Fourteen Percent of Those Who Contracted COVID-19 Face Long-Term Challenges

Post-COVID-19 condition, also called long COVID, chronic COVID-19, long-haul COVID-19, and postacute COVID-19, among other terms, describes long-term effects from COVID-19 infection lasting weeks to months and longer.¹

The World Health Organization defines long COVID as symptoms occurring 3 months after probable or confirmed COVID-19 onset and lasting for at least 2 months.² Evidence-based treatments for long COVID have been elusive, and many individuals resort to untried and sometimes dangerous remedies.³

Vaccination Helps

Long COVID is more prevalent among unvaccinated individuals and can occur in those who have not tested positive for the infection or were unaware they had an infection.¹ Some patients experience multiorgan involvement and may be at increased risk for new health conditions, such as diabetes, heart conditions, or neurologic conditions, compared with individuals who have never had COVID-19.⁴ One of the most troubling symptoms is “brain fog”—the inability to focus or process information well.^1,3 Since July 2021, the Americans with Disabilities Act has recognized post–COVID-19 condition as a disability.⁵

With no test to prove that long COVID is present, diagnosticians must rely on symptoms. Table 1^1,4 lists symptoms that can occur.

Because long COVID’s definitions vary and investigators use various sampling procedures, prevalence estimates are inconsistent. A self-report symptom tracking study with 4182 individuals found rates of symptomatic persistence of 13.3% at 1 month after acute illness and 4.5% at 2 months.⁶ Additionally, investigators in the United Kingdom asked 20,000 individuals who had had a positive SARS-CoV-2 test to answer a single question and found that 13.7% reported symptom persistence at 12 weeks.⁷

In the United States, investigators have employed 8 waves of the COVID States Project, a large-scale (N = 16,091) inter-net-based survey associated with an academic consortium that was repeated approximately every 6 weeks between February 5, 2021, and July 6, 2022.6 This study involved adults in all 50 states and the District of Columbia with a mean age of 40.5 years. Investigators found that 14.7% reported continued COVID-19 symptoms at or more than 2 months after acute illness. When they drilled down for national sociodemographic distributions, a process called reweighting, they found a prevalence of 13.9%. Women were approximately 2 times more likely than men to experience long COVID, and the point prevalence estimates were similar at 6 and 12 months. Infection earlier in the pandemic with the ancestral COVID-19 virus was more likely to be associated with long COVID than later infections with the Epsilon or Omicron variants. Adherence to the primary vaccine series was associated with a lower risk of long COVID, but partial vaccination was not. Thus, vaccination seems to reduce but not eliminate long COVID risk.⁶

Inflammation May Be Key

It appears that long COVID is the result of a prolonged, proacted low-grade inflammatory process. Because no diagnostic tests exist to confirm a diagnosis and investigators have been unable to identify a cause, treatment must be individualized. Affected patients often use polypharmacy and self-care to relieve symptoms.

When the health care team delivers care, it can be classified as symptomatic, supportive, and rehabilitative, as described in Table 2.^1,8,9 Pharmacists should note that a systematic review of 9 studies indicates that vitamin C may help with fatigue; the review’s authors postulate that its anti-inflammatory, antioxidant, and immunomodulating properties may be helpful.⁸ The results of 1 small study (N = 52) showed that low-dose naltrexone improved well-being and reduced symptomatology, but larger studies are needed.¹⁰

Conclusion

Unfortunately, some patients and prescribers have taken a “kitchen sink” approach to long COVID, using treatments that empirically or intuitively might help.³ The National Institutes of Health has committed $1.15 billion to its Recover program, which aims to identify long COVID’s biologic underpinnings,¹¹ and is also preparing to investigate nirmatrelvir tablets copackaged with ritonavir tablets (Paxlovid) for long COVID, with results not expected until 2024.12 Clinical trials using cannabidiol, lithium, nitrite supplements, and even singing to improve lung capacity are underway.¹³ Meanwhile, the kitchen-sink approach may be all we have at our disposal.

References

1. Post-COVID conditions: information for healthcare providers. CDC. Updated September 22, 2022. Accessed November 26, 2022. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/post-covid-conditions.html#management

2. A clinical case definition of post COVID-19 condition by a Delphi consensus, 6 October 2021 World Health Organization. October 6, 2021. Accessed September 21, 2022. https://www.who.int/publications/i/item/WHO-2019-nCoV-Post_COVID-19_condition-Clinical_case_definition-2021.1

3. Stead Sellers F. Desperate covid long-haulers turn to costly, unproven treatments. New York Times. November 25, 2022. Accessed November 26, 2022. https://www.washingtonpost.com/health/2022/11/25/long-covid-treatments-unproven-brain-fog/

4. Banerjee I, Robinson J, Sathian B. Treatment of long COVID or post COVID syndrome: a pharmacological approach. Nepal J Epidemiol. 2022;12(3):1220-1223. doi:10.3126/nje.v12i3.48532

5. Guidance on “long COVID” as a disability under the ADA, section 504, and section 1557. US Department of Health and Human Services. July 26, 2021. Accessed November 26, 2022. https://www.hhs.gov/civil-rights/for-providers/civil-rights-covid19/guidance-long-covid-disability/index.html

6. Perlis RH, Santillana M, Ognyanova K, et al. Prevalence and correlates of long COVID symptoms among US adults. JAMA Netw Open. 2022;5(10):e2238804. doi:10.1001/jamanetworkopen.2022.38804

7. Prevalence of ongoing symptoms following coronavirus (COVID-19) infection in the UK: 1 April 2021. Office for National Statistics. April 1, 2021. Accessed November 26, 2022. https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/bulletins/prevalenceofongoingsymptomsfollowingcoronaviruscovid19infectionintheuk/1april2021

8. Vollbracht C, Kraft K. Feasibility of vitamin C in the treatment of post viral fatigue with focus on long COVID, based on a systematic review of IV vitamin C on fatigue. Nutrients. 2021;13(4):1154. doi:10.3390/nu13041154

9. Treatment of ME/CFS. CDC. Updated January 28, 2021. Accessed November 26, 2022. https://www.cdc.gov/me-cfs/treatment/index.html

10. O'Kelly B, Vidal L, McHugh T, Woo J, Avramovic G, Lambert JS. Safety and efficacy of low dose naltrexone in a long covid cohort; an interventional pre-post study. Brain Behav Immun Health. 2022;24:100485. doi:10.1016/j.bbih.2022.100485

11. Subbaraman N. US health agency will invest $1 billion to investigate ‘long COVID.’ Nature. March 4, 2021. Accessed November 26, 2022. https://www.nature.com/articles/d41586-021-00586-y

12. Singh V. National Institutes of Health’s long COVID initiative to assess Pfizer’s antiviral pill as potential treatment. Yahoo Finance. October 28, 2022. Accessed November 26, 2022. https://finance.yahoo.com/news/national-institutes-healths-long-covid-123936764.html

13. Long COVID treatment trials. ClinicalTrials.gov. Accessed November 26, 2022. https://clinicaltrials.gov/ct2/results?cond=long+COVID&age_v=&gndr=&type=Intr&rslt=&Search=Apply

About the Author

Jeannette Y. Wick, MBA, RPh, FASCP, is the director of pharmacy professional development in the Department of Pharmacy Practice at the University of Connecticut School of Pharmacy in Storrs.