Antiviral, immunomodulatory, and neuroprotective effect of lithium.

Currently, in psychiatry, lithium is a drug of choice as a mood stabilizer in the maintenance treatment of bipolar disorder for the prevention of manic and depressive recurrences. The second most important psychiatric use of lithium is probably increasing the efficacy of antidepressants in treatment-resistant depression. In addition to its mood-stabilizing properties, lithium exerts antisuicidal, antiviral, immunomodulatory, and neuroprotective effects. The goal of the review is to describe the experimental and clinical studies on the last three properties of lithium. Antiviral effects of lithium pertain mostly to DNA viruses, especially herpes viruses. The therapeutic effects of lithium in systemic and topical administration on labial and genital herpes were demonstrated in clinical studies. There is also some evidence, mostly in experimental studies, that lithium possesses antiviral activity against RNA viruses, including coronaviruses. The immunomodulatory effect of lithium can mitigate "low-grade inflammatory" conditions in bipolar illness. The neuroprotective properties of lithium make this ion a plausible candidate for the prevention and treatment of neurodegenerative disorders. A favorable effect of lithium was shown in experimental models of neurodegenerative disorders. On the clinical level, some preventive action against dementia and moderately therapeutic activity in Alzheimer's disease, and mild cognitive impairment were observed. Despite promising results of lithium obtained in animal models of Huntington's disease and amyotrophic lateral sclerosis, they have not been confirmed in clinical studies. A suggestion for common mechanisms of antiviral, immunomodulatory, and neuroprotective effects of lithium is advanced.

Potential mechanisms underlying lithium treatment for Alzheimer's disease and COVID-19.

Disruption of intracellular Ca2+ homeostasis plays an important role as an upstream pathology in Alzheimer's disease (AD), and correction of Ca2+ dysregulation has been increasingly proposed as a target of future effective disease-modified drugs for treating AD. Calcium dysregulation is also an upstream pathology for the COVID-19 virus SARS-CoV-2 infection and replication, leading to host cell damage. Clinically available drugs that can inhibit the disturbed intracellular Ca2+ homeostasis have been repurposed to treat COVID-19 patients. This narrative review aims at exploring the underlying mechanism by which lithium, a first line drug for the treatment of bipolar disorder, inhibits Ca2+ dysregulation and associated downstream pathology in both AD and COVID-19. It is suggested that lithium can be repurposed to treat AD patients, especially those afflicted with COVID-19.

Association between serum lithium level and incidence of COVID-19 infection.

An antiviral effect of lithium has been proposed, but never investigated for coronavirus disease 2019 (COVID-19). Using electronic health records of 26 554 patients with documented serum lithium levels during the pandemic, we show that the 6-month COVID-19 infection incidence was lower among matched patients with 'therapeutic' (0.50-1.00) versus 'subtherapeutic' (0.05-0.50) lithium levels (hazard ratio (HR) = 0.82, 95% CI 0.69-0.97, P = 0.017) and among patients with 'therapeutic' lithium levels versus matched patients using valproate (HR = 0.79, 95% CI 0.67-0.92, P = 0.0023). Lower rates of infection were observed for both new COVID-19 diagnoses and positive polymerase chain reaction tests, regardless of underlying psychiatric diagnosis and vaccination status.

Supratherapeutic lithium levels in COVID-19 infection.

Lithium levels are often checked in the inpatient setting when a patient has clear indications of acute kidney injury. Lithium levels can become supratherapeutic in COVID-19 infection even after normalization of creatinine. Lithium levels should be checked routinely in patients with COVID-19 infection in order to avoid supratherapeutic levels.

Lithium and coronaviral infections. A scoping review.

The current rapid spread of the novel coronavirus (2019-nCoV) originating from Wuhan, China, calls for a rapid response from the research community. Lithium is widely used to treat bipolar disorder, but has been shown to exhibit antiviral activity. This brief review took a systematic approach to identify five in vitro studies reporting on the influence of lithium on coronaviral infections. We propose that in the case of urgent need, lithium be explored as a potential treatment or prophylaxis for the novel Wuhan coronavirus (2019-nCoV).

Lithium as a candidate treatment for COVID-19: Promises and pitfalls.

The pandemic of respiratory illness caused by a novel coronavirus (SARS-nCoV-2) is a global health crisis. Despite numerous preliminary results, there is as yet no treatment of proven efficacy for this condition. In this context, the pharmacological properties of lithium, better known as a treatment for mood disorders, merit closer examination. Lithium has shown in vitro efficacy at inhibiting the replication of coronaviruses responsible for gastrointestinal and respiratory diseases in animals. It has immunomodulatory properties that may be of additional benefit in moderating the host inflammatory response to the novel coronavirus (SARS-CoV-2). Furthermore, there is evidence that lithium may exert a protective action against upper respiratory infections and influenza-like illnesses in patients taking it for other indications. These promising reports must be balanced against the narrow therapeutic index and high risk of toxicity associated with lithium therapy, its documented interactions with several commonly used drugs, and the absence of evidence of its efficacy against coronaviruses responsible for human disease. Nevertheless, naturalistic studies of the risk of COVID-19 in patients already receiving lithium could provide indirect evidence of its efficacy, and understanding the putative antiviral and immune-regulatory mechanisms of lithium in models of SARS-CoV-2 infection may provide leads for the development of safer and more effective treatments with a specific action against COVID-19.