{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T16:51:20Z","timestamp":1780505480893,"version":"3.54.1"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T00:00:00Z","timestamp":1691971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>SARS-CoV-2 elicits a hyper-inflammatory response that contributes to increased morbidity and mortality in patients with COVID-19. In the case of HIV infection, despite effective anti-retroviral therapy, people living with HIV (PLWH) experience chronic systemic immune activation, which renders them particularly vulnerable to the life-threatening pulmonary, cardiovascular and other complications of SARS-CoV-2 co-infection. The focus of the study was a comparison of the concentrations of systemic indicators o\\f innate immune dysfunction in SARS-CoV-2-PCR-positive patients (n=174) admitted with COVID-19, 37 of whom were co-infected with HIV.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Participants were recruited from May 2020 to November 2021. Biomarkers included platelet-associated cytokines, chemokines, and growth factors (IL-1\u03b2, IL-6, IL-8, MIP-1\u03b1, RANTES, PDGF-BB, TGF-\u03b21 and TNF-\u03b1) and endothelial associated markers (IL-1\u03b2, IL-1Ra, ICAM-1 and VEGF).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PLWH were significantly younger (p=0.002) and more likely to be female (p=0.001); median CD4+ T-cell count was 256 (IQR 115 -388) cells\/\u03bcL and the median HIV viral load (VL) was 20 (IQR 20 -12,980) copies\/mL. Fractional inspired oxygen (FiO2) was high in both groups, but higher in patients without HIV infection (p=0.0165), reflecting a greater need for oxygen supplementation. With the exception of PDGF-BB, the levels of all the biomarkers of innate immune activation were increased in SARS-CoV-2\/HIV-co-infected and SARS-CoV-2\/HIV-uninfected sub-groups relative to those of a control group of healthy participants. The magnitudes of the increases in the levels of these biomarkers were comparable between the SARS-CoV-2 -infected sub-groups, the one exception being RANTES, which was significantly higher in the sub-group without HIV. After adjusting for age, sex, and diabetes in the multivariable model, only the association between HIV status and VEGF was statistically significant (p=0.034). VEGF was significantly higher in PLWH with a CD4+ T-cell count &amp;gt;200 cells\/\u03bcL (p=0.040) and those with a suppressed VL (p=0.0077).<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These findings suggest that HIV co-infection is not associated with increased intensity of the systemic innate inflammatory response during SARS-CoV-2 co-infection, which may underpin the equivalent durations of hospital stay, outcome and mortality rates in the SARS-CoV-2\/HIV-infected and -uninfected sub-groups investigated in the current study. The apparent association of increased levels of plasma VEGF with SARS-CoV-2\/HIV co-infection does, however, merit further investigation.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1235914","type":"journal-article","created":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T17:45:56Z","timestamp":1692035156000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Comparison of platelet-and endothelial-associated biomarkers of disease activity in people hospitalized with Covid-19 with and without HIV co-infection"],"prefix":"10.3389","volume":"14","author":[{"given":"Mieke A.","family":"van der Mescht","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen C.","family":"Steel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zelda","family":"de Beer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fareed","family":"Abdullah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Ueckermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa M.","family":"Rossouw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,8,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2018.12.756","article-title":"Cytokine release syndrome with chimeric antigen receptor T cell therapy","volume":"25","author":"Frey","year":"2019","journal-title":"Biol Blood Marrow Transplant"},{"key":"B2","doi-asserted-by":"publisher","first-page":"107995","DOI":"10.1016\/j.intimp.2021.107995","article-title":"Platelets in the perspective of COVID-19; pathophysiology of thrombocytopenia and its implication as prognostic and therapeutic opportunity","volume":"99","author":"Delshad","year":"2021","journal-title":"Int immunopharmacol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/jon.12770","article-title":"COVID-19 as a blood clotting disorder masquerading as a respiratory illness: a cerebrovascular perspective and therapeutic implications for stroke thrombectomy","volume":"30","author":"Janardhan","year":"2020","journal-title":"J Neuroimaging"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14849","article-title":"Thromboinflammation and the hypercoagulability of COVID-19","volume":"18","author":"Connors","year":"2020","journal-title":"J Thromb Haemost"},{"key":"B5","doi-asserted-by":"publisher","first-page":"8234","DOI":"10.3390\/ijms21218234","article-title":"Erythrocyte, platelet, serum ferritin, and P-selectin pathophysiology implicated in severe hypercoagulation and vascular complications in COVID-19","volume":"21","author":"Venter","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.776861","article-title":"Emerging role of platelet-endothelium interactions in the pathogenesis of severe SARS-CoV-2 infection-associated myocardial injury","volume":"13","author":"Rossouw","year":"2022","journal-title":"Front Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.310795","article-title":"Circulating platelets as mediators of immunity, inflammation, and thrombosis","volume":"122","author":"Koupenova","year":"2018","journal-title":"Circ Res"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2018.00121","article-title":"Platelets in immune response to virus and immunopathology of viral infections","volume":"5","author":"Hottz","year":"2018","journal-title":"Front Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.319117","article-title":"SARS-CoV-2 initiates programmed cell death in platelets","volume":"129","author":"Koupenova","year":"2021","journal-title":"Circ Res"},{"key":"B10","doi-asserted-by":"publisher","first-page":"109390","DOI":"10.1016\/j.intimp.2022.109390","article-title":"Toll-like receptor 7 regulates cardiovascular diseases","volume":"113","author":"Shafeghat","year":"2022","journal-title":"Int Immunopharmacol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1055\/a-1581-4355","article-title":"Platelets and COVID-19","volume":"41","author":"Rohlfing","year":"2021","journal-title":"Hamostaseologie"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-11-462432","article-title":"Emerging roles for platelets as immune and inflammatory cells","volume":"123","author":"Morrell","year":"2014","journal-title":"Blood J Am Soc Hematol"},{"key":"B13","volume-title":"Mid-year population estimates 2022","year":"2022"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0152588","article-title":"D-dimer levels before HIV seroconversion remain elevated even after viral suppression and are associated with an increased risk of non-AIDS events","volume":"11","author":"Freiberg","year":"2016","journal-title":"PloS One"},{"key":"B15","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1007\/s00395-008-0733-0","article-title":"The role of inflammatory cytokines in endothelial dysfunction","volume":"103","author":"Zhang","year":"2008","journal-title":"Basic Res Cardiol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.congress-2021.OA90","article-title":"Impact of persistent D-dimer elevation following recovery from COVID-19","volume":"16","author":"Lehmann","year":"2021","journal-title":"PloS One"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0050203","article-title":"Inflammatory and coagulation biomarkers and mortality in patients with HIV infection","volume":"5","author":"Kuller","year":"2008","journal-title":"PloS Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e32832995fa","article-title":"HIV increases markers of cardiovascular risk: results from a randomized, treatment interruption trial","volume":"23","author":"Calmy","year":"2009","journal-title":"AIDS"},{"key":"B19","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1111\/j.1468-1293.2010.00835.x","article-title":"IL-6 and D-dimer levels are associated with vascular dysfunction in patients with untreated HIV infection","volume":"11","author":"Baker","year":"2010","journal-title":"HIV Med"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021012250","article-title":"Vasculopathy in COVID-19","volume":"140","author":"Flaumenhaft","year":"2022","journal-title":"Blood"},{"key":"B21","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"2020","journal-title":"Lancet"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e531","DOI":"10.1212\/NXI.0000000000000531","article-title":"HIV is associated with endothelial activation despite ART, in a sub-Saharan African setting","volume":"6","author":"Kamtchum-Tatuene","year":"2019","journal-title":"Neurology-Neuroimmunol Neuroinflamm"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V93.12.4232","article-title":"Infection with human immunodeficiency virus-1 increases expression of vascular endothelial cell growth factor in T cells: implications for acquired immunodeficiency syndrome-associated vasculopathy","volume":"93","author":"Ascherl","year":"1999","journal-title":"Blood"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2004.037531","article-title":"Insular lesions, ECG abnorMalities, and outcome in acute stroke","volume":"76","author":"Christensen","year":"2005","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2014.4761","article-title":"The role of vascular endothelial growth factor in neurodegeneration and cognitive decline: exploring interactions with biomarkers of Alzheimer disease","volume":"72","author":"Hohman","year":"2015","journal-title":"JAMA Neurol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2007050629","article-title":"HIV-1 upregulates VEGF in podocytes","volume":"19","author":"Korgaonkar","year":"2008","journal-title":"J Am Soc Nephrol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1823","DOI":"10.1097\/QAD.0b013e3283489d1f","article-title":"The effect of HIV infection and HAART on inflammatory biomarkers in a population-based cohort of US women","volume":"25","author":"Keating","year":"2011","journal-title":"AIDS (London England)"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1235914\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T17:45:59Z","timestamp":1692035159000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1235914\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,14]]},"references-count":27,"alternative-id":["10.3389\/fimmu.2023.1235914"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1235914","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,14]]},"article-number":"1235914"}}