COVID-19 vaccination for the prevention and treatment of long COVID: A systematic review and meta-analysis.

Empirical evidence addressing the association between SARS-CoV-2 vaccination and long COVID would guide public health priorities and inform personal health decisions. Herein, the co-primary objectives are to determine the differential risk of long COVID in vaccinated versus unvaccinated patients, and the trajectory of long COVID following vaccination. Of 2775 articles identified via systematic search, 17 were included, and 6 were meta-analyzed. Meta-analytic results determined that at least one vaccine dose was associated with a protective effect against long COVID (OR 0.539, 95% CI 0.295-0.987, p = 0.045, N = 257 817). Qualitative analysis revealed that trajectories of pre-existing long COVID following vaccination were mixed, with most patients reporting no changes. The evidence herein supports SARS-CoV-2 vaccination for the prevention of long COVID, and recommends long COVID patients adhere to standard SARS-CoV-2 vaccination schedules.

Registered clinical trials investigating treatment of long COVID: a scoping review and recommendations for research.

BACKGROUND: A considerable proportion of individuals report persistent, debilitating and disparate symptoms despite resolution of acute COVID-19 infection (i.e. long COVID). Numerous registered clinical trials investigating treatment of long COVID are expected to be completed in 2021-2022. The aim of this review is to provide a scope of the candidate treatments for long COVID. A synthesis of ongoing long COVID clinical trials can inform methodologic approaches for future studies and identify key research vistas. METHODS: Scoping searches were conducted on multiple national and international clinical trial registries. Interventional trials testing treatments for long COVID were selected. The search timeline was from database inception to 28 July 2021. RESULTS: This scoping review included 59 clinical trial registration records from 22 countries with a total projected enrolment of 6718. Considerable heterogeneity was exhibited amongst component records with respect to the characterization of long COVID (i.e. name, symptoms- including frequency, intensity, trajectory and duration- mode of ascertainment, and definition of acute phase). In addition, the majority of proposed interventions were non-pharmacological and either targeted multiple long COVID symptoms simultaneously, or focussed on treatment of respiratory/pulmonary sequelae. Multiple interventions targeted inflammation, as well as tissue oxygenation and cellular recovery, and several interventions were repurposed from analogous conditions. CONCLUSIONS: The results of this scoping review investigating ongoing clinical trials testing candidate treatments for long COVID suggest that a greater degree of definitional stringency and homogeneity is needed insofar as the characterization of long COVID and inclusion/exclusion criteria.

Fatigue and cognitive impairment in Post-COVID-19 Syndrome: A systematic review and meta-analysis.

IMPORTANCE: COVID-19 is associated with clinically significant symptoms despite resolution of the acute infection (i.e., post-COVID-19 syndrome). Fatigue and cognitive impairment are amongst the most common and debilitating symptoms of post-COVID-19 syndrome. OBJECTIVE: To quantify the proportion of individuals experiencing fatigue and cognitive impairment 12 or more weeks following COVID-19 diagnosis, and to characterize the inflammatory correlates and functional consequences of post-COVID-19 syndrome. DATA SOURCES: Systematic searches were conducted without language restrictions from database inception to June 8, 2021 on PubMed/MEDLINE, The Cochrane Library, PsycInfo, Embase, Web of Science, Google/Google Scholar, and select reference lists. STUDY SELECTION: Primary research articles which evaluated individuals at least 12 weeks after confirmed COVID-19 diagnosis and specifically reported on fatigue, cognitive impairment, inflammatory parameters, and/or functional outcomes were selected. DATA EXTRACTION & SYNTHESIS: Two reviewers independently extracted published summary data and assessed methodological quality and risk of bias. A meta-analysis of proportions was conducted to pool Freeman-Tukey double arcsine transformed proportions using the random-effects restricted maximum-likelihood model. MAIN OUTCOMES & MEASURES: The co-primary outcomes were the proportions of individuals reporting fatigue and cognitive impairment, respectively, 12 or more weeks following COVID-19 infection. The secondary outcomes were inflammatory correlates and functional consequences associated with post-COVID-19 syndrome. RESULTS: The literature search yielded 10,979 studies, and 81 studies were selected for inclusion. The fatigue meta-analysis comprised 68 studies, the cognitive impairment meta-analysis comprised 43 studies, and 48 studies were included in the narrative synthesis. Meta-analysis revealed that the proportion of individuals experiencing fatigue 12 or more weeks following COVID-19 diagnosis was 0.32 (95% CI, 0.27, 0.37; p < 0.001; n = 25,268; I2 = 99.1%). The proportion of individuals exhibiting cognitive impairment was 0.22 (95% CI, 0.17, 0.28; p < 0.001; n = 13,232; I2 = 98.0). Moreover, narrative synthesis revealed elevations in proinflammatory markers and considerable functional impairment in a subset of individuals. CONCLUSIONS & RELEVANCE: A significant proportion of individuals experience persistent fatigue and/or cognitive impairment following resolution of acute COVID-19. The frequency and debilitating nature of the foregoing symptoms provides the impetus to characterize the underlying neurobiological substrates and how to best treat these phenomena. STUDY REGISTRATION: PROSPERO (CRD42021256965).

Onset and frequency of depression in post-COVID-19 syndrome: A systematic review.

Following recovery from COVID-19, an increasing proportion of individuals have reported the persistence and/or new onset of symptoms which collectively have been identified as post-COVID-19 syndrome by the National Institute for Health and Care Excellence. Although depressive symptoms in the acute phase of COVID-19 have been well characterized, the frequency of depression following recovery of the acute phase remains unknown. Herein, we sought to determine the frequency of depressive symptoms and clinically-significant depression more than 12 weeks following SARS-CoV-2 infection. A systematic search of PubMed, Ovid Medline and Google Scholar for studies published between January 1, 2020 and June 5, 2021 was conducted. Frequency and factors associated with depression in post-COVID-19 syndrome were recorded and qualitatively assessed through narrative synthesis. Methodological quality and risk of bias was assessed using a modified version of the Newcastle-Ottawa Scale (NOS) for prospective cohort studies. Of 316 articles identified through our systematic search, eight studies were included. The frequency of depressive symptoms +12 weeks following SARS-CoV-2 infection ranged from 11 to 28%. The frequency of clinically-significant depression and/or severe depressive symptoms ranged from 3 to 12%. The severity of acute COVID-19 was not associated with the frequency of depressive symptoms. However, the component studies were highly heterogeneous with respect to mode of ascertainment, time of assessment, and location and age of patients. The majority of studies did not include an unexposed control group. Future research should endeavour to produce a standardized classification of post-COVID-19 syndrome, and as well as include unexposed control groups.

Suicide reduction in Canada during the COVID-19 pandemic: lessons informing national prevention strategies for suicide reduction.

OBJECTIVE: The objective of this research was to evaluate the impact of federal, public health and social support programs on national suicide rates in Canada. DESIGN: Cross-sectional study. SETTING: Canadian National Database (i.e., Statistics Canada) and Statista. PARTICIPANTS: Population-level data, and economic and consumer market data. MAIN OUTCOME MEASURES: Suicide mortality data, population data and unemployment data were obtained from available statistical databases (e.g. Statistics Canada). We quantified suicide rate by dividing the total number of suicide deaths by the national population expressed as a rate per 100,000 population. RESULTS: Overall suicide mortality rate decreased in Canada from 10.82 deaths per 100,000 in the March 2019 - February 2020 period to 7.34 per 100,000 (i.e. absolute difference of 1300 deaths) in the March 2020 - February 2021 period. The overall Canadian unemployment rate changed from an average monthly rate of 5.7% in 2019 to 9.5% in 2020. CONCLUSION: Our results indicate that for the first post-pandemic interval evaluated (i.e., March 2020 - February 2021), suicide rates in Canada decreased against a background of extraordinary public health measures intended to mitigate community spread of COVID-19. An externality of public health measures was a significant rise in national unemployment rates in population measures of distress. Our results suggest that government interventions that broadly aim to reduce measures of insecurity (i.e., economic, housing, health), and timely psychiatric services, should be prioritised as part of a national suicide reduction strategy, not only during but after termination of the COVID-19 pandemic.

Comparing mortality from covid-19 to mortality due to overdose: A micromort analysis.

OBJECTIVE: To compare the mortality risk due to covid-19 with death due to overdose in British Columbia, Canada. The opioid epidemic was declared a public health emergency in 2016. METHODS: Mortality risk was calculated in micromorts with covid-19 data for January-October 2020, derived from the BC center for Disease Control, and illicit drug toxicity deaths for January 2010-September 2020, derived from the BC Coroners Service. Age-stratified covid-19 incidence and deaths per 100,000 population and age-stratified illicit drug toxicity death rates per 100,000 population were calculated. A micromort is a unit of risk equivalent to a one-in-a-million chance of death. RESULTS: During the covid-19 pandemic, illicit drug toxicity deaths reached 1.0 micromorts per day, representing an increase of 0.5 micromorts per day relative to 2019 rates. In comparison, covid-19 mortality risk was 0.05 micromorts per day among individuals from the general population living in British Columbia and 21.1 micromorts per day among those infected with covid-19. Covid-related mortality risk was significantly lower among individuals aged <60 years, relative to older adults, whereas drug toxicity-related mortality was highest for individuals aged 30-59 years. CONCLUSIONS: The mortality associated with covid-19 is apparent and distributed unevenly across subpopulations. The mortality due to overdose has increased during covid-19 and exceeds mortality due to covid-19. Our results instantiate the triple threat caused by covid-19 (i.e., public health crisis, economic crisis and mental health crisis) and quantitatively highlight the externality of increased mortality due to deaths of despair in response to public health efforts to reduce covid-related mortality.

Association Between Mood Disorders and Risk of COVID-19 Infection, Hospitalization, and Death: A Systematic Review and Meta-analysis.

Importance: Preexisting noncommunicable diseases (eg, diabetes) increase the risk of COVID-19 infection, hospitalization, and death. Mood disorders are associated with impaired immune function and social determinants that increase the risk of COVID-19. Determining whether preexisting mood disorders represent a risk of COVID-19 would inform public health priorities. Objective: To assess whether preexisting mood disorders are associated with a higher risk of COVID-19 susceptibility, hospitalization, severe complications, and death. Data Sources: Systematic searches were conducted for studies reporting data on COVID-19 outcomes in populations with and without mood disorders on PubMed/MEDLINE, The Cochrane Library, PsycInfo, Embase, Web of Science, Google/Google Scholar, LitCovid, and select reference lists. The search timeline was from database inception to February 1, 2021. Study Selection: Primary research articles that reported quantitative COVID-19 outcome data in persons with mood disorders vs persons without mood disorders of any age, sex, and nationality were selected. Of 1950 articles identified through this search strategy, 21 studies were included in the analysis. Data Extraction and Synthesis: The modified Newcastle-Ottawa Scale was used to assess methodological quality and risk of bias of component studies. Reported adjusted odds ratios (ORs) were pooled with unadjusted ORs calculated from summary data to generate 4 random-effects summary ORs, each corresponding to a primary outcome. Main Outcomes and Measures: The 4 a priori primary outcomes were COVID-19 susceptibility, COVID-19 hospitalization, COVID-19 severe events, and COVID-19 death. The hypothesis was formulated before study search. Outcome measures between individuals with and without mood disorders were compared. Results: This review included 21 studies that involved more than 91 million individuals. Significantly higher odds of COVID-19 hospitalization (OR, 1.31; 95% CI, 1.12-1.53; P = .001; n = 26 554 397) and death (OR, 1.51; 95% CI, 1.34-1.69; P < .001; n = 25 808 660) were found in persons with preexisting mood disorders compared with those without mood disorders. There was no association between mood disorders and COVID-19 susceptibility (OR, 1.27; 95% CI, 0.73-2.19; n = 65 514 469) or severe events (OR, 0.94; 95% CI, 0.87-1.03; n = 83 240). Visual inspection of the composite funnel plot for asymmetry indicated the presence of publication bias; however, the Egger regression intercept test result was not statistically significant. Conclusions and Relevance: The results of this systematic review and meta-analysis examining the association between preexisting mood disorders and COVID-19 outcomes suggest that individuals with preexisting mood disorders are at higher risk of COVID-19 hospitalization and death and should be categorized as an at-risk group on the basis of a preexisting condition.

Real-world effectiveness of repeated ketamine infusions for treatment resistant depression during the COVID-19 pandemic.

Herein we evaluate the impact of COVID-19 restrictions on antidepressant effectiveness of intravenous (IV) ketamine in adults with treatment-resistant depression (TRD). We conducted a case series analysis of adults with TRD (n = 267) who received four ketamine infusions at an outpatient clinic in Ontario, Canada, during COVID-19 restrictions (from March 2020 - February 2021; n = 107), compared to patients who received treatment in the previous year (March 2019 - February 2020; n = 160). Both groups experienced significant and comparable improvements in depressive symptoms, suicidal ideation, and anxiety with repeated ketamine infusions. Effectiveness of IV ketamine was not attenuated during the COVID-19 period.

Government response moderates the mental health impact of COVID-19: A systematic review and meta-analysis of depression outcomes across countries.

BACKGROUND: The COVID-19 pandemic represents a public health, economic and mental health crisis. We hypothesized that timely government implementation of stringent measures to reduce viral transmission would benefit mental health, as evidenced by reduced rates of depressive symptoms (i.e., Patient Health Questionnaire [PHQ]-9≥10, PHQ-2≥3). METHODS: The systematic review herein (PROSPERO CRD42020200647) evaluated to what extent differences in government-imposed stringency and timeliness of response to COVID-19 moderate the prevalence of depressive symptoms across 33 countries (k=114, N=640,037). We included data from six lower-middle-income countries, nine upper-middle-income countries, and 18 higher-income countries. Government-imposed stringency and timeliness in response were operationalized using the Oxford COVID-19 Government Response ("Stringency") Index. RESULTS: The overall proportion of study participants with clinically significant depressive symptoms was 21.39% (95% CI 19.37-23.47). The prevalence of clinically significant depressive symptoms was significantly lower in countries wherein governments implemented stringent policies promptly. The moderating effect of government response remained significant after including the national frequency of COVID cases at the time of study commencement, Healthcare Access and Quality index, and the inclusion of COVID patients in the study. LIMITATIONS: Factors that may have confounded our results include, for example, differences in lockdown duration, lack of study participant and outcome assessor blinding, and retrospective assessment of depressive symptom severity. CONCLUSIONS: Governments that enacted stringent measures to contain the spread of COVID-19 benefited not only the physical, but also the mental health of their population.