ABSTRACT
Background: COVID-19 survivors can experience lingering symptoms known as PASC that appear in different phenotypes. The etiology remains elusive and endothelial dysfunction has been postulated as a main driver of PASC. Method(s): Prospective cohort including COVID- and COVID+ with (COVID+PASC+) or without (COVID+PASC-) PASC. We measured endothelial function using Endopat, an FDA approved test, with derived reactive hyperemic index RHI (endothelial dysfunction<=1.67) and arterial elasticity (augmentation index standardized at 75 bpm or AI@75;(lower =better). PASC symptoms were categorized into three non-exclusive phenotypes: Cardiopulmonary CP (postexertional malaise, shortness of breath, cough, palpitations), Neurocognitive N (change in smell/taste, neuropathy, 'brain fog', headache), and General G (fatigue, gastrointestinal or bladder problems). Result(s): We included 491 participants with 109 of the 186 with confirmed COVID+ experiencing PASC. Median number of days between COVID diagnosis and study visit was 249 days (IQR: 144, 510). Among COVID+PASC+, the median number of symptoms was 7.0 (IQR: 3.0,13.0);97 experienced symptoms categorized as G, 90 as N, and 87 as CP. COVID+ PASC+ had the lowest RHI (1.77+/-0.47) and the largest proportion [46.79% (n=51)] with RHI<=1.67 (Figure). AI@75 was the lowest in COVID- (3.11+/-15.97) followed by COVID+PASC- (3.57 +/- 16.34). Within COVID+PASC+, the mean AI@75 among G was 10.11+/-14.85, 11.36+/-14.67 with N, and highest (12.01 +/- 14.48) with CP. Symptoms' number was positively associated with AI@75 (p=0.01). The estimated mean difference in AI@75 between COVID+ PASC+ with CP and COVID+ PASC- was 8.44+/-2.46 (p=0.001), between COVID+ PASC+ with CP phenotype and COVID- was 8.9+/-1.91 (p< .0001), and between COVID+ PASC+ with CP phenotype and COVID+ PASC without CP phenotype was 7.51+/-3.75 (p=0.04) Conclusion(s): PASC was associated with worse arterial elasticity and within PASC, the cardiopulmonary phenotype had the highest arterial stiffness. (Figure Presented).
ABSTRACT
Background: It is known that survivors of acute SARS-CoV-2 infection can experience a complex disease known as post-acute sequelae of COVID-19 (PASC). The clinical manifestations of acute COVID-19 have been well characterized however less is known about the risk of new onset diabetes mellitus (DM) in the post-acute phase of COVID-19. Method(s): An adult cohort with confirmed COVID-19 (by diagnosis or positive test) and without COVID-19 was sampled from a large national health research network between January 1st, 2020 and July 8th, 2022. We investigated the outcomes of a new diagnosis of DM (type I or II) occurring after COVID-19 through 12 months after infection. Risk estimates [incidence, relative risk (RR), attributable risk] were used to describe the probability of incident post-COVID diabetes. Hazard ratios and 95% confidence intervals were used to describe risk factors associated with new diabetes. Result(s): The 3-month probability of new diabetes was 2.48/1,000 among COVID+ and the relative risk (RR) of new diabetes was highest at 12 months [8.94 (8.54, 9.36)]. Vitamin D deficiency [HR: 1.52 (95% CI: 1.42, 1.63)] was associated with increased risk of T2DM and having vitamin D deficiency with either obesity (BMI > 30 kg/m2) or kidney dysfunction (GFR < 60) was associated with more than five times increased risk of T1DM. Conclusion(s): We observed a large proportion of excess diabetes starting at 3 months post COVID infection. Traditional risk factors for diabetes, omicron variant, and vitamin D deficiency are associated with increased risk of new diabetes outcome. PASC care should involve identification and management of diabetes. (Figure Presented).
ABSTRACT
Background: Post-acute sequelae of COVID-19 (PASC) is marked by persistent or newly developing symptoms beyond 4 weeks of infection. Investigating gut integrity, oxidized lipids and inflammatory markers is important for understanding PASC pathogenesis. Method(s): A cross-sectional study including COVID+ with PASC, COVID+ without PASC, and COVID- participants. We measured plasma markers by enzyme-linked immunosorbent assay to assess gut-barrier integrity: zonulin for intestinal permeability, lipopolysaccharide-binding protein (LBP) for microbial translocation, and fatty acid binding protein I-FABP for intestinal integrity, and to assess inflammation: high-sensitivity C-reactive protein (hsCRP) and oxidized low-density lipoprotein (Ox-LDL) assays. Result(s): 415 participants were enrolled in our study. 62.17% (n=258) were COVID- and 20.48% (n=85) had PASC. COVID- participants had lower age (43.68+/-13.69 vs. 46.45+/-13.45 years;p=0.04), lower BMI (27.91+/-6.05 vs. 31.28+/-9.03;p< .0001), 39.15% (n=101) were female sex [vs. 54.14% (n=85);p=0.003], and 41.86% (n=108) were non-white race [vs. 32.48% (n=51);p=0.06] compared to COVID+. Zonulin (p< .0001), and Ox-LDL (p< .0001) were associated with COVID and PASC status. The mean Zonulin among COVID- was 3755960.41+/-2541177.0 ng/mL, 3912178.91+/-2649882.95 ng/mL among COVID+ without PASC, and the highest (5899694.16+/-4110456.4 ng/ mL) among PASC. The mean Ox-LDL was lowest (51845.21+/-24328.46 U/L) among COVID-, 60530.09+/-26497.47 U/L among COVID+ without PASC, and 81917.21+/-32148.59 U/L among PASC. The estimated mean difference in Zonulin among PASC compared to COVID- was 2143734+/-368522 ng/mL (p< .0001) and compared to COVID+ without PASC was 1987515+/-471965 ng/mL (p< .0001). The estimated mean difference in Ox-LDL among PASC compared to COVID- was 30072+/-3311.02 U/L (p<.0001) and compared to COVID+ without PASC was 21387+/-4240.41 (p<.0001). Zonulin was positively associated with hs-CRP and Ox-LDL. For every unit increase in Zonulin we would expect hsCRP to increase by 86.14+/-15.09/100000 ng/mL (p<.0001) and OX-LDL to increase by 22.2+/-4.05/10000 ng/mL (p<.0001). Conclusion(s): PASC is associated with increased gut permeability, which in turn is associated with oxidized LDL and hsCRP. (Figure Presented).
ABSTRACT
Background: Sex differences in immunological responses to COVID-19 infection and mechanisms that may contribute towards post-acute sequelae of SARS-Co-V2 (PASC) have been reported. However, evidence on the effects of COVID infection on vascular dysfunction and PASC are limited. Method(s): FDA approved EndoPAT device was used to measure endothelial function [Reactive Hyperemia Index (RHI)] and arterial stiffness [Augmentation Index standardized at 75 beats/min (AI@75;higher AI = worse arterial elasticity)] in an adult cohort (age >=18 years) with a history of COVID-19 infection (COVID+) or confirmed SARS-CoV2 antibody negative (COVID-). Generalized linear regression was used to compute estimates of RHI and AI@75. Adjusted models included age, sex, race, blood pressure, lipids, body mass index (BMI), smoking status, and pre-existing comorbidities. Two-way interactions were used to determine if the effects of COVID or PASC status on endothelial function depends on age, sex, race, smoking status, or prevalent comorbidities. Result(s): 61.99% (n=305) of study participants were COVID- and 187 (38.01%) were COVID+. Among COVID+, 57.22% (n=107) were female, 31.72% (n=59) were non-white race, and the average age was 46.64+/-13.79 years. COVIDparticipants had a smaller proportion (38.03%) of female sex (p< .0001), lower BMI [COVID+ (30.79+/-8.95 kg/m2) vs. COVID- (27.76+/-5.89 kg/m2);p< .0001], and higher proportion of smokers [COVID+ (17.78%) vs. COVID- (58.22%);p< .0001]. The average follow-up was 349.68+/-276.76 days and 109 (22.15%) COVID+ experienced PASC. 42.48% (n=80) of COVID+ and 41.64% (n=127) of COVID- had RHI<= 1.67 (p=0.8). The average AI@75 among COVID+ without PASC was 3.63+/-16.24, with PASC was 10.5+/-14.72, and 3.11+/-15.97 among COVID- (p=0.0001). Male sex had the lowest AI@75 (-0.08+/-14.9) compared to female sex (10.75+/-15.3;< .0001). In adjusted models, PASC, female sex had 8.14+/-2.95 higher AI@75 compared to PASC, male sex (p=0.006), 18.58+/-2.99 higher AI@75 compared to COVID+ without PASC, male sex (p< .0001), 13.81+/-2.11 higher AI@75 compared to COVID-, male sex (p< .0001), and 4.97+/-2.28 higher AI@75 compared to COVID-, female sex (p=0.03). Sex was not associated with RHI or modified the effect of COVID or PASC status on endothelial function Conclusion(s): The effect of COVID and PASC status on arterial stiffness depends on sex. Female sex is associated with increased arterial stiffness (worse arterial elasticity) in the post-acute phase of COVID-19. (Figure Presented).
ABSTRACT
Background: COVID-19 has the most impact on people with comorbidities likely due to a higher inflammatory state. Zinc (Zn) is known for its substantial involvement in immune response as an antioxidant and anti-inflammatory agent. Zn plasma levels' clinical significance at COVID diagnosis is not yet established. We investigated the effects of Zn deficiency and inflammation on COVID-19 outcomes. Methods: Plasma Zn levels were collected from patients during the acute phase of a confirmed COVID-19 diagnosis. Data was dichotomized into Zn deficient (Zn<75 μ g/dL) and Zn sufficient (Zn ≥75 μ g/dL). Soluble tumor necrosis factor alpha receptor II (sTNF-RII) and intestinal fatty-acid binding protein (I-FABP) were also measured. COVID-19 outcomes were classified according to the WHO clinical progression scale (0-10), then stratified into 3 groups [grp 1= (WHO score 0-4) asymptomatic or mild disease;moderate grp 2= (WHO 5-6), and severe grp 3= (7-10)]. Hazard ratios (AHRs) and 95% Confidence Intervals (CIs) were computed using cumulative logit regression and adjusted for demographics, BMI, comorbidities, inflammation markers, and laboratory data. Results: We included 149 patients with a confirmed COVID-19 diagnosis. The median age (interquartile range [IQR]) was 53 years (38.0, 63.0);42% of the patients were female, 52% non-white, and 86% had at least one comorbidity. Overall, 50% of patients were in grp 1= asymptomatic or mild, whereas 8.5% had the worse outcome (grp 3). More than half of the participants (54%) had sufficient zinc levels. There was not enough evidence to suggest any differences regarding age, gender, body mass index (BMI), hemoglobin, white blood cells, transaminases enzymes, I-FABP, and sTNF-RII between the Zn-sufficient and deficient arms (p>0.05). However, 21% of the Zn sufficient arm were non-White compared to 31% in the deficient arm (p= 0.0004). Patients with zinc deficiency had a median BMI of 31.96 kg/m2 (IQR: 26.69, 36.44) and a median sTNF-RII of 3027.00 (IQR: 2446.00, 4468.00). In adjusted models, as zinc levels decreased, the risk of severe COVID-19 outcomes increased [AHR: 0.24 (95% CI: 0.06, 0.93)]. As sTNF-RII increases, but not I-FABP, the risk of severe COVID-19 outcomes rises two-fold [AHR: 2.17 (95% CI: 1.10, 4.31)]. Conclusion: Zinc deficiency and higher levels of sTNF-RII during acute COVID-19 presentation are independently associated with worse outcomes, suggesting a potential relationship between these 2 variables in COVID-19 progression.