COVID-19 Realities: Beyond a Respiratory Virus, Addressing Optimism in Pandemic Management

COVID-19 in blue and green with virus symbol

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A recent commentary in MedPage Today by Dr. Amesh Adalja¹ may have painted an overly optimistic picture of the realities the United States is facing with COVID-19. The commentary contends that COVID-19 should be managed in “line with how other common respiratory viruses are managed.” However, not all airborne viruses are primarily respiratory. There is disagreement with this contention in the scientific community as to whether SARS-CoV-2 should be considered a respiratory virus since it affects every organ system of the body, and COVID-19 may be more of a neurological² and cardiovascular disease³ than respiratory. SARS-CoV-2 is not the same as respiratory syncytial virus (RSV) or influenza. It uses a different receptor, ACE2, to enter cells, a receptor found throughout the body.

SARS-CoV-2 is more lethal and more likely to cause chronic disability,⁴ but most importantly, it has a propensity to spread to others from those who are not symptomatic.
 
The premise of the commentary appears to be based on an overly optimistic view of treatment effectiveness and an underestimation of the severity of the long-term sequelae of SARS-CoV-2 infections. The author states: “Today, in 2024, there are more tools for monitoring and managing COVID-19 than for any other respiratory virus: spanning from home tests to wastewater monitoring, to potent antivirals, to highly effective vaccines, to a wealth of clinical guidance to manage cases and mitigate complications.”

Current vaccines are effective but not optimal. The new XBB monovalent booster has been reported to be 54% effective in preventing symptomatic infection at 52 days post-vaccination.⁵ The median patient follow-up period in the study was 60 days. One would like vaccine effectiveness to be in years and not a few weeks. Vaccines also give protection against hospitalizations and long COVID, but this protection wanes over a period of several months. In addition, the virus has the ability to quickly mutate.It also commonly causes post-vaccination infections and reinfections in those who have had COVID-19. Thus, the 69% vaccine protection rate against long COVID⁶ can easily be overpowered.
 
The United Kingdom's workforce has been crippled with chronic illnesses,⁷ with 2.8 million of UK’s citizens being inactive due to chronic illness. This figure has increased by 700,000 since the pandemic first started and corresponds to an equivalent decrease in workforce participation. In 2022, the Brookings Institute estimated that up to 4 million people in the United States were not working because of long COVID.⁸

The US has largely handled this problem by not collecting adequate data. Although wastewater correlates with increases and decreases in SARS-CoV-2 infections, the actual number of SARS-CoV-2 patient infections is not being counted and, thus, can be minimized. SARS-CoV-2 acquisitions by health care workers are not mandatorily reported. One report out of Germany found that almost 50% of health care workers in 3 medical centers developed long COVID with symptoms greater than 90 days.⁹ The long COVID developed after predominantly mild acute disease. The mean age was 40 years, and only 2.3% required inpatient care.

In the US, the reporting of patient acquisitions of COVID-19 has become optional,¹⁰ but when hospital-onset infections were being tracked, the metric only captured patients who were currently hospitalized and developed an infection 14 or more days after admission.¹¹ With a median hospital stay of 4.6 days,¹² the metric only gives a small snapshot of nosocomial SARS-CoV-2 infections.

We should not be minimizing COVID-19 by comparing it to RSV and influenza. There is both clinical¹³ and laboratory¹⁴ evidence that COVID-19 is causing immune dysfunction, which may be augmenting these infections. Abnormally large surges of RSV observed in Sweden¹⁵ support the immune dysfunction argument since Sweden largely avoided lockdowns and mandatory masking.

We need to have a warp speed for the next generation of vaccines, vaccines which last longer than a few months and can prevent spread. Mucosal vaccines hold great promise for reducing spread, but they have been slow to come to market.¹⁶

Antivirals are also lacking. Paxlovid is effective, but it is underutilized. There has also been observed resistance in viral database samples. Resistance to Paxlovid may well become a significant clinical problem if Paxlovid is widely used as the sole antiviral agent.¹⁷

Finally, not any recommendations to stop the universal use of N-95 masks for preventing the spread of COVID-19 has not only placed many frail and immunocompromised individuals at risk but is adversely affecting our supply chain and manufacturing capability,¹⁸ leaving us vulnerable for the next pandemic.

The CDC needs to give an unambiguous message about the urgent need for COVID-19 vaccinations and not one minimizing the disease by green-lighting the safety of asymptomatic spreaders mingling in our community. This advice is not based upon the known characteristics of SARS-CoV-2 and will cause confusion in our society along with undermining confidence in our governmental institutions.
 
Instead, we need to strengthen isolation requirements along with protecting the vulnerable. And we need to prepare for the next pandemic through increasing standards for ventilation and the use of N95 masks for all airborne pathogens.

References

1. Adalja A. When It Comes to Isolation, COVID Shouldn't Be Singled Out From the Pack. MedPage Today. 2024 Feb. 20, 2024. Accessed February 26, 2024. https://www.medpagetoday.com/opinion/second-opinions/108817?xid=nl_secondopinion_2024-02-20&eun=g536787d0r

2. Sutherland S. Long COVID Now Looks like a Neurological Disease, Helping Doctors to Focus Treatments. Scientific America. 2023 March 1, 2023. Accessed February 26, 2024. https://www.scientificamerican.com/article/long-covid-now-looks-like-a-neurological-disease-helping-doctors-to-focus-treatments1/

3. Merschel M. Beyond breathing: How COVID-19 affects your heart, brain and other organs. American Heart Association News. 2024 January 16, 2024. Accessed February 26, 2024. https://www.heart.org/en/news/2024/01/16/how-covid-19-affects-your-heart-brain-and-other-organs

4. Xie Y, Choi T, Al-Aly Z. Long-term outcomes following hospital admission for COVID-19 versus seasonal influenza: a cohort study. Lancet Infect Dis. 2023.Accessed February 26, 2024. https://pubmed.ncbi.nlm.nih.gov/38104583/

5. Link-Gelles R, Ciesla AA, Mak J, Miller JD, Silk BJ, Lambrou AS, et al. Early Estimates of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccine Effectiveness Against Symptomatic SARS-CoV-2 Infection Attributable to Co-Circulating Omicron Variants Among Immunocompetent Adults - Increasing Community Access to Testing Program, United States, September 2023-January 2024. MMWR Morb Mortal Wkly Rep. 2024;73(4):77-83. Accessed February 26, 2024. https://pubmed.ncbi.nlm.nih.gov/38300853/

6. Marra AR, Kobayashi T, Callado GY, Pardo I, Gutfreund MC, Hsieh MK, et al. The effectiveness of COVID-19 vaccine in the prevention of post-COVID conditions: a systematic literature review and meta-analysis of the latest research. Antimicrob Steward Health Epidemiol. 2023;3(1):e168. Accessed February 26, 2024. https://pubmed.ncbi.nlm.nih.gov/38028898/

7. Elliott L. Record long-term sickness bodes ill for UK economic growth. The Guardian. 2024. Accessed February 26, 2024. https://www.theguardian.com/business/2024/feb/17/record-long-term-sickness-bodes-ill-for-uk-economic-growth

8. New data shows long COVID is keeping as many as 4 million people out of work. 2022. Accessed February 26, 2024. https://www.brookings.edu/articles/new-data-shows-long-covid-is-keeping-as-many-as-4-million-people-out-of-work/.

9. Gruber R, Montilva Ludewig MV, Wessels C, Schlang G, Jedhoff S, Herbrandt S, Mattner F. Long-term symptoms after SARS-CoV-2 infection in a cohort of hospital employees: duration and predictive factors. BMC Infect Dis. 2024;24(1):119. Accessed February 26, 2024. https://pubmed.ncbi.nlm.nih.gov/38262969/

10. COVID-19 Guidance for Hospital Reporting and FAQs For Hospitals, Hospital Laboratory, and Acute Care Facility Data. 2023. Accessed February 26, 2024. chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.healthwatchusa.org/downloads/20230611-covid-19-faqs-hospitals-hospital-laboratory-acute-care-facility-data-reporting.pdf

11. COVID-19 Guidance for Hospital Reporting and FAQs For Hospitals, Hospital Laboratory, and Acute Care Facility DataReporting. 2022. Accessed February 26, 2024. chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.healthwatchusa.org/downloads/20221215-covid-19-faqs-hospitals-hospital-laboratory-acute-care-facility-data-reporting.pdf

12. Davis M. Typical US Hospital Stay Costs 384 Hours of Work With Average Earnings. Value Penguin. 2023 Oct. 16, 2023. Accessed February 26, 2024. https://www.valuepenguin.com/hospital-bill-costs-study

13. Wang L, Davis PB, Berger N, Kaelber DC, Volkow N, Xu R. Association of COVID-19 with respiratory syncytial virus (RSV) infections in children aged 0-5 years in the USA in 2022: a multicentre retrospective cohort study. Fam Med Community Health. 2023;11(4). Accessed February 26, 2024. https://pubmed.ncbi.nlm.nih.gov/37832975/

14. Phetsouphanh C, Darley DR, Wilson DB, Howe A, Munier CML, Patel SK, et al. Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection. Nat Immunol. 2022;23(2):210-6. Accessed February 26, 2024. https://pubmed.ncbi.nlm.nih.gov/35027728/

15. Sweden TPHAo. Current weekly report on RS virus: The Public Health Agency of Sweeden; 2023. Accessed February 26, 2024. https://www.folkhalsomyndigheten.se/folkhalsorapportering-statistik/statistik-a-o/sjukdomsstatistik/rsv-veckorapporter/aktuell-veckorapport-om-rsv/.

16. Croda J. Exploring the potential benefits of mucosal COVID-19 vaccines: opportunities and challenges. Lancet Infect Dis. 2023;23(10):1099-100. Accessed February 26, 2024. https://pubmed.ncbi.nlm.nih.gov/37352881/

17. Heilmann E, Costacurta F, Moghadasi SA, Ye C, Pavan M, Bassani D, et al. SARS-CoV-2 3CL(pro) mutations selected in a VSV-based system confer resistance to nirmatrelvir, ensitrelvir, and GC376. Sci Transl Med. 2023;15(678):eabq7360. Accessed February 26, 2024. https://pubmed.ncbi.nlm.nih.gov/36194133/

18. Tita B. The U.S. Invested Millions to Produce Masks at Home. Now Nobody’s Buying. Wall Street Journal. February 4, 2024. Accessed February 26, 2024. https://www.wsj.com/health/healthcare/the-u-s-invested-millions-to-produce-masks-at-home-now-nobodys-buying-fee1c49f