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  1. Article: Case series: Maraviroc and pravastatin as a therapeutic option to treat long COVID/Post-acute sequelae of COVID (PASC).

    Patterson, Bruce K / Yogendra, Ram / Guevara-Coto, Jose / Mora-Rodriguez, Rodrigo A / Osgood, Eric / Bream, John / Parikh, Purvi / Kreimer, Mark / Jeffers, Devon / Rutland, Cedric / Kaplan, Gary / Zgoda, Michael

    Frontiers in medicine

    2023  Volume 10, Page(s) 1122529

    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 ... ...

    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.
    Language English
    Publishing date 2023-02-08
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2775999-4
    ISSN 2296-858X
    ISSN 2296-858X
    DOI 10.3389/fmed.2023.1122529
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: 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

    Patterson, Bruce K. / Yogendra, Ram / Francisco, Edgar B. / Long, Emily / Pise, Amruta / Osgood, Eric / Bream, John / Kreimer, Mark / Jeffers, Devon / Beaty, Christopher / Heide, Richard Vander / Guevara-Coto, Jose / Mora-Rodríguez, Rodrigo A

    medRxiv

    Abstract: There have been concerning reports about people experiencing new onset persistent complications (greater than 30 days) following approved SARS-CoV-2 vaccines (BNT162b2 (Pfizer), mRNA-1273 (Moderna), Janssen (Johnson and Johnson), and ChAdOx1 nCoV-19 ( ... ...

    Abstract There have been concerning reports about people experiencing new onset persistent complications (greater than 30 days) following approved SARS-CoV-2 vaccines (BNT162b2 (Pfizer), mRNA-1273 (Moderna), Janssen (Johnson and Johnson), and ChAdOx1 nCoV-19 (AstraZeneca)). We sought to determine the immunologic abnormalities in these patients and to investigate whether the potential etiology was similar to Post-Acute Sequalae of COVID (PASC), or long COVID. We studied 50 individuals who received one of the approved COVID-19 vaccines and who experienced new onset PASC-like symptoms along with 45 individuals post-vaccination without symptoms as controls. We performed multiplex cytokine/chemokine profiling with machine learning as well as SARS-CoV-2 S1 protein detection on CD16+ monocyte subsets using flow cytometry and mass spectrometry. We determined that post-vaccination individuals with PASC-like symptoms had similar symptoms to PASC patients. When analyzing their immune profile, Post-vaccination individuals had statistically significant elevations of sCD40L (p<0.001), CCL5 (p=0.017), IL-6 (p=0.043), and IL-8 (p=0.022). Machine learning characterized these individuals as PASC using previously developed algorithms. Of the S1 positive post-vaccination patients, we demonstrated by liquid chromatography/ mass spectrometry that these CD16+ cells from post-vaccination patients from all 4 vaccine manufacturers contained S1, S1 mutant and S2 peptide sequences. Post-COVID vaccination individuals with PASC-like symptoms exhibit markers of platelet activation and pro-inflammatory cytokine production, which may be driven by the persistence of SARS-CoV-2 S1 proteins in intermediate and non-classical monocytes. The data from this study also cannot make any inferences on epidemiology and prevalence for persistent post-COVID vaccine symptoms. Thus, further studies and research need to be done to understand the risk factors, likelihood and prevalence of these symptoms.
    Keywords covid19
    Language English
    Publishing date 2024-03-24
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2024.03.24.24304286
    Database COVID19

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