ABSTRACT
Background. HIV is a significant risk factor for acquiring SARS-CoV-2 infection and is associated with increased risk of mortality from COVID-19. Information on the clinical characteristics of persons living with HIV(PLWH) hospitalized due to COVID-19 infection are inconsistent and sparse. As Miami area is currently the epicenter of new HIV infection, an understanding of the clinical characteristics of COVID-19 in hospitalized HIV patients in South Florida is needful. Methods. This is a single center retrospective case series analysis of individuals with HIV hospitalized with COVID-19 from March 1, 2020 to March 31, 2021. We analyzed relevant data related to demographics, comorbidities, clinical presentation, HIV viral load and CD4 profiles, serum inflammatory markers, COVID-19 treatment and survival. Results. 25 patients were identified. The demographic, socioeconomic and clinical data are described in Table 1. 88% of subjects. were on HIV antiretroviral treatment (ART) but only 60% had CD4 counts > 200cells/mm3. More study results are shown in Figures 1 and 2. The serum ferritin ranged from 29 to 40,577ng/ mL while serum creatinine ranged from 0.51 to 2.8mg/dL, mean 1.04± 0.46 mg/ dL. The Pearson correlation between serum ferritin and serum creatinine (SCreat) was 0.715, p < 0.001 and between lymphopenia and SCreat, it was 0.544, p=0.005. 40% of subjects with CD4 < 200 cells/mm3 died compared to 33% with CD4 > 200 cells/mm3. Conclusion. This first case series of hospitalized COVID-19 patients in PLWH illustrate important demographic and socioeconomic trends with an imbalance towards African Americans. The group mortality rate appear to be higher compared to the overall mortality rate of COVID-19 reported in the general population or other published HIV-COVID-19 coinfection case series. This is not surprising given the fact that only 64% of the cohort had undetected viral load and only 60% had CD4 counts > 200 despite reported 88% ART use. Correlations between lymphopenia and serum ferritin on one hand and serum creatinine on the other hand should be further explored in a larger case series or prospective study. Since COVID-19 mortality is related to HIV severity, improving socioeconomic status and ART compliance could play a big role in positively improving outcome of hospitalized HIV-COVID 19 patients.
ABSTRACT
The coronavirus SARS-CoV-2 is cause of a global pandemic of a pneumonia-like disease termed Coronavirus Disease 2019 (COVID-19). COVID-19 presents a high mortality rate, estimated at 3.4%. More than 1 out of 4 hospitalized COVID-19 patients require admission to an Intensive Care Unit (ICU) for respiratory support, and a large proportion of these ICU-COVID-19 patients, between 17% and 46%, have died. In these patients COVID-19 infection causes an inflammatory response in the lungs that can progress to inflammation with cytokine storm, Acute Lung Injury (ALI), Acute Respiratory Distress Syndrome (ARDS), thromboembolic events, disseminated intravascular coagulation, organ failure, and death. Mesenchymal Stem Cells (MSCs) are potent immunomodulatory cells that recognize sites of injury, limit effector T cell reactions, and positively modulate regulatory cell populations. MSCs also stimulate local tissue regeneration via paracrine effects inducing angiogenic, anti-fibrotic and remodeling responses. MSCs can be derived in large number from the Umbilical Cord (UC). UC-MSCs, utilized in the allogeneic setting, have demonstrated safety and efficacy in clinical trials for a number of disease conditions including inflammatory and immune-based diseases. UC-MSCs have been shown to inhibit inflammation and fibrosis in the lungs and have been utilized to treat patients with severe COVID-19 in pilot, uncontrolled clinical trials, that reported promising results. UC-MSCs processed at our facility have been authorized by the FDA for clinical trials in patients with an Alzheimer's Disease, and in patients with Type 1 Diabetes (T1D). We hypothesize that UC-MSC will also exert beneficial therapeutic effects in COVID-19 patients with cytokine storm and ARDS. We propose an early phase controlled, randomized clinical trial in COVID-19 patients with ALI/ARDS. Subjects in the treatment group will be treated with two doses of UC-MSC (l00 × 106 cells). The first dose will be infused within 24 hours following study enrollment. A second dose will be administered 72 ± 6 hours after the first infusion. Subject in the control group will receive infusion of vehicle (DPBS supplemented with 1% HSA and 70 U/kg unfractionated Heparin, delivered IV) following the same timeline. Subjects will be evaluated daily during the first 6 days, then at 14, 28, 60, and 90 days following enrollment (see Schedule of Assessment for time window details). Safety will be determined by adverse events (AEs) and serious adverse events (SAEs) during the follow-up period. Efficacy will be defined by clinical outcomes, as well as a variety of pulmonary, biochemical and immunological tests. Success of the current study will provide a framework for larger controlled, randomized clinical trials and a means of accelerating a possible solution for this urgent but unmet medical need. The proposed early phase clinical trial will be performed at the University of Miami (UM), in the facilities of the Diabetes Research Institute (DRI), UHealth Intensive Care Unit (ICU) and the Clinical Translational Research Site (CTRS) at the University of Miami Miller School of Medicine and at the Jackson Memorial Hospital (JMH).