapid test for RSV, influenza A virus, influenza B virus, and SARS-CoV-2.20 The test still needs approval in the United States but is available in Europe for €4.5. This equates to roughly $5. In February 2023, the FDA authorized, the Lucira COVID-19 & Flu Home Test,22 which can provide results in 30 minutes. The FDA has also authorized a triple at-home polymerase chain reaction test called Pixel by Labcorp. However, the swab must be sent by FedEx to a laboratory, and results take 24 to 48 hours. As of September 26, 2023, this lab test lists for $129.00.23

The United States needs to catch up on test availability and affordability. Even a single home COVID-19 antigen test costs between $8 and $10, and it is suggested that at least 2 antigen tests are taken24 2 days apart to rule out an infection.

Vaccines are available for influenza, SARS-CoV-2, and RSV. Getting all
3 vaccinations is important because the CDC is warning of another possible “tripledemic” this fall.25 The RSV vaccine was approved in May 2023 for individuals 60 years and older.26 The RSV vaccine for children has been approved for those up to 24 months. The FDA has approved the Pfizer RSV vaccine (Abrysvo) for expectant mothers,27, which provides a degree of passive immunity to their unborn child.28 Influenza and SARS-CoV-2 vaccinations29 can be administered at the same time, but there is an 8% to 11% increase in mild reactions, such as muscle soreness, fatigue, and headache. Placing the vaccines in different arms may reduce local reactions if one obtains the high-dose or adjuvant nfluenza vaccine. At this time, spacing out the RSV vaccine is recommended because limited data indicate that giving it with the influenza and SARS-CoV-2 vaccines may lessen effectiveness.25

The 2022 influenza vaccine reduced hospitalizations30 by almost 75% in children and almost 50% in adults. The bivalent SARS-CoV-2 booster31 has an effectiveness of 43% to 56% in reducing hospitalizations over 8 months. The SARS-CoV-2 booster to be available this fall will be a univalent XBB formulation. Prevention of infection is much lower. In those 65 years or older, there is only 37% vaccine effectiveness 14 days or more after receiving a bivalent booster. Unlike influenza, SARS-CoV-2 has only partial seasonality, and boosters are recommended throughout the year.

The goal of SARS-CoV-2 vaccination is preventing not only hospitalizations and deaths but also long COVID. The best way to do so is to prevent infections. Thus, vaccination should be viewed as only a part of our strategies to mitigate the impending tripledemic.

Unfortunately, these pathogens are firmly entrenched in our biosphere. A recent study by Feng et al observed32 that white-tailed deer harbor a variety of SARS-CoV-2 variants. Transmission from deer to humans can occur. The study analyzed 8830 white-tailed deer in the United States. Nasal and oral samples had a positivity rate of 10.7%. A similar spread is starting in Europe, with a Dublin deer herd33 becoming infected with SARS-CoV-2. SARS-CoV-2 can also reside in rodents34 and other mammals, including household pets. Animal hosts also exist for RSV and influenza, with strains of the latter often named after the reservoir.

The SARS-CoV-2 lineages found in white-tailed deer include the legacy
variants Alpha, Gamma, Delta, and Omicron. Natural or vaccine immunity to the latest variant might not provide adequate protection to legacy variants that may jump from animal hosts to humans. Thus, we must not abandon public health35 and only rely on personal protection. This is a recipe which may force us to endure another tripledemic.
This is a recipe that may force us to endure another tripledemic. Instead, we should prevent all respiratory illnesses to the highest degree possible, with strategies adopted and supported by society.


  1. Guo Z, Zhang Z, Prajapati M, Li Y. Lymphopenia caused by virus infections and the mechanisms beyond. Viruses. 2021;13(9):1876. doi:10.3390/v13091876
  2. Dao TL, Hoang VT, Colson P, Million M, Gautret P. Co-infection of SARS-CoV-2 and influenza viruses: a systematic review and meta-analysis. J Clin Virol Plus. 2021;1(3):100036. doi:10.1016/j.jcvp.2021.100036
  3. Weekly US influenza surveillance report. CDC. Updated August 18, 2023. Accessed August 22, 2023.
  4. COVID-19 is a leading cause of death in children and young people in the US. University of Oxford. January 31, 2023. Accessed August 22, 2023.
  5. Xie Y, Choi T, Al-Aly Z. Risk of death in patients hospitalized for COVID-19 vs seasonal influenza in fall-winter 2022-2023. JAMA. 2023;329(19):1697-1699. doi:10.1001/jama.2023.5348
  6. Kavanagh K. Immunodysfunction: a cause of stealth COVID-19 illness and death. Infection Control Today. Published online January 17, 2023. Accessed August 22, 2023.
  7. Kavanagh K, Brusselaers N, Cormier L. Is the rise in RSV infections associated with immune debt or SARS-CoV-2 immune dysfunction? Infection Control Today. Published online February 23, 2023. Accessed August 22, 2023.
  8. Kavanagh K. COVID-19: study suggests long-term damage to immune system. Infection Control Today. Published online March 21, 2023. Accessed August 22, 2023.
  9. Our mission—to strengthen and develop public health. Public Health Agency of Sweden. Accessed August 22, 2023.
  10. Current weekly report on influenza. Public Health Agency of Sweden. May 26, 2023. Accessed August 22, 2023.
  11. Current weekly report on RS virus. Public Health Agency of Sweden. May 26, 2023. Accessed August 22, 2023.
  12. Wang L, Davis PB, Berger NA, Kaelber DC, Volkow ND, Xu R. Disrupted seasonality and association of COVID-19 with medically attended respiratory syncytial virus infections among young children in the US: January 2010-January 2023. medRxiv. Preprint posted online May 16, 2023. doi:10.1101/2023.05.12.23289898
  13. The challenges of defining, understanding, and addressing long COVID. Pfizer. Accessed August 22, 2023.
  14. Klein J, Wood J, Jaycox J, et al. Distinguishing features of long COVID identified through immune profiling. medRxiv. Preprint posted online August 10, 2022. doi:10.1101/2022.08.09.22278592
  15. Phetsouphanh C, Darley DR, Wilson DB, et al. Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection. Nat Immunol. 2022;23(2):210-216. doi:10.1038/s41590-021-01113-x
  16. Banholzer N, Zürcher K, Jent P, et al. SARS-CoV-2 transmission with and without mask wearing or air cleaners in schools in Switzerland: a modeling study of epidemiological, environmental, and molecular data. PLoS Med. 2023;20(5):e1004226. doi:10.1371/journal.pmed.1004226
  17. Gottlieb S. The 100 most influential people of 2021: Lidia Morawska. Time. Published online September 15, 2021. Accessed August 22, 2023.
  18. Puthussery JV, Ghumra DP, McBrearty KR, et al. Real-time environmental surveillance of SARS-CoV-2 aerosols. Nat Commun. 2023;14(1):3692.
  19. White House says COVID testing protocols still in place after Israeli delegation members test positive. C-SPAN. July 18, 2023. Accessed August 22, 2023.
  20. 4-in-1 combo test. Measie. Accessed August 22, 2023.
  21. Kritz F. FDA: you can now test for COVID, flu, and RSV at home. Verywell Health. May 25, 2022. Accessed August 22, 2023.
  22. FDA authorizes first over-the-counter at-home test to detect both influenza and COVID-19 viruses. News release. FDA. Updated March 1, 2023. Accessed August 22, 2023.
  23. COVID-19+flu+RSV test home collection kit. Labcorp OnDemand. Accessed August 22, 2023.
  24. COVID-19 testing: what you need to know. CDC. Updated May 11, 2023. Accessed August 22, 2023.
  25. Edwards E. The CDC is preparing for a winter with “3 bugs out there”: Covid, flu and RSV. NBC News. July 22, 2023. Accessed August 22, 2023.
  26. Cosdon N. FDA approves Pfizer’s Abrysvo vaccine for older adults. Infection Control Today. Published online June 1, 2023. Accessed August 22, 2023.
  27. Fitch J. FDA approves first maternal vaccine aimed at preventing RSV in infants. Infection Control Today. Published online August 22, 2023. Accessed August 22, 2023.
  28. Joseph A. Europe recommends the approval of Pfizer’s RSV vaccine for older adults and in pregnancy. STAT. Published online July 21, 2023. Accessed August 22, 2023.
  29. Getting a flu vaccine and a COVID-19 vaccine at the same time. CDC. Updated October 25, 2022. Accessed August 22, 2023.
  30. Flu vaccine provided substantial protection this season. CDC. Updated February 22, 2023. Accessed August 22, 2023.
  31. COVID data tracker. CDC. Published March 28, 2020. Accessed August 22, 2023.
  32. Feng A, Bevins S, Chandler J, et al. Transmission of SARS-CoV-2 in free-ranging white-tailed deer in the United States. Nat Commun. 2023;14(1):4078.
  33. Rains M. Dublin deer herd first in Europe to be infected with COVID-19 virus, raising concerns about further spread. Science. Published online July 19, 2023. Accessed August 22, 2023.
  34. Wang Y, Lenoch J, Kohler D, et al. SARS-CoV-2 exposure in Norway rats (Rattus norvegicus) from New York City. mBio. 2023;14(2):e0362122. doi:10.1128/mbio.03621-22
  35. Spencer C. How to lose a century of progress. The Atlantic. Published online June 30, 2023. Accessed August 22, 2023.

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