Detection of SARS-CoV-2 IgG antibodies and inflammatory cytokines in saliva-a pilot study.

Objective: The pandemic caused by SARS-CoV-2 virus continues to have a profound effect worldwide. However, COVID-19 induced oral facial manifestations have not been fully described. We conducted a prospective study to demonstrate feasibility of anti-SARS-CoV-2 IgG and inflammatory cytokine detection in saliva. Our primary objective was to determine whether COVID-19 PCR positive patients with xerostomia or loss of taste had altered serum or saliva cytokine levels compared to COVID-19 PCR positive patients without those oral symptoms. Our secondary objective was to determine the correlation between serum and saliva COVID-19 antibody levels. Materials and methods: For cytokine analysis, saliva and serum were obtained from 17 participants with PCR-confirmed COVID-19 infection at three sequential time points, yielding 48 saliva samples and 19 paired saliva-serum samples from 14 of the 17 patients. For COVID-19 antibody analyses, an additional 27 paired saliva-serum samples from 22 patients were purchased. Results: The saliva antibody assay had 88.64% sensitivity [95% Confidence Interval (CI) 75.44%, 96.21%] to detect SARS-CoV-2 IgG antibodies compared to serum antibody. Among the inflammatory cytokines assessed - IL-6, TNF-α, IFN-γ, IL-10, IL-12p70, IL-1ß, IL-8, IL-13, IL-2, IL-5, IL-7 and IL-17A, xerostomia correlated with lower levels of saliva IL-2 and TNF-α, and elevated levels of serum IL-12p70 and IL-10 (p < 0.05). Loss of taste was observed in patients with elevated serum IL-8 (p < 0.05). Conclusions: Further studies are needed to construct a robust saliva-based COVID-19 assay to assess antibody and inflammatory cytokine response, which has potential utility as a non-invasive monitoring modality during COVID-19 convalescence.

The Role of Oral Health in the Acquisition and Severity of SARS-CoV-2: A Retrospective Chart Review.

Objective: Studies have shown that gingival crevices may be a significant route for SARS-CoV-2 entry. However, the role of oral health in the acquisition and severity of COVID-19 is not known. Design: A retrospective analysis was performed using electronic health record data from a large urban academic medical center between 12/1/2019 and 8/24/2020. A total of 387 COVID-19 positive cases were identified and matched 1:1 by age, sex, and race to 387 controls without COVID-19 diagnoses. Demographics, number of missing teeth and alveolar crestal height were determined from radiographs and medical/dental charts. In a subgroup of 107 cases and controls, we also examined the rate of change in alveolar crestal height. A conditional logistic regression model was utilized to assess association between alveolar crestal height and missing teeth with COVID-19 status and with hospitalization status among COVID-19 cases. Results: Increased alveolar bone loss, OR = 4.302 (2.510 - 7.376), fewer missing teeth, OR = 0.897 (0.835-0.965) and lack of smoking history distinguished COVID-19 cases from controls. After adjusting for time between examinations, cases with COVID-19 had greater alveolar bone loss compared to controls (0.641 ± 0.613 mm vs 0.260 ± 0.631 mm, p < 0.01.) Among cases with COVID-19, increased number of missing teeth OR = 2.1871 (1.146- 4.174) was significantly associated with hospitalization. Conclusions: Alveolar bone loss and missing teeth are positively associated with the acquisition and severity of COVID-19 disease, respectively.

Differences in Muscle Quantity and Quality by HIV Serostatus and Sex.

OBJECTIVE: People with HIV (PWH) experience greater declines in both muscle function and muscle mass with aging. Whether changes in muscle quality and quantity with aging differ between men and women with HIV and the implications on muscle function are not established. DESIGN: In coordinated substudies of the Multicenter AIDS Cohort Study and Women's Interagency HIV Study, participants completed physical function and falls assessments; total trunk/thigh density, inversely related to fatty infiltration, and area were quantified from computed tomography (CT) scans. METHODS: Generalized linear models were used to explore variables affecting density/area, and associations between area/density and physical function and falls. RESULTS: CT scans were available on 387 men (198 PWH) and 184 women (118 PWH). HIV serostatus was associated with greater lateralis, paraspinal, and hamstring area, but lower psoas area and density. Older age and female sex were associated with smaller trunk muscle area and lower density. Both lower muscle area and muscle density were associated with several measures of impaired physical function. The odds of falling were lower with greater hamstring density, but not associated with other measurers of muscle area or density. CONCLUSIONS: In summary, older adults with HIV appear to have smaller and less dense (fattier) psoas, a key component in truncal stability and hip flexion that could have implications on physical function. The longitudinal associations of muscle area and density with physical function require careful investigation, with a particular focus on characteristics and interventions that can preserve muscle area, density, and function over time.

Diabetic ketoacidosis and mortality in COVID-19 infection.

AIM: - Patients with diabetes have increased morbidity and mortality from COVID-19. Case reports describe patients with simultaneous COVID-19 and diabetic acidosis (DKA), however there is limited data on the prevalence, predictors and outcomes of DKA in these patients. METHODS: - Patients with COVID-19 were identified from the electronic medical record. DKA was defined by standardized criteria. Proportional hazard regression models were used to determine risk factors for, and mortality from DKA in COVID-19. RESULTS: - Of 2366 patients admitted for COVID-19, 157 (6.6%) patients developed DKA, 94% of whom had antecedent type 2 diabetes, 0.6% had antecedent type 1 diabetes, and 5.7% patients had no prior diagnosis of diabetes. Patients with DKA had increased hospital length of stay and in-patient mortality. Higher HbA1c predicted increased risk of incident DKA (HR 1.47 per 1% increase, 95% CI 1.40-1.54). Risk factors for mortality included older age (HR 1.07 per 5 years, 95% CI 1.06-1.08) and need for pressors (HR 2.33, 95% CI 1.82-2.98). Glucocorticoid use was protective in patients with and without DKA. CONCLUSION: - The combination of DKA and COVID-19 is associated with greater mortality, driven by older age and COVID-19 severity.

Frailty in Postmenopausal African American and Hispanic HIV-Infected Women.

Studies suggest frailty occurs earlier in HIV-infected individuals, but data in postmenopausal HIV-infected women are lacking. We assessed the prevalence of frailty and association with anthropometric measures in HIV-infected and uninfected postmenopausal women. Fried's frailty phenotype was measured in HIV-infected and uninfected Hispanic and African American postmenopausal women participating in a study of bone metabolism; fat and lean mass were measured by whole body dual energy x-ray absorptiometry (DXA). Multivariable logistic regression evaluated frailty risk factors. The study was conducted at Columbia University Medical Center between 2002 and 2007. The participants were 61 HIV-infected and 27 uninfected Hispanic and African American postmenopausal women. The study compared prevalence and predictors of frailty in HIV-infected and uninfected postmenopausal women. Prevalence of frailty tended to be higher among HIV-infected than uninfected controls (11.5% vs 0% p=0.07). Surprisingly, among HIV-infected women, total body fat, not lean mass, was associated with frailty in multivariate analysis. Higher prevalence of frailty in African American and Hispanic HIV-infected postmenopausal women (11.5%) was similar to the 11% prevalence reported in minority women who were 10 years older in the general population. Our data suggest that frailty occurs earlier in HIV-infected postmenopausal women, but larger longitudinal studies are necessary to confirm whether musculoskeletal aging is accelerated by HIV infection.

Bone quality assessed using quantitative ultrasound at the distal radius does not differ in antiretroviral therapy-naïve HIV-positive and HIV-negative Rwandan women.

OBJECTIVES: The incidence of fractures appears to be increased in HIV-infected individuals. METHODS: We assessed bone quality using quantitative ultrasound (QUS) in HIV-infected and uninfected Rwandan women. A Sunlight Omnisense 7000 QUS was used to measure the speed of ultrasound (SOS) at the distal radius in 646 antiretroviral therapy (ART)-naïve HIV-infected women and 211 HIV-uninfected women. The Z-scores for SOS were based on data for women of the same age from the manufacturer's reference material. RESULTS: The mean CD4 cell count was 285 (± 166) cells/µL in the HIV-positive women. SOS Z-scores adjusted and unadjusted for body mass index did not differ between the groups. SOS did not differ by CD4 count (< 200 vs. ≥ 200 cells/µL: 4016 (± 117) vs. 4028 (± 107) m/s, respectively; p=0.19. CONCLUSIONS: In HIV-positive ART-naïve Rwandan women with advanced HIV disease, bone quality at the distal radius was similar to that in HIV-negative controls.

Fall frequency and associated factors among men and women with or at risk for HIV infection.

OBJECTIVES: Falls and fall-related injuries are a major public health concern. HIV-infected adults have been shown to have a high incidence of falls. Identification of major risk factors for falls that are unique to HIV infection or similar to those in the general population will inform development of future interventions for fall prevention. METHODS: HIV-infected and uninfected men and women participating in the Hearing and Balance Substudy of the Multicenter AIDS Cohort Study and Women's Interagency HIV Study were asked about balance symptoms and falls during the prior 12 months. Falls were categorized as 0, 1, or ≥ 2; proportional odds logistic regression models were used to investigate relationships between falls and demographic and clinical variables and multivariable models were created. RESULTS: Twenty-four per cent of 303 HIV-infected participants reported at least one fall compared with 18% of 233 HIV-uninfected participants (P = 0.27). HIV-infected participants were demographically different from HIV-uninfected participants, and were more likely to report clinical imbalance symptoms (P ≤ 0.035). In univariate analyses, more falls were associated with hepatitis C, female sex, obesity, smoking, and clinical imbalance symptoms, but not age, HIV serostatus or other comorbidities. In multivariable analyses, female sex and imbalance symptoms were independently associated with more falls. Among HIV-infected participants, smoking, a higher number of medications, and imbalance symptoms remained independent fall predictors, while current protease inhibitor use was protective. CONCLUSIONS: Similar rates of falls among HIV-infected and uninfected participants were largely explained by a high prevalence of imbalance symptoms. Routine assessment of falls and dizziness/imbalance symptoms should be considered, with interventions targeted at reducing symptomatology.

Increased bone resorption during tenofovir plus lopinavir/ritonavir therapy in Chinese individuals with HIV.

UNLABELLED: We sought to evaluate the effects of antiretroviral therapy on skeletal metabolism in Chinese individuals with human immunodeficiency virus. Patients switched to tenofovir/lamivudine + lopinavir/ritonavir after treatment failure had an increase in bone resorption marker levels by nearly 60%, which is greater than the magnitude previously described in non-Chinese populations. INTRODUCTION: Few studies have evaluated the effects of antiretroviral therapy on skeletal metabolism in Asian populations infected with human immunodeficiency virus (HIV). METHODS: We performed a secondary analysis of bone turnover markers (BTM) at baseline and 2 years in stored plasma samples collected from 2/2009 to 1/2013 as part of a multi-center trial. Two groups were compared: (1) treatment-naïve patients initiated on zidovudine (AZT)/lamivudine (3TC) plus nevirapine (NVP) and (2) patients who failed first-line therapy and were switched to tenofovir (TDF)/3TC plus lopinavir/ritonavir (LPVr). Tests included the bone resorption marker, C-terminal cross-linking telopeptide of type-1 collagen (CTX), and the bone formation marker procollagen type 1 N-terminal propeptide (P1NP). RESULTS: In the TDF/3TC + LPVr group, samples were available from 59 patients at baseline and 56 patients at 2 years. Of these, 36 patients had samples available from both time points. In the AZT/3TC + NVP group, plasma samples were analyzed from 82 participants at baseline and of those, 61 had samples at 2 years. Median change over 2 years was greater in the TDF/3TC + LPVr group for both CTX (+0.24 ng/mL, interquartile ranges (IQR) 0.10-0.43 vs. +0.09 ng/mL, IQR -0.03 to 0.18, p = 0.001) and P1NP (+25.5 ng/mL, IQR 2.4-51.3 vs. +7.11 ng/mL, IQR -4.3 to 21.6, p = 0.012). Differences remained after adjusting for potential confounders in the multivariable analysis. CONCLUSIONS: Switching to TDF/3TC + LPVr after treatment failure resulted in greater increases in BTMs than initiation with AZT/3TC + NVP in Chinese patients with HIV. Following this change, bone resorption marker levels increased by nearly 60 %, which is greater than the 25-35% increase from baseline described previously in non-Chinese populations. Further studies are warranted to elucidate these findings.

Bone structure and turnover in type 2 diabetes mellitus.

SUMMARY: We compared skeletal parameters in type 2 diabetic (T2DM) and non-diabetic postmenopausal women. Bone structure by dual energy x-ray absorptiometry (DXA) and HR-pQCT was not different, although procollagen type 1 amino-terminal propeptide (P1NP) and osteocalcin levels were lower in T2DM. INTRODUCTION: T2DM is associated with increased fracture risk, but, paradoxically, with higher cross-sectional bone density (BMD) as measured by DXA. We sought explanations to this puzzle by investigating detailed structural and biochemical skeletal parameters in T2DM. METHODS: Cross-sectional comparison of 25 postmenopausal T2DM women and 25 matched controls using DXA, high-resolution peripheral quantitative computed tomography (HR-pQCT) and biochemical bone turnover markers. RESULTS: BMD by DXA did not differ between T2DM and controls. HR-pQCT assessment also did not differ, with the exception of cortical area at the tibia, which tended to be lower in the diabetics (difference of 12 ± 6 [mean ± SD] mm, p = 0.06). P1NP and osteocalcin levels were lower in T2DM as compared to controls (P1NP, 34.3 ± 16 vs. 57.3 ± 28 ng/ml; p = 0.005; osteocalcin, 4.5 ± 2 vs. 6.2 ± 2 nmol/L; p = 0.001). CONCLUSIONS: Postmenopausal women with T2DM had lower levels of bone formation markers as compared to controls. Aside from a possible decrease in cortical bone area at a weight-bearing site, bone structure was not altered in T2DM. Lower bone turnover may be a skeletal parameter that is present in T2DM.

Vitamin D deficiency in HIV-infected postmenopausal Hispanic and African-American women.

UNLABELLED: We evaluated vitamin D status in HIV+ and HIV- postmenopausal African-American (AA) and Hispanic women. Most women (74-78%) had insufficient 25-hydroxyvitamin D (25OHD) levels, regardless of HIV status. 25OHD was lower in AA women and women lacking supplement use, providing support for screening and supplementation. Among HIV+ women, 25OHD was associated with current CD4 but not type of antiretroviral therapy. INTRODUCTION: To evaluate vitamin D status and factors associated with vitamin D deficiency and insufficiency in HIV-infected (HIV+) postmenopausal minority women. METHODS: In this cross-sectional study, 89 HIV+ and 95 HIV- postmenopausal women (33% AA and 67% Hispanic) underwent assessment of 25OHD, 1,25-dihydroxyvitamin D, parathyroid hormone, markers of bone turnover and bone mineral density by dual energy X-ray absorptiometry. RESULTS: The prevalence of low 25OHD did not differ by HIV status; the majority of both HIV+ and HIV- women (74-78%) had insufficient levels (<30 ng/ml). Regardless of HIV status, 25OHD was significantly lower in AA subjects, and higher in subjects who used both calcium and multivitamins. In HIV+ women on antiretroviral therapy (ART), 25OHD was directly associated with current CD4 count (r=0.32; p<0.01) independent of age, ethnicity, BMI, or history of AIDS-defining illness. No association was observed between 1,25(OH)(2)D and CD4 count or between serum 25OHD, 1,25(OH)(2)D or PTH and type of ART. CONCLUSIONS: In postmenopausal minority women, vitamin D deficiency was highly prevalent and associated with AA race and lack of supplement use, as well as lower current CD4 cell count. These results provide support for screening and repletion of vitamin D in HIV+ patients.

Effects of HIV infection and antiretroviral therapy with ritonavir on induction of osteoclast-like cells in postmenopausal women.

SUMMARY: Ritonavir (RTV) is a commonly used antiretroviral associated with bone loss. We show that peripheral blood mononuclear cells (PBMCs) from human immunodeficiency virus (HIV)-positive women on RTV are more likely to differentiate into osteoclast-like cells when cultured with their own sera than PBMCs and sera from HIV- women or HIV+ on other antiretrovirals. INTRODUCTION: RTV increases differentiation of human adherent PBMCs to functional osteoclasts in vitro, and antiretroviral regimens containing RTV have been associated with low bone mineral density (BMD) and bone loss. METHODS: BMD, proresorptive cytokines, bone turnover markers (BTMs), and induction of osteoclast-like cells from adherent PBMCs incubated either with macrophage colony-stimulating factor (MCSF) and receptor activator of nuclear factor κB ligand (RANKL) or with autologous serum were compared in 51 HIV- and 68 HIV+ postmenopausal women. RESULTS: BMD was lower, and serum proresorptive cytokines and BTMs were higher in HIV+ versus HIV- women. Differentiation of osteoclast-like cells from adherent PBMCs exposed to either MCSF/RANKL or autologous serum was greater in HIV+ women. Induction of osteoclast-like cells was greater from PBMCs exposed to autologous sera from HIV+ women on RTV-containing versus other regimens (172 ± 14% versus 110 ± 10%, p < 0.001). Serum-based induction of osteoclast-like cells from adherent PBMCs correlated with certain BTMs but not BMD. CONCLUSIONS: HIV infection and antiretroviral therapy are associated with higher BTMs and increased differentiation of osteoclast-like cells from adherent PBMCs, especially in women on regimens containing RTV. HIV+ postmenopausal women receiving RTV may be at greater risk for bone loss.