Is it just my imagination or are Covid-19 cases going down as influenza cases are surging out of control during this flu season?

No, you are not imagining! Although during respiratory tract infection (RTI) season several viruses such as rhinovirus, respiratory syncytial virus (RSV) and coronavirus may cocirculate, influenza virus frequently outcompetes many RTI viruses, likely through a phenomenon called “viral interference.” 1-4

A negative viral interference is observed when a virus that has already infected a host makes that host resistant to infection by the second virus (isn’t that fascinating?). Although there a lot of virus, host and environmental variables that affect infection risk, potential mechanisms for this interference include a rapid and robust innate immune response to the first virus such as through upregulation of interferon (IFN) production which can protect against unrelated viruses, thereby creating a temporary “antiviral state.1-4

A negative viral interference has been shown between influenza-A virus (IAV) and SARS-CoV-2 by a cool 2024 study using the air-liquid interface culture model of the differentiated human airway epithelium. 4 Replicating IAV induced a robust interferon response and suppressed SARS-CoV-2 replication in both sequential and simultaneous infections. In contrast, SARS-CoV-2 did not demonstrate significant viral interference with IAV.  The researchers took their experiment a step further and found that oseltamivir (Tamiflu), an anti-IAV agent, restored SARS-CoV-2 replication with IAV coinfection by reducing induction of IFN!

One explanation for the inability of SARS-CoV-2 to interfere with the production of influenza virus is its slower induction of IFN stimulating genes likely due to its more effective mechanisms of antagonizing the IFN response with infected cells.4 Another explanation is that SARS-CoV-2 has a slower growth rate than IAV, making it more susceptible to being “outgunned” by faster growing viruses. Some strains of IAV may also cause more damage to the epithelial cells than SARS-CoV-2 thus reducing the number of host cells available for SARs-CoV-2 infection.2 Last, secreted IFNs (eg, IFN λ) can also bind to receptors present at the surface of infected and neighboring state blocking the second virus from infecting the host.1

So, it looks like competition among living forms in this world also applies to the world of viruses!

Bonus Pearl: Did you know that the concept of viral interference was first described in the 1960s following observation that oral administration of live enterovirus vaccines decreased detection of several unrelated respiratory viruses such as influenza virus, RSV and human adenovirus?1

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References

  1. Piret J, Bolvin G. Viral interference between respiratory viruses. Emerg Infect Dis 2022;28:273-280. Viral Interference between Respiratory Viruses – PubMed
  2. Gilbert-Girard S, Piret J, Carbonneau J, et al. Viral interference between severe acute respiratory syndrome coronavirus 2 and influenza A viruses. PLOS Pathogens 2024;20(7):e1012017. Viral interference between severe acute respiratory syndrome coronavirus 2 and influenza A viruses – PubMed
  3. Kaaijk P, Swaans N, Nicolaie AM, et al. Contribution of influenza viruses, other respiratory viruses and viral co-infections to influenza-like illness in older adults. Viruses 2022;14, 797. Contribution of Influenza Viruses, Other Respiratory Viruses and Viral Co-Infections to Influenza-like Illness in Older Adults – PubMed
  4. Cheemarla NR, Watkins TA, Mihaylova VT, et al. Viral interference during influenza A-SARS-CoV-2 coinfection of the human airway epithelium and reversal by oseltamivir. J Infect Dis 2024;229:1430-4. Viral Interference During Influenza A-SARS-CoV-2 Coinfection of the Human Airway Epithelium and Reversal by Oseltamivir – PubMed

Disclosures/Disclaimers: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

 

Is it just my imagination or are Covid-19 cases going down as influenza cases are surging out of control during this flu season?

Does a positive routine PCR test for Covid-19 virus mean the person is infectious?

Not necessarily! Although a positive routine PCR test for Covid-19 indicates the presence of the virus in a clinical specimen, it does not mean that the virus is still viable or transmissible, particularly as the patient may be recovering from Covid-19. Viral cultures are often needed to help answer this question. 1-5

In a study of 9 hospitalized patients with Covid-19, no viable Covid-19 virus could be found by culture in any specimen beyond 8 days following onset of symptoms despite a positive routine PCR for up to 13 days. Successful growth of the virus was dependent in part on viral load, with samples containing <106 copies/mL never yielding any viable virus.1  

In the same study, none of stools that were positive for Covid-19 virus by PCR were positive by culture.  The authors concluded that there is “little residual risk of infectivity” beyond day 10 of symptoms when sputum contains less than 100,000 viral RNA copies /ml.  Of note, the patients in this study were young- to middle-aged without significant underlying disease and had milder disease, so the results may not necessarily be generalizable to other patients with Covid-19. 1

The discrepancy between a positive PCR and negative culture has been seen with other respiratory pathogens,  such as respiratory syncytial virus (RSV) and influenza. In a study involving experimentally infected subjects with RSV, the average duration of viral shedding was 9.2 days by PCR compared to 7.2 days by viral culture.2 In another study involving patients with symptomatic influenza, virus could be detected for up to 7 days with PCR compared to 1-2 days by viral culture.3

Factors that may explain this discrepancy include suboptimal sample transport, low viral titers,  and the presence of neutralizing antibody in the clinical specimen.2,3

So, despite our incomplete knowledge, don’t assume that PCR positivity means the presence of live virus capable of transmitting Covid-19!

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References

  1. Wolfel R, Corman VM, Guggemos W, et al. Virological assessment of hospitalized patients with COVID-19. Nature 2020; April 1. https://www.nature.com/articles/s41586-020-2196-x
  2. Falsey AR, Formica MA, Treanor JJ, et al. Comparison of quantitative reverse transcriptase-PCR to viral culture for assessment of respiratory syncytial virus shedding. J Clin Microbiol 2003;41:4160-65. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC193781/pdf/0106.pdf
  3. Van Elden LJR, Nijhuis M, Schipper P, et al . Simultaneous detection of influenza viruses A and B using real-time quantitative PCR. J Clin Microbiol 2001;39:196-200. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC87701/
  4. Cangelosi GA, Meschke JS. Dead or alive:molecular assessment of microbial viability. App Environ Microbiol 2014;80:5884-91.
  5. European Centre for Disease Prevention and Control. Novel coronavirus (SARS-CoV-2). https://www.ecdc.europa.eu/en/publications-data/novel-coronavirus-sars-cov-2-discharge-criteria-confirmed-covid-19-cases

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

Does a positive routine PCR test for Covid-19 virus mean the person is infectious?