Since the outbreak of the SARS-CoV-2 pandemic in 2019, nearly 300 million people around the world have been infected with the virus and over 5 million have died (1). While the majority of infected individuals survive the disease, up to 87% suffer from at least one residual symptom two months after the acute syndrome has resolved (2). Persistent fatigue, dyspnea, joint pain, and angina after recovery, as well as decreased quality of life, contribute to an increased risk of morbidity and mortality from causes both directly related and unrelated to COVID-19 (2, 3). In fact, patients recovering from severe COVID-19 are more than twice as likely to die within one year following the initial infection (3). Surprisingly, patients recovering from severe COVID-19 face an increased risk of hospitalization for both respiratory and non-respiratory conditions, including respiratory failure, multiorgan dysfunction, liver disease, and diabetes, likely due to the multisystem cellular damage caused by the virus (4, 5).
Long-term symptoms and increased mortality even after recovery from COVID-19 might stem from the cellular mechanisms of the initial infection. Although researchers initially considered COVID-19 to be mainly a respiratory disease, increasing evidence shows that the virus damages multiple systems in the body by using the abundant angiotensin-converting enzyme 2 (ACE2) as a receptor for entry into cells in many organ systems, including the gastrointestinal, nervous, and cardiovascular systems (5-9). However, the mechanisms by which these systems are harmed are not fully understood but extend past the invasion of ACE2 receptors; although the enzyme is expressed in most organ systems, it exists at low concentrations in the vascular and central nervous systems, suggesting that the virus affects the brain, nerves, and blood vessels via a different route as well (9).
Another way the virus causes immense damage is by inciting the pro-inflammatory reactions from the immune system (7, 8). To fight off SARS-CoV-2 infection, the release of an immense amount of pro-inflammatory proteins can inadvertently cause overwhelming inflammation, buildup of the iron storage protein ferritin, organ failure and eventually death (7, 10). Some researchers believe this state of inflammation and hypercoagulation caused by the virus’ affinity for ACE2 and its effect of increasing cytokine levels directly increases COVID-19 patients’ chance of death from related and unrelated causes for at least two months after recovery (7, 10). Notably, only around 20% of deaths of recovering COVID-19 patients were caused by conditions directly related to the disease itself — e.g., respiratory failure — suggesting that the physiological stress caused by the virus has significant consequences on all systems of the body and contributes to increased mortality after recovery (3).
To prevent these deaths, researchers and public health officials continue to urge people to seek vaccination. The approved vaccines in the United States — produced by Moderna, Pfizer-BioNTech, and Janssen, respectively — all provide significant protection against severe symptoms and hospitalization from COVID-19, especially for individuals over the age of 65 (11). The risk of death for individuals who sustained mild or moderate cases of COVID-19 is much lower than those with severe cases, a fact that offers hope to vaccinated people (3, 5, 7). Vaccines also reduce the risk of spreading the virus to immunocompromised, elderly, and other high-risk individuals (11). While they do not completely prevent infection with COVID-19, vaccines significantly reduce the chance of major adverse consequences from infection (3, 11).
References
1: World Health Organization (WHO), 2022. WHO coronavirus (COVID-19) dashboard. World Health Organization. Dataset. Link: https://covid19.who.int/.
2: Carfi, A., Bernabei, R. and Landi, F. 2020. Persistent symptoms in patients after acute COVID-19. JAMA, vol. 324. DOI: 10.1001/jama.2020.12603.
3: Mainous, A., Rooks, B., Wu, V. and Orlando, F. 2021. COVID-19 post-acute sequelae among adults: 12 month mortality risk. Frontiers in Medicine, vol. 8. DOI: 10.3389/fmed.2021.778434.
4: Mainous, A., Rooks, B. and Orlando, F. 2021. Risk of new hospitalization post-COVID-19 infection for non-COVID-19 conditions. Journal of the American Board of Family Medicine, vol. 34. DOI: 10.3122/jabfm.2021.05.210170.
5: Ayoubkhani, D., Khunti, K., Nafilyan, V., Maddox, T., Humberstone, B., Diamond, I. and Banerjee, A. 2021. Post-COVID syndrome in individuals admitted to hospital with COVID-19: retrospective cohort study. BMJ, vol. 372. DOI: 10.1136/bmj.n693.
6: Xiao, F., Tang, M., Zheng, X., Liu, Y., Li, X., and Shan, H. 2020. Evidence for gastrointestinal infection of SARS-CoV-2. American Gastrointestinal Association Brief Communication, vol. 158. DOI: 10.1053/j.gastro.2020.02.055.
7: Del Rio, C., Collins, L. and Malani, P. 2020. Long-term health consequences of COVID-19. JAMA, vol. 324. DOI: 10.1001/jama.2020.19719.
8: Ni, W., Yang, X., Yang, D., Bao, J., Li, R., Xiao, Y., Hou, C., Wang, H., Liu, J., Yang, D., Xu, Y., Cao, Z. and Gao, Z. 2020. Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19. Critical Care, vol. 24. DOI: 10.1186/s13054-020-03120-0.
9: Li, Y., Bai, W. and Hashikawa, T. 2020. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. Journal of Medical Virology, vol. 92. DOI: 10.1002/jmv.25728.
10: Ragab, D., Eldin, H., Taeimah, M., Khattab, R. and Salem, R. 2020. The COVID-19 cytokine storm: what we know so far. Frontiers in Immunology, vol. 11. DOI: 10.3389/fimmu.2020.01446.
11: Moline, H., Whitaker, M., Deng, L., et al. 2021. Effectiveness of COVID-19 vaccines in preventing hospitalization among adults aged ≥65 years. Morbidity and Mortality Weekly Report, vol. 70. DOI: 10.15585/mmwr.mm7032e3.
