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

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.

COVID-19 Vaccine Could Trigger the Relapse of Secondary Hypersomnia.

The coronavirus disease (COVID-19) has brought significant social and economic disruptions and devastating impacts on public health, and vaccines are being developed to combat the disease. Timely vaccination may prevent complications and morbidity but may also potentially result in unforeseen outcomes in some special clinical populations. We report on a case of hypersomnia relapse after the COVID-19 vaccination, with the aim of informing the development of the guideline on vaccination in specific groups. A 19-year old female presented with persistent daytime sleepiness after receiving the COVID-19 vaccine. She had a known history of hypersomnia secondary to infectious mononucleosis but has fully recovered for 8 months. A series of examinations were performed on this patient. Neurologic and psychiatric examinations were unremarkable. Despite normal nocturnal subjective sleep quality (Pittsburgh Sleep Quality Index score = 5, Insomnia Severity Index score = 7), her Epworth sleepiness scale score (15) suggested an abnormal level of subjective sleepiness. Consistent with the subjective report, the objective assessment by Multiple Sleep Latency Test found mean sleep latency was 1.3 min with no sleep onset rapid-eye-movement (REM) period. We speculate that COVID-19 vaccine may potentially trigger the relapse of hypersomnia. The immune memory could be an explanation for the increased response to vaccine in patients with secondary hypersomnia. Caution should be warranted when administering COVID-19 vaccine in patients with hypersomnia secondary to infections.

Insomnia symptoms during the early and late stages of the COVID-19 pandemic in China: a systematic review and meta-analysis.

BACKGROUND: Evidence suggests that the outbreak of the coronavirus disease 2019 (COVID-19) and the prevention/control measures for COVID-19 may cause insomnia during the acute phase of COVID-19 pandemic in China. However, it is unclear whether insomnia sustains during the later phases of the pandemic. METHODS: We searched PubMed/Medline, EMBASE, PsycINFO and China National Knowledge Infrastructure from the 27th December 2019 to the 2nd February 2021. As early stage studies on COVID-19 pandemic in China were defined as those conducted prior to April 1st, 2020, while late stage studies were those conducted after April 1st, 2020. RESULTS: A total of 98 studies with 193,889 participants were included. The pooled prevalence of insomnia symptoms among all populations was 39.1% (95% CI 36.2-42.0%); the pooled prevalence of insomnia symptoms during the early and late stages of COVID-19 in China were 37.0% (95% CI 34.1-39.9%) and 41.8% (95% CI 33.6-50.0%), respectively. Importantly, there was no significant difference regarding the prevalence of insomnia symptoms between the early and late stages of COVID-19. Meta-regression showed that healthcare workers, COVID-19 patients, patients with chronic medical conditions and patients with mental disorders had a higher prevalence of insomnia symptoms compared to the general population. This association remained significant in healthcare workers and patients with chronic medical conditions after adjusting for age, gender, areas of high or low prevalence of COVID-19 cases, anxiety and depression. CONCLUSIONS: Over one third of our sample present insomnia symptoms during the early stage of COVID-19 pandemic in China. Interestingly, prevalence of insomnia symptoms sustains high during the late stage of the pandemic despite the control of the disease and the amelioration of its adverse effects. Our findings suggest that insomnia symptoms related to COVID-19 appear to persist of over time.

Mental and neurological disorders and risk of COVID-19 susceptibility, illness severity and mortality: A systematic review, meta-analysis and call for action.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has evolved into a worldwide pandemic, and has been found to be closely associated with mental and neurological disorders. We aimed to comprehensively quantify the association between mental and neurological disorders, both pre-existing and subsequent, and the risk of susceptibility, severity and mortality of COVID-19. METHODS: In this systematic review and meta-analysis, we searched PubMed, Web of Science, Embase, PsycINFO, and Cochrane library databases for studies published from the inception up to January 16, 2021 and updated at July 7, 2021. Observational studies including cohort and case-control, cross-sectional studies and case series that reported risk estimates of the association between mental or neurological disorders and COVID-19 susceptibility, illness severity and mortality were included. Two researchers independently extracted data and conducted the quality assessment. Based on I2 heterogeneity, we used a random effects model to calculate pooled odds ratios (OR) and 95% confidence intervals (95% CI). Subgroup analyses and meta-regression analysis were also performed. This study was registered on PROSPERO (registration number: CRD 42021230832). FINDING: A total of 149 studies (227,351,954 participants, 89,235,737 COVID-19 patients) were included in this analysis, in which 27 reported morbidity (132,727,798), 56 reported illness severity (83,097,968) and 115 reported mortality (88,878,662). Overall, mental and neurological disorders were associated with a significant high risk of infection (pre-existing mental: OR 1·67, 95% CI 1·12-2·49; and pre-existing neurological: 2·05, 1·58-2·67), illness severity (mental: pre-existing, 1·40, 1·25-1·57; sequelae, 4·85, 2·53-9·32; neurological: pre-existing, 1·43, 1·09-1·88; sequelae, 2·17, 1·45-3·24), and mortality (mental: pre-existing, 1·47, 1·26-1·72; neurological: pre-existing, 2·08, 1·61-2·69; sequelae, 2·03, 1·66-2·49) from COVID-19. Subgroup analysis revealed that association with illness severity was stronger among younger COVID-19 patients, and those with subsequent mental disorders, living in low- and middle-income regions. Younger patients with mental and neurological disorders were associated with higher mortality than elders. For type-specific mental disorders, susceptibility to contracting COVID-19 was associated with pre-existing mood disorders, anxiety, and attention-deficit hyperactivity disorder (ADHD); illness severity was associated with both pre-existing and subsequent mood disorders as well as sleep disturbance; and mortality was associated with pre-existing schizophrenia. For neurological disorders, susceptibility was associated with pre-existing dementia; both severity and mortality were associated with subsequent delirium and altered mental status; besides, mortality was associated with pre-existing and subsequent dementia and multiple specific neurological diseases. Heterogeneities were substantial across studies in most analysis. INTERPRETATION: The findings show an important role of mental and neurological disorders in the context of COVID-19 and provide clues and directions for identifying and protecting vulnerable populations in the pandemic. Early detection and intervention for neurological and mental disorders are urgently needed to control morbidity and mortality induced by the COVID-19 pandemic. However, there was substantial heterogeneity among the included studies, and the results should be interpreted with caution. More studies are needed to explore long-term mental and neurological sequela, as well as the underlying brain mechanisms for the sake of elucidating the causal pathways for these associations. FUNDING: This study is supported by grants from the National Key Research and Development Program of China, the National Natural Science Foundation of China, Special Research Fund of PKUHSC for Prevention and Control of COVID-19, and the Fundamental Research Funds for the Central Universities.

Attitudes toward COVID-19 vaccination and willingness to pay: comparison of people with and without mental disorders in China.

BACKGROUND: Acceptance and willingness to pay for the COVID-19 vaccine are unknown. AIMS: We compared attitudes toward COVID-19 vaccination in people suffering from depression or anxiety disorder and people without mental disorders, and their willingness to pay for it. METHOD: Adults with depression or anxiety disorder (n = 79) and healthy controls (n = 134) living in Chongqing, China, completed a cross-sectional study between 13 and 26 January 2021. We used a validated survey to assess eight aspects related to attitudes toward the COVID-19 vaccines. Psychiatric symptoms were assessed by the 21-item Depression, Anxiety and Stress Scale. RESULTS: Seventy-six people with depression or anxiety disorder (96.2%) and 134 healthy controls (100%) reported willingness to receive the COVID-19 vaccine. A significantly higher proportion of people with depression or anxiety disorder (64.5%) were more willing to pay for the COVID-19 vaccine than healthy controls (38.1%) (P ≤ 0.001). After multivariate adjustment, severity of depression and anxiety was significantly associated with willingness to pay for COVID-19 vaccination among psychiatric patients (P = 0.048). Non-healthcare workers (P = 0.039), health insurance (P = 0.003), living with children (P = 0.006) and internalised stigma (P = 0.002) were significant factors associated with willingness to pay for COVID-19 vaccine in healthy controls. CONCLUSIONS: To conclude, psychiatric patients in Chongqing, China, showed high acceptance and willingness to pay for the COVID-19 vaccine. Factors associated with willingness to pay for the COVID-19 vaccine differed between psychiatric patients and healthy controls.

Prevalence and Risk Factors of Mental Health Symptoms and Suicidal Behavior Among University Students in Wuhan, China During the COVID-19 Pandemic.

Background: University students who are exposed to coronavirus disease 2019 (COVID-19) could be mentally distressed. We aimed to evaluate the pattern and risk factors of mental health and suicidal behavior among students who experienced long-term school closure due to the COVID-19 pandemic. Methods: This large-sample, cross-sectional, online survey was conducted from June 29, 2020, to July 18, 2020. Eleven thousand two hundred fifty four participants were recruited from 30 universities located in Wuhan, Hubei Province, China. The prevalence of symptoms of depression, anxiety, insomnia, and posttraumatic stress disorder (PTSD) and suicidal behavior was evaluated using the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Insomnia Severity Index, Posttraumatic Stress Disorder Checklist for DSM-5, and questions about suicidal ideation and attempts, respectively. Logistic regression was used to explore risk factors for mental health problems and suicidal behavior. Results: The prevalence of mental health problems was 41.5% for depressive symptoms, 32.6% for anxiety symptoms, 35.0% for insomnia symptoms, 8.5% for PTSD symptoms, and 2.0% for suicidal behavior. Participants with high stress during the pandemic were at higher risk of symptoms of depression [adjusted odds ratio (OR) = 1.67, 95% confidence interval (CI) = 1.43-1.95, p < 0.01), anxiety (adjusted OR = 1.90, 95% CI = 1.63-2.23, p < 0.01), insomnia (adjusted OR = 1.64, 95% CI = 1.44-1.87, p < 0.01), PTSD (adjusted OR = 1.71, 95% CI = 1.38-2.11, p < 0.01) and suicidal behavior (adjusted OR = 3.51, 95% CI = 2.28-5.40, p < 0.01). Distant relationship with parents, changes in lifestyle and alcohol use during the pandemic were associated with higher risk of mental health symptoms and suicidal behavior, whereas regular physical exercise reduced the risk of mental health problems. Conclusions: The psychological symptoms and suicidal behavior were relatively high among students who attended university in Wuhan, China after 6 months of the COVID-19 outbreak in China. Comprehensive mental health services and suicide prevention strategies are essential for university students during the COVID-19 pandemic.