Long-COVID-19 syndrome: an overview
Abstract
The Long-COVID-19 syndrome has emerged as global epidemic, affecting individuals after an acute infection caused by the Severe acute respiratory syndrome coronavirus 2, impacting multiple organs, including the heart. The most common symptoms encompass fatigue and shortness of breath, which could persist for months after an acute COVID-19 infection. Numerous studies have researched the pathophysiology of Long-COVID-19 syndrome, suggesting that local tissue damage and hyperinflation could be employed as possible mechanisms of Long-COVID-19 syndrome. Many blood biomarkers (blood urea nitrogen, D-dimer, lymphopenia, troponin-1, interleukin-6, and CRP) and clinical risk factors (CRP female sex, a history of psychiatric disorders, and the presence of more than five symptoms during the first week of an acute illness) are shown to be associated with the development of Long-COVID-19 syndrome. Currently, the evidence-based specific pharmacological treatments for the Long-COVID-19 syndrome are lacking. Several studies have shown an association between antiviral drugs (such as nirmatrelvir, ensitrelvir, and molnupiravir) and vaccination against COVID-19 with a reduced risk of developing Long-COVID-19 syndrome. This narrative review discusses the possible pathophysiology, risk factors, and treatments for Long-COVID-19 syndrome with particular reference to the cardiovascular system.
References
1. World Health Organization. WHO Coronavirus (COVID-19) Dashboard [Available from: https://covid19.who.int/.
2. Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med. 2020;382(13):1199-207.
3. Soriano JB, Murthy S, Marshall JC, Relan P, Diaz JV, Condition WHOCCDWGoP-C-. A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect Dis. 2022;22(4):e102-e7.
4. Robertson MM, Qasmieh SA, Kulkarni SG, Teasdale CA, Jones HE, McNairy M, et al. The Epidemiology of Long Coronavirus Disease in US Adults. Clin Infect Dis. 2023;76(9):1636-45.
5. Liu Q, Mak JWY, Su Q, Yeoh YK, Lui GC, Ng SSS, et al. Gut microbiota dynamics in a prospective cohort of patients with post-acute COVID-19 syndrome. Gut. 2022;71(3):544-52.
6. Post COVID-19 condition (long COVID): World Health Organization.; [Available from: https://www.who.int/srilanka/news/detail/16-10-2021-post-covid-19-condition.
7. Brodin P. Immune determinants of COVID-19 disease presentation and severity. Nat Med. 2021;27(1):28-33.
8. Datta SD, Talwar A, Lee JT. A Proposed Framework and Timeline of the Spectrum of Disease Due to SARS-CoV-2 Infection: Illness Beyond Acute Infection and Public Health Implications. JAMA. 2020;324(22):2251-2.
9. Nalbandian A, Sehgal K, Gupta A, Madhavan MV, McGroder C, Stevens JS, et al. Post-acute COVID-19 syndrome. Nat Med. 2021;27(4):601-15.
10. Fernandez-de-Las-Penas C, Palacios-Cena D, Gomez-Mayordomo V, Cuadrado ML, Florencio LL. Defining Post-COVID Symptoms (Post-Acute COVID, Long COVID, Persistent Post-COVID): An Integrative Classification. Int J Environ Res Public Health. 2021;18(5).
11. Greenhalgh T, Knight M, A'Court C, Buxton M, Husain L. Management of post-acute covid-19 in primary care. BMJ. 2020;370:m3026.
12. Klein J, Wood J, Jaycox J, Lu P, Dhodapkar RM, Gehlhausen JR, et al. Distinguishing features of Long COVID identified through immune profiling. medRxiv. 2022.
13. Glynne P, Tahmasebi N, Gant V, Gupta R. Long COVID following mild SARS-CoV-2 infection: characteristic T cell alterations and response to antihistamines. J Investig Med. 2022;70(1):61-7.
14. Arthur JM, Forrest JC, Boehme KW, Kennedy JL, Owens S, Herzog C, et al. Development of ACE2 autoantibodies after SARS-CoV-2 infection. PLoS One. 2021;16(9):e0257016.
15. Peluso MJ, Lu S, Tang AF, Durstenfeld MS, Ho HE, Goldberg SA, et al. Markers of Immune Activation and Inflammation in Individuals With Postacute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 Infection. J Infect Dis. 2021;224(11):1839-48.
16. Perumal R, Shunmugam L, Naidoo K, Abdool Karim SS, Wilkins D, Garzino-Demo A, et al. Long COVID: a review and proposed visualization of the complexity of long COVID. Front Immunol. 2023;14:1117464.
17. Cheung CCL, Goh D, Lim X, Tien TZ, Lim JCT, Lee JN, et al. Residual SARS-CoV-2 viral antigens detected in GI and hepatic tissues from five recovered patients with COVID-19. Gut. 2022;71(1):226-9.
18. Swank Z, Senussi Y, Manickas-Hill Z, Yu XG, Li JZ, Alter G, et al. Persistent Circulating Severe Acute Respiratory Syndrome Coronavirus 2 Spike Is Associated With Post-acute Coronavirus Disease 2019 Sequelae. Clin Infect Dis. 2023;76(3):e487-e90.
19. Jacobs JJL. Persistent SARS-2 infections contribute to long COVID-19. Med Hypotheses. 2021;149:110538.
20. Tavakolpour S, Rakhshandehroo T, Wei EX, Rashidian M. Lymphopenia during the COVID-19 infection: What it shows and what can be learned. Immunol Lett. 2020;225:31-2.
21. Kavi L. Postural tachycardia syndrome and long COVID: an update. Br J Gen Pract. 2022;72(714):8-9.
22. Dani M, Dirksen A, Taraborrelli P, Torocastro M, Panagopoulos D, Sutton R, et al. Autonomic dysfunction in 'long COVID': rationale, physiology and management strategies. Clin Med (Lond). 2021;21(1):e63-e7.
23. Hampshire A, Trender W, Chamberlain SR, Jolly AE, Grant JE, Patrick F, et al. Cognitive deficits in people who have recovered from COVID-19. EClinicalMedicine. 2021;39:101044.
24. Lukiw WJ, Pogue A, Hill JM. SARS-CoV-2 Infectivity and Neurological Targets in the Brain. Cell Mol Neurobiol. 2022;42(1):217-24.
25. Yong SJ. Persistent Brainstem Dysfunction in Long-COVID: A Hypothesis. ACS Chem Neurosci. 2021;12(4):573-80.
26. Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395(10234):1417-8.
27. Kang W, Maher L, Michaud M, Bae SW, Kim S, Lee HS, et al. Development of a Novel Orthotopic Gastric Cancer Mouse Model. Biol Proced Online. 2021;23(1):1.
28. Guler SA, Ebner L, Aubry-Beigelman C, Bridevaux PO, Brutsche M, Clarenbach C, et al. Pulmonary function and radiological features 4 months after COVID-19: first results from the national prospective observational Swiss COVID-19 lung study. Eur Respir J. 2021;57(4).
29. Vrints CJM, Krychtiuk KA, Van Craenenbroeck EM, Segers VF, Price S, Heidbuchel H. Endothelialitis plays a central role in the pathophysiology of severe COVID-19 and its cardiovascular complications. Acta Cardiol. 2021;76(2):109-24.
30. Nishiga M, Wang DW, Han Y, Lewis DB, Wu JC. COVID-19 and cardiovascular disease: from basic mechanisms to clinical perspectives. Nat Rev Cardiol. 2020;17(9):543-58.
31. Chung MK, Zidar DA, Bristow MR, Cameron SJ, Chan T, Harding CV, 3rd, et al. COVID-19 and Cardiovascular Disease: From Bench to Bedside. Circ Res. 2021;128(8):1214-36.
32. Liang L, Yang B, Jiang N, Fu W, He X, Zhou Y, et al. Three-month Follow-up Study of Survivors of Coronavirus Disease 2019 after Discharge. J Korean Med Sci. 2020;35(47):e418.
33. Lamers MM, Beumer J, van der Vaart J, Knoops K, Puschhof J, Breugem TI, et al. SARS-CoV-2 productively infects human gut enterocytes. Science. 2020;369(6499):50-4.
34. Giannos P, Prokopidis K. Gut dysbiosis and long COVID-19: Feeling gutted. J Med Virol. 2022;94(7):2917-8.
35. Giron LB, Peluso MJ, Ding J, Kenny G, Zilberstein NF, Koshy J, et al. Markers of fungal translocation are elevated during post-acute sequelae of SARS-CoV-2 and induce NF-kappaB signaling. JCI Insight. 2022;7(15).
36. Espin E, Yang C, Shannon CP, Assadian S, He D, Tebbutt SJ. Cellular and molecular biomarkers of long COVID: a scoping review. EBioMedicine. 2023;91:104552.
37. Zhao YM, Shang YM, Song WB, Li QQ, Xie H, Xu QF, et al. Follow-up study of the pulmonary function and related physiological characteristics of COVID-19 survivors three months after recovery. EClinicalMedicine. 2020;25:100463.
38. Raman B, Cassar MP, Tunnicliffe EM, Filippini N, Griffanti L, Alfaro-Almagro F, et al. Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge. EClinicalMedicine. 2021;31:100683.
39. Townsend L, Dyer AH, Jones K, Dunne J, Mooney A, Gaffney F, et al. Persistent fatigue following SARS-CoV-2 infection is common and independent of severity of initial infection. PLoS One. 2020;15(11):e0240784.
40. Moreno-Perez O, Merino E, Leon-Ramirez JM, Andres M, Ramos JM, Arenas-Jimenez J, et al. Post-acute COVID-19 syndrome. Incidence and risk factors: A Mediterranean cohort study. J Infect. 2021;82(3):378-83.
41. Stavem K, Ghanima W, Olsen MK, Gilboe HM, Einvik G. Persistent symptoms 1.5-6 months after COVID-19 in non-hospitalised subjects: a population-based cohort study. Thorax. 2021;76(4):405-7.
42. Taboada M, Carinena A, Moreno E, Rodriguez N, Dominguez MJ, Casal A, et al. Post-COVID-19 functional status six-months after hospitalization. J Infect. 2021;82(4):e31-e3.
43. Bowe B, Xie Y, Al-Aly Z. Acute and postacute sequelae associated with SARS-CoV-2 reinfection. Nat Med. 2022;28(11):2398-405.
44. Xie Y, Xu E, Bowe B, Al-Aly Z. Long-term cardiovascular outcomes of COVID-19. Nat Med. 2022;28(3):583-90.
45. Roca-Fernandez A, Wamil M, Telford A, Carapella V, Borlotti A, Monteiro D, et al. Cardiac abnormalities in Long COVID 1-year post-SARS-CoV-2 infection. Open Heart. 2023;10(1).
46. Puntmann VO, Carerj ML, Wieters I, Fahim M, Arendt C, Hoffmann J, et al. Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020;5(11):1265-73.
47. Farshidfar F, Koleini N, Ardehali H. Cardiovascular complications of COVID-19. JCI Insight. 2021;6(13).
48. Bojkova D, Wagner JUG, Shumliakivska M, Aslan GS, Saleem U, Hansen A, et al. SARS-CoV-2 infects and induces cytotoxic effects in human cardiomyocytes. Cardiovasc Res. 2020;116(14):2207-15.
49. Peiris JS, Chu CM, Cheng VC, Chan KS, Hung IF, Poon LL, et al. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet. 2003;361(9371):1767-72.
50. Wei ZY, Geng YJ, Huang J, Qian HY. Pathogenesis and management of myocardial injury in coronavirus disease 2019. Eur J Heart Fail. 2020;22(11):1994-2006.
51. Teuwen LA, Geldhof V, Pasut A, Carmeliet P. COVID-19: the vasculature unleashed. Nat Rev Immunol. 2020;20(7):389-91.
52. Shi S, Qin M, Shen B, Cai Y, Liu T, Yang F, et al. Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. JAMA Cardiol. 2020;5(7):802-10.
53. Potpara T, Angiolillo DJ, Bikdeli B, Capodanno D, Cole O, Yataco AC, et al. Antithrombotic Therapy in Arterial Thrombosis and Thromboembolism in COVID-19: An American College of Chest Physicians Expert Panel Report. Chest. 2023.
54. Thomas RJ, Balady G, Banka G, Beckie TM, Chiu J, Gokak S, et al. 2018 ACC/AHA Clinical Performance and Quality Measures for Cardiac Rehabilitation: A Report of the American College of Cardiology/American Heart Association Task Force on Performance Measures. J Am Coll Cardiol. 2018;71(16):1814-37.
55. Candelaria D, Randall S, Ladak L, Gallagher R. Health-related quality of life and exercise-based cardiac rehabilitation in contemporary acute coronary syndrome patients: a systematic review and meta-analysis. Qual Life Res. 2020;29(3):579-92.
56. Jimeno-Almazan A, Pallares JG, Buendia-Romero A, Martinez-Cava A, Franco-Lopez F, Sanchez-Alcaraz Martinez BJ, et al. Post-COVID-19 Syndrome and the Potential Benefits of Exercise. Int J Environ Res Public Health. 2021;18(10).
57. Xie Y, Choi T, Al-Aly Z. Association of Treatment With Nirmatrelvir and the Risk of Post-COVID-19 Condition. JAMA Intern Med. 2023;183(6):554-64.
58. Xie Y, Choi T, Al-Aly Z. Molnupiravir and risk of post-acute sequelae of covid-19: cohort study. BMJ. 2023;381:e074572.
59. Mukae H, Yotsuyanagi H, Ohmagari N, Doi Y, Imamura T, Sonoyama T, et al. A Randomized Phase 2/3 Study of Ensitrelvir, a Novel Oral SARS-CoV-2 3C-Like Protease Inhibitor, in Japanese Patients with Mild-to-Moderate COVID-19 or Asymptomatic SARS-CoV-2 Infection: Results of the Phase 2a Part. Antimicrob Agents Chemother. 2022;66(10):e0069722.
60. Bramante CT, Buse JB, Liebovitz DM, Nicklas JM, Puskarich MA, Cohen K, et al. Outpatient treatment of COVID-19 and incidence of post-COVID-19 condition over 10 months (COVID-OUT): a multicentre, randomised, quadruple-blind, parallel-group, phase 3 trial. Lancet Infect Dis. 2023;23(10):1119-29.
61. Ayoubkhani D BM, King S. Self-reported long COVID after two doses of a
coronavirus (COVID-19) vaccine in the UK: 26 January 2022.
62. 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.
2. Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med. 2020;382(13):1199-207.
3. Soriano JB, Murthy S, Marshall JC, Relan P, Diaz JV, Condition WHOCCDWGoP-C-. A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect Dis. 2022;22(4):e102-e7.
4. Robertson MM, Qasmieh SA, Kulkarni SG, Teasdale CA, Jones HE, McNairy M, et al. The Epidemiology of Long Coronavirus Disease in US Adults. Clin Infect Dis. 2023;76(9):1636-45.
5. Liu Q, Mak JWY, Su Q, Yeoh YK, Lui GC, Ng SSS, et al. Gut microbiota dynamics in a prospective cohort of patients with post-acute COVID-19 syndrome. Gut. 2022;71(3):544-52.
6. Post COVID-19 condition (long COVID): World Health Organization.; [Available from: https://www.who.int/srilanka/news/detail/16-10-2021-post-covid-19-condition.
7. Brodin P. Immune determinants of COVID-19 disease presentation and severity. Nat Med. 2021;27(1):28-33.
8. Datta SD, Talwar A, Lee JT. A Proposed Framework and Timeline of the Spectrum of Disease Due to SARS-CoV-2 Infection: Illness Beyond Acute Infection and Public Health Implications. JAMA. 2020;324(22):2251-2.
9. Nalbandian A, Sehgal K, Gupta A, Madhavan MV, McGroder C, Stevens JS, et al. Post-acute COVID-19 syndrome. Nat Med. 2021;27(4):601-15.
10. Fernandez-de-Las-Penas C, Palacios-Cena D, Gomez-Mayordomo V, Cuadrado ML, Florencio LL. Defining Post-COVID Symptoms (Post-Acute COVID, Long COVID, Persistent Post-COVID): An Integrative Classification. Int J Environ Res Public Health. 2021;18(5).
11. Greenhalgh T, Knight M, A'Court C, Buxton M, Husain L. Management of post-acute covid-19 in primary care. BMJ. 2020;370:m3026.
12. Klein J, Wood J, Jaycox J, Lu P, Dhodapkar RM, Gehlhausen JR, et al. Distinguishing features of Long COVID identified through immune profiling. medRxiv. 2022.
13. Glynne P, Tahmasebi N, Gant V, Gupta R. Long COVID following mild SARS-CoV-2 infection: characteristic T cell alterations and response to antihistamines. J Investig Med. 2022;70(1):61-7.
14. Arthur JM, Forrest JC, Boehme KW, Kennedy JL, Owens S, Herzog C, et al. Development of ACE2 autoantibodies after SARS-CoV-2 infection. PLoS One. 2021;16(9):e0257016.
15. Peluso MJ, Lu S, Tang AF, Durstenfeld MS, Ho HE, Goldberg SA, et al. Markers of Immune Activation and Inflammation in Individuals With Postacute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 Infection. J Infect Dis. 2021;224(11):1839-48.
16. Perumal R, Shunmugam L, Naidoo K, Abdool Karim SS, Wilkins D, Garzino-Demo A, et al. Long COVID: a review and proposed visualization of the complexity of long COVID. Front Immunol. 2023;14:1117464.
17. Cheung CCL, Goh D, Lim X, Tien TZ, Lim JCT, Lee JN, et al. Residual SARS-CoV-2 viral antigens detected in GI and hepatic tissues from five recovered patients with COVID-19. Gut. 2022;71(1):226-9.
18. Swank Z, Senussi Y, Manickas-Hill Z, Yu XG, Li JZ, Alter G, et al. Persistent Circulating Severe Acute Respiratory Syndrome Coronavirus 2 Spike Is Associated With Post-acute Coronavirus Disease 2019 Sequelae. Clin Infect Dis. 2023;76(3):e487-e90.
19. Jacobs JJL. Persistent SARS-2 infections contribute to long COVID-19. Med Hypotheses. 2021;149:110538.
20. Tavakolpour S, Rakhshandehroo T, Wei EX, Rashidian M. Lymphopenia during the COVID-19 infection: What it shows and what can be learned. Immunol Lett. 2020;225:31-2.
21. Kavi L. Postural tachycardia syndrome and long COVID: an update. Br J Gen Pract. 2022;72(714):8-9.
22. Dani M, Dirksen A, Taraborrelli P, Torocastro M, Panagopoulos D, Sutton R, et al. Autonomic dysfunction in 'long COVID': rationale, physiology and management strategies. Clin Med (Lond). 2021;21(1):e63-e7.
23. Hampshire A, Trender W, Chamberlain SR, Jolly AE, Grant JE, Patrick F, et al. Cognitive deficits in people who have recovered from COVID-19. EClinicalMedicine. 2021;39:101044.
24. Lukiw WJ, Pogue A, Hill JM. SARS-CoV-2 Infectivity and Neurological Targets in the Brain. Cell Mol Neurobiol. 2022;42(1):217-24.
25. Yong SJ. Persistent Brainstem Dysfunction in Long-COVID: A Hypothesis. ACS Chem Neurosci. 2021;12(4):573-80.
26. Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395(10234):1417-8.
27. Kang W, Maher L, Michaud M, Bae SW, Kim S, Lee HS, et al. Development of a Novel Orthotopic Gastric Cancer Mouse Model. Biol Proced Online. 2021;23(1):1.
28. Guler SA, Ebner L, Aubry-Beigelman C, Bridevaux PO, Brutsche M, Clarenbach C, et al. Pulmonary function and radiological features 4 months after COVID-19: first results from the national prospective observational Swiss COVID-19 lung study. Eur Respir J. 2021;57(4).
29. Vrints CJM, Krychtiuk KA, Van Craenenbroeck EM, Segers VF, Price S, Heidbuchel H. Endothelialitis plays a central role in the pathophysiology of severe COVID-19 and its cardiovascular complications. Acta Cardiol. 2021;76(2):109-24.
30. Nishiga M, Wang DW, Han Y, Lewis DB, Wu JC. COVID-19 and cardiovascular disease: from basic mechanisms to clinical perspectives. Nat Rev Cardiol. 2020;17(9):543-58.
31. Chung MK, Zidar DA, Bristow MR, Cameron SJ, Chan T, Harding CV, 3rd, et al. COVID-19 and Cardiovascular Disease: From Bench to Bedside. Circ Res. 2021;128(8):1214-36.
32. Liang L, Yang B, Jiang N, Fu W, He X, Zhou Y, et al. Three-month Follow-up Study of Survivors of Coronavirus Disease 2019 after Discharge. J Korean Med Sci. 2020;35(47):e418.
33. Lamers MM, Beumer J, van der Vaart J, Knoops K, Puschhof J, Breugem TI, et al. SARS-CoV-2 productively infects human gut enterocytes. Science. 2020;369(6499):50-4.
34. Giannos P, Prokopidis K. Gut dysbiosis and long COVID-19: Feeling gutted. J Med Virol. 2022;94(7):2917-8.
35. Giron LB, Peluso MJ, Ding J, Kenny G, Zilberstein NF, Koshy J, et al. Markers of fungal translocation are elevated during post-acute sequelae of SARS-CoV-2 and induce NF-kappaB signaling. JCI Insight. 2022;7(15).
36. Espin E, Yang C, Shannon CP, Assadian S, He D, Tebbutt SJ. Cellular and molecular biomarkers of long COVID: a scoping review. EBioMedicine. 2023;91:104552.
37. Zhao YM, Shang YM, Song WB, Li QQ, Xie H, Xu QF, et al. Follow-up study of the pulmonary function and related physiological characteristics of COVID-19 survivors three months after recovery. EClinicalMedicine. 2020;25:100463.
38. Raman B, Cassar MP, Tunnicliffe EM, Filippini N, Griffanti L, Alfaro-Almagro F, et al. Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge. EClinicalMedicine. 2021;31:100683.
39. Townsend L, Dyer AH, Jones K, Dunne J, Mooney A, Gaffney F, et al. Persistent fatigue following SARS-CoV-2 infection is common and independent of severity of initial infection. PLoS One. 2020;15(11):e0240784.
40. Moreno-Perez O, Merino E, Leon-Ramirez JM, Andres M, Ramos JM, Arenas-Jimenez J, et al. Post-acute COVID-19 syndrome. Incidence and risk factors: A Mediterranean cohort study. J Infect. 2021;82(3):378-83.
41. Stavem K, Ghanima W, Olsen MK, Gilboe HM, Einvik G. Persistent symptoms 1.5-6 months after COVID-19 in non-hospitalised subjects: a population-based cohort study. Thorax. 2021;76(4):405-7.
42. Taboada M, Carinena A, Moreno E, Rodriguez N, Dominguez MJ, Casal A, et al. Post-COVID-19 functional status six-months after hospitalization. J Infect. 2021;82(4):e31-e3.
43. Bowe B, Xie Y, Al-Aly Z. Acute and postacute sequelae associated with SARS-CoV-2 reinfection. Nat Med. 2022;28(11):2398-405.
44. Xie Y, Xu E, Bowe B, Al-Aly Z. Long-term cardiovascular outcomes of COVID-19. Nat Med. 2022;28(3):583-90.
45. Roca-Fernandez A, Wamil M, Telford A, Carapella V, Borlotti A, Monteiro D, et al. Cardiac abnormalities in Long COVID 1-year post-SARS-CoV-2 infection. Open Heart. 2023;10(1).
46. Puntmann VO, Carerj ML, Wieters I, Fahim M, Arendt C, Hoffmann J, et al. Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020;5(11):1265-73.
47. Farshidfar F, Koleini N, Ardehali H. Cardiovascular complications of COVID-19. JCI Insight. 2021;6(13).
48. Bojkova D, Wagner JUG, Shumliakivska M, Aslan GS, Saleem U, Hansen A, et al. SARS-CoV-2 infects and induces cytotoxic effects in human cardiomyocytes. Cardiovasc Res. 2020;116(14):2207-15.
49. Peiris JS, Chu CM, Cheng VC, Chan KS, Hung IF, Poon LL, et al. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet. 2003;361(9371):1767-72.
50. Wei ZY, Geng YJ, Huang J, Qian HY. Pathogenesis and management of myocardial injury in coronavirus disease 2019. Eur J Heart Fail. 2020;22(11):1994-2006.
51. Teuwen LA, Geldhof V, Pasut A, Carmeliet P. COVID-19: the vasculature unleashed. Nat Rev Immunol. 2020;20(7):389-91.
52. Shi S, Qin M, Shen B, Cai Y, Liu T, Yang F, et al. Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. JAMA Cardiol. 2020;5(7):802-10.
53. Potpara T, Angiolillo DJ, Bikdeli B, Capodanno D, Cole O, Yataco AC, et al. Antithrombotic Therapy in Arterial Thrombosis and Thromboembolism in COVID-19: An American College of Chest Physicians Expert Panel Report. Chest. 2023.
54. Thomas RJ, Balady G, Banka G, Beckie TM, Chiu J, Gokak S, et al. 2018 ACC/AHA Clinical Performance and Quality Measures for Cardiac Rehabilitation: A Report of the American College of Cardiology/American Heart Association Task Force on Performance Measures. J Am Coll Cardiol. 2018;71(16):1814-37.
55. Candelaria D, Randall S, Ladak L, Gallagher R. Health-related quality of life and exercise-based cardiac rehabilitation in contemporary acute coronary syndrome patients: a systematic review and meta-analysis. Qual Life Res. 2020;29(3):579-92.
56. Jimeno-Almazan A, Pallares JG, Buendia-Romero A, Martinez-Cava A, Franco-Lopez F, Sanchez-Alcaraz Martinez BJ, et al. Post-COVID-19 Syndrome and the Potential Benefits of Exercise. Int J Environ Res Public Health. 2021;18(10).
57. Xie Y, Choi T, Al-Aly Z. Association of Treatment With Nirmatrelvir and the Risk of Post-COVID-19 Condition. JAMA Intern Med. 2023;183(6):554-64.
58. Xie Y, Choi T, Al-Aly Z. Molnupiravir and risk of post-acute sequelae of covid-19: cohort study. BMJ. 2023;381:e074572.
59. Mukae H, Yotsuyanagi H, Ohmagari N, Doi Y, Imamura T, Sonoyama T, et al. A Randomized Phase 2/3 Study of Ensitrelvir, a Novel Oral SARS-CoV-2 3C-Like Protease Inhibitor, in Japanese Patients with Mild-to-Moderate COVID-19 or Asymptomatic SARS-CoV-2 Infection: Results of the Phase 2a Part. Antimicrob Agents Chemother. 2022;66(10):e0069722.
60. Bramante CT, Buse JB, Liebovitz DM, Nicklas JM, Puskarich MA, Cohen K, et al. Outpatient treatment of COVID-19 and incidence of post-COVID-19 condition over 10 months (COVID-OUT): a multicentre, randomised, quadruple-blind, parallel-group, phase 3 trial. Lancet Infect Dis. 2023;23(10):1119-29.
61. Ayoubkhani D BM, King S. Self-reported long COVID after two doses of a
coronavirus (COVID-19) vaccine in the UK: 26 January 2022.
62. 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.