Lithium toxicity at therapeutic doses as a fallout of COVID-19 infection: a case series and possible mechanisms

Abstract

Supplemental Digital Content is available in the text.

Case Reports

“…The common features of the previous case reports and the current report were the elevated lithium levels and confusion, [15][16][17] and all indicators were that lithium had been prescribed appropriately and that the levels had been stable and in a therapeutic range before the acute illness. Patient 1 in our series had an elevated lithium level (1.4 mEq/L) over 1 year before becoming infected with SARS-CoV-2, and his toxic state emerged over 1 month after the infection.…”

“…While lithium may have protective features that diminish the probability of infection with SARS-CoV-2, 12 – 14 many taking lithium still become ill with COVID-19. There have been 3 published case reports of lithium toxicity associated with COVID-19 to date 15 – 17 that emphasize the temporal relationship between the illness COVID-19 and lithium toxicity. Herein, we add 2 additional cases that demonstrate the association lithium toxicity with acute kidney injury, as measured by the estimated glomular filtration rate (eGFR) and clinical symptoms.…”

Letter to Editor. Therapy with lithium as a protective factor against SARS-CoV-2 infection? Observations from the disease outbreak.

“…In the analyzed group, SARS-CoV-2 infection occurred in approximately ¼ of patients -in the majority of them the infection was mild, one patient died of pneumonia and two patients developed lithium intoxication. It is worth adding that so far four other cases of lithium intoxication in the course of COVID-19 have been described in the literature, and one of the mentioned risk factors for occurrence of this complication is dehydration during infection [12,18].…”

“…Among the proposed mechanisms of the antiviral and immunomodulatory effects of lithium are: (1) inhibition of the activity of glycogen synthase kinase 3β (GSK-3β) -it is a pro-inflammatory protein, inducing apoptosis and the expression of proinflammatory cytokines, e.g., IL-6 (interleukin 6) and TNF-alpha (tumor necrosis factor α); (2) competition of lithium ion with magnesium ions: magnesium is a cofactor of enzymes necessary in the process of viral replication -its substitution by lithium inactivates viral polymerases; (3) increased activity of B lymphocytes (stimulation of antibody production), increased proliferation of T lymphocytes, decreased ratio of regulatory to cytotoxic T lymphocytes -possible influence of lithium on gene expression in lymphocytes; (4) inhibition of the phosphatidylinositol signaling pathway; (5) stimulation of autophagy; (6) inhibition of cyclooxygenase 2 expression [5,[10][11][12][13][14][15].…”

Lithium Therapy in COVID-19 with Bipolar Affective Disorder—A Case Series

“…4 BPAD patients on lithium maintenance therapy have been reported to come to emergency units with manifest signs of lithium toxicity after contracting COVID-19. 5,6 Here, we report the management of two such patients of BPAD who came to a tertiary COVID care center a few weeks apart. We highlight the need for early identification of and intervention for toxicity in BPAD patients on lithium therapy who contract COVID-19.…”