Schizophrenia, Bipolar, or Major Depressive Disorder and Postacute Sequelae of COVID-19, 2025, Vekaria et al.

[SNT Gatchaman]

Schizophrenia, Bipolar, or Major Depressive Disorder and Postacute Sequelae of COVID-19

Spoiler: Authors

Veer Vekaria; Rohith Kumar Thiruvalluru; Zoe Verzani; Sajjad Abedian; Mark Olfson; Braja Gopal Patra; Yunyu Xiao; Katherine S Salamon; Karin Hoth; Frank Blancero; Maxwell M Hornig-Rohan; Teresa Akintonwa; Mahfuza Sabiha; Mark G Weiner; Thomas W Carton; Rainu Kaushal; Jyotishman Pathak; Recover PCORnet Ehr consortium; Selvin Soby; Parsa Mirhaji; Sara J Deakyne Davies; Suchitra Rao; Priya Alekapatti; Nathan M Pajor; Soumitra Sengupta; Curtis Kieler; W Schuyler Jones; Nita Deshpande; Tony Pan; Carol R Horowitz; Heidi T May; Benjamin D Horne; Bradley W Taylor; Alexander Stoddard; Reza Shaker; David Liebovitz; Vesna Mitrovic; Saul Blecker; Nathalia Ladino; Marion R Sills; Soledad A Fernandez; Neena Thomas; Daniel Fort; Wenke Hwang; Cynthia H Chuang; Alan Schroeder; Keith E Morse; Sharon J Herring; Yuriy Bisyuk; Mark J Pletcher; Susan Kim; Mei Liu; Jiang Bian; Elizabeth A Chrischilles; David A Williams; Xing Song; Abu S Mosa; Jim Svoboda; Carol R Geary; Michael J Becich; Jonathan Arnold; Ramkiran Gouripeddi; Lindsay G Cowell; Wei-Qi Wei; Rainu Kaushal; Thomas Campion; Thomas W Carton; Anna Legrand; Elizabeth Nauman; Mark Weiner Weiner; Sajjad Abedian Abedian; Dominique Brown; Christopher Cameron; Andrea Cohen; Marietou Dione; Rosie Ferris; Wilson Jacobs; Michael Koropsak; Alexandra LaMar; Colby Lewis; Dmitry Morozyuk; Peter Morrisey; Duncan Orlander; Jyotishman Pathak; Mahfuza Sabiha; Edward J Schenck; Catherine Sinfield; Stephenson Strobel; Zoe Verzani; Fei Wang; Zhenxing Xu; Chengxi Zang; Yongkang Zhang

IMPORTANCE
Given the increased vulnerability to COVID-19 among those with a serious mental illness (SMI), it remains unclear whether these individuals face a higher risk of developing postacute sequelae of SARS-CoV-2 (PASC). Understanding this association could inform secondary prevention efforts.

OBJECTIVE
To identify the risk of developing PASC in patients with an SMI.

DESIGN, SETTING, AND PARTICIPANTS
This longitudinal cohort study used data derived from large-scale electronic health records (EHRs) between March 2020 and April 2023, inclusive of 180-day follow-up. Patients included adults aged 21 years or older with a confirmed COVID-19 infection evidenced by a relevant laboratory result, diagnosis, or prescription order.

EXPOSURES
Evidence of an SMI diagnosis (schizophrenia, bipolar disorder, or recurrent major depressive disorder) recorded before COVID-19 infection.

MAIN OUTCOMES AND MEASURES
Evidence of PASC symptoms within 30 to 180 days’ follow-up after COVID-19 infection reported as odds ratios (OR) mutually adjusted for age, sex, race and ethnicity, insurance type, Charlson Comorbidity Index (CCI) score, and COVID-19 severity.

RESULTS
A total of 1 625 857 patients with a COVID-19 infection were included (mean [SD] age, 52 [17] years; 998 237 [61.4%] female, 204 237 [12.6%] non-Hispanic Black, 219 220 [13.5%] Hispanic, 833 411 [51.3%] non-Hispanic White, and 1 228 664 [75.6%] urban patients), of whom 258 523 (15.9%) had an SMI and 403 641 (24.8%) developed PASC. Individuals with an SMI had increased adjusted odds of developing PASC (OR, 1.10; 95% CI, 1.08-1.11;P < .001). Variables associated with greater odds of PASC among the study population included older age compared with age 22 to 34 years (35 to 44 years: OR, 1.04; 95% CI, 1.03-1.06; 45 to 64 years: OR, 1.11; 95% CI, 1.10-1.12; ≥65 years: OR, 1.18; 95% CI, 1.17-1.20), non-Hispanic Black and Hispanic compared with non-Hispanic White race and ethnicity (non-Hispanic Black: OR, 1.08; 95% CI, 1.07-1.10; Hispanic: OR, 1.12; 95% CI, 1.11-1.13), higher chronic disease burden vs no chronic disease (CCI 1 to 3: OR, 1.13; 95% CI, 1.12-1.14; CCI ≥4: OR, 1.23; 95% CI, 1.22-1.25), and hospitalization with initial COVID-19 infection vs no hospitalization (hospitalized: OR, 1.80; 95% CI, 1.77-1.82; hospitalized with ventilation: OR, 2.17; 95% CI, 2.12-2.22;P < .001). Compared with public insurance, commercial health insurance was associated with lower odds of PASC (OR, 0.85; 95% CI, 0.84-0.86).

CONCLUSIONS AND RELEVANCE
In this cohort study of patients infected with COVID-19, patients with SMI compared with those without SMI were at increased risk of PASC, underscoring the need for coordinated mental health and COVID-19 care strategies.

Web | PDF | JAMA Network Open | Open Access

 

[Utsikt]

The finding that 27.7% of patients with SMI developed PASC, with significantly increased adjusted odds (OR = 1.10), aligns with research indicating that PASC commonly occurs among adults with SMI.3 Chronic stress and immune dysregulation associated with an SMI can exacerbate the risk of PASC, making these individuals more prone to persistent symptoms due to underlying physical and mental health vulnerabilities.19

19 is this:

Post-COVID-19 Depressive Symptoms: Epidemiology, Pathophysiology, and Pharmacological Treatment - PMC

The Coronavirus Disease 2019 (COVID-19) pandemic is still spreading worldwide over 2 years since its outbreak. The psychopathological implications in COVID-19 survivors such as depression, anxiety, and cognitive impairments are now recognized as ...

pmc.ncbi.nlm.nih.gov

It’s a shame they include references to so speculative claims.

Spoiler: Text on psychological factors

Psychological Stressor Induced by SARS-CoV-2 Infection

Apart from a direct effect of SARS-CoV-2 infection, significant psychological stressors may play a major role in the development of psychopathological outcomes in COVID-19 patients. Social isolation, quarantine, uncertainty about the future, wide exposure to media, and survivor guilt experienced by infected patients may induce depressive symptoms following the infection [97, 98].

During the COVID-19 pandemic, people have been forbidden to visit affected relatives during hospital stays, thus enhancing the feeling of isolation, loneliness, boredom, and fear about an uncertain future. Moreover, quarantine for infected patients also leads to loneliness and social isolation [99, 100].

Evidence from animal models has shown that social isolation alters activity, neurochemical function, and the neuroendocrine system, inducing pathological behavior and symptoms of anxiety, depression, and memory loss [101].

Psychological stress is known to activate the HPA axis and sympathetic nervous system (SNS), notably associated with mental health conditions including anxiety and depression [102]. Sustained psychological stress induces changes in levels of hormones and responsiveness of neurons and HPA to glucocorticoids [91, 103], thus affecting mood through immune modulation in the CNS [104].

Moreover, psychological stress may induce a proinflammatory microglia phenotype, contributing to neuroinflammation [105]. From a clinical point of view, exposure to early or recent stress is associated with a higher risk of an MDD episode [106], also affecting the brain structure and functional connectivity [107, 108], cognitive impairment [109], and incidence of suicidality [108].

Taken together, immune-neuroendocrine mechanisms directly induced by SARS-CoV-2 infection and by COVID-19-related psychological stressors could explain depressive symptomatology.