Case series: 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. One explanation 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 propose targeting these receptors using the CCR5 antagonist, maraviroc, along with pravastatin, a fractalkine inhibitor, 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 6 to 12 weeks on a combination of maraviroc 300 mg per oral twice a day and pravastatin 10 mg per oral daily. Subjective neurological, autonomic, respiratory, cardiac and fatigue 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.

CCR5/CXCR3 antagonist TAK-779 prevents diffuse alveolar damage of the lung in the murine model of the acute respiratory distress syndrome

“…At the same time, maraviroc strongly inhibits SARS-CoV-2 Mpro and suppresses the coronavirus infection development ( Shamsi et al, 2020 ). In “long-term COVID-19,” the combination of maraviroc and pravastatin improved clinical indicators among 18 patients in a case study ( Patterson et al, 2023 ). As of today, two clinical trials (NCT04435522 and NCT04710199) have been completed and two (NCT04441385 and NCT04475991) have been terminated.…”

Scrutinizing Clinical Biomarkers in a Large Cohort of Patients with Lyme Disease and Other Tick-Borne Infections

“…In SARS-CoV-2 infection, which shares certain similarities with Lyme disease, including lymphopenia in the early stages of the disease [ 57 , 58 ] and chronic symptoms [ 66 ], cytokine profiling in patients revealed differences that could be associated with symptom severity and a likelihood of developing chronic symptoms [ 66 ]. Persistent activation through the CCR5 receptor on monocytes triggering downstream signaling cascades involving platelets and endothelial cells may be responsible for the symptoms of post-acute sequelae of COVID-19 [ 66 , 67 ]. Investigations into immune processes related to TBIs may lead to discovering the mechanisms behind chronic symptoms.…”

CCR5/CXCR3 antagonist TAK-779 prevents diffuse alveolar damage of the lung in murine model of the SARS-CoV-2-related acute respiratory distress syndrome

“…At the same time, maraviroc strongly inhibits SARS-CoV-2 Mpro and supresses the coronavirus infection development [89]. In “long COVID-19”, the combination of maraviroc and pravastatin improved clinical indicators among 18 patients in a case study [90]. As of today, two clinical trials (NCT04435522 and NCT04710199) have been completed and two (NCT04441385 and NCT04475991) have been terminated.…”