Long COVID Definition, Symptoms, Risk Factors, Epidemiology and Autoimmunity: A Narrative Review

Overview

Journal Am J Med Open

Specialty General Medicine

Date 2024 Jul 22

PMID 39034937

Authors

Pawel Kozlowski

Aleksandra Leszczynska

Olga Ciepiela

Affiliations

Soon will be listed here.

Abstract

The virus called SARS-CoV-2 emerged in 2019 and quickly spread worldwide, causing COVID-19. It has greatly impacted on everyday life, healthcare systems, and the global economy. In order to save as many lives as possible, precautions such as social distancing, quarantine, and testing policies were implemented, and effective vaccines were developed. A growing amount of data collected worldwide allowed the characterization of this new disease, which turned out to be more complex than other common respiratory tract infections. An increasing number of convalescents presented with a variety of nonspecific symptoms emerging after the acute infection. This possible new global health problem was identified and labelled as long COVID. Since then, a great effort has been made by clinicians and the scientific community to understand the underlying mechanisms and to develop preventive measures and effective treatment. The role of autoimmunity induced by SARS-CoV-2 infection in the development of long COVID is discussed in this review. We aim to deliver a description of several conditions with an autoimmune background observed in COVID-19 convalescents, including Guillain-Barré syndrome, antiphospholipid syndrome and related thrombosis, and Kawasaki disease highlighting a relationship between SARS-CoV-2 infection and the development of autoimmunity. However, further studies are required to determine its true clinical significance.

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References

Breton G, Mendoza P, Hagglof T, Oliveira T, Schaefer-Babajew D, Gaebler C . Persistent cellular immunity to SARS-CoV-2 infection. J Exp Med. 2021; 218(4). PMC: 7845919. DOI: 10.1084/jem.20202515. View

Kunutsor S, Laukkanen J . Renal complications in COVID-19: a systematic review and meta-analysis. Ann Med. 2020; 52(7):345-353. PMC: 7877945. DOI: 10.1080/07853890.2020.1790643. View

Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H . Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020; 130(5):2620-2629. PMC: 7190990. DOI: 10.1172/JCI137244. View

Rocchi G, Giovanetti M, Benedetti F, Borsetti A, Ceccarelli G, Zella D . Gut Microbiota and COVID-19: Potential Implications for Disease Severity. Pathogens. 2022; 11(9). PMC: 9503814. DOI: 10.3390/pathogens11091050. View

Reinke S, Thakur A, Gartlan C, Bezbradica J, Milicic A . Inflammasome-Mediated Immunogenicity of Clinical and Experimental Vaccine Adjuvants. Vaccines (Basel). 2020; 8(3). PMC: 7565252. DOI: 10.3390/vaccines8030554. View

Brogan P, Burns J, Cornish J, Diwakar V, Eleftheriou D, Gordon J . Lifetime cardiovascular management of patients with previous Kawasaki disease. Heart. 2019; 106(6):411-420. PMC: 7057818. DOI: 10.1136/heartjnl-2019-315925. View

Yuki N, Hartung H . Guillain-Barré syndrome. N Engl J Med. 2012; 366(24):2294-304. DOI: 10.1056/NEJMra1114525. View

Puchner A, Saferding V, Bonelli M, Mikami Y, Hofmann M, Brunner J . Non-classical monocytes as mediators of tissue destruction in arthritis. Ann Rheum Dis. 2018; 77(10):1490-1497. PMC: 6161666. DOI: 10.1136/annrheumdis-2018-213250. View

Suthar M, Zimmerman M, Kauffman R, Mantus G, Linderman S, Hudson W . Rapid Generation of Neutralizing Antibody Responses in COVID-19 Patients. Cell Rep Med. 2020; 1(3):100040. PMC: 7276302. DOI: 10.1016/j.xcrm.2020.100040. View

10.

Alshrari A, Hudu S, Imran M, Asdaq S, Ali A, Rabbani S . Innovations and development of Covid-19 vaccines: A patent review. J Infect Public Health. 2021; 15(1):123-131. PMC: 8539827. DOI: 10.1016/j.jiph.2021.10.021. View

11.

Sa Ribero M, Jouvenet N, Dreux M, Nisole S . Interplay between SARS-CoV-2 and the type I interferon response. PLoS Pathog. 2020; 16(7):e1008737. PMC: 7390284. DOI: 10.1371/journal.ppat.1008737. View

12.

Heurich A, Hofmann-Winkler H, Gierer S, Liepold T, Jahn O, Pohlmann S . TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein. J Virol. 2013; 88(2):1293-307. PMC: 3911672. DOI: 10.1128/JVI.02202-13. View

13.

Toyka K . Eighty three years of the Guillain-Barré syndrome: clinical and immunopathologic aspects, current and future treatments. Rev Neurol (Paris). 1999; 155(10):849-56. View

14.

Li H, Liu L, Zhang D, Xu J, Dai H, Tang N . SARS-CoV-2 and viral sepsis: observations and hypotheses. Lancet. 2020; 395(10235):1517-1520. PMC: 7164875. DOI: 10.1016/S0140-6736(20)30920-X. View

15.

McArdle S, Chodaczek G, Ray N, Ley K . Intravital live cell triggered imaging system reveals monocyte patrolling and macrophage migration in atherosclerotic arteries. J Biomed Opt. 2015; 20(2):26005. PMC: 4339534. DOI: 10.1117/1.JBO.20.2.026005. View

16.

Warner S, Libby P . Human vascular smooth muscle cells. Target for and source of tumor necrosis factor. J Immunol. 1989; 142(1):100-9. View

17.

Dutta D, Liu J, Xiong H . NLRP3 inflammasome activation and SARS-CoV-2-mediated hyperinflammation, cytokine storm and neurological syndromes. Int J Physiol Pathophysiol Pharmacol. 2022; 14(3):138-160. PMC: 9301183. View

18.

Greenhalgh T, Knight M, ACourt C, Buxton M, Husain L . Management of post-acute covid-19 in primary care. BMJ. 2020; 370:m3026. DOI: 10.1136/bmj.m3026. View

19.

Misharin A, Cuda C, Saber R, Turner J, Gierut A, Haines 3rd G . Nonclassical Ly6C(-) monocytes drive the development of inflammatory arthritis in mice. Cell Rep. 2014; 9(2):591-604. PMC: 4223808. DOI: 10.1016/j.celrep.2014.09.032. View

20.

Hirayama T, Hongo Y, Kaida K, Kano O . Guillain-Barré syndrome after COVID-19 in Japan. BMJ Case Rep. 2020; 13(10). PMC: 7597510. DOI: 10.1136/bcr-2020-239218. View