Targeting the Monocytic-Endothelial-Platelet Axis with Maraviroc and Pravastatin as a Therapeutic Option to Treat Long COVID/ Post-Acute Sequelae of COVID (PASC)

Abstract

Post-acute sequelae of COVID (PASC), or long COVID, is a multisystem complication of SARS-CoV-2 infection that continues to debilitate millions worldwide thus highlighting the public health importance of identifying effective therapeutics to alleviate this illness. The pathophysiology behind PASC may be attributed to the recent discovery of persistent S1 protein subunit of SARS-CoV-2 in CD16+ monocytes up to 15 months after infection. CD16+ monocytes, which express both CCR5 and fractalkine receptors (CX3CR1), play a role in vascular homeostasis and endothelial immune surveillance. We believe targeting these receptors using the CCR5 antagonist, maraviroc, along with pravastatin, could disrupt the monocytic-endothelial-platelet axis that may be central to the etiology of PASC. Using five validated clinical scales (NYHA, MRC Dyspnea, COMPASS-31, modified Rankin, and Fatigue Severity Score) to measure 18 participants’ response to treatment, we observed significant clinical improvement in six to twelve weeks on a combination of maraviroc 300mg PO BID and pravastatin 10 mg PO daily. Subjective neurological (p=0.002), autonomic (p<0.0001), respiratory (p=0.0153), cardiac (p=0.002) and fatigue (p<0.0001) symptoms scores all decreased which correlated with statistically significant decreases in vascular markers sCD40L and VEGF. These findings suggest that by interrupting the monocytic-endothelial-platelet axis, maraviroc and pravastatin may restore the immune dysregulation observed in PASC and could be potential therapeutic options. This sets the framework for a future double-blinded, placebo-controlled randomized trial to further investigate the drug efficacy of maraviroc and pravastatin in treating PASC.

Persistence of S1 Spike Protein in CD16+ Monocytes up to 245 Days in SARS-CoV-2 Negative Post COVID-19 Vaccination Individuals with Post-Acute Sequalae of COVID-19 (PASC)-Like Symptoms

“…Elevated IL-8 was a unique marker in post- vaccination individuals with PASC-like symptoms. We recently found a statistically significant correlation between decreased IL-8 and improvement in the NYHA cardiac symptom score in PASC following treatment with a CCR5 antagonist and statin 11 .…”

SARS-CoV-2 S1 Protein Persistence in SARS-CoV-2 Negative Post-Vaccination Individuals with Long COVID/ PASC-Like Symptoms

“…Elevated IL-8 was a unique marker relative to PASC in post-vaccination individuals with PASC-like symptoms. We recently found a statistically signi cant correlation between decreased IL-8 and improvement in the NYHA cardiac symptom score in PASC following treatment with a CCR5 antagonist and statin 11 .…”

“…NCM bind to fractalkine expressed on vascular endothelial cells through the expression of the fractalkine receptor CX3CR1 on the surface of NCM 11 . Fractalkine is also upregulated by IL-1, IFN-γ, and TNF-α 12 , cytokines that we have reported to be elevated in PASC 9 .…”

Lots of long COVID treatment leads, but few are proven

“…In a preprint, Patterson and colleagues describe their results with Maraviroc and Pravastatin in 18 patients, who showed a statistically significant decrease in levels of inflammatory immune markers and subjective symptoms in weeks 6 to 12. For instance, in the case of fatigue, most patients went from a symptom score greater than 60 to less than 40 ( 19 ). IncellDx has patented the use of Maraviroc for treating coronavirus infections including COVID-19 ( 20 ).…”