J Korean Med Sci.  2022 Jul;37(27):e213. 10.3346/jkms.2022.37.e213.

Persistent Symptoms After Acute COVID-19 Infection in Omicron Era

• Jung YH
• Ha EH
• Choe KW
• Lee S
• Jo DH
• Lee WJ

• KMID: 2531251
• DOI: http://doi.org/10.3346/jkms.2022.37.e213

Abstract

Background
We aim to compare the clinical characteristics and subjectively reported symptoms of the acute coronavirus disease (COVID) phase and those of the post-acute COVID phase to examine varying factors that affect the number of persistent symptoms and their categories.
Methods
We categorized 1,122 patients who visited the post coronavirus disease 2019 (COVID-19) clinic into two groups: “acute group” (< 4 weeks following diagnosis of COVID-19) and “post-acute group” (> 4 weeks following diagnosis of COVID-19). We statistically compared clinical characteristics between the two groups and determined which factors are associated with the number of persistent symptoms and their categories.
Results
The persistent symptoms of post COVID-19 conditions were classified into three categories as follows: Category A (the prevalence of symptoms is higher in the acute-visit group than in the post-acute-visit group), Category B (the prevalence of symptoms is not different between the two groups) and Category C (the prevalence of symptoms is higher in the post-acute-visit group than in the acute-visit group). Category A mainly included respiratory symptoms. Category B had generalized weakness, weight loss, cardiologic symptoms, hypogeusia, hyposmia, anxiety, and various gastrointestinal symptoms. Category C included fatigue, decreased attention, depression, blurred vision, hair loss, and sexual dysfunction. Anxiety, depression, fatigue and age were also associated with the number of symptoms and their categories, and anxiety is the most correlated factor (P < 0.001) among them.
Conclusion
The persistent symptoms of post COVID-19 condition involve multi-organ and continue for four weeks or greater. Therefore, long-term observation and multidisciplinary interventions are essential for patients with post COVID-19 conditions.

Keyword

Omicron Variant; COVID-19; Post COVID-19 Conditions

Figure

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  Fig. 1 Symptoms of post coronavirus disease 2019 condition.

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  Fig. 2 Three categories of persistent symptoms after acute COVID-19 infection. Category A: symptoms in which the prevalence is higher in the acute group than in the post-acute group; Category B: symptoms in which the prevalence is not significantly different between the two groups; Category C: symptoms in which the prevalence is higher in the post-acute group than in the acute group.

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  Fig. 3 The relative difference between acute-visit group and post-acute group. The numbers mean the ratio of the symptom numbers of the “post-acute group” in each symptom category, when that of “acute group” is normalized to 100.

Reference

1. Araf Y, Akter F, Tang Yd, Fatemi R, Parvez SA, Zheng C, et al. Omicron variant of SARS-CoV-2: genomics, transmissibility, and responses to current COVID-19 vaccines. J Med Virol. 2022; 94(5):1825–1832. PMID: 35023191.

2. Ryu BH, Hong SI, Lim SJ, Cho Y, Hwang C, Kang H, et al. Clinical features of adult COVID-19 patients without risk factors before and after the nationwide SARS-CoV-2 B.1.617.2 (Delta)-variant outbreak in Korea: experience from Gyeongsangnam-do. J Korean Med Sci. 2021; 36(49):e341. PMID: 34931500.

3. Seok H, Lim S, Kim JY, Park CH, Kim JH, Woo ML, et al. Infectivity of coronavirus disease 2019: a prospective cohort study in the Korean metropolitan area. J Korean Med Sci. 2022; 37(14):e106. PMID: 35411726.

4. Yelin D, Moschopoulos CD, Margalit I, Gkrania-Klotsas E, Landi F, Stahl JP, et al. ESCMID rapid guidelines for assessment and management of long COVID. Clin Microbiol Infect. 2022; 28(7):S1198-743X(22)00092-1.

5. Nasserie T, Hittle M, Goodman SN. Assessment of the frequency and variety of persistent symptoms among patients with COVID-19: a systematic review. JAMA Netw Open. 2021; 4(5):e2111417. PMID: 34037731.

6. Kim Y, Bitna-Ha , Kim SW, Chang HH, Kwon KT, Bae S, et al. Post-acute COVID-19 syndrome in patients after 12 months from COVID-19 infection in Korea. BMC Infect Dis. 2022; 22(1):93. PMID: 35086489.

7. Kim Y, Kim SW, Chang HH, Kwon KT, Bae S, Hwang S. Significance and associated factors of long-term sequelae in patients after acute COVID-19 infection in Korea. Infect Chemother. 2021; 53(3):463–476. PMID: 34405592.

8. Moldofsky H, Patcai J. Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome; a case-controlled study. BMC Neurol. 2011; 11(1):37. PMID: 21435231.

9. Park HY, Park WB, Lee SH, Kim JL, Lee JJ, Lee H, et al. Posttraumatic stress disorder and depression of survivors 12 months after the outbreak of Middle East respiratory syndrome in South Korea. BMC Public Health. 2020; 20(1):605. PMID: 32410603.

10. World Health Organization. Coronavirus disease (COVID-19): post COVID-19 condition. Updated 2021. Accessed April 22, 2022. http://www.who.int/news-room/questions-and-answers/item/coronavirus-disease-(covid-19)-post-covid-19-condition .

11. World Health Organization. Coronavirus disease (COVID-19): post COVID-19 condition. Updated 2021. Accessed April 22, 2022. http://www.who.int/news-room/questions-and-answers/item/coronavirus-disease-(covid-19)-post-covid-19-condition .

12. Goërtz YMJ, Van Herck M, Delbressine JM, Vaes AW, Meys R, Machado FVC, et al. Persistent symptoms 3 months after a SARS-CoV-2 infection: the post-COVID-19 syndrome? ERJ Open Res. 2020; 6(4):00542-2020. PMID: 33257910.

13. Jennings G, Monaghan A, Xue F, Mockler D, Romero-Ortuño R. A systematic review of persistent symptoms and residual abnormal functioning following acute COVID-19: ongoing symptomatic phase vs. post-COVID-19 syndrome. J Clin Med. 2021; 10(24):5913. PMID: 34945213.

14. Aiyegbusi OL, Hughes SE, Turner G, Rivera SC, McMullan C, Chandan JS, et al. Symptoms, complications and management of long COVID: a review. J R Soc Med. 2021; 114(9):428–442. PMID: 34265229.

15. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983; 67(6):361–370. PMID: 6880820.

16. Bjelland I, Dahl AA, Haug TT, Neckelmann D. The validity of the Hospital Anxiety and Depression Scale. An updated literature review. J Psychosom Res. 2002; 52(2):69–77. PMID: 11832252.

17. Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol. 1989; 46(10):1121–1123. PMID: 2803071.

18. Hjollund NH, Andersen JH, Bech P. Assessment of fatigue in chronic disease: a bibliographic study of fatigue measurement scales. Health Qual Life Outcomes. 2007; 5(1):12. PMID: 17326844.

19. Tenforde MW, Kim SS, Lindsell CJ, Billig Rose E, Shapiro NI, Files DC, et al. Symptom duration and risk factors for delayed return to usual health among outpatients with COVID-19 in a multistate health care systems network—United States, March–June 2020. MMWR Morb Mortal Wkly Rep. 2020; 69(30):993–998. PMID: 32730238.

20. Gupta A, Madhavan MV, Sehgal K, Nair N, Mahajan S, Sehrawat TS, et al. Extrapulmonary manifestations of COVID-19. Nat Med. 2020; 26(7):1017–1032. PMID: 32651579.

21. Crook H, Raza S, Nowell J, Young M, Edison P. Long COVID-mechanisms, risk factors, and management. BMJ. 2021; 374(1648):n1648. PMID: 34312178.

22. Ehrenfeld M, Tincani A, Andreoli L, Cattalini M, Greenbaum A, Kanduc D, et al. COVID-19 and autoimmunity. Autoimmun Rev. 2020; 19(8):102597. PMID: 32535093.

23. Karlsson AC, Humbert M, Buggert M. The known unknowns of T cell immunity to COVID-19. Sci Immunol. 2020; 5(53):eabe8063. PMID: 33208380.

24. Ramakrishnan RK, Kashour T, Hamid Q, Halwani R, Tleyjeh IM. Unraveling the mystery surrounding post-acute sequelae of COVID-19. Front Immunol. 2021; 12:686029. PMID: 34276671.

25. Taquet M, Dercon Q, Harrison PJ. Six-month sequelae of post-vaccination SARS-CoV-2 infection: a retrospective cohort study of 10,024 breakthrough infections. Brain Behav Immun. 2022; 103:154–162. PMID: 35447302.

26. Ayoubkhani D, Bermingham C, Pouwels KB, Glickman M, Nafilyan V, Zaccardi F, et al. Trajectory of long covid symptoms after COVID-19 vaccination: community based cohort study. BMJ. 2022; 377:e069676. PMID: 35584816.