ABSTRACT
Background: Neurocognitive dysfunction is common in long COVID and in people living with HIV (PWH). It is unknown whether PWH experience different disturbances in neurocognitive function following COVID-19 compared to HIVseronegative people. Method(s): The amfAR-Johns Hopkins University COVID Recovery Study is a prospective observational cohort study consisting of four groups: participants who had SARS-CoV-2 infection for the first time within 30 days prior to enrollment with HIV (PWH, arm 1) and without HIV (arm 2);participants with no history of SARS-CoV-2 infection with HIV (arm 3) and without HIV (arm 4). 93.5% of the cohort had received a COVID-19 vaccine prior to enrollment. Cognitive tests were administered at 1-and 4-months post symptom onset (arms 1-2) or post-enrollment (arms 3-4) in seven domains. Age standardized scores (all tests) and age-sex-and education-standardized scores (verbal fluency) were obtained. Standardized scores were compared using the Mann-Whitney U Test and the Kruskal-Wallis test. Result(s): PWH scored lower than HIV-seronegative participants at 1 and 4 months post-COVID on three tests: the Hopkins Verbal Learning Test-Revised (HVLT-R) learning (M1, p=0.011, M4, p=0.015), HVLT-R memory (M1, p=0.029, M4, p=0.007), and category-cued verbal fluency (VF;M1&4, p< 0.001). For the majority of timepoints, PWH who were post-COVID produced equivalent scores as PWH who never had COVID (p-levels > 0.05). Comparing post-COVID HIV-seronegative people to those who never had COVID, post-COVID participants scored lower than never-COVID participants on the Oral Trail Making Test part A (OTMT) test of processing speed at month 1 (p=0.033). Between month 1 and 4, HIV-seronegative people who were post-COVID showed improvements in HVLT-R Recognition (p=0.039), OTMT A (p=0.003), and OTMT B test of executive function (p=0.032). Conclusion(s): Neurocognitive scores in PWH were independent of COVID status, suggesting that higher frequencies of post-COVID neurocognitive dysfunction in PWH compared to HIV-seronegative people are due to HIV-associated factors more so than COVID. HIV-seronegative, post-COVID people demonstrate diminished recognition memory, processing speed, and executive function at 1 month post-COVID that improves by 4 months. Post-COVID neurocognitive dysfunction is present, if temporary, even in a highly vaccinated cohort of people.
ABSTRACT
Background: HIV is a risk factor for severe acute COVID-19, but it is unknown whether HIV is a risk factor for long COVID. Method(s): We conducted a prospective observational cohort study of US adults with HIV (PWH) and HIV-seronegative adults with first SARS-CoV-2 infection within 4 weeks together with people who never had COVID-19. At enrollment, participants recalled the presence and severity of 49 long COVID-associated symptoms in the month prior to COVID-19. The same symptom survey was administered at 1, 2, 4, and 6 months post-COVID or post-enrollment for never- COVID participants. Post-COVID participants donated blood 1 and 4 months post-COVID, and never-COVID participants donated blood 0-1 times. Antibody titers to 18 coronavirus antigens and levels of 30 cytokines and hormones were quantified (Meso Scale Discovery). The Mann Whitney U test was used to compare continuous variables between groups, and Pearson's chi-squared test for categorical variables. Spearman correlation analyses were used to build networks of associations between cytokines and symptoms. Result(s): 341 participants enrolled between June 2021 and September 2022. Of these, 73 were PWH post-COVID, 121 were HIV-seronegative post-COVID, 78 were PWH never-COVID, and 69 were HIV-seronegative never-COVID. Over 85% of participants were vaccinated prior to COVID-19. Most participants with HIV were male sex at birth (83% post-COVID, 59% never-COVID), on ART ( >95%), with median CD4 counts >500. Over 60% of participants reported 1+ new or worsened symptoms 2-6 months post-COVID, with higher percentages in PWH at 2 months post-COVID (p< 0.05). PWH were more likely to report body ache, pain, confusion, memory problems, and thirst and had higher levels of creatine phosphokinase post-COVID than HIV-seronegative people. SARS-CoV-2 and non-SARS human coronavirus antibody titers did not differ between PWH and HIV-seronegative post-COVID participants. Cytokine associations with each other (network density) were significantly enriched at 1 month post-COVID in both PWH and HIV-seronegative people, with significantly less enrichment at 4 months post-COVID and in never- COVID participants. Levels of four analytes (cortisol, C5a, TGF-beta1, and TIM-3) associated with specific symptoms of long COVID. Conclusion(s): PWH may experience more symptoms post-COVID with a slightly different symptom profile than people without HIV. Inflammatory networks were active in PWH and people without HIV at 1 month post-COVID.