- - In our previous OE Original (COVID-19: Long-Lasting Health Effects Among Survivors), we found consistent evidence showing that COVID-19 survivors recovered within 6 months had been suffering significant negative impacts of COVID-19.
- - In the present OE Original, we further examine evidence from studies reporting sequelae over 6 months after recovery from COVID-19.
- Improvements were observed among COVID-19 survivors over time, but some COVID-19 survivors are still being negatively affected by the disease 12 months after symptom onset or discharge from hospitalization, such as reduced quality of life, lung diffusion impairment, and radiographic abnormalities.
- - To inform better caring for COVID-19 survivors, ongoing longitudinal follow-up with the aim to understand in-depth the natural history and pathogenesis of long-term sequelae of COVID-19 is required.
- Since the outbreak of the COVID-19 pandemic in December 2019, there have been over 257 million COVID-19 cases around the world, and more than 5 million people have died due to the disease (as of November 22, 2021; Johns Hopkins Coronavirus Resource Center).
- While advances have been made in vaccination and treatment, it is important that we also continue following up with those individuals who have recovered from COVID-19. Concerning results regarding the long-term sequelae after recovery from COVID-19, in which COVID-19 survivors were reported to suffer from persisting COVID-19-related symptoms such as pain, discomfort, depression and anxiety, etc. have been accumulating (Carfì et al., 2020; Huang et al., 2021; Liu et al., 2020; Logue et al., 2021; Morin et al., 2021; Puntmann et al., 2020; Rajpal et al., 2021; Xiong et al., 2021; Zhao et al., 2020).
- Our previous OE Original (COVID-19: Long-Lasting Health Effects Among Survivors) has reviewed the sequelae up to 6 months after recovery from COVID-19. In the present OE Original, we further examine evidence from studies reporting sequelae among COVID-19 survivors who have recovered from the disease for over 6 months.
A recap of the sequelae up to 6 months after recovery from COVID-19
In our previous OE Original (COVID-19: Long-Lasting Health Effects Among Survivors), we identified several studies focusing on the sequelae up to 6 months after recovery from COVID-19 and found that conclusions across these studies were consistent, suggesting that COVID-19 survivors might suffer from long-lasting negative impacts of SARS-CoV-2 infection on their physical, mental health and quality of life. The summary of findings of these studies is shown in Table 1.
Since the last OE Original, newly emerging evidence also supports our previous conclusions. For instance, a study published in JAMA found that 4 months after hospitalization, in an uncontrolled cohort study of 478 survivors of COVID-19, at least 1 new-onset symptom was reported 51% of COVID-19 survivors (244/478), including fatigue (31%, 134/431), cognitive symptoms (21%, 86/416), and dyspnea (16%, 78/478). Abnormalities from Computed tomographic (CT) lung scans were reported in 63% of 171 patients. Fibrotic lesions were
observed in 19% of these 171 patients.
Carfì et al. (2020)
At the time of evaluation (mean: 60.3 days; SD: 13.6 after onset of the first COVID-19 symptom), 87.4% (125/143) of patients still had COVID-19 symptoms, among whom, over 60% (79/125) reported 3 or more COVID-19-related symptoms. The most frequently reported symptoms included fatigue (53.1%, 76/143), dyspnea (43.4%, 62/143), joint pain, (27.3%, 39/143) and chest pain (21.7%, 31/143). The study also found that about 44.1% (63/143) of patients felt worsened QoL.
Huang et al. (2021)
About 6 months (median: 186 days, IQR: 175 to 199) after recovery, Over 75% of the patients (1265/1655) reported at least one persisting symptom such as fatigue or muscle weakness (63%, 1038/1655), sleep difficulties (26%, 437/1655), hair loss (22%, 359/1655), and smell disorder (11%, 176/1655). In terms of QoL, about 27% (431/1616) of the COVID-19 survivors felt pain and discomfort, 23% (367/1617) of them had depression or anxiety, 7% (113/1622) had problems with walking around, 2% (25/1611) had issues with usual activity, and 1% (11/1622) had difficulties in washing or dishing.
Liu et al. (2020)
Four weeks after discharge from hospital, chest CT results showed that the lung abnormalities in recovered patients had gradually resolved. About17.7% (9/51) of patients had focal ground-glass opacity before discharge, while this proportion reduced to 9.8% (5/51) 4 weeks after discharge. The proportions of patients with multiple ground-glass opacities, consolidation, and interlobular septal thickening decreased from 80.4% (41/51), 49% (25/51), 80.4% (41/51) before discharge to 23.5% (12/51), 2% (1/51), and 35.3% (18/51) four weeks after discharge, respectively.
Puntmann et al. (2020)
The median (IQR) duration between the positive COVID-19 testing and the cardiovascular MRI examination was 71 (64-92) days. 78% (78/100) COVID-19 survivors showed abnormal cardiovascular MRI findings, including myocardial inflammation (which is defined by abnormal myocardial native T1 and T2 measures, 60%, 60/100), myocardial late gadolinium enhancement (32%, 32/100), and pericardial enhancement (22%, 22/100).
Xiong et al. (2021)
Over 3 months after discharge from the hospital, general symptoms (referring to the overall discomfort of COVID-19 survivors, including fatigue, sweating, myalgia, arthralgia, chills, limb oedema, and dizziness) were seen in 49.6% (267/538) of patients. Other clinical sequelae commonly observed among COVID-19 survivors included respiratory symptoms (e.g., postactivity polypnoea, nonmotor polypnoea, chest distress, chest pain, cough, sputum, and throat pain) (39%, 210/538), alopecia (28.6%, 154/538), psychosocial symptoms (e.g., somnipathy, depression, anxiety, dysphoria, and feelings of inferiority) (22.7%, 122/538), and cardiovascular-related symptoms (e.g., resting heart rate increases, discontinuous flushing, and newly diagnosed hypertension) (13%, 70/538).
Zhao et al. (2020)
Three months after discharge from the hospital, the most common symptom among COVID-19 survivors was gastrointestinal symptoms (30.91%, 17/55), followed by headache (18.18%, 10/55), fatigue (16.36%, 9/55), exertional dyspnea (14.55%, 8/55), as well as cough and sputum (1.81%, 1/55). A high proportion of patients showed radiological abnormalities (74.55%, 41/55). Lung dysfunction, mainly referring to abnormal carbon monoxide diffusion capacity, was found in about one-fourth of the patients (25.45%, 14/55).
SD: standard deviation; QoL: quality of life; IQR: Interquartile range; CT: computed tomography; MRI: magnetic resonance imaging.
The sequelae over 6 months after recovery from COVID-19
A number of studies reported the impact of COVID-19 on patients who had recovered from the disease over 6 months (Havervall et al., 2021; L. Huang et al., 2021; Seeßle et al., 2021; Wu et al., 2021).
- In a cohort study, Havervall et al. (2021) assessed the persisting symptoms and functional impairment in Swedish health care workers who had recovered from mild COVID-19 for 8 months. About 15% of the COVID-19 survivors reported at least 1 moderate to severe symptoms (such as fatigue, myalgia, fever, anosmia, ageusia, dyspnea, cough, heart palpitations, concentrations deficit, vertigo, memory deficit, nausea, abdominal ache, diarrhea, hearing impairment, headache, numbness, mental fatigue, sleep disorders, depression, anxiety, skin disorders and alopecia) lasting for at least 8 months, while such percentage in those who were not previously infected with SARS-CoV-2 was only around 3%. The risk was significantly higher [relative risk (RR): 4.4; 95% confidence interval (CI): 2.9 to 6.7].
Moreover, there was a significantly higher risk that the COVID-19 survivors’ work life (RR: 1.8; 95% CI: 1.2 to 2.9), social life (RR: 2.5; 95% CI: 1.8 to 3.6), and home life (RR: 2.3; 95% CI: 1.6 to 3.4) were moderately to markedly disrupted by the long-lasting COVID-19 symptoms, compared to those who were not previously infected (Havervall et al., 2021).
- In a prospective, longitudinal, cohort study, Wu et al. (2021) found that the conditions, (referring to pulmonary physiology and exercise capacity) of most of the COVID-19 survivors were gradually improving, yet 11% (9/83) and 33% (27/83) of COVID-19 survivors had reduced forced vital capacity (FVC) measurements (< 80% predicted value) and impaired diffusing capacity of the lungs for carbon monoxide (DLCO) at 12 months (< 80% predicted value) at 12 months after discharge from hospitalization, respectively. About 12 months after discharge, radiological changes persisted in about 24% (20/83) COVID-19 survivors.
- Seeßle et al. (2021) follow up with 96 COVID-19 survivors up to 12 months after symptom onset. Around 78% of patients who had recovered from COVID-19 for about 12 months still had persisting symptoms. Two most frequently reported symptoms were reduced exercise capacity (56.3%) and fatigue (53.1%), followed by dyspnea (37.5%), as well as problems with concentration (39.6%), finding words (32.3%), and sleeping (26%).
Additionally, Seeßle et al. (2021) evaluated the impact of COVID-19 on the quality of life (QoL) among COVID-19 survivors using the standardized 12-item Short Form Survey (SF-12) questionnaire, consisting of the Physical Component Scale (PCS) and the Mental Component Scale (MCS). The results showed that patients with at least 1 persisting COVID-19 symptom had a significantly reduced PCS (P = 0.006) and MCS (P = 0.031) scores, compared with patients without symptoms.
- Huang et al. (2021) conducted a cohort study (No. of participants: 1276) to examine the consequences between 6 months and 12 months after symptom onset among COVID-19 survivors. Generally, there was a trend in which patients conditions were improving over time, as 68% (831/1227) and 49% (620/1272) of the COVID-19 survivors reported at least 1 persisting symptom (defined as one of the following: fatigue or muscle weakness, sleep difficulties, hair loss, smell disorder, palpitations, joint pain, decreased appetite, taste order, dizziness, diarrhea or vomiting, chest pain, sore throat or difficult to swallow, skin rash, myalgia, headache) at 6 months and 12 months (P < 0·0001) after symptom onset, respectively.
However, compared to 6 months, the proportion of COVID-19 survivors with dyspnea [from 26% (313/1185) to 30% (380/1271), P = 0.014] at 12 months after symptom onset increased with statistical significance (Huang et al., 2021). Furthermore, using the EuroQol five-dimension five-level (EQ-5D-5L) questionnaire, Huang et al. (2021) identified that more COVID-19 survivors had mobility problems with walking around [12 months vs. 6 months: 9% (115/1271) vs. 6% (76/1191), P = 0.0058], personal care issues with washing or dishing [2% (20/1271) vs. 1% (9/1191), P = 0.033], and anxiety or depression [26% (331/1271) vs. 23% (274/1187), P = 0.014] at 12 months after symptom onset, compared to 6 months.
Current evidence suggests that some COVID-19 survivors are still suffering from the negative impact of the disease, such as reduced quality of life, lung diffusion impairment, and radiographic abnormalities, even 12 months after symptom onset or discharge from hospitalization. Ongoing longitudinal follow-up is warranted to understand in-depth the natural history and pathogenesis of long-term sequelae of COVID-19 so as to inform better caring for COVID-19 survivors.
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