Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Jun 30:12:686029.
doi: 10.3389/fimmu.2021.686029. eCollection 2021.

Unraveling the Mystery Surrounding Post-Acute Sequelae of COVID-19

Rakhee K Ramakrishnan  1   2 , Tarek Kashour  3 , Qutayba Hamid  1   4 , Rabih Halwani  1   2   5 , Imad M Tleyjeh  6   7   8   9
Affiliations
Review

Unraveling the Mystery Surrounding Post-Acute Sequelae of COVID-19

Rakhee K Ramakrishnan et al. Front Immunol. .

Abstract

More than one year since its emergence, corona virus disease 2019 (COVID-19) is still looming large with a paucity of treatment options. To add to this burden, a sizeable subset of patients who have recovered from acute COVID-19 infection have reported lingering symptoms, leading to significant disability and impairment of their daily life activities. These patients are considered to suffer from what has been termed as "chronic" or "long" COVID-19 or a form of post-acute sequelae of COVID-19, and patients experiencing this syndrome have been termed COVID-19 long-haulers. Despite recovery from infection, the persistence of atypical chronic symptoms, including extreme fatigue, shortness of breath, joint pains, brain fogs, anxiety and depression, that could last for months implies an underlying disease pathology that persist beyond the acute presentation of the disease. As opposed to the direct effects of the virus itself, the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is believed to be largely responsible for the appearance of these lasting symptoms, possibly through facilitating an ongoing inflammatory process. In this review, we hypothesize potential immunological mechanisms underlying these persistent and prolonged effects, and describe the multi-organ long-term manifestations of COVID-19.

Keywords: SARS-CoV-2; chronic COVID-19; clinical manifestations; immunopathology; long COVID-19; long-haulers; post-acute COVID-19 syndrome; post-acute sequelae of COVID-19.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Development of post-acute sequelae of COVID-19 (PASC). This figure illustrates the development of PASC with time across the spectrum of severities presented by COVID-19. DM, diabetes mellitus; HTN, hypertension; IHD, ischemic heart disease; COPD, chronic obstructive pulmonary disease; CKD, chronic kidney disease.
Figure 2
Figure 2
Potential immunopathological mechanims underlying multi-organ sequelae of post-acute sequelae of COVID-19 (PASC).
See this image and copyright information in PMC

References

    1. Centers for Disease Control and Prevention . Post-Covid Conditions. In: Information for Healthcare Providers (2021). Available at: https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/post-covid-c....
    1. Bai Y, Yao L, Wei T, Tian F, Jin DY, Chen L, et al. . Presumed Asymptomatic Carrier Transmission of COVID-19. Jama (2020) 323(14):1406–7. 10.1001/jama.2020.2565 - DOI - PMC - PubMed
    1. Carfì A, Bernabei R, Landi F. Persistent Symptoms in Patients After Acute COVID-19. Jama (2020) 324(6):603–5. 10.1001/jama.2020.12603 - DOI - PMC - PubMed
    1. Nishiura H, Kobayashi T, Miyama T, Suzuki A, Jung SM, Hayashi K, et al. . Estimation of the Asymptomatic Ratio of Novel Coronavirus Infections (COVID-19). Int J Infect Dis (2020) 94:154–5. 10.1016/j.ijid.2020.03.020 - DOI - PMC - PubMed
    1. Greenhalgh T, Knight M, A’Court C, Buxton M, Husain L. Management of Post-Acute Covid-19 in Primary Care. BMJ (Clinical Res ed) (2020) 370:m3026. 10.1136/bmj.m3026 - DOI - PubMed

Publication types