Accepted for Publication: May 25, 2021.
Published Online: July 28, 2021. doi:10.1001/jamapsychiatry.2021.1818
Corresponding Author: Roger S. McIntyre, MD, University Health Network, 399 Bathurst St, MP 9-325, Toronto, ON M5T 2S8, Canada (roger.mcintyre@uhn.ca).
Author Contributions: Dr McIntyre had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Ceban, Lee, Xiong, Gill, Mansur, Rosenblat, Ho, McIntyre.
Acquisition, analysis, or interpretation of data: Ceban, Nogo, Carvalho, Lee, Nasri, Lui, Subramaniapillai, Liu, Joseph, Teopiz, Cao, Lin, Rosenblat, McIntyre.
Drafting of the manuscript: Ceban, Nogo, Carvalho, Lui, Liu, Teopiz, McIntyre.
Critical revision of the manuscript for important intellectual content: Ceban, Nogo, Carvalho, Lee, Nasri, Xiong, Subramaniapillai, Gill, Joseph, Cao, Mansur, Lin, Rosenblat, Ho, McIntyre.
Statistical analysis: Ceban, Carvalho.
Administrative, technical, or material support: Nogo, Carvalho, Nasri, Xiong, Lui, Subramaniapillai, Gill, Liu, Joseph, Rosenblat.
Supervision: Nogo, Lee, Mansur, Lin, Rosenblat, Ho, McIntyre.
Conflict of Interest Disclosures: Ms Lee reported receiving personal fees from Braxia Scientific Corp outside the submitted work. Ms Lui is a contractor to Braxia Scientific Corp. Ms Teopiz reported receiving personal fees from Braxia Scientific Corp outside the submitted work. Dr Rosenblat is the medical director of Braxia Health (formally known as the Canadian Rapid Treatment Center of Excellence and is a fully owned subsidiary of Braxia Scientific Corp), which provides ketamine and esketamine treatment for depression, and has received research grant support from the American Psychiatric Association, American Society of Psychopharmacology, Canadian Cancer Society, Canadian Psychiatric Association, Joseph M. West Family Memorial Fund, Timeposters Fellowship, University Health Network Centre for Mental Health, and University of Toronto and speaking, consultation, or research fees from Allergan, COMPASS, Janssen, Lundbeck, and Sunovion. Dr McIntyre reported receiving grant support from Canadian Institutes of Health Research, Global Alliance for Chronic Diseases, and Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, and AbbVie. Dr McIntyre is a chief executive officer of Braxia Scientific Corp.
2.Wiersinga
WJ , Rhodes
A , Cheng
AC , Peacock
SJ , Prescott
HC . Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review.
JAMA. 2020;324(8):782-793. doi:
10.1001/jama.2020.12839 3.Jordan
RE , Adab
P , Cheng
KK . Covid-19: risk factors for severe disease and death.
BMJ. 2020;368:m1198. doi:
10.1136/bmj.m1198 6.Rosenblat
JD , Cha
DS , Mansur
RB , McIntyre
RS . Inflamed moods: a review of the interactions between inflammation and mood disorders.
Prog Neuropsychopharmacol Biol Psychiatry. 2014;53:23-34. doi:
10.1016/j.pnpbp.2014.01.013 10.Varatharaj
A , Thomas
N , Ellul
MA ,
et al. Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study.
Lancet Psychiatry. 2020;7(10):875-882. doi:
10.1016/S2215-0366(20)30287-X 12.Taquet
M , Geddes
JR , Husain
M , Luciano
S , Harrison
PJ . 6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records.
Lancet Psychiatry. 2021;8(5):416-427. doi:
10.1016/S2215-0366(21)00084-5
15.Mazereel
V , Van Assche
K , Detraux
J , De Hert
M. COVID-19 vaccination for people with severe mental illness: why, what, and how?
Lancet Psychiatry. 2021;8(5):444-450. doi:
10.1016/S2215-0366(20)30564-2
18.Stroup
DF , Berlin
JA , Morton
SC ,
et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. JAMA. 2000;283(15):2008-2012. doi:10.1001/jama.283.15.2008
20.Stang
A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses.
Eur J Epidemiol. 2010;25(9):603-605. doi:
10.1007/s10654-010-9491-z 21.Higgins
JPT , Li
T , Deeks
JJ .
Choosing effect measures and computing estimates of effect. In:
Cochrane Handbook for Systematic Reviews of Interventions. Cochrane; 2019:143-176. doi:
10.1002/9781119536604.ch6
22.Chang
TS , Ding
Y , Freund
MK ,
et al. Prior diagnoses and medications as risk factors for COVID-19 in a Los Angeles Health System. Preprint posted online July 4, 2020.
medRxiv. doi:
10.1101/2020.07.03.20145581 23.Chang M, Moonesinghe R, Truman BI. COVID-19 hospitalization by race and ethnicity: association with chronic conditions among Medicare beneficiaries, January 1-September 30, 2020.
J Racial Ethn Health Disparities. 2021:1-10. doi:
10.1007/s40615-020-00960-y 24.Haimovich
AD , Warner
F , Young
HP ,
et al. Patient factors associated with SARS-CoV-2 in an admitted emergency department population.
Ann Emerg Med. 2020;1(4):569-577. doi:
10.1002/emp2.12145 25.Izurieta
HS , Graham
DJ , Jiao
Y ,
et al. Natural history of coronavirus disease 2019: risk factors for hospitalizations and deaths among >26 million US Medicare beneficiaries.
J Infect Dis. 2021;223(6):945-956. doi:
10.1093/infdis/jiaa767 26.Jeon
HL , Kwon
JS , Park
SH , Shin
JY . Association of mental disorders with SARS-CoV-2 infection and severe health outcomes: nationwide cohort study.
Br J Psychiatry. 2021:1-8. doi:
10.1192/bjp.2020.251PubMedGoogle Scholar 27.Ji
W , Huh
K , Kang
M ,
et al. Effect of underlying comorbidities on the infection and severity of COVID-19 in Korea: a nationwide case-control study.
J Korean Med Sci. 2020;35(25):e237. doi:
10.3346/jkms.2020.35.e237
PubMedGoogle Scholar 28.Orlando
V , Rea
F , Savaré
L ,
et al. Development and validation of a clinical risk score to predict the risk of SARS-CoV-2 infection from administrative data: a population-based cohort study from Italy.
PLoS One. 2021;16(1):e0237202. doi:
10.1371/journal.pone.0237202
PubMedGoogle Scholar 29.Poblador-Plou
B , Carmona-Pírez
J , Ioakeim-Skoufa
I ,
et al; EpiChron Group. Baseline chronic comorbidity and mortality in laboratory-confirmed COVID-19 cases: results from the PRECOVID study in Spain.
Int J Environ Res Public Health. 2020;17(14):5171. doi:
10.3390/ijerph17145171
PubMedGoogle ScholarCrossref 30.Rodríguez-Molinero
A , Gálvez-Barrón
C , Miñarro
A ,
et al; COVID-19 Research Group of CSAPG. Association between COVID-19 prognosis and disease presentation, comorbidities and chronic treatment of hospitalized patients.
PLoS One. 2020;15(10):e0239571. doi:
10.1371/journal.pone.0239571
PubMedGoogle Scholar 32.Yang
H , Chen
W , Hu
Y ,
et al. Pre-pandemic psychiatric disorders and risk of COVID-19: a UK Biobank cohort analysis.
Lancet Healthy Longev. 2020;1(2):e69-e79. doi:
10.1016/S2666-7568(20)30013-1 34.Taquet
M , Luciano
S , Geddes
JR , Harrison
PJ . Bidirectional associations between COVID-19 and psychiatric disorder: retrospective cohort studies of 62 354 COVID-19 cases in the USA.
Lancet Psychiatry. 2021;8(2):130-140. doi:
10.1016/S2215-0366(20)30462-4 35.van der Meer
D , Pinzón-Espinosa
J , Lin
BD ,
et al. Associations between psychiatric disorders, COVID-19 testing probability and COVID-19 testing results: findings from a population-based study.
B J Psych Open. 2020;6(5):e87. doi:
10.1192/bjo.2020.75
PubMedGoogle Scholar 36.Yanover
C , Mizrahi
B , Kalkstein
N ,
et al. What factors increase the risk of complications in SARS-CoV-2-infected patients? a cohort study in a nationwide Israeli health organization.
JMIR Public Health Surveill. 2020;6(3):e20872. doi:
10.2196/20872
PubMedGoogle Scholar 37.Kundi
H , Çetin
EHÖ , Canpolat
U ,
et al. The role of frailty on adverse outcomes among older patients with COVID-19.
J Infect. 2020;81(6):944-951. doi:
10.1016/j.jinf.2020.09.029 38.Douville
NJ , Douville
CB , Mentz
G ,
et al. Clinically applicable approach for predicting mechanical ventilation in patients with COVID-19.
Br J Anaesth. 2021;126(3):578-589. doi:
10.1016/j.bja.2020.11.034 39.Azar
K , Shen
Z , Romanelli
RJ ,
et al. Disparities in outcomes among COVID-19 patients in a large health care system in California.
Health Aff (Millwood). 2020;39(7):1253-1262. doi:
10.1377/hlthaff.2020.00598
41.Wang
Q , Xu
R , Volkow
ND . Increased risk of COVID-19 infection and mortality in people with mental disorders: analysis from electronic health records in the United States.
World Psychiatry. 2021;20(1):124-130. doi:
10.1002/wps.20806 42.Salvatore
M , Gu
T , Mack
JA ,
et al. A phenome-wide association study (PheWAS) of COVID-19 outcomes by race using the electronic health records data in Michigan Medicine.
J Clin Med. 2021;10(7):1351. doi:
10.3390/jcm10071351 43.Barili
F , Parolari
A , Kappetein
PA , Freemantle
N . Statistical Primer: heterogeneity, random- or fixed-effects model analyses?
Interact CardioVasc Thorac Surg. 2018;27(3):317-321. doi:
10.1093/icvts/ivy163 44.Deeks JJ, Higgins JPT, Altman DG, eds. Analysing data and undertaking meta-analyses. In:
Cochrane Handbook for Systematic Reviews of Interventions. Cochrane; 2008:243-296. doi:
10.1002/9780470712184.ch9 45.Schünemann H.J., Higgins JPT, Vist GE, et al, eds.
Completing ‘Summary of findings’ tables and grading the certainty of the evidence. In:
Cochrane Handbook for Systematic Reviews of Interventions. Cochrane; 2019:375-402. doi:
10.1002/9781119536604.ch14 47.Abrams
EM , Szefler
SJ . COVID-19 and the impact of social determinants of health.
Lancet Respir Med. 2020;8(7):659-661. doi:
10.1016/S2213-2600(20)30234-4
50.Dickerson
F , Schroeder
J , Katsafanas
E ,
et al. Cigarette smoking by patients with serious mental illness, 1999–2016: an increasing disparity.
Psychiatr Serv. 2018;69(2):147-153. doi:
10.1176/appi.ps.201700118 51.Covey
LS , Glassman
AH , Stetner
F . Cigarette smoking and major depression.
J Addict Dis. 1998;17(1):35-46. doi:
10.1300/J069v17n01_04 52.Wang
QQ , Kaelber
DC , Xu
R , Volkow
ND . COVID-19 risk and outcomes in patients with substance use disorders: analyses from electronic health records in the United States.
Mol Psychiatry. 2021;26(1):30-39. doi:
10.1038/s41380-020-00880-7 53.Hert MDE, Correll CU, Bobes J, et al. Physical illness in patients with severe mental disorders, I: prevalence, impact of medications and disparities in health care.
World Psychiatry. 2011;10(1):52-77. doi:
10.1002/j.2051-5545.2011.tb00014.x 57.Dowlati
Y , Herrmann
N , Swardfager
W ,
et al. A meta-analysis of cytokines in major depression.
Biol Psychiatry. 2010;67(5):446-457. doi:
10.1016/j.biopsych.2009.09.033 58.Giamarellos-Bourboulis
E , Netea
MG , Rovina
N ,
et al. Complex immune dysregulation in COVID-19 patients with severe respiratory failure.
Cell Host Microbe. 2020;27(6):992-1000.e3. doi:
10.1016/j.chom.2020.04.009
59.Obiora
E , Hubbard
R , Sanders
RD , Myles
PR . The impact of benzodiazepines on occurrence of pneumonia and mortality from pneumonia: a nested case-control and survival analysis in a population-based cohort.
Thorax. 2013;68(2):163-170. doi:
10.1136/thoraxjnl-2012-202374
PubMedGoogle ScholarCrossref 60.Dzahini
O , Singh
N , Taylor
D , Haddad
PM . Antipsychotic drug use and pneumonia: systematic review and meta-analysis.
J Psychopharmacol. 2018;32(11):1167-1181. doi:
10.1177/0269881118795333 62.Govind
R , Fonseca de Freitas
D , Pritchard
M , Hayes
RD , MacCabe
JH . Clozapine treatment and risk of COVID-19 infection: retrospective cohort study.
Br J Psychiatry. 2020:1-7. doi:
10.1192/bjp.2020.151
PubMedGoogle Scholar 64.Beurel
E , Jope
RS . Inflammation and lithium: clues to mechanisms contributing to suicide-linked traits.
Transl Psychiatry. 2014;4(12):e488. doi:
10.1038/tp.2014.129 65.Landén
M , Larsson
H , Lichtenstein
P , Westin
J , Song
J . Respiratory infections during lithium and valproate medication: a within-individual prospective study of 50,000 patients with bipolar disorder.
Int J Bipolar Disord. 2021;9(1):4. doi:
10.1186/s40345-020-00208-y 66.Nobile
B , Durand
M , Olié
E ,
et al. Clomipramine could be useful in preventing neurological complications of SARS-CoV-2 infection.
J Neuroimmune Pharmacol. 2020;15(3):347-348. doi:
10.1007/s11481-020-09939-2 67.Hoertel
N , Sánchez-Rico
M , Vernet
R ,
et al; AP-HP / Universities/INSERM COVID-19 Research Collaboration and AP-HP COVID CDR Initiative. Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study.
Mol Psychiatry. 2021. doi:
10.1038/s41380-021-01021-4
PubMedGoogle Scholar 69.Seftel
D , Boulware
DR . Prospective cohort of fluvoxamine for early treatment of coronavirus disease 19.
Open Forum Infect Dis. 2021;8(2):ofab050. doi:
10.1093/ofid/ofab050 70.Lenze
EJ , Mattar
C , Zorumski
CF ,
et al. Fluvoxamine vs placebo and clinical deterioration in outpatients with symptomatic COVID-19: a randomized clinical trial.
JAMA. 2020;324(22):2292-2300. doi:
10.1001/jama.2020.22760 72.Zimniak
M , Kirschner
L , Hilpert
H , Seibel
J , Bodem
J . The serotonin reuptake inhibitor fluoxetine inhibits SARS-CoV-2. Published online June 17, 2020. bioRxiv 5809.
73.Rosenthal
N , Cao
Z , Gundrum
J , Sianis
J , Safo
S . Risk factors associated with in-hospital mortality in a US national sample of patients with COVID-19.
JAMA Netw Open. 2020;3(12):e2029058. doi:
10.1001/jamanetworkopen.2020.29058 75.Kim
W , Han
JM , Lee
KE . Predictors of mortality in patients with COVID-19: a systematic review and meta-analysis.
Korean J Clin Pharmacy. 2020;30(3):169-176. doi:
10.24304/kjcp.2020.30.3.169 76.Zhang
F , Xiong
Y , Wei
Y ,
et al. Obesity predisposes to the risk of higher mortality in young COVID-19 patients.
J Med Virol. 2020;92(11):2536-2542. doi:
10.1002/jmv.26039 78.Yoo
JY , Dutra
SVO , Fanfan
D ,
et al. Comparative analysis of COVID-19 guidelines from six countries: a qualitative study on the US, China, South Korea, the UK, Brazil, and Haiti.
BMC Public Health. 2020;20(1):1853. doi:
10.1186/s12889-020-09924-7 79.Page
MJ , Higgins
JPT , Sterne
JAC . Assessing risk of bias due to missing results in a synthesis. In: Cochrane Handbook for Systematic Reviews of Interventions. Cochrane; 2019:349-374.