Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 
Print this page Email this page Users Online: 1474

  Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 15  |  Issue : 8  |  Page : 181-186  

An evaluation of persistence of postdischarge symptoms in survivors of COVID-19 infection


1 Principal Medical Officer, Dockyard Dispensary, Naval Dockyard, Fort, Mumbai, India
2 Department of Community Medicine, AFMC, Pune, Maharashtra, India

Date of Submission05-Sep-2021
Date of Decision14-Dec-2021
Date of Acceptance14-Dec-2021
Date of Web Publication11-Mar-2022

Correspondence Address:
Dr. Saurabh Bobdey
Department of Community Medicine, AFMC, Pune, Maharashtra
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mjdrdypu.mjdrdypu_729_21

Rights and Permissions
  Abstract 


Background: The COVID-19 pandemic has affected almost 100 million people worldwide. Although the disease spectrum has still not been fully understood, there have been the reports of the persistence of symptoms well beyond the acute stage or after discharge from the hospital. Therefore, there is a need to document the persistence of symptoms to identify and provide physical as well as psychosocial support for ensuring the complete recovery of COVID-19 survivors. The present study examines the postacute stage persistence of symptoms in severe acute respiratory syndrome-coronavirus-2 patients. Materials and Methods: A longitudinal follow-up study was conducted on 1170 patients discharged from COVID hospital. All the study participants were contacted after discharge and at 7-day intervals for 42 days, and details of the persistence of symptoms were sought from them. Results: It was found that 43.8% of patients had persistence of symptoms, and 12.4% had symptoms even after 30 days of discharge from the hospital. Among symptoms, the most common persisting symptom was found to be fatigue (26%) followed by respiratory difficulty. The presence of comorbidity (odds ratio 1.61, 95% confidence interval 1.56–2.25, P < 0.01) and moderate/severe disease were found to be independent risk factors for the persistence of COVID-related symptoms. Conclusion: The findings of the study indicate that a large number of COVID-19 survivors continue to suffer from COVID-19 symptoms well after the recovery from the acute stage (discharge from hospital). Therefore, there is a genuine need for instituting measures for the monitoring of patients postdischarge and if required providing treatment to those having persistent symptoms of COVID-19.

Keywords: Chronic COVID, long COVID, persistence of symptoms, postacute COVID


How to cite this article:
Mookkiah I, Kaur M, Yadav AK, Bobdey S, Teli P, Faujdar DS, Bhaskar S V, Adhya S, Kaushik S K. An evaluation of persistence of postdischarge symptoms in survivors of COVID-19 infection. Med J DY Patil Vidyapeeth 2022;15, Suppl S2:181-6

How to cite this URL:
Mookkiah I, Kaur M, Yadav AK, Bobdey S, Teli P, Faujdar DS, Bhaskar S V, Adhya S, Kaushik S K. An evaluation of persistence of postdischarge symptoms in survivors of COVID-19 infection. Med J DY Patil Vidyapeeth [serial online] 2022 [cited 2023 Jan 31];15, Suppl S2:181-6. Available from: https://www.mjdrdypv.org/text.asp?2022/15/8/181/339391




  Introduction Top


In the recent past, millions of people globally have been affected by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. Globally, by the end of 2020, SARS-CoV-2 had affected more than 8 million people and had claimed 1.8 million lives.[1] Despite the vast numbers of individuals who have suffered from COVID-19, the course of the disease, including the complete spectrum of clinical presentation, the persistence of signs and symptoms, and the impact on general well-being, have not been fully understood and described. Numerous symptoms such as fatigue, fever, headache, sore throat, cough, dyspnea, nausea, vomiting, diarrhea, and loss of taste/smell have been reported by the individuals affected by COVID-19 infection.[2],[3] However, unlike other common viral infections, there have been the reports of patients still complaining of persistence of symptoms beyond weeks after onset or discharge from hospitals/COVID care centers. One of the earliest reports found that almost 87% of patients who had recovered from COVID-19 had at least one symptom, whereas 32% had one or two symptoms and 55% had three or more persistent symptoms.[4]

Some researchers have reported “Long COVID” as the term used by patients to describe diverse symptoms of COVID-19 that persist well beyond the acute illness.[5] Formal definitions of “post-acute” (symptoms beyond 3 − 4 weeks) and “chronic” (symptoms beyond 12 weeks) COVID-19 are yet to be established.[6],[7] Nonetheless, notwithstanding the lack of formal coinage of a term/definition, the persistence of symptoms of COVID-19 well beyond the acute stage has been reported widely and required to be accepted as a clinical entity. Therefore, to understand this novel disease in totality, there is a need to widen the focus beyond mortality and establish surveillance mechanisms for the identification of persistent symptoms and long-term effects on general health, well-being, and physical function of COVID-19 survivors. With this background, the present study was conducted to examine the postacute persistence of symptoms in SARS-CoV-2 patients after discharge from the hospital.


  Materials and Methods Top


The present study was a follow-up longitudinal study conducted on 1170 patients discharged from COVID hospital between August 01, 2020 and October 31, 2020. All patients meeting the inclusion criteria, i.e., aged 18 years or older; diagnosis of viral Real-Time Reverse Transcription – Polymerase Chain Reaction (RT-PCR)-confirmed COVID-19 infection; and history of hospitalization were enrolled in the study. The COVID hospital followed the discharge policy recommended by ICMR, i.e., mild cases were discharged after 10 days of symptom onset, moderate cases were discharged after 10 days of symptom onset in case of absence of fever without antipyretics, resolution of breathlessness, and no oxygen requirement, and severe cases were discharged on clinical recovery and after one negative test by RT-PCR (after resolution of symptoms). Individuals who had expired during or after hospitalization, patients who could not comprehend Hindi/English and documented the cases of dementia or delirium who could not comprehend and provide consent were excluded from the study. All the eligible participants were contacted after 07 days of discharge and thereafter every 07 days up to 42 days. All the participants were explained the details of the study, and consent was collected verbally at the beginning of the interview. Participants were assured that all the data would be de-identified and stored and handled anonymously. The study had the approval of the Institutional Ethical Committee vide IEC letter no. IEC/2020 dated July 22, 20.

Data collection

The instrument used in the study contained a two-part questionnaire. Part one of the questionnaire comprised demographic data, clinical history (date of the test, date of admission, the number of days of hospitalization, and the requirement of oxygen), and comorbidity was recorded using a self-report version of the Charlson Comorbidity Index.[8] Part two of the questionnaire was clinical symptoms at the time of onset and thereafter at various stages of telephonic follow-up. Symptoms during the onset and at the time of the survey were assessed using a checklist of self-reported symptoms, largely adopted from the WHO/ISARIC platform.[9]

Statistical analysis

All the collected data were entered in an Excel spreadsheet, and these data were cross-checked with the physical data for any discrepancy. All the data were analyzed using the Statistical Package for the Social Sciences (SPSS) 19.0 statistical package (Chicago, IL, USA), and a two-sided P < 0.05 was considered statistically significant. The categorical variables are presented as frequency rates and percentages, and continuous variables are described using mean ± standard deviation values. Data analysis was performed using the descriptive and inferential statistics (Chi-square and binary logistic regression).


  Results Top


In the present study, 1170 patients were contacted telephonically. Six respondents were excluded due to underage, eight respondents were excluded due to inability to comprehend Hindi or English, and 258 individuals did not pick up the call or the number was not reachable on multiple occasions. Finally, the data of 898 respondents were used for further analyses.

Demographic and other baseline features of the study population are depicted in [Table 1]. The mean age of the study population (n = 898) was 41.49 (±14.90) years, and 76.2% of respondents were males. About 29.1% of the individuals had preexisting comorbidity. About 9.2% of individuals had multiple comorbidities, and the most common comorbidity was hypertension (9.4%). About 81.8% (735) cases were classified as mild, 11.6% (104) as moderate, and 6.6% (59) as severe COVID-19. One hundred and sixty-three (18.2%) of study participants were provided with some form of oxygen support.
Table 1: Patient characteristics

Click here to view


During the follow-up, patients were contacted after 07 days of discharge and thereafter every 07 days up to 42 days. At the time of the evaluation, 505 (56.2%) were completely free of any COVID-19-related symptoms, whereas 393 (43.8%) patients had persistence of symptoms and 111 (12.4%) had symptoms even after 30 days from discharge. Fatigue (26%) was the most common persisting symptom, followed by respiratory difficulty (8.70%), cough (4.8%), and bodyache (3.2%). [Figure 1] shows the percentages of patients presenting with specific coronavirus disease-2019 (COVID-19)-related symptoms during the time of onset/hospitalization of the disease (left) and at the time of the follow-up visit (right). The distribution of persistence of symptoms as per the clinical severity (mild/moderate/severe) is provided in [Table 2].
Figure 1: Persistence of COVID symptoms

Click here to view
Table 2: Persistence of symptoms as per clinical severity (mild/moderate/severe)

Click here to view


To further identify the factors associated with the persistence of symptoms, factors variables such as age, sex, comorbidity, and clinical severity of the disease were considered in univariate analysis. Age, presence of comorbidity, and clinical severity of the disease during the acute phase were found to be significant (P < 0.05) risk factors for persistence of symptoms and were subsequently included in multivariate analysis. On multivariate analysis, the presence of comorbidity (odds ratio 1.61, 95% confidence interval 1.56–2.25 P < 0.01) and moderate/severe COVID-19 disease were found to be independently associated with persistence of COVID-related symptoms [Table 3].
Table 3: Factors influencing persistence of symptoms of coronavirus disease

Click here to view



  Discussion Top


The present study reports the persistence of symptoms after discharge from the hospital in a sizeable number of confirmed COVID patients. We found that 43.8% of patients after discharge still complained of persistence of symptoms of which fatigue and difficulty in breathing were the most common symptoms. The findings are in line with Carfi et al. who also found persistence of fatigue and dyspnea 60 days after the onset of the first COVID-19 symptom.[4] Similarly, Goertz et al. in their study of 2159 hospitalized and nonhospitalized patients found that fatigue and dyspnea were the two most prevalent persistent symptoms in COVID patients.[10] The findings of the present study are also in accordance with abundant published literature of many physical and psychological sequelae observed in viral infections and particularly in SARS.[11],[12],[13] In our study, we found that individuals with comorbidities and clinically severe COVID-19 infection were more likely to experience persistence of symptoms. Similar association of persistent symptoms with comorbidities and symptom load during the acute phase of COVID-19 has been reported by many studies, and published literature indicates that persistent symptoms are more common in people with conditions such as asthma, diabetes, hypertension, etc., those having COVID infection meriting hospitalization.[4],[10],[14],[15],[16] The exact mechanism of these largely variable persistent symptoms is unknown. It may be due to different etiologies and more than one mechanism even in the same patient. It is suggested that persistent symptoms may be due to direct viral damage, immune response damage, or opportunistic bacterial infections.[17],[18] Further, mental health issues and posttraumatic symptoms might interact with physiological symptoms in complex ways leading to further worsening/prolongation of symptoms.[19],[20]

The variety of symptoms that persist after recovery from the acute stage of COVID-19 is known as “Long COVID,” “Post-acute COVID,” or “Chronic COVID.”[21],[22],[23] Thus, “Long COVID” is an illness in which patients who have recovered from COVID-19 continue to have symptoms for longer than normally expected postdischarge from the hospital. The National Institute for Health and Care Excellence, in collaboration with the Scottish Intercollegiate Guidelines Network and the Royal College of General Practitioners, has proposed the following definition for post-COVID-19 syndrome: “signs and symptoms that develop during or after an infection consistent with COVID-19, continue for more than 12 weeks and are not explained by an alternative diagnosis.”[24] In addition, other studies have also attempted to classify post-COVID patients according to the severity of the symptoms and end-organ damage.[25] As evidence and clinical experience in this timeframe accumulate, multiorgan sequelae of COVID-19 outside the acute period of infection and chronicity of symptoms are gradually being recognized as a significant clinical entity. Therefore, it is important to formalize appropriate nomenclature for the persistence of COVID symptoms postacute stage and be ratified by global health organizations. The recognition of post-COVID as an important clinical entity would aid current and future clinical trials, as well as regular reviews of existing evidence by working groups and task forces, both of which are critical in building up a comprehensive information database to better understand COVID-19's natural history and pathophysiology.[26]

In a time when the world, especially India, is grappling with active cases of COVID-19, our research highlights the persistence of COVID symptoms after the acute stage has passed. However, there are some limitations to our analysis that should be acknowledged, the first of which is the relatively short period of follow-up of 06 weeks after recovery from the acute stage, as recent publications indicate that post-COVID syndrome is described as the continuation of symptoms beyond 12 weeks after the onset of acute symptoms. This can be explained by the fact that there were no recommendations for post-COVID syndrome when the research was conceived and conducted, as COVID-19 was thought to be more of an acute disease, and there was limited literature on the chronicity of symptoms. Our research is interesting in that it presents follow-up of a large number of patients and brings to light the clinical entity of persistence of COVID symptoms at a time when the majority of the medical fraternity is focused on treating the acute phase of the disease. Second, the research falls short of providing a biochemical/hematological link with the persistence of symptoms since only basic demographic and testing data were available.

A systematic review for the assessment of the frequency and variety of persistent symptoms among patients with COVID-19 published by Nasserie et al. have shown that as much as 72% of COVID patients experienced at least one persistent symptom.[27] Thus, our study and numerous other studies across the globe have shown that a large proportion of COVID survivors experience persistence of COVID symptoms postrecovery, these patients may be classified as “Long COVID,” “Post-acute COVID” or “Chronic COVID”, based on criteria's provided by different national and international bodies, but the crux of the matter is that it is of paramount importance to understand the health-care issues of recovered COVID patients and develop comprehensive multidisciplinary management program to cater for health-care needs of the COVID survivors. Therefore, it is imperative for our health-care system to establish dedicated clinics where follow-up care should be a priority, especially for those at high risk of post-COVID sequale.


  Conclusion Top


The present study illustrates the burden of persistent symptoms in a large number of COVID patients. It urges the clinicians and researchers to expand the focus beyond the acute phase of COVID-19 and continue monitoring the patients after discharge for long-term effects of COVID-19. Given the high prevalence of persistent symptoms, the study also highlights that there is a need for a multidisciplinary approach for further research in the identification and management of persistent physical, emotional, and cognitive symptoms in COVID-19 survivors.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Johns Hopkins University & Medicine. Coronavirus Resource Center. Available from: https://coronavirus.jhu.edu/. [Last accessed on 2020 Sep 16].  Back to cited text no. 1
    
2.
Li LQ, Huang T, Wang YQ, Wang ZP, Liang Y, Huang TB, et al. COVID-19 patients' clinical characteristics, discharge rate, and fatality rate of meta-analysis. J Med Virol 2020;92:577-83.  Back to cited text no. 2
    
3.
Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;382:1708-20.  Back to cited text no. 3
    
4.
Carfì A, Bernabei R, Landi F, Gemelli Against COVID-19 Post-Acute Care Study Group. Persistent symptoms in patients after acute COVID-19. JAMA 2020;324:603-5.  Back to cited text no. 4
    
5.
Perego E, Callard F, Stras L, Melville-Jóhannesson B, Pope R, Alwan N. Why the patient-made term 'long covid' is needed [Version 1; peer review: Awaiting peer review]. Wellcome Open Res 2020;5:224.  Back to cited text no. 5
    
6.
Greenhalgh T, Knight M, A'Court C, Buxton M, Husain L. Management of post-acute covid-19 in primary care. BMJ 2020;370:m3026.  Back to cited text no. 6
    
7.
COVID Symptom Study. How Long Does COVID-19 Last? (Blog). London: Kings College London; 2020. Available from: https://covid.joinzoe.com/post/covid-long-term. [Last accessed on 2020 Aug 24].  Back to cited text no. 7
    
8.
Katz JN, Chang LC, Sangha O, Fossel AH, Bates DW. Can comorbidity be measured by questionnaire rather than medical record review? Med Care 1996;34:73-84.  Back to cited text no. 8
    
9.
Docherty AB, Harrison EM, Green CA, Hardwick HE, Pius R, Norman L, et al. Features of 20 133 UK patients in hospital with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol: Prospective observational cohort study. BMJ 2020;369:m1985.  Back to cited text no. 9
    
10.
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;6:00542-2020. doi: 10.1183/23120541.00542-2020.  Back to cited text no. 10
    
11.
Lam MH, Wing YK, Yu MW, Leung CM, Ma RC, Kong AP, et al. Mental morbidities and chronic fatigue in severe acute respiratory syndrome survivors: Long-term follow-up. Arch Intern Med 2009;169:2142-7.  Back to cited text no. 11
    
12.
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;11:37.  Back to cited text no. 12
    
13.
Schanke AK, Stanghelle JK. Fatigue in polio survivors. Spinal Cord 2001;39:243-51.  Back to cited text no. 13
    
14.
Halpin SJ, McIvor C, Whyatt G, Adams A, Harvey O, McLean L, et al. Postdischarge symptoms and rehabilitation needs in survivors of COVID-19 infection: A cross-sectional evaluation. J Med Virol 2021;93:1013-22.  Back to cited text no. 14
    
15.
Tenforde MW, Kim SS, Lindsell CJ, Rose EB, 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;69:993-8.  Back to cited text no. 15
    
16.
Arnold DT, Hamilton FW, Milne A, Morley AJ, Viner J, Attwood M, et al. Patient outcomes after hospitalisation with COVID-19 and implications for follow-up: Results from a prospective UK cohort. Thorax 2021;76:399-401.  Back to cited text no. 16
    
17.
British Society for Immunology: Long-Term Immunological Health Consequences of COVID-19. British Society for Immunology; 2020. Available from: https://www.immunology.org/sites/default/files/BSI_Briefing_Note_August_2020_FINAL.pdf. [Last accessed on 2020 Aug 24].  Back to cited text no. 17
    
18.
Topol EJ, Verghese A, Iwasaki A. COVID Immune Responses Explained. Medscape; 2020. Available from: https://www.medscape.com/viewarticle/93362. [Last accessed on 2020 Aug 23].  Back to cited text no. 18
    
19.
Mazza MG, De Lorenzo R, Conte C, Poletti S, Vai B, Bollettini I, et al. Anxiety and depression in COVID-19 survivors: Role of inflammatory and clinical predictors. Brain Behav Immun 2020;89:594-600.  Back to cited text no. 19
    
20.
Troyer EA, Kohn JN, Hong S. Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms. Brain Behav Immun 2020;87:34-9.  Back to cited text no. 20
    
21.
Mahase E. Long covid could be four different syndromes, review suggests. BMJ 2020;371:m3981.  Back to cited text no. 21
    
22.
Raveendran AV. Long COVID-19: Challenges in the diagnosis and proposed diagnostic criteria. Diabetes Metab Syndr 2021;15:145-6.  Back to cited text no. 22
    
23.
Baig AM. Chronic COVID syndrome: Need for an appropriate medical terminology for long-COVID and COVID long-haulers. J Med Virol 2021;93:2555-6. doi: 10.1002/jmv.26624.  Back to cited text no. 23
    
24.
Venkatesan P. NICE guideline on long COVID. Lancet Respir Med 2021;9:129.  Back to cited text no. 24
    
25.
Al-Jahdhami I, Al-Naamani K, Al-Mawali A. The post-acute COVID-19 syndrome (Long COVID). Oman Med J 2021;36:e220.  Back to cited text no. 25
    
26.
Nalbandian A, Sehgal K, Gupta A, Madhavan MV, McGroder C, Stevens JS, et al. Post-acute COVID-19 syndrome. Nat Med 2021;27:601-15.  Back to cited text no. 26
    
27.
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:e2111417.  Back to cited text no. 27
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

Top
   
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
   Abstract
  Introduction
   Materials and Me...
  Results
  Discussion
  Conclusion
   References
   Article Figures
   Article Tables

 Article Access Statistics
    Viewed847    
    Printed29    
    Emailed0    
    PDF Downloaded46    
    Comments [Add]    

Recommend this journal