A systematic review and meta-analysis of long term physical and mental sequelae of COVID-19 pandemic: call for research priority and action

Abstract

The long-term physical and mental sequelae of COVID-19 are a growing public health concern, yet there is considerable uncertainty about their prevalence, persistence and predictors. We conducted a comprehensive, up-to-date meta-analysis of survivors' health consequences and sequelae for COVID-19. PubMed, Embase and the Cochrane Library were searched through Sep 30th, 2021. Observational studies that reported the prevalence of sequelae of COVID-19 were included. Two reviewers independently undertook the data extraction and quality assessment. Of the 36,625 records identified, a total of 151 studies were included involving 1,285,407 participants from thirty-two countries. At least one sequelae symptom occurred in 50.1% (95% CI 45.4-54.8) of COVID-19 survivors for up to 12 months after infection. The most common investigation findings included abnormalities on lung CT (56.9%, 95% CI 46.2-67.3) and abnormal pulmonary function tests (45.6%, 95% CI 36.3-55.0), followed by generalized symptoms, such as fatigue (28.7%, 95% CI 21.0-37.0), psychiatric symptoms (19.7%, 95% CI 16.1-23.6) mainly depression (18.3%, 95% CI 13.3-23.8) and PTSD (17.9%, 95% CI 11.6-25.3), and neurological symptoms (18.7%, 95% CI 16.2-21.4), such as cognitive deficits (19.7%, 95% CI 8.8-33.4) and memory impairment (17.5%, 95% CI 8.1-29.6). Subgroup analysis showed that participants with a higher risk of long-term sequelae were older, mostly male, living in a high-income country, with more severe status at acute infection. Individuals with severe infection suffered more from PTSD, sleep disturbance, cognitive deficits, concentration impairment, and gustatory dysfunction. Survivors with mild infection had high burden of anxiety and memory impairment after recovery. Our findings suggest that after recovery from acute COVID-19, half of survivors still have a high burden of either physical or mental sequelae up to at least 12 months. It is important to provide urgent and appropriate prevention and intervention management to preclude persistent or emerging long-term sequelae and to promote the physical and psychiatric wellbeing of COVID-19 survivors.

Fig. 1

Flow chart of study selection.

Fig. 2. The pooled prevalence of sequelae by organ system and specific symptoms of COVID-19.

(Symptoms reported by more than five studies are shown in Fig. 2). In total, 50.1% of patients were estimated to have at least one symptom at follow-up, and the objectively examined respiratory system was most commonly affected, followed by generalized symptoms, subjective respiratory symptoms, psychiatric symptoms, and the neurological system. The prevalence of patients re-testing positive by SARS-COV-2SARS-COV-2 nucleic acid PCR and readmission to the hospital were estimated to be 9.9% and 13.6%, respectively.

Fig. 3. Subgroup analysis of sequelae of COVID-19 by mean age, sex proportion, region of studies, severity of disease and follow-up duration.

NS No. of studies, NP No. of participants. COVID-19 survivors of senior age, male sex, living in a high-income country, had a more severe health statuses at acute infection and within 6 months since recovery appeared to have higher prevalence of long-term sequelae than their contrast groups; A Subgroup analysis among different follow-up duration; B Subgroup analysis among asymptomatic participants in the community, mild/moderate patients and severe patients in hospital; C Subgroup analysis by mean age of participants; D Subgroup analysis by sex proportion of studies; E Subgroup analysis between high-income country and middle or low-income country.

Fig. 4. The pooled prevalence of neuropsychiatric sequelae and subgroup analysis.

83 studies investigated neuropsychiatric symptoms, prevalence of the specific symptoms were as follows: 19.7% for any psychiatric illness, 18.3% for depression, 17.9% for PTSD, 16.2% for anxiety and 13.5% for sleep disturbance in psychiatric symptoms and 18.7% for any neurological symptoms, 19.7% for cognitive deficits, 17.5% for memory impairment, and 15.7% for loss of taste or smell in neurological symptoms. Patients were found to exhibit neuropsychiatric symptoms even 6 months after infection and mild patients who were not hospitalized were also presented with neuropsychiatric syndromes.

Fig. 5. Framework of long-term sequelae, risk factors, and prevention and intervention strategies for long COVID-19.

Potential risk facotrs were categorized into three groups: the pre-illness group included age, sex and pre-existind conditions; the acute illness stage group included severity of illness, hospital length and abnormal objective tests during hospitalization; the convalescent stage included access to oxygen supplementation, abnormal objective tests during follow up and perception of stigma from community.