Post-acute Sequelae in COVID-19 Survivors: an Overview

Adekunle Sanyaolu, Aleksandra Marinkovic, Stephanie Prakash, Anne Zhao, Vyshnavy Balendra, Nafees Haider, Isha Jain, Teodora Simic, Chuku Okorie, Adekunle Sanyaolu, Aleksandra Marinkovic, Stephanie Prakash, Anne Zhao, Vyshnavy Balendra, Nafees Haider, Isha Jain, Teodora Simic, Chuku Okorie

Abstract

In the acute phase of SARS-CoV-2 infection, varying degrees of clinical manifestations have been noticed in patients. Some patients who recovered from the infection developed long-term effects which have become of interest to the scientific and medical communities, as it relates to pathogenesis and the multidisciplinary approach to treatment. Long COVID (long-term or long-haul) is the collective term used to define recovered individuals of SARS-CoV-2 infection who have presented with persistent COVID symptoms, as well as the emergence of disorders and complications. Following the review of literature from major scientific databases, this paper investigated long COVID and the resulting post-sequela effects on survivors, regardless of initial disease severity. The clinical manifestations and multisystem complications of the disease specifically, cardiovascular, neurologic and psychologic, hematologic, pulmonary, dermatologic, and other ailments were discussed. Patients with chronic COVID-19 were found to experience heart thrombosis leading to myocardial infarction, inflammation, lung fibrosis, stroke, venous thromboembolism, arterial thromboembolism, "brain fog", general mood dysfunctions, dermatological issues, and fatigue. As the disease continues to progress and spread, and with the emergence of new variants the management of these persisting symptoms will pose a challenge for healthcare providers and medical systems in the next period of the pandemic. However, more information is needed about long COVID, particularly concerning certain patient populations, variability in follow-up times, the prevalence of comorbidities, and the evolution of the spread of infection. Thus, continued research needs to be conducted concerning the disease pathology to develop preventative measures and management strategies to treat long COVID.

Keywords: Chronic COVID-19; Late sequelae after coronavirus; Long COVID-19: Long-term effects of COVID; Long-haulers; Post-acute SARS-CoV-2.

Conflict of interest statement

Conflict of InterestThe authors declare no competing interests.

© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022.

Figures

Fig. 1
Fig. 1
COVID-19 symptom timeline. Note: Data recreated from Nalbandian et al. defining persistent symptoms seen among post-acute COVID-19 patients [13]

References

    1. JHU. Coronavirus resource center. Johns Hopkins University of Medicine. 2021. . Accessed 24 Mar 2022.
    1. Demongeot J, Oshinubi K, Rachdi M, Seligmann H, Thuderoz F, et al. Estimation of daily reproduction numbers during the COVID-19 outbreak. Computation. 2021; 9(10): 109. 10.3390/computation9100109. . Accessed 3 Dec 2021.
    1. CDC. COVID-19: Delta variant: what we know about the science. Centers for Disease Control and Prevention. 2021. . Accessed 3 Dec 2021.
    1. WHO. Tracking SARS-CoV-2 variants. World Health Organization. 2022. . Accessed 23 Mar 2022.
    1. University of Wisconsin-Madison. Antivirals, some antibodies, work well against BA.2 omicron variant of COVID-19 virus. ScienceDaily. 2022. . Accessed 24 Mar 2022.
    1. Takashita E, Kinoshita N, Yamayoshi S, Fujisaki S, Ito M, et al. Efficacy of antiviral agents against the SARS-CoV-2 Omicron subvariant BA.2. NEJM. 2022. 10.1056/NEJMc2201933. . Accessed 24 Mar 2022.
    1. Crook H, Raza S, Nowell J, Young M, Edison P. Long COVID - mechanisms, risk factors, and management. BMJ. 2021; 374: n1648. 10.1136/bmj.n1648. . Accessed 3 Dec 2021.
    1. Antonelli M, Penfold RS, Merino J, Sudre CH, Molteni E, et al. Risk factors and disease profile of post-vaccination SARS-CoV-2 infection in UK users of the COVID Symptom Study app: a prospective, community-based, nested, case-control study. Lancet. 2021; 22(1): P43-55. 10.1016/S1473-3099(21)00460-6. . Accessed 24 Mar 2022.
    1. CDC. COVID-19: post-COVID conditions: information for healthcare providers. Centers for Disease Control and Prevention. 9 July 2021. . Accessed 3 Dec 2021.
    1. Davis HE, Assaf GS, McCorkell L, Wei H, Low RJ, et al. Characterizing long COVID in an international cohort: 7 months of symptoms and their impact. EClinicalMedicine. 2021; 38:101019. 10.1016/j.eclinm.2021.101019. . Accessed 3 Dec 2021.
    1. Venkatesan P. NICE guideline on long COVID. Lancet Respir Med 2021; 9(2): 129. 10.1016/S2213-2600(21)00031-X. . Accessed 24 Mar 2022.
    1. Desai AD, Lavelle M, Boursiquot BC, Wan E. Long-term complications of COVID-19. American Journal of Physiology: Cell Physiology. 2021. 10.1152/ajpcell.00375.2021. Accessed 3 Dec 2021.
    1. Nalbandian A, Sehgal K, Gupta A, Madhavan MV, McGroder C, et al. Post-acute COVID-19 syndrome. Nat Med. 2021; 27: 601–615. 10.1038/s41591-021-01283-z. . Accessed 24 Mar 2022.
    1. Seyed Alinaghi S, Afsahi AM, MohsseniPour M, Behnezhad F, Salehi MA, et al. Late complications of COVID-19; a systematic review of current evidence. Arch Acad Emerg Med. 2021;9(1): e14. 10.22037/aaem. v9i1.1058. . Accessed 23 Mar 2022.
    1. Rohrer-Meck K, Marchena D, Rubin-Miller L, Bregman H, Lo J, et al. Nearly 1 in 10 COVID patients seek treatment for long-term symptoms. Epic Health Res Netw. 2021. . Accessed 3 Dec 2021.
    1. Whitaker M, Elliott J, Chadeau-Hyam M, Riley S, Darzi A, et al. Persistent symptoms following SARS-CoV-2 infection in a random community sample of 508,707 people. medRXiv. 2021. 10.1101/2021.06.28.21259452. . Accessed 3 Dec 2021.
    1. Rasmussen AL, Popescu SV. SARS-CoV-2 transmission without symptoms. Science. 2021; 371(6535): 1206-1207. 10.1126/science.abf9569. . Accessed 3 Dec 2021.
    1. Wang EY, Mao T, Klein J, Dai Y, Huck JD, et al. Diverse functional autoantibodies in patients with COVID-19. Nature. 2021; 595(7866): 283-288. 10.1038/s41586-021-03631-y. . Accessed 24 Mar 2022.
    1. CDC. The possibility of COVID-19 after vaccination: breakthrough infections. Centers for Disease Control and Prevention. 2021. . Accessed 24 Mar 2022.
    1. Aiyegbusi OL, Hughes SE, Turner G, Rivera SC, McMullan C, et al. Symptoms, complications and management of long COVID: a review. Journal of the Royal Society of Medicine. 2021; 114(9): 428-442. 10.1177/01410768211032850. Accessed 4 Dec 2021.
    1. Tosato M, Carfì M, Martis I, Pais C, Ciciarello F, et al. Prevalence and predictors of persistence of COVID-19 symptoms in older adults: a single-center study. JAMDA. 2021; 22(9): P1840-1844. 10.1016/j.jamda.2021.07.003. . Accessed 6 Dec 2021.
    1. Xie Y, Xu E, Bowe B, Al-Aly Z. Long-term cardiovascular outcomes of COVID-19. Nat Med. 2022; 28(3): 583-590. 10.1038/s41591-022-01689-3. . Accessed 24 Mar 2022.
    1. Radiological Society of North America. ‘Long COVID’ linked to lasting airways disease. ScienceDaily. 2022. . Accessed 24 Mar 2022.
    1. Cho JL, Villacreses R, Nagpal P, Guo J, Pezzulo AA, et al. Quantitative chest CT assessment of small airways disease in post-acute SARS-CoV-2 infection. Radiology. 2022. 10.1148/radiol.212170. Accessed 24 Mar 2022.
    1. Elicker BM. What are the long-term pulmonary sequelae of COVID-19 infection? Radiology. 2022. 10.1148/radiol.220449. Accessed 24 Mar 2022.
    1. Bitirgen G, Korkmaz C, Zamani A, Ozkagnici A, Zengin N, et al. Corneal confocal microscopy identifies corneal nerve fibre loss and increased dendritic cells in patients with long COVID. Br J Ophthalmol. 2021; 0:1–7. 10.1136/bjophthalmol-2021-319450. , Accessed 4 Dec 2021.
    1. Karolinska Institutet. Elevated inflammation persists in immune cells months after mild COVID-19. ScienceDaily. 2022. , Accessed 24 Mar 2022.
    1. Bohnacker S, Hartung F, Henkel F, Quaranta A, Kolmert J, et al. Mild COVID-19 imprints a long-term inflammatory eicosanoid- and chemokine memory in monocyte-derived macrophages. Mucosal Immunol. 2022. 10.1038/s41385-021-00482-8. . Accessed 24 Mar 2022.
    1. Fernández-Castañeda A, Lu P, Geraghty AC, Song E, Lee MH, et al. Mild respiratory SARS-CoV-2 infection can cause multi-lineage cellular dysregulation and myelin loss in the brain. bioRxiv. 2022: 2022.01.07.475453. Doi: 10.1101/2022.01.07.475453. . Accessed 24 Mar 2022.
    1. Stephenson T, Pereira SP, Shafran R, De Stavola B, Rojas N, et al. Long COVID - the physical and mental health of children and non-hospitalised young people 3 months after SARS-CoV-2 infection; a national matched cohort study (The CLoCk) Study. Research Square. 2021. 10.21203/-798316/v1. . Accessed 6 Dec 2021.
    1. Martelletti P, Bentivegna E, Spuntarelli V, Luciani M. Long-COVID headache. SN Compr Clin Med. 2021; 3: 1704-1706. 10.1007/s42399-021-00964-7. . Accessed 11 Dec 2021.
    1. Hu K, PAtel J, Swiston C, Patel BC. Ophthalmic manifestations of coronavirus (COVID-19). StatPearls. 2022. . Accessed 24 Mar 2022.
    1. Zhou L, Xu Z, Castiglione GM, Soiberman US, Eberhart CG, et al. ACE2, and TMPRSS2 are expressed on the human ocular surface, suggesting susceptibility to SARS-CoV-2 infection. bioRxiv. 2020: 2020.05.09.086165. 10.1101/2020.05.09.086165. . Accessed 24 Mar 2022.
    1. Yordi S, Ehlers JP. COVID-19 and the eye. Cleve Clin J Med 2020. 10.3949/ccjm.87a.ccc068. . Accessed 24 Mar 2022.
    1. Chan L, Chaudhary K, Saha A, Chauhan K, Vaid A, et al. AKI in hospitalized patients with COVID-19. J Am Soc Nephrol. 2021; 32(1): 151-160. 10.1681/ASN.2020050615. . Accessed 6 Dec 2021.
    1. Bowe B, Xie Y, Xu E, Al-Aly Z. Kidney outcomes in long COVID. JASN. 2021; 32(11): 2851-2862. 10.1681/ASN.2021060734. . Accessed 11 Dec 2021.
    1. Akter F, Mannan A, Mehedi HMH, Rob A, Ahmed S, et al. Clinical characteristics and short-term outcomes after recovery from COVID-19 in patients with and without diabetes in Bangladesh. Diabetes Metab Syndr. 2020; 14(6): 2031-2038. 10.1016/j.dsx.2020.10.016. . Accessed 7 Dec 2021.
    1. Pennington Biomedical Research Center. Exercise may treat long COVID-induced diabetes, depression. ScienceDaily. 2022. <. Accessed 24 Mar 2022.
    1. Fogarty H, Townsend L, Morrin H, Ahmad A, Comerford C, et al. Persistent endotheliopathy in the pathogenesis of long COVID syndrome. J Thromb Haemost. 2021; 19:2546–2553. 10.1111/jth.15490. . Accessed 5 Dec 2021.
    1. Genovese G, Moltrasio C, Berti E, Marzano AV. Skin manifestations associated with COVID-19: current knowledge and future perspectives. Dermatology. 2021; 237(1): 1-12. 10.1159/000512932. . Accessed 24 Mar 2022.
    1. Jamshidi P, Hajikhani B, Mirsaeidi M, Vahidnezhad H, Dadashi M, et al. Skin manifestations in COVID-19 patients: are they indicators for disease severity? A systematic review. Front. Med. 2021; 8: 634208. 10.3389/fmed.2021.634208. . Accessed 24 Mar 2022.
    1. Andina D, Belloni-Fortina A, Bodemer C, Bonifazi E, Chiriac A, et al. Skin manifestations of COVID-19 in children: part 3. Clin Exp Dermatol. 2021; 46(3): 462-472. 10.1111/ced.14483. , Accessed 24 Mar 2022.
    1. Walton GE, Gibson GR, Hunter KA. Mechanisms linking the human gut microbiome to prophylactic and treatment strategies for COVID-19. Br J Nutr. 2021; 126(2): 219-227. 10.1017/S0007114520003980. . Accessed 20 Mar 2022.
    1. Yamamoto S, Saito M, Tamura A, Prawisuda D, Mizutani T, et. al. The human microbiome and COVID-19: a systematic review. PLoS ONE. 2021. 10.1371/journal.pone.0253293. . Accessed 20 Mar 2022.
    1. Karaarslan F, Güneri FD, Kardeş S. Long COVID: rheumatologic/musculoskeletal symptoms in hospitalized COVID-19 survivors at 3 and 6 months. Clin Rheumatol. 2021 29: 1–8. 10.1007/s10067-021-05942-x. . Accessed 7 Dec 2021.
    1. Ursini F, Ruscitti P, Raimondo V, DeAngelis R, Cacciapaglia F, et al. Spectrum of short-term inflammatory musculoskeletal manifestations after COVID-19 vaccine administration: a report of 66 cases. Ann Rheum Dis. 2022; 81: 440-441. 10.1136/annrheumdis-2021-221587. . Accessed 24 Mar 2022.
    1. Ahmed H, Patel K, Greenwood DC, Halpin S, Lewthwaite P, et al. Long-term clinical outcomes in survivors of severe acute respiratory syndrome and Middle East respiratory syndrome coronavirus outbreaks after hospitalisation or ICU admission: a systematic review and meta-analysis. J Rehabil Med. 2020; 52(5). 10.2340/16501977-2694. . Accessed 10 Dec 2021.
    1. Halpin SJ, McIvor C, Whyatt G, Adams A, Harvey O et al. Postdischarge symptoms and rehabilitation needs in survivors of COVID-19 infection: a cross-sectional evaluation. J Med Virol. 2020. 10.1002/jmv.26368. . Accessed 10 Dec 2021.
    1. Abdelrahman Z, Li M, Wang X. Comparative review of SARS-CoV-2, SARS-CoV, MERS-CoV, and influenza A respiratory viruses. Front Immunol 2020. 10.3389/fimmu.2020.552909. Accessed 10 Dec 2021.
    1. Jacobs LG, Paleoudis EG, Lesky-Di Bari D, Nyirenda T, Friedman T, et al. Persistence of symptoms and quality of life at 35 days after hospitalization for COVID-19 infection. PLoS ONE. 2020; 15(12): e0243882. 10.1371/journal.pone.0243882. . Accessed 11 Dec 2021.
    1. Vanichkachorn G, Newcomb R, Cowl CT, Murad MH, Breeher L, et al. Post–COVID-19 syndrome (long haul syndrome): description of a multidisciplinary clinic at Mayo Clinic and characteristics of the initial patient cohort. Mayo Clin Proc. 2021; 96(7): 1782-1791. . Accessed 10 Dec 2021.
    1. Callard F, Perego E. How and why patients made long COVID. Soc Sci Med. 2021; 268: 113426. 10.1016/j.socscimed.2020.113426. . Accessed 10 Dec 2021.
    1. Bloomberg B, Cox RJ, Langeland. Long COVID: a growing problem in need of intervention. Cell Rep Med. 2022; 3(3): 100552. 10.1016/j.xcrm.2022.100552. . Accessed 24 Mar 2022.
    1. Faria NR, Mellan TA, Whittaker C, Claro IM, Candido DDS, Mishra S, et al. Genomics and epidemiology of a novel SARS-CoV-2 lineage in Manaus, Brazil. medRxiv. 2021. 10.1101/2021.02.26.21252554. . Accessed 24 Mar 2022.
    1. Kang M, Xin H, Yuan J, Ali ST, Liang Z, et al. Transmission dynamics and epidemiological characteristics of Delta variant infections in China. medRxiv. 2021. 10.1101/2021.08.12.21261991. . Accessed 11 Dec 2021.
    1. Sudre CH, Murray B, Varsavsky T, Graham MS, Penfold RS. Attributes and predictors of long COVID. Nat Med. 2021; 27: 626-631. 10.1038/s41591-021-01292-y. . Accessed 11 Dec 2021.
    1. Bell ML, Catalfamo CJ, Farland LV, Ernst KC, Jacobs ET. Post-acute sequelae of COVID-19 in a non-hospitalized cohort: results from the Arizona CoVHORT. PLoS ONE. 2021. 10.1371/journal.pone.0254347. . Accessed 11 Dec 2021.
    1. Groff D, Sun A, Ssentongo AE, Ba DM, Parsons N, et al. Short-term and long-term rates of postacute sequelae of SARS-CoV-2 infection: a systematic review. JAMA Netw Open. 2021; 4(10): e2128568. 10.1001/jamanetworkopen.2021.28568. . Accessed 11 Dec 2021.
    1. Radtke T, Ulyte A, Puhan MA, Kriemler S. Long-term symptoms after SARS-CoV-2 infection in children and adolescents. JAMA. 2021; 326(9): 869-871. 10.1001/jama.2021.11880. . Accessed 11 Dec 2021.
    1. Molteni E, Sudre CH, Canas LS, Bhopal SS, Hughes RC, et al. Illness duration and symptom profile in symptomatic UK school-aged children tested for SARS-CoV-2. Lancet Child Adolesc Health. 2021; 5: 708-718. 10.1016/S2352-4642(21)00198-X. . Accessed 11 Dec 2021.
    1. Sanyaolu A, Okorie C, Desai P, Prakash S, Patidar R, et al. A review of multisystem inflammatory syndrome cases in coronavirus disease-19 infection. Asclepius Med Case Rep. 2020; 3(1): 1-4. . Accessed 27 Jan 2022.
    1. Hoste L, Van Paemel R, Haerynck F. Multisystem inflammatory syndrome in children related to COVID-19: a systematic review. Eur J Pediatr. 2021; 180(7): 2019-2034. 10.1007/s00431-021-03993-5. . Accessed 24 Mar 2022.
    1. Feldstein LR, Rose EB, Horwitz SM, Collins JP, Newhams MM, et al. Multisystem inflammatory syndrome in U.S. children and adolescents. N Engl J Med. 2020; 383(4): 334-346. 10.1056/NEJMoa2021680. . Accessed 24 Mar 2022.
    1. Higgins V, Sohaei D, Diamandis EP, Prassas I. COVID-19: from an acute to chronic disease? Potential long-term health consequences. Critical Reviews in Clinical Laboratory Science. 2020: 297-310. 10.1080/10408363.2020.1860895. . Accessed 10 Dec 2021.
    1. ZOE COVID Study. How long does COVID-19 last? ZOE. 2021. . Accessed 11 Dec 2021.
    1. Ibrahim AG, Ciullo A, Li C, Garcia G, Peck K, et al. Engineered extracellular vesicles antagonize SARS-CoV-2 infection by inhibiting mTOR signaling. Biomater Biosyst. 2022; 6: 100042. 10.1016/j.bbiosy.2022.100042. . Accessed 24 Mar 2022.
    1. McElvaney OJ, McEvoy NL, Boland F, McElvaney OF, Hogan G, et al. A randomized, double-blind, placebo-controlled trial of intravenous alpha-1 antitrypsin for acute respiratory distress syndrome secondary to COVID-19. Med (New York, N.Y.). 2022 10.1016/j.medj.2022.03.001. . Accessed 24 Mar 2022.
    1. RCSI. Clinical trial reveals new treatment option for COVID-19. ScienceDaily. 2022. . Accessed 24 Mar 2022.
    1. Barnes GD, Burnett A, Allen A, Blumenstein M, Clark NP, et al. Thromboembolism and anticoagulant therapy during the COVID-19 pandemic: interim clinical guidance from the anticoagulation forum. J Thromb Thrombolysis. 2020; 50: 72-81. . Accessed 11 Dec 2021.
    1. Raj SR, Black BK, Biaggioni I, Paranjape SY, Ramirez M, et al. Propranolol decreases tachycardia and improves symptoms in the postural tachycardia syndrome: less is more. Circulation. 2009; 120(9): 725-734. 10.1161/circulationaha.108.846501. . Accessed 11 Dec 2021.
    1. Di Toro A, Bozzani A, Tavazzi G, Urtis M, Giuliani L, et al. Long COVID-19: Long-term effects? Eur Heart J Suppl. 2021; 23(E): 1-5. 10.1093/eurheart/suab080. . Accessed 11 Dec 2021.

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться