Comparing SARS-CoV-2 neutralizing antibody levels in convalescent unvaccinated, convalescent vaccinated, and naive vaccinated subjects.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 and spread rapidly. The purpose of this study was to compare neutralizing antibodies (NAbs) following the original booster vaccine in convalescent and naive vaccinated individuals and in a third comparison group consisting of unvaccinated convalescent plasma donors. Methods: We assessed NAbs before and 2 months after a booster vaccine in 68 adults who had completed the initial vaccine series for SARS-CoV-2. Of these subjects, 58 had no history of prior infection (naïve vaccinated group) and 10 had been infected with SARS-COV-2 prior to the completing the first vaccine series (convalescent vaccinated group). A third comparison group included unvaccinated convalescent plasma donors (n = 55) from an earlier study with NAbs assessed approximately 2 months after a positive test for SARS-CoV-2. Results: Prior to the booster, convalescent vaccinated subjects had higher NAbs compared to naive vaccinated subjects (p = 0.02). Two months following the booster, NAbs increased in both vaccinated groups. The naive vaccinated group increased more than the convalescent vaccinated group (p = 0.02). NAbs in the naive vaccinated group were almost four times higher than NAbs in the 55 unvaccinated subjects, while the convalescent vaccinated group had levels 2.5 times higher p < 0.01. Conclusion: NAbs in both vaccinated/boosted groups were significantly higher than in the convalescent unvaccinated group (p < 0.01). Our data indicates that subjects with a single infection with SARS-CoV-2 did not have the same levels of neutralizing antibodies that we observed in subjects who were either in the convalescent vaccinated or the naive vaccinated groups.

Severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) serology in the vaccination era and post booster vaccination.

Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has caused over 6 million deaths world-wide. In the pre-vaccination era, we noted a 5·3% SARS-CoV-2 IgG antibody positivity rate in 81,624 subjects. Methods: Utilizing assays for serum SARS-CoV-2 spike (S) protein antibody (Roche) and neutralizing antibody (Diazyme), both >90% IgG, we measured antibodies in 13,189 subjects in the post-vaccination era, and in 69 subjects before and 60 days after booster vaccination. Results: In 2021, in 10,267 subjects, 25·0% had negative S protein levels (<0.80 U/L), 24·4% had low positive levels (0.80-250 U/L), and 50·7% had high positive levels (>250 U/L). Median neutralizing antibody levels were 1·16 and 2·06 AU/mL in the low and high positive groups, respectively. In 2022, we evaluated 2,016 subjects where samples were diluted 1:100 if S protein antibody levels were >250 U/L. Median S protein and neutralizing antibody levels were 2,065 U/L (86.3% positivity) and 2·68 AU/mL (68.0% positivity), respectively. Antibody levels were also measured in 69 subjects before and 60 days after receiving SARS-CoV-2 booster vaccinations. Treatment resulted in a 15-fold increase in S protein antibody levels from 1,010 to 17,236 U/L, and a 6-fold increase in neutralizing antibody from 1·51 to 12·51 AU/mL in neutralizing antibody levels, respectively (both P<0.00001), with a wide variability in response. Conclusions: Our data indicate that by early 2022 86% of subjects had positive SARS-CoV-2 S protein antibody levels, and that these levels and neutralizing antibody levels were increased 15-fold and 6-fold, respectively, 60 days after SARS-Cov-2 booster vaccination.

Impact of Diabetes on Hospitalized Patients With Chronic Medical Conditions.

AIM: To measure cost and length of stay in patients with and without a diagnosis of diabetes admitted with cardiovascular, pulmonary, or cerebrovascular disease. METHODS: Retrospective study used International Classification of Diseases, 10th Revision, Clinical Modification codes to identify patients with diabetes, cardiovascular, pulmonary, or cerebrovascular disease. The All Patients Refined Diagnosis Related Groups, which classify patients according to admission diagnosis, severity of illness, and risk of mortality, was used to determine actual (discharge) diagnoses. Total admission cost and length of stay were compared using the Wilcoxon rank-sum test. RESULTS: Study reviewed 48,572 subjects who met inclusion criteria. When compared with patients without diabetes of similar age, sex, race, risk of mortality, and severity of illness and controlling for length of stay, individuals with diabetes had similar total admission costs. Lengths of stay were similar for individuals with and without diabetes admitted with a diagnosis of cerebrovascular disease or respiratory infection. However, patients with a primary diagnosis of congestive heart failure and a secondary diagnosis of diabetes incurred longer lengths of stay. CONCLUSION: Individuals with diabetes and congestive heart failure have longer lengths of stay than those without diabetes. To decrease the economic burden of diabetes and chronic conditions, primary care providers and hospitals need to implement guidelines regarding the management of care for individuals with two or more chronic conditions.

Corona Virus Disease-19 serology, inflammatory markers, hospitalizations, case finding, and aging.

Most deaths from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection occur in older subjects. We assessed the utility of serum inflammatory markers interleukin-6 (IL-6), C reactive protein (CRP), and ferritin (Roche, Indianapolis, IN), and SARS-CoV-2 immunoglobulin G (IgG), immunoglobulin M (IgM), and neutralizing antibodies (Diazyme, Poway, CA). In controls, non-hospitalized subjects, and hospitalized subjects assessed for SARS-CoV-2 RNA (n = 278), median IgG levels in arbitrary units (AU)/mL were 0.05 in negative subjects, 14.83 in positive outpatients, and 30.61 in positive hospitalized patients (P<0.0001). Neutralizing antibody levels correlated significantly with IgG (r = 0.875; P<0.0001). Having combined values of IL-6 ≥10 pg/mL and CRP ≥10 mg/L occurred in 97.7% of inpatients versus 1.8% of outpatients (odds ratio 3,861, C statistic 0.976, P = 1.00 x 10-12). Antibody or ferritin levels did not add significantly to predicting hospitalization. Antibody testing in family members and contacts of SARS-CoV-2 RNA positive cases (n = 759) was invaluable for case finding. Persistent IgM levels were associated with chronic COVID-19 symptoms. In 81,624 screened subjects, IgG levels were positive (≥1.0 AU/mL) in 5.21%, while IgM levels were positive in 2.96% of subjects. In positive subjects median IgG levels in AU/mL were 3.14 if <30 years of age, 4.38 if 30-44 years of age, 7.89 if 45-54 years of age, 9.52 if 55-64 years of age, and 10.64 if ≥65 years of age (P = 2.96 x 10-38). Our data indicate that: 1) combined IL-6 ≥10 pg/mL and CRP ≥10 mg/L identify SARS-CoV-2 positive subjects requiring hospitalization; 2) IgG levels were significantly correlated with neutralizing antibody levels with a wide range of responses; 3) IgG levels have significant utility for case finding in exposed subjects; 4) persistently elevated IgM levels are associated with chronic symptoms; and 5) IgG levels are significantly higher in positive older subjects than their younger counterparts.

Comparison of Dexamethasone 4mg vs 8mg Doses in Total Joint Arthroplasty Patients: A Retrospective Analysis.

Introduction Dexamethasone is commonly administered intraoperatively to control postoperative nausea and vomiting (PONV) and pain. There is limited evidence of the ideal dosage of dexamethasone during surgery. Dexamethasone administration may increase blood glucose levels, posing unique challenges in maintaining acceptable blood glucose levels in patients with diabetes. Objective Compare two doses of dexamethasone (4mg and 8mg) for outcomes in patients undergoing hip and knee arthroplasty. Methods Medical records of 3,194 patients having undergone total hip arthroplasty (THA) and total knee arthroplasty (TKA) between January 1, 2016 and December 31, 2017 who were administered dexamethasone were reviewed. The eligible population included male and female patients aged 18-89, who underwent elective hip and knee replacement surgery and were administered dexamethasone intraoperatively. Demographics, clinical variables, and preoperative diabetic status were recorded. Primary outcomes included: blood glucose levels, incidence of PONV, post-anesthesia care unit (PACU) time, and length of stay (LOS). Postoperative complications such as periprosthetic joint injection and urinary tract infections (UTI) were also examined within 90 days of surgery. The 30-day readmissions rate was also collected for analysis. Results There was no PONV in the entire patient population. There were no significant differences between 4mg and 8mg dexamethasone in patients with or without diabetes, for preop to postop blood glucose difference, surgical timing, and post-operative complications. Conclusion Dexamethasone in both 4mg and 8mg dose was effective in PONV prophylaxis. The effects of 4mg and 8mg dexamethasone were the same in individuals with and without diabetes and the increases in blood glucose were not significantly different. Dexamethasone should not be withheld, as its benefits seem to outweigh the risks even in patients with diabetes.

SARS-CoV-2 serology and virology trends in donors and recipients of convalescent plasma.

SARS-CoV-2 has infected millions worldwide. The virus is novel, and currently there is no approved treatment. Convalescent plasma may offer a treatment option. We evaluated trends of IgM/IgG antibodies/plasma viral load in donors and recipients of convalescent plasma. 114/139 (82 %) donors had positive IgG antibodies. 46/114 donors tested positive a second time by NP swab. Among those retested, the median IgG declined (p < 0.01) between tests. 25/139 donors with confirmed SARS-CoV-2 were negative for IgG antibodies. This suggests that having had the infection does not necessarily convey immunity, or there is a short duration of immunity associated with a decline in antibodies. Plasma viral load obtained on 35/39 plasma recipients showed 22 (62.9 %) had non-detectable levels on average 14.5 days from positive test versus 6.2 days in those with detectable levels (p < 0.01). There was a relationship between IgG and viral load. IgG was higher in those with non-detectable viral loads. There was no relationship between viral load and blood type (p = 0.87) or death (0.80). Recipients with detectable viral load had lower IgG levels; there was no relationship between viral load, blood type or death.

Factors Associated with Good Patient Outcomes Following Convalescent Plasma in COVID-19: A Prospective Phase II Clinical Trial.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is a viral respiratory syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This novel virus was discovered in Wuhan City, Hubei Province, China, in December 2019. As of September 6, 2020, confirmed cases have risen to more than 27,000,000 worldwide and more than 885,000 people have died. Currently, no cure or standard treatment for COVID-19 exists. We conducted a prospective single-arm open-label phase II clinical trial assessing the safety and efficacy of convalescent plasma in hospitalized patients with COVID-19. METHODS: Convalescent plasma with sufficient total anti-SARS-CoV-2 IgG titer (1:320) obtained from recovered donors was administered to adult patients with either severe or critical COVID-19 illness. Primary outcomes were adverse events in association with plasma administration, and hospital mortality. Secondary outcomes included disease progression, recovery, length of stay, and hospital discharge. RESULTS: Of the 38 patients included in the analysis, 24 (63%) recovered and were discharged, and 14 (37%) died. Patients who received convalescent plasma early in the disease course (severe illness group) as compared to the patients that received convalescent plasma later in the disease progression (critical illness group) had significantly lower hospital mortality 13% vs 55% (p < 0.02) and shorter mean hospital length of stay 15.4 vs 33 days (p < 0.01). One patient experienced a transient transfusion reaction. No other adverse effects of convalescent plasma infusion were observed. CONCLUSIONS: Our results suggest that convalescent plasma with adequate anti-SARS-CoV-2 antibody titer is safe and has the potential for positive impact on clinical outcomes including recovery and survival if given to patients early in the course of COVID-19 disease. TRIAL REGISTRATION: ClinicalTrials.gov. Identifier, NCT04343261, IND #19805.

Hyperinsulinemia and elevated systolic blood pressure independently predict white matter hyperintensities with associated cognitive decrement in the middle-aged offspring of dementia patients.

Cerebrovascular disease is an independent risk factor for dementia that may also be synergistic with Alzheimer's disease. In recent years attention has switched from cerebral infarcts to microvascular disease as the primary cause of cerebrovascular cognitive decline, with damage to the white matter the primary mechanism. Uncertainties remain regarding the risks posed by different types vascular threat, the extent to which cerebrovascular damage occurs in middle age, and whether relatively "normal" amounts of white matter damage are accompanied by meaningful degrees of cognitive decline. We explored these issues via laboratory, cardiovascular, cognitive, and magnetic resonance imaging (MRI) data in 67 middle-aged cognitively normal offspring of dementia patients. The sample was enriched for vascular risk. Plasma insulin, 24-h systolic blood pressure, body mass index, age, and % small dense LDL cholesterol were the strongest correlates of MRI white matter hyperintensity (WMH) volume. With shared variance controlled for, 24 h systolic BP, plasma insulin, and age remained as significant predictors of WMH volume. An interaction variable (24 h BP * insulin) did not improve the prediction of WMH. WMH volume correlated negatively with cognition. No evidence for an ApoE ε4 effect emerged for either WMH or cognition. Hypertension and hyperinsulinemia appear to pose independent, consequential threats to the cerebral small vessel vasculature in middle age, reflected in the presence of areas of WMH on MRI scans. Our data show that even modest WMH volumes in middle age are associated with cognitive decrement, underscoring the importance of aggressive treatment and lifestyle modifications to address vascular risk throughout adulthood.

Educational Intervention Along With Standardization of Diabetes Care Increased Inpatient HbA(1c) Testing: A Pilot Program.

OBJECTIVE: To continuously improve safe coordination of diabetes care throughout the hospital by ongoing implementation of standardized, hospital-wide staff education, and glucose management policies/protocols. METHODS: In December 2013, a hospital-wide multidisciplinary task force was formed to standardize the care for all patients being admitted to Saint Francis Hospital and Medical Center with the diagnosis of diabetes. The purpose of this team was to help develop policies and procedures on glucose management and educate staff on the current clinical practice guidelines. Prior to creating system-wide changes, the team decided to pilot the project on two units. RESULTS: A total of 144 patients with a primary or secondary diagnosis of diabetes were admitted to these two units between June 1 and July 31, 2014. The study group was found to have anincreaseinthe percentage of HbA(1c) tests (P < .01) being done when compared with 1173 patients in the rest of hospital. As a result of staff education, there was a decrease in hypoglycemia events (P = .05), and hyperglycemia events (P < .01) in the study group immediately following education; however during the follow-up period, the rate of hypoglycemic events was unchanged in both groups. CONCLUSION: Standardization of inpatient diabetes management with staff and patient education increased the testing of HbA(1c) in hospitalized patients and has potential to improve quality of care and patient safety.

Assessment of pain and treatment satisfaction in patients with painful diabetic peripheral neuropathy.

INTRODUCTION: Painful diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus and can have debilitating consequences with a significant impact on quality of life. This study was done to evaluate treatment satisfaction and to describe pain experienced from DPN by patients at our Center. METHODS: Patients > or = 18 years of age with a diagnosis of diabetes, were offered a self-administered questionnaire by their health-care provider. In addition to information related to their diabetes, patients were asked if they experienced nerve pain, the characteristics of the nerve pain, impact on activitylevel, sleep, quality of life, and satisfaction with current therapy. RESULTS: A total of 98 patients, 53.1% female, met the inclusion criteria and were included in the analysis. Thirty-one patients (31.6%) reported neuropathic pain, with 83.3% having experienced nerve pain for > or = one year and the majority (67.7%) reporting nerve pain primarily in their feet. Impact of nerve pain on quality of life was noted by 61.3% of patients although 64.5% of patients reported that nerve pain did not cause them to avoid activities. CONCLUSION: Painful DPN is a complication of diabetes mellitus and has a significant impact on quality of life. The results of our questionnaire found about a third of patients with long-standing diabetes have DPN of which about two thirds reported that it affected their quality of life. Surprisingly, almost half of the patients reported being satisfied with their treatment despite severe nerve pain.

Effect of zoledronic acid on bone density and markers of bone turnover in a community clinic.

OBJECTIVE: This study aims to document the efficacy of zoledronic acid by comparing bone densities and markers of bone turnover, in patients with osteoporosis. METHODS: Bone mineral density (BMD) and urinary N-telopeptide, a marker of bone turnover, were compared before and after treatment with intravenous zoledronic acid. RESULTS: 52 participants had atleast two doses of zoledronic acid over 36 months. Significant increases in BMD were found in the spine (t=4.38, P<0.01) and decrease in bone turnover marker N-telopeptide (t=3.30, P=0.002). Small but significant correlations were determined between prior steroid use and change in BMD in the spine (r=0.35, P<0.05), and family history of osteoporosis and change in BMD in the right femur (r=0.38, P<0.05). CONCLUSION: Annual infusions of zoledronic acid for at least two years, revealed a significant increase in bone density at the spine and a decrease in urinary N-telopeptide in patients treated at our center.

Daily physical movement and bone mineral density among a mixed racial cohort of women.

PURPOSE: The impact of lifestyle physical activity on bone mineral density (BMD) is unclear. We examined the influence of physical activities typical of everyday life on BMD among 151 women (52.0 +/- 0.9 yr). These women were of low socioeconomic status, and 57.6% were Hispanic, 17.2% black, and 24.5% white. METHODS: BMD was measured at the calcaneus by ultrasound with a Hologic Sahara sonometer. We measured physical activity with two questions from the Yale Physical Activity Survey that assessed h x d(-1) spent in motion typical of the past month and number of flights of stairs climbed up daily. Multivariate ANCOVA adjusted for adiposity and nutrients and medications known to influence BMD determined whether BMD differed between categories of physical activity (<2 vs > or = 2 flights x d(-1) and <7 vs > or = 7 h x d(-1)), menopausal status (pre- vs post-), and ethnic group (white vs nonwhite). RESULTS: Among the premenopausal women (N = 63, 43.2+/-0.9 yr), adjusted mean calcaneal BMD and BMD T-score were similar between categories of stair climbing and accumulated daily movement regardless of ethnic origin (P > 0.05). Among the postmenopausal women (N = 88, 58.1 +/- 1.0 yr), adjusted mean calcaneal BMD (0.561 +/- 0.019 g x cm(-2) vs 0.503 +/- 0.016) (P = 0.022) and BMD T-score (-0.172 +/- 0.166 vs -0.695 +/- 0.143) (P = 0.020) were higher with more flights of stairs climbed daily in the Hispanic and black women only. Similarly, calcaneal BMD (0.579 +/- 0.023 g x cm(-2) vs 0.505 +/- 0.014) (P = 0.010) and BMD T-score (-0.020 +/- 0.209 vs -0.678 +/- 0.129) (P = 0.010) were higher with greater amounts of daily movement in only the older Hispanic and black women. CONCLUSION: Lifestyle physical activity positively impacted BMD indicators in a mixed racial cohort of postmenopausal women. Older Hispanic and black women should be encouraged to engage in physical activities typical of everyday life to attenuate age-related bone loss.