Glucose variability is a marker for COVID-19 severity and mortality.

Objective: We aimed to investigate the association between glucose coefficient of variation (CV) and mortality and disease severity in hospitalized patients with coronavirus disease-19 (COVID-19). Subjects and Methods: Retrospective cohort study in a tertiary center of patients with COVID-19 admitted to designated departments between March 11th, 2020, and November 2nd, 2020. We divided patients based on quartiles of glucose CV after stratification to those with and without diabetes mellitus (DM). Main outcomes were length of stay and in-hospital mortality. Results: The cohort included 565 patients with a mean age of 67.71 ± 15.45 years, and 62.3% were male. Of the entire cohort, 44.4% had DM. The median glucose CV was 32.8% and 20.5% in patients with and without DM, respectively. In patients with DM, higher glucose CV was associated with a longer hospitalization in the unadjusted model (OR = 2.7, 95% CI [1.3,5.6] for Q4), and when adjusted for age, sex, comorbidities, and laboratory markers, this association was no longer statistically significant (OR = 1.3, 95% CI [0.4,4.5] for Q4). In patients with and without DM, higher glucose CV was associated with higher rates of in-hospital mortality in the unadjusted model, but adjustment for comorbidities and laboratory markers eliminated the association (OR = 0.5, 95% CI [0.1,3.4] for Q4 in patients with DM). Conclusion: Higher glucose CV was associated with increased in-hospital mortality and length of stay, but this association disappeared when the adjustment included laboratory result data. Glucose CV can serve as a simple and cheap marker for mortality and severity of disease in patients with COVID-19.

Fourth Dose of BNT162b2 Vaccine for Patients with Autoimmune Rheumatic Diseases in a Nationwide Setting.

OBJECTIVE: The effectiveness of COVID-19 vaccinations wanes due to immune evasion of the B.1.1.529 (Omicron) variant and diminished antibody titers over time. We aim to evaluate the benefit of a fourth vaccination dose in patients with autoimmune rheumatic diseases (ARD). METHODS: A retrospective analysis included ARD patients 18 years or older in the Clalit health management organization in Israel, insured 52% of the entire population, from January 16, 2022, to March 31, 2022, when the predominant SARS-CoV-2 variant was Omicron. We compared patients without previous COVID-19 infection who received three doses of the BNT162b2 vaccine (control) to those who received the fourth dose. The primary outcome was COVID-19 infection, which was analyzed using multivariate Cox regression in the entire cohort and within ARD subgroups. Secondary outcomes were COVID-19-related hospitalizations and death. RESULTS: We included 43,748 ARD patients, of whom 27,766 and 15,982 were in the control and fourth vaccination groups, respectively. COVID-19 infection occurred in 6,942 (25.0%) of the control group and 1,754 (11.0%) of the fourth dose group (p < 0.001). Patients vaccinated with the fourth dose had a lower risk for COVID-19 infection in the entire cohort (HR 0.54, 95% CI 0.52-0.58) and throughout every subgroup regardless of the baseline characteristic or medical treatment except for rituximab. A similar association was observed in COVID-19-related hospitalization (HR 0.36, 95% C.I 0.22-0.61) and COVID-19-related death (HR 0.41, 95% C.I 0.24-0.71). CONCLUSION: Fourth BNT162b2 vaccination of ARD patients was associated with favourable outcomes compared to three doses among patients with no history of COVID-19 infection.

BNT162b2 mRNA COVID-19 vaccine and booster in patients with autoimmune rheumatic diseases: a national cohort study.

INTRODUCTION: Emerging evidence supports the immunogenic response to mRNA COVID-19 vaccine in patients with autoimmune rheumatic diseases (ARD). However, large-scale data about the association between vaccination, and COVID-19 outcomes in patients with ARD is limited. METHODS: We used data from Clalit Health Services, which covers more than half of the population in Israel. Patients with ARD older than 18 were included between 20 December 2020 and 30 September 2021, when the BNT162b2 mRNA COVID-19 vaccine, and later a third booster dose, were available. The primary outcome was a documented positive SARS-CoV-2 PCR test. We used a Cox regression models with vaccination status as time-dependent covariate and calculated the HR for the study outcome. RESULTS: We included 127 928 patients with ARD, of whom, by the end of the study follow-up, there were 27 350 (21.3%) unvaccinated patients, 31 407 (24.5%) vaccinated patients and 69 171 (54.1%) patients who also received a third booster-dose. We identified 8470 (6.6%) patients with a positive SARS-CoV-2 PCR test during the study period. The HR for SARS-CoV-2 infection among the vaccination group was 0.143 (0.095 to 0.214, p<0.001), and among the booster group was 0.017 (0.009 to 0.035, p<0.001). Similar results were found regardless of the type of ARD group or antirheumatic therapy. CONCLUSION: Our results indicate that both the BNT162b2 mRNA COVID-19 vaccine and the booster are associated with better COVID-19 outcomes in patients with ARD.

A Randomized Clinical Trial of Linagliptin vs. Standard of Care in Patients Hospitalized With Diabetes and COVID-19

Objective To assess the effect of linagliptin vs. standard therapy in improving clinical outcomes in patients hospitalized with diabetes and coronavirus disease 2019 (COVID-19). Materials and Methods We did an open-label, prospective, multicenter, randomized clinical trial in 3 Israeli hospitals between October 1, 2020, and April 4, 2021. Eligible patients were adults with type 2 diabetes mellitus and a diagnosis of COVID-19. A total of 64 patients, 32 in each group, were randomized to receive linagliptin 5 mg PO daily throughout the hospitalization or standard of care therapy. The primary outcome was time to clinical improvement within 28 days after randomization, defined as a 2-point reduction on an ordinal scale ranging from 0 (discharged without disease) to 8 (death). Results The mean age was 67 ± 14 years, and most patients were male (59.4%). Median time to clinical improvement was 7 days (interquartile range (IQR) 3.5-15) in the linagliptin group compared with 8 days (IQR 3.5–28) in the standard of care group (hazard ratio, 1.22;95% CI, 0.70–2.15;p = 0.49). In-hospital mortality was 5 (15.6%) and 8 (25.0%) in the linagliptin and standard of care groups, respectively (odds ratio, 0.56;95% CI, 0.16–1.93). The trial was prematurely terminated due to the control of the COVID-19 outbreak in Israel. Conclusions In this randomized clinical trial of hospitalized adult patients with diabetes and COVID-19 who received linagliptin, there was no difference in the time to clinical improvement compared with the standard of care. Clinical Trial Registration ClinicalTrials.gov, identifier NCT04371978.