Masks Reduce Viral Inoculum of SARS-CoV2

Thank you for allowing us to respond to the important points made by Dr. Bhargava on our paper published in the J Gen Intern Med. To respond to the first point, we completely agree that the interplay between pathogen and host is a complicated one that depends on many features of both the virus and the host, including co-morbidities, age, immune status, and nutritional status of the latter. We were trying to bring in one more factor that could be related to the severity of COVID-19 disease, which is that of the viral inoculum, but that is not in any way meant to detract from the important host factors already known and well-described in the literature to date to influence the severity of COVID-19 disease. There have been many excellent descriptions of the risk factors that could predispose to severe COVID-19 disease, including the possibility of vitamin D deficiency as raised by the author. However, our paper joins a number of others at this point1,2,3,4,5,6 to describe one factor—which is the effect of the viral inoculum—on severity of COVID-19 outcomes, which was the sole purpose of the commentary.

In terms of the second point, there was no implication of our commentary that people should be deliberately infected with SARS-CoV-2. In fact, as practicing infectious diseases physicians, we feel very strongly, that—given the case-fatality rate of the infection—challenge trials should not be performed for SARS-CoV-2. Our article discusses the hypothesis that viral inoculum may be one factor that contributes to the severity of disease for COVID-19, as it does for a number of viral infections in both animals and humans, but there is no implication of performing challenge trials in this article.

Finally, the mechanism by which a high viral inoculum may lead to more severe disease is via a dysregulated and overwhelmed innate immune response to a higher viral dose for infections in which immunopathology plays a role in viral pathogenesis 7, such as COVID-19. Indeed, the imbalanced host response and cytokine storm described by the author is one of the reasons by which dexamethasone helps decrease the mortality of COVID-19 patients in those with severe infection. We think that viral inoculum may be one of the factors contributing to this dysregulated immune response but agree with the author that co-morbidities and other factors in the host (including age) play important roles in disease outcomes. Therefore, we agree with the author that facial masking, along with other important COVID-19 mitigation public health strategies, such as social distancing, testing in nursing homes and good infection control, and hand hygiene, are all important. Our commentary was focused on a single factor that could contribute to disease severity that had not been raised much in the literature, but the excellent work done to date to define other risk factors is acknowledged and appreciated.

Thank you again for the opportunity to respond to the important points raised in this letter—M. Gandhi, C. Beyrer, E. Goosby

References

  1. 1.

    Guallar MP, Meiriño R, Donat-Vargas C, Corral O, Jouvé N, Soriano V. Inoculum at the time of SARS-CoV-2 exposure and risk of disease severity. Int J Infect Dis 2020;97:290-292. https://doi.org/10.1016/j.ijid.2020.06.035

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Little P et al. Reducing risks from coronavirus transmission in the home—the role of viral load. BMJ 2020;369:m1728. https://doi.org/10.1136/bmj.m1728

  3. 3.

    Ryan KA. Dose-dependent response to infection with SARS-CoV-2 in the ferret model: evidence of protection to re-challenge. bioRxiv 2020.05.29.123810. https://doi.org/10.1101/2020.05.29.12381

  4. 4.

    Van Damme W, Dahake R, van de Pas R, Vanham G, Assefa Y. COVID-19: Does the infectious inoculum dose-response relationship contribute to understanding heterogeneity in disease severity and transmission dynamics? Medical Hypotheses 2020; 110431. https://doi.org/10.1016/j.mehy.2020.110431.

  5. 5.

    Karimzadeh S, Bhopal R, Nguyen Tien H. Review of infective dose, routes of transmission, and outcome of COVID-19 caused by the SARS-CoV-2 virus: comparison with other respiratory viruses. Preprints 2020 2020070613

  6. 6.

    Bielecki M, Züst R, Siegrist D, Meyerhofer D, Gerardo Crameri GA, Stanga Z, Stettbacher A, Buehrer TW, Deuel JW. Social Distancing Alters the Clinical Course of COVID-19 in Young Adults: A Comparative Cohort Study. Clinical Infectious Diseases 2020

  7. 7.

    Rouse BT, Sehrawat S. Immunity and immunopathology to viruses: what decides the outcome? Nat Rev Immunol 2010;10(7):514-526

    CAS  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Monica Gandhi MD, MPH.

Ethics declarations

Conflicts of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Gandhi, M., Beyrer, C. & Goosby, E. Masks Reduce Viral Inoculum of SARS-CoV2. J GEN INTERN MED (2021). https://doi.org/10.1007/s11606-020-06406-9

Download citation