Transient leukocytopenia following combination therapy for COVID-19

Abstract

Background Combination therapy with dexamethasone, remdesivir, and baricitinib has become a promising treatment for moderate or severe COVID-19; however, we have observed transient leukocytopenia in COVID-19 patients who received combination therapy. Methods Twelve consecutive COVID-19 patients treated with combination therapy were included in this retrospective analysis. Blood cell counts collected at the following three time points were analyzed: before the start of therapy (period 1), within 24 h of starting therapy (period 2), and within 48 h of period 2 (period 3). Results The leukocyte count significantly decreased in period 2 compared to period 1 and then significantly increased in period 3 without withdrawal of baricitinib. The neutrophil count transiently decreased in period 2 and recovered in period 3. Conclusions Clinicians should be aware of transient leukocytopenia in patients with COVID-19 during the early phase of combination therapy.

Transient Leukopenia Induced by Combination Therapy for Severe SARS-CoV-2 Pneumonia

“…The first evidence that combination therapy for SARS-CoV-2 can induce transient leukocytopenia was derived from a retrospective analysis that included 12 SARS-CoV-2 patients requiring supplemental oxygen in the form of a nasal cannula, high-flow nasal cannula or MV treated with combination therapy of dexamethasone, remdesivir and baricitinib. Leukocytopenia occurred within 24 hours in all 12 patients and resolved quickly even without medication discontinuation [ 3 ] .…”

“…Second, as baricitinib is a reversible inhibitor of Janus kinase (JAK) 1/JAK2, which suppresses cytokine-induced phosphorylation of signal transducer and activator of transcription 3 (STAT3), it potentially induces short-term leukopenia. Finally, inhibition of STAT3 phosphorylation reduces intracellular adhesion molecule 1 (ICAM1) expression, which might inhibit neutrophilic adhesion to blood vessel walls and facilitate extravascular migration [ 3 ] .…”

“…Following this data, the SAR-CoV-2 treatment protocol in hundreds of hospitals was changed to a 10-day course of IV remdesivir and dexamethasone and a 14-day course of oral baricitinib. However, the data regarding the side effects of this combination therapy are limited to case reports [ 3 ] . This case report aims to highlight transient leukopenia as a potentially life-threatening side effect of this combination therapy.…”

Oral anti-COVID-19 drugs that were recently evaluated by FDA or EMA: a review

“…Combined with steroids, baricitinib also seems to be as efficient as anakinra when it comes to the mortality rate [86]. In spite of concerns on its safety [87][88][89][90][91][92][93], the meta-analyses generally show that baricitinib is suitable for treatment of COVID-19 [94][95][96][97][98][99][100][101][102][103]. Baricitinib is authorised for emergency use along with remdesivir by FDA [106,108,109] in 1 mg and 2 mg pills.…”

Combination Therapies against COVID-19

“…A living guideline from the WHO published 14 January 2022 strongly recommended the use of baricitinib as an alternative to interleukin-6 (IL-6) receptor blockers, in combination with corticosteroids, in patients with severe or critical COVID-19 (https://www.who.int/teams/health-care-r eadiness/covid-19/therapeutics). Of note, baricitinib, used alone or as a combination with remdesivir, may bring about some adverse effects, such as liver injury [89] and transient leukocytopenia [90]. Tipifarnib is a mighty farnesyltransferase inhibitor with the potential as an anticancer remedy and has completed phase III clinical trial [74].…”