ABSTRACT
Introduction: Obstructive sleep apnea (OSA) is considered a low-grade chronic inflammatory disease. OSA impairs endothelial function and increases cardiovascular mortality. Hydroxychloroquine (HCQ), an antiinflammatory drug, seems to reduce cardiovascular mortality. In animal and in vitro models, HCQ improved endothelial function. Its effects on endothelial function of patients with OSA is unknown. Hypothesis: Hydroxychloroquine can improve endothelial function in patients with OSA. Methods: Adults older than 65 years with an apnea-hypopnea index (AHI) greater than 15 events/hour were allocated to receive either 400mg of HCQ or placebo daily for eight-weeks. The randomization was computer-generated and pharmacycontrolled. Participants and outcome evaluators were blinded to the group allocation. Home sleep apnea test and measurements of flow-mediated dilation of brachial artery (FMD) and peripheral artery tonometry (PAT) were performed at baseline and follow-up in a research facility. The primary outcomes were the change in FMD (Δ%FMD) and change in PAT reactive-hyperemia index (ΔRHI). Change in AHI (ΔAHI) was a secondary outcome. Generalized estimating equations were used to verify time∗group interaction. Results: Fourteen patients were assigned to the HCQ group and fifteen patients to the placebo group between April 2019 and May 2020 with no losses to follow-up. The recruitment was interrupted due to COVID-19 pandemic. Mean Δ%FMD was 0.35 (95% CI -4.26 to 4.97) in placebo group and 0.48 (95% CI -4.08 to 5.04) in HCQ group. Mean ΔRHI was 0.02 (95% CI -0.11 to 0.07) in placebo group and 0.05 (95% CI -0.24 to 0.13) in HCQ group. Mean ΔAHI was 7 (95% CI -1 to 15) in placebo group and -4 (95% CI -11 to 2) in HCQ group. P values for time∗group interaction were 0.97, 0.74 and 0.04, respectively. No important adverse events have occurred. Conclusions: In this trial, HCQ did not improve endothelial function measured by FMD and PAT in older adults with OSA. A slight but significant reduction in AHI was observed in HCQ group, suggesting that some specific inflammatory mechanisms participate in OSA causation that could become a future therapeutic approach.
ABSTRACT
Background: Data on the persistence of COVID-19 antibodies against SARSCoV-2 in maintenance hemodialysis (MHD) patients from the U.S. is still scarce and an association with race and ethnicity is unknown. We explore antibody dynamics in MHD patients from three U.S. states with a diverse racial and ethnic background. Methods: We obtained consent from MHD patients with COVID-19, confirmed by RT-PCR, from 12 clinics. Phase 1 antibody testing was done between June and August 2020. Re-testing was done 6-8 months later. Antibodies were tested with an emergency use authorized assay (Diazyme DZ-LITE SARS-CoV-2 IgG CLIA kit). Linear mixedeffects models were employed to estimate the IgG half-life in patients with repeated IgG measurements. Patients were stratified by sex, race, ethnicity, obesity, and medians of age, dialysis vintage and body mass index. Results: 104 patients (age 63.8±13 years, 67 (64.4%) males;48 (46.2%) Africa-American, and 34 (32.7%) Hispanics) were studied. IgG was obtained 82 days (range 13 to 151) and 253 days (range 170 to 309) post-COVID-19. At initial testing, 101 (97.1%) patients were positive for IgG. 89 of them were available for repeated testing, where 74 (83.1%) showed persistent IgG. The luminescence signal was declined by 35.5 AU/ mL (95% CI 28.7 to 42.4) from 47.8 ± 44.9 to 12.3 ± 21.1 AU/mL (P<0.0001;paired t-test;Figure.1). The estimated half-life of IgG was 62.8 days (95% CI 56.8 to 68.8). We observed no significant differences in the stratified analysis (Table 1;all p > 0.05). Conclusions: The half-life of IgG against SARS-CoV-2 was approximately 63 days, corroborating reports from both the general and other MHD populations. Importantly, we found no association between IgG half-life, race and ethnicity.
ABSTRACT
BACKGROUND AND AIMS: Dialysis patients are at higher risk for severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. Longevity of antibody response to SARS-CoV-2 infection remains unclear. It is reported that maintenance hemodialysis (MHD) patients can mount an antibody response that is similar in intensity and timing to the non-dialysis population. We aim to investigate the prevalence and persistence of antibodies in hemodialysis patients. METHOD: We measured IgG and IgM antibodies in MHD patients as part of a quality improvement project. Four New York City dialysis clinics participated in this study. Strict policy of RT-PCR testing was implemented in clinics for patients with signs and symptoms of Coronavirus Disease 2019 (COVID-19). Initial antibody testing was done on June 10 and July 13, 2020 (phase 1) and retesting was done for previously positive patients between December 9 and 17, 2020 (phase 2). Upon obtaining verbal consent, 3.5 ml of pre-dialysis blood samples were taken via vascular access. SARS-CoV-2 antibodies were determined using the emergency use authorized Diazyme DZ-Lite SARS-CoV-2 IgM / IgG CLIA assays with 100% sensitivity and 98% specificity. Detection of formed immune-complexes is achieved with N-(4-amino-butyl)-N-ethylisoluminol;the luminescence signal is reported as units per ml (AU/ml), values ≥ 1.00 AU/ml are considered as 'reactive' and < 1.00 AU/ml as 'non-reactive.' RESULTS: A total of 429 MHD patients were studied in phase 1. Antibodies were present in 130 (30.3%) and only 55 patients with Covid-19 diagnosis confirmed by RTPCR test were reactive for IgG antibodies. The time to antibody testing was 73 days (median 77;range 30-111) days. In the phase 2 antibody testing, IgG antibodies were only detected in 47 patients (85.5%) 242 days (median 245, range 204 to 268) after clinical diagnosis of Covid-19. Between the two phases of antibody testing, the luminescence signal declined by 40.9 AU/mL (95% confidence interval 31.5 to 50.3) from 54.1±45.3 to 13.2±20.9 AU/mL (P<0.0001 by paired t-test;Figure 1). In univariate logistic regression, a higher number of days between clinical diagnosis of COVID-19 and the second antibody measurement was associated with a lower seropositivity rate (odds ratio 0.929, 95% confidence interval 0.864 to 0.998, P=0.044). Antibody persistence was not associated with age, gender, race, and ethnicity. CONCLUSION: We observed that about 6 out of 7 MHD patients maintain SARSCoV-2 antibodies over 6-9 months but there is a significant decline of IgG level. The time between clinical diagnosis and IgG testing was associated with IgG decline. Follow up study to understand antibody dynamics in MHD population is a crucial step once vaccines become available.