Favorable COVID‐19 course despite significant comorbidities in a ruxolitinib‐treated patient with primary myelofibrosis

Abstract

Advanced age and comorbidities are risk factors for severe SARS-CoV-2 infection and development of ARDS. 1,2 Elevated inflammatory parameters such as an increased white blood cell (WBC) count, C-reactive protein (CRP), interleukin-6 (IL-6), and soluble IL-2 receptor correlate with ARDS and multiorgan failure (MOF) in COVID-19 patients, 2 comparable to the so-called "cytokine storm" syndrome. Frontline treatment of COVID-19 infection consists of supportive care. In addition, off-label and experimental treatment options

STAT2 signaling restricts viral dissemination but drives severe pneumonia in SARS-CoV-2 infected hamsters

“…In conclusion, hamsters may be preferred above mice as infection model for the preclinical assessment of antiviral therapies, of vaccines, and of approaches that aim at tempering the COVID-19 immune pathogenesis in critically ill patients 18,65 . The latter may be achieved by repurposing anti-inflammatory drugs 66 such as IL-6 receptor antagonists (e.g., Tocilizumab) [67][68][69][70] or small molecule Jak/STAT inhibitors (e.g., Ruxolitinib 71,72 or Tofacitinib). Educated by our finding that STAT2 signaling plays a dual role in also limiting viral dissemination, targeting the virusinduced cytokine response and overshooting of macrophage activation may need to be complemented by (directly acting) antivirals 73 .…”

High mortality rate in COVID-19 patients with myeloproliferative neoplasms after abrupt withdrawal of ruxolitinib

“…The biological plausibility of this effect may be related to the devastating enhancement of inflammation ("cytokine storm") that follows the abrupt suspension of Ruxo, leading to the "ruxolitinib discontinuation syndrome", which in turn may lead to fatal clinical complications and multiorgan failure [13,14]. On the other hand, in observational studies, Ruxo itself has proven effective in improving survival in COVID-19 patients from the general population [15][16][17].…”

Small molecule stabilization of non-native protein-protein interactions of SARS-CoV-2 N protein as a mechanism of action against COVID-19

“…From this list, Ruxolitinib is already being tested in several clinical trials against COVID-19, and some results proving its effectiveness have been published (Koschmieder et al, 2020 ; La Rosée et al, 2020 ). In our simulations, this molecule was able to stabilize IF-1 and IF-2 , with a TIE of −81 and −114 kcal/mol respectively.…”