Post-COVID-19 fatigue among COVID-19 in patients discharged from hospital: A meta-analysis.

Dear Editor,

In this Journal, Xiaoyu Fang et al. reported post-discharge persistent symptoms and health-related quality of life after hospitalization for COVID-19, suggesting that we should pay more attention to patients' symptoms after discharge. We had a valuable opportunity to carefully read this interesting manuscript and additional published studies.

We found that a number of published studies explored the symptoms of patients with COVID-19 after discharge. Xiong et al. found that most discharged patients had symptoms of fatigue. Chaolin Huang reported 6-month consequences of COVID-19 in patients discharged from the hospital; 76% of patients (1265 of 1655) reported at least one symptom at follow-up.

It was found that physical, cognitive, and psychological impairments persisted for multiple years in many cases. As COVID-19 research progresses, it has become increasingly apparent that a high proportion of patients experience persistent symptoms, such as fatigue. A unified taxonomy for fatigue in neurological disorders to define fatigue objectively, which, in our opinion, can be used as a template for post-COVID-19 fatigue. We define post-COVID-19 fatigue as the decrease in physical and/or mental performance that results from the changes in central, psychological, and/or peripheral factors due to COVID-19, such as fatigue, anxiety, dyspnea, sleep difficulties, hair loss, smell disorder, decreased appetite, joint pain, and so forth.

PubMed, Web of Science, Embase, and Cochrane Library databases were extensively searched for all compliant studies published from January 1, 2020, to December 25, 2021. The search strategy used the following keywords: “COVID-19,” “2019-nCoV,” “SARS-CoV-2,” “2019 novel coronavirus,” “coronavirus disease 2019,” “severe acute respiratory syndrome coronavirus 2,” “Post-COVID-19,” “Fatigue,” and “persistent symptoms.” The reference lists of included studies and relevant reviews were searched for additional studies. The inclusion criteria were as follows: (1) adult patients with COVID-19 confirmed by reverse transcriptase–polymerase chain reaction; (2) peer-reviewed original studies in English; (3) individual study populations with at least 15 cases; and (4) key available data of the included studies, four-table data, or effect [95% confidence interval (CI)] clearly stated. Case reports, repeated articles, review papers, and preprints were eliminated. After searching PubMed and other websites, six eligible studies encompassing 3976 patients with COVID-19 were included in our meta-analysis. Six studies reported persistent symptoms of patients with COVID-19 discharged from the hospital. The general information of included studies is summarized in Table 1 . , , , , , We focused on several of the most common symptoms after discharge, such as fatigue, anxiety, and dyspnea.

Table 1

The basic information of the included literature. Total: number of patient included in the study; Any one of them: Any of fatigue,anxiety,Dyspnea,sleep difficulties,hair loss,smell disorder ,decreased appetite,joint pain etc.; N: no data.

Author	Year	Total	Any one of them(n)	Fatigue (n)	Anxiety (n)	Dyspnea (n)
Xiaoyu Fang[1]	2021	1233	630	400	141	44
Qiutang Xiong[2]	2021	538	267	152	35	140
Chaolin Huang[3]	2020	1655	1265	1038	367	N
Angelo Carfì[5]	2020	143	125	76	N	62
Eve Garrigues[6]	2020	120	N	66	N	50
Marwa Tolba[7]	2020	287	256	209	109	81

The results of six studies listed in Fig. 1 showed fatigue in 51% of patients (95% CI, 0.35–0.66; P < 0.01). The anxiety rate in four other was 19% (95% CI, 0.10–0.28; P < 0.01), and the dyspnea rate in five studies was 28% (95% CI, 0.12–0.45) during the follow-up (P < 0.01). It indicated that, out of every 100 patients, 51 experienced fatigue for any reason after discharge, 19 felt anxiety after discharge, and 28 had difficulty breathing after discharge. This suggested that these symptoms might indeed be the sequelae of recovery for COVID-19 survivors.

Fig. 1

Forest plot of fatigue,anxiety and dyspnea rates of among COVID-19 in patients discharged from hospital. ES: fatigue,anxiety and dyspnea rates.

The reasons for fatigue may be as follows. The central factors contributing to COVID-19 fatigue include neurotransmitter levels, inflammation, and so forth. Some negative psychological factors included stress, anxiety, depression, and anger. When these are taken together, it is presumed that they may be a significant contributor to fatigue. Also, some studies suggest that COVID-19 may directly impact skeletal muscle, hence contributing to fatigue.

We found that most patients after discharge from the hospital had at least one of the aforementioned related symptoms. After acute infection, COVID-19 survivors mainly suffered from fatigue or muscle weakness, and anxiety or dyspnea. Similar to Rudroff and colleagues[4], we should regard fatigue as a decline in physical or mental performance rather than just focusing on one of them. Further, the increase in age is related to the increase in the severity of the disease course, and the severity of the disease is related to patients' symptoms after discharge. New variants of coronavirus may have a different profile of fatigue, which warrants further investigation. Fatigue, along with other symptoms, may also affect the ability to function and work. Our aim is to advise medical staff to better understand the long-term prognosis of patients with COVID-19 after discharge so as to prevent various complications, including physical and mental fatigue. Many comorbidities such as cardiovascular disease, hypertension, diabetes, chronic kidney disease, chronic obstructive pulmonary disease, and cancer, present with fatigue as a common symptom, The health status of these patients with underlying diseases after discharge from the hospital deserves our attention because it is difficult for us to identify the causes of fatigue. Therefore, after the acute infection is relieved, we should pay attention to fatigue among patients after discharge from the hospital.

Fundings

This study was supported by Hangzhou Science and Technology Bureau fund (No. 20191203B96;No. 20191203B105); Youth Fund of Zhejiang Academy of Medical Sciences (No. 2019Y009);Medical and Technology Project of Zhejiang Province (No. 2,020,362,651, No. 2021KY890); Clinical Research Fund of Zhejiang Medical Association (No. 2020ZYC-A13); Hangzhou Health and Family Planning Technology Plan Key Projects (No.2017ZD02); Zhejiang Medical and Health Science and Technology Plan Project(No.2019RC245); Hangzhou Agricultural and Social Development Research Active Design Project (No.20190101A03). Zhejiang Traditional Chinese Medicine Scientific Research Fund Project(No.2022ZB280).The funders have no role in the data collection, data analysis, preparation of manuscript and decision to submission.

Declaration of Competing Interest

The authors declare no conflict of interest