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Suicidal ideation following self-reported COVID-19-like symptoms or serology-confirmed SARS-CoV-2 infection in France: A propensity score weighted analysis from a cohort study [1]

['Camille Davisse-Paturet', 'Université Paris-Saclay', 'Inserm', 'Uvsq', 'Cesp', 'Paris', 'Massimiliano Orri', 'Mcgill University', 'Department Of Psychiatry', 'Montreal']

Date: 2023-04

The present study does not have a registered prospective protocol. An unpublished, informal analysis plan was made and discussed among study authors prior to the implementation of statistical analyses.

Data collection methods included both self-computer-assisted web interviews (CAWIs) and computer-assisted telephone interviews (CATIs). From the 371,000 randomly selected individuals invited to participate, 36.22% (134,391) actually participated at baseline in May 2020 (02/05/2020 to 02/06/2020). The first follow-up took place in Autumn 2020 (26/10/2020 to 14/12/2020, 107,759 participants), and the second follow-up took place in Summer 2021 (24/06/2021 to 09/08/2021, 85,074 participants). The EpiCov study timeline as well as data collected and used are resumed in Fig 1 .

The Epidémiologie et conditions de vie sous le COVID-19 (EpiCov) study is a longitudinal, French cohort from the general population, aiming to provide information on the virus’ dissemination and the pandemic’s consequences on the daily life and health of individuals [ 16 ]. Eligibility criteria were to be at least 15 years of age in 2020, to reside in mainland France or three oversea territories (Martinique, Guadeloupe, and Réunion), and to not live in a medical retirement home or a jail. A total of 371,000 individuals were randomly selected from France’s national tax database, with an expected participation rate of about 50% and a sampling design overrepresenting less densely populated and more socioeconomically disadvantaged areas [ 17 ].

At the second follow-up in Summer 2021, suicidal ideation were ascertained with the question, “Since December 2020, have you thought about ‘killing yourself by suicide’?” Killing oneself by suicide is the closest translation of the actual French word used in the questionnaire “se suicider.” The outcome of interest was a binary variable representing the occurrence of suicidal ideation at least once between December 2020 and July 2021 (yes versus no).

In this study, COVID-19-like symptoms were symptoms described as most suspicious in 2020 by the French Public Health Agency. They referred to any unusual episode of sudden loss of taste/smell or any unusual episode of fever alongside a cough, shortness of breath, or chest oppression. At baseline in May 2020, participants reported COVID-19-like symptoms since the 17th of March 2020. At first follow-up in Autumn 2020, they reported COVID-19-like symptoms since February 2020. Pooling the two, this study’s self-reported COVID-19-like symptoms (yes versus no) were self-report of COVID-19-like symptoms at least once from February 2020 to Autumn 2020.

The exact methodology for serology testing has been described elsewhere [ 16 ]. Briefly, consent to participate to SARS-CoV-2 serology testing with blood sampling kit was collected at the first follow-up in Autumn 2020. A total of 63,524 dried-blood-spot samples were screened for antibodies against SARS-CoV-2’s spike protein S1 domain, with a commercial ELISA kit. Samples with a serology-confirmed SARS-CoV-2 infection had an optical density ratio of at least 0.7. We pooled suspicious serologies (i.e., with an optical density ratio between 0.7 and 1.1) with positive ones (i.e., optical density ratio >1.1) as a decline in circulating antibodies might occur with time [ 18 ]. Of note, 94.4% of blood samples were collected before January 2021 and the start of the vaccination campaign in France. Serology-confirmed SARS-CoV-2 infections were therefore unlikely to be due to vaccination.

The following indicators, made available by The National Institute for Statistics and Economic Studies (INSEE), were taken into account: deciles of household income per consumption unit studied as a five-category covariate (less resourceful, medium-low, medium, medium-high, wealthiest), household structure (single, couple without children, couple with children, single-parent, participant living with parents, complex household), urban density of living area (oversea territories, less than 2,000 urban units, between 2,000 and 1,999,999 urban units, Paris area), residence in a deprived neighborhood (yes or no), and hospitalization rates in place of residence during the first lockdown (lowest, medium-low, medium-high, highest quartile). An urban unit is a built area with less than 200 meters between two buildings, comprising at least 2,000 inhabitants. A deprived neighborhood is an administrative category, describing an area where particular budgetary efforts are made by the State to tackle inequalities regarding education, early life care, housing and living conditions, employment, social cohesion, security, and crime prevention.

The following health-related covariates were also ascertained: perceived general health status at baseline (very good to good, quite good, poor to very poor), baseline body mass index (BMI; less than 18.5 kg/m 2 , between 18.5 and less than 25 kg/m 2 , between 25 and less than 30 kg/m 2 , 30 kg/m 2 or more), pre-pandemic somatic conditions (yes or no), pre-pandemic mental health disorder (yes or no), baseline tobacco use (current, past, never), and baseline alcohol use (daily, often, occasional, rare, never). Pre-pandemic mental health disorder included self-reported anxiety, depression, and mental disability, assessed at baseline, history of at least one suicide attempt before November 2019, assessed at first follow-up, and self-report of at least one physician diagnosis of anxiety, mood, bipolar, eating, personality or substance use disorder, or schizophrenia before the pandemic, assessed at second follow-up. A detailed description of the pre-pandemic mental health disorder covariate is available in S1 Supporting Information.

The following sociodemographic covariates were ascertained at baseline and included in propensity scores: gender (man, woman), age (years), participant’s and participant’s parents’ place of birth (participant and parents born in mainland France, participant or parents born in oversea territories, participant born in France of parents born abroad, participant born abroad), highest educational attainment (none, lower secondary school certificate, professional certificate, higher secondary school certificate, bachelor degree or equivalent, Master degree or more), occupational grade (employed, student, unemployed, retired, other including housemakers), perceived financial situation (comfortable, decent, short, difficult or unbearable without taking loans), physical space in participant’s usual accommodation (less than one room per person, yes or no), residence not in usual housing during the first lockdown (yes or no, the first lockdown lasted from the 17/03/2020 to the 11/05/2020), access to safe outdoor space during the first lockdown (balcony or garden, including common ones, yes or no), and usual living area, ranked according to the intensity of the first COVID-19 wave in France (less affected areas, Grand-Est, Hauts-de-France, Ile-de-France). More information regarding the first COVID-19 epidemic wave in France are available in S2 Supporting Information.

Covariate selection for propensity score modeling was based on current literature, including recommendations from the International COVID-19 Suicide Prevention Research Collaboration [ 19 ]. In accordance with propensity score methodology [ 20 ], included factors were related to both COVID-19 and suicidal ideation or only to suicidal ideation [ 8 ]. Directed acyclic graphs (DAGs) supported framework conceptualization for the assessment of suicidal ideation related to COVID-19 and minimize bias though appropriate covariate selection [ 21 , 22 ] (S3 Supporting Information).

Statistical analyses

Suicidal ideation in 2020 as well as life course suicide attempts were assessed at the first follow-up in Autumn 2020 (Fig 1). The related questions were, respectively, “In the last 12 months, have you thought about ‘killing yourself by suicide’?” and “In your lifetime, have you ever attempted suicide? If so, when was the last one?” Yet, mediators are not supposed to be included in propensity score calculation. Suicidal ideation and suicide attempts in 2020 could act as mediator in the association of self-reported COVID-19-like symptoms in 2020 and serology-confirmed SARS-CoV-2 infection in 2020 with suicidal ideation in 2021. But, in EpiCov, no data were available regarding the first occurrence of COVID-19-like symptoms in 2020 or date of SARS-CoV-2 infection in 2020. We could therefore not ascertain if suicidal ideation or suicide attempt in 2020 occurred before or after the two COVID-19 exposures. To ensure no mediator was included in propensity score calculation, participants reporting suicidal ideation or a history of suicide attempt in 2020 or who did not provide information on the timing of their last suicide attempt had to be removed from the statistical analyses. Participants who reported a last suicide attempt before 2020 were included in the pre-pandemic mental health disorder covariate. Excluded participants are detailed in Fig 2. Do not wish to answer modalities had to be removed because of small sample size.

Inverse probability weighting and modified Poisson regression models. First, propensity scores associated with (a) reporting COVID-19-like symptoms or (b) having a serology-confirmed SARS-CoV-2 infection were computed using logistic regression models based on the covariates described above. Then, propensity scores were included in statistical models using inverse probability weights (IPWs; S5 Supporting Information). Balance after IPWeighting was considered satisfactory if (1) absolute standardized mean differences (SMDs) between each covariate, as well as each modality of each covariate were below 10%, and (2) variance ratios of propensity scores computed after weighting were between 0.5 and 2 [15,20]. Covariates distribution after weighting was also assessed with chi-squared and Student t tests. Lastly, IPWeighted modified Poisson regression models with robust error variance were used to assess the association between both COVID-19 exposures in 2020 and suicidal ideation in 2021 [24]. If after IPWeighting residual distribution differences remained for some covariates, regression models were further adjusted for these incompletely balanced covariates. Models were therefore further adjusted for highest educational attainment for the self-reported COVID-19-like symptoms in 2020 model, and for highest educational attainment, perceived financial situation, household income, and residence in deprived neighborhood for the serology-confirmed SARS-CoV-2 infection in 2020 model.

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[1] Url: https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004171

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