Respiratory infections during lithium and valproate medication: a within-individual prospective study of 50,000 patients with bipolar disorder

Landén, Mikael; Larsson, Henrik; Lichtenstein, Paul; Westin, Johan; Song, Jie

doi:10.1186/s40345-020-00208-y

Cited by 16 publications

(14 citation statements)

References 36 publications

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“…63 Moreover, lithium exerts substantial immune-modulating and anti-inflammatory effects, 64 and valproate has been associated with a lower risk of respiratory infections. 65 Preliminary results from controlled and observational studies [66][67][68][69][70] also suggest that conventional antidepressants provide protective effects against COVID-19 complications. The foregoing finding would be in accordance with preclinical work documenting anti-inflammatory and/or anti-SARS-CoV-2 replication effects of select selective serotonin reuptake inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Association Between Mood Disorders and Risk of COVID-19 Infection, Hospitalization, and Death

et al. 2021

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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,

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Section: Discussionmentioning

confidence: 99%

Association Between Mood Disorders and Risk of COVID-19 Infection, Hospitalization, and Death

et al. 2021

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“…We propose that inhibition of N phosphorylation underlies the antiviral activity of lithium and other GSK-3 inhibitors; however, GSK-3 also regulates inflammatory responses ( 47 ), and lithium has been reported to have antiviral activity against other viruses, notably human herpes viruses ( 21 ), and more generally to reduce risk of respiratory infections ( 48 ). Thus, modulation of the inflammatory response by lithium may also contribute to the reduced risk of COVID-19 in patients taking lithium ( 49 ).…”

Section: Discussionmentioning

confidence: 99%

Targeting the coronavirus nucleocapsid protein through GSK-3 inhibition

Liu

Verma

García

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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The coronaviruses responsible for severe acute respiratory syndrome (SARS-CoV), COVID-19 (SARS-CoV-2), Middle East respiratory syndrome-CoV, and other coronavirus infections express a nucleocapsid protein (N) that is essential for viral replication, transcription, and virion assembly. Phosphorylation of N from SARS-CoV by glycogen synthase kinase 3 (GSK-3) is required for its function and inhibition of GSK-3 with lithium impairs N phosphorylation, viral transcription, and replication. Here we report that the SARS-CoV-2 N protein contains GSK-3 consensus sequences and that this motif is conserved in diverse coronaviruses, raising the possibility that SARS-CoV-2 may be sensitive to GSK-3 inhibitors, including lithium. We conducted a retrospective analysis of lithium use in patients from three major health systems who were PCR-tested for SARS-CoV-2. We found that patients taking lithium have a significantly reduced risk of COVID-19 (odds ratio = 0.51 [0.35–0.74], P = 0.005). We also show that the SARS-CoV-2 N protein is phosphorylated by GSK-3. Knockout of GSK3A and GSK3B demonstrates that GSK-3 is essential for N phosphorylation. Alternative GSK-3 inhibitors block N phosphorylation and impair replication in SARS-CoV-2 infected lung epithelial cells in a cell-type–dependent manner. Targeting GSK-3 may therefore provide an approach to treat COVID-19 and future coronavirus outbreaks.

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“…Valproate, a mood stabilizer, also may be associated with an increased risk of respiratory infections ( 92 ). By contrast, lithium, another mood stabilizer, seems to be associated with a decreased risk of respiratory infections and demonstrated potential antiviral properties at a preclinical level ( 92 , 93 ). Lithium has even been proposed as a candidate treatment for COVID-19.…”

Section: Discussionmentioning

confidence: 99%

COVID-19-Related Mortality Risk in People With Severe Mental Illness: A Systematic and Critical Review

et al. 2022

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Background: Increasing clinical evidence suggests that people with severe mental illness (SMI), including schizophrenia spectrum disorders, bipolar disorder (BD), and major depressive disorder (MDD), are at higher risk of dying from COVID-19. Several systematic reviews examining the association between psychiatric disorders and COVID-19-related mortality have recently been published. Although these reviews have been conducted thoroughly, certain methodological limitations may hinder the accuracy of their research findings.Methods: A systematic literature search, using the PubMed, Embase, Web of Science, and Scopus databases (from inception to July 23, 2021), was conducted for observational studies assessing the risk of death associated with COVID-19 infection in adult patients with pre-existing schizophrenia spectrum disorders, BD, or MDD. Methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS).Results: Of 1,446 records screened, 13 articles investigating the rates of death in patients with pre-existing SMI were included in this systematic review. Quality assessment scores of the included studies ranged from moderate to high. Most results seem to indicate that patients with SMI, particularly patients with schizophrenia spectrum disorders, are at significantly higher risk of COVID-19-related mortality, as compared to patients without SMI. However, the extent of the variation in COVID-19-related mortality rates between studies including people with schizophrenia spectrum disorders was large because of a low level of precision of the estimated mortality outcome(s) in certain studies. Most studies on MDD and BD did not include specific information on the mood state or disease severity of patients. Due to a lack of data, it remains unknown to what extent patients with BD are at increased risk of COVID-19-related mortality. A variety of factors are likely to contribute to the increased mortality risk of COVID-19 in these patients. These include male sex, older age, somatic comorbidities (particularly cardiovascular diseases), as well as disease-specific characteristics.Conclusion: Methodological limitations hamper the accuracy of COVID-19-related mortality estimates for the main categories of SMIs. Nevertheless, evidence suggests that SMI is associated with excess COVID-19 mortality. Policy makers therefore must consider these vulnerable individuals as a high-risk group that should be given particular attention. This means that targeted interventions to maximize vaccination uptake among these patients are required to address the higher burden of COVID-19 infection in this already disadvantaged group.

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Respiratory infections during lithium and valproate medication: a within-individual prospective study of 50,000 patients with bipolar disorder

Cited by 16 publications

References 36 publications

Association Between Mood Disorders and Risk of COVID-19 Infection, Hospitalization, and Death

Association Between Mood Disorders and Risk of COVID-19 Infection, Hospitalization, and Death

Targeting the coronavirus nucleocapsid protein through GSK-3 inhibition

COVID-19-Related Mortality Risk in People With Severe Mental Illness: A Systematic and Critical Review

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