Safety and efficacy of apremilast in adults hospitalized with COVID-19

Introduction: Apremilast, a nonbiologic oral phosphodiesterase 4 (PDE4) inhibitor, was evaluated as a treatment for the hyperinflammatory response in patients (pts) hospitalized with severe COVID-19. Aims and Objectives: To assess the safety and effectiveness of apremilast plus standard of care (SoC) in pts hospitalized with severe COVID-19. Method(s): COMMUNITY (EudraCT 2020-002594-10) was a phase 3, double-blind, randomized, multinational, platform trial in adult pts hospitalized with COVID-19. Pts received apremilast 30 mg BID (APR) or placebo (PBO) for 14 days or until hospital discharge, whichever occurred first. Supportive care (per study center practices) was allowed except for CYP3A inducers and concurrent PDE4 antagonists. Result(s): From November 24, 2020 to June 4, 2021, 384 pts were enrolled (APR+SoC: n=194;PBO+SoC: n=190);enrollment halted early due to futility. Mean age was 56.5 years;59% were men. Most pts had a COVID-19 clinical severity score of 4 (48%) or 3 (29%) (range: 1-8, 1=death). Median (95% CI) time to confirmed clinical recovery through Day 29 (primary endpoint) was 14 (11-15) days for both groups (P=0.8779). All-cause mortality incidence rates through Day 29 (key secondary endpoint) were 18% (APR+SoC) and 17% (PBO+SoC) (P=0.9665). Treatmentemergent adverse event (TEAE) rates were similar between APR+SoC (54%;n=189) and PBO+SoC (55%;n=187) groups. TEAEs Common Terminology Criteria AE grade >=3 occurred in 25% of APR+SoC pts and 30% of PBO+SoC pts. Serious TEAE rates were 27% (APR+SoC) and 30% (PBO+SoC). Conclusion(s): Although APR+SoC did not improve survival in pts hospitalized with severe COVID-19, APR was well tolerated with a safety profile consistent with the established safety profile.

Antibodies Response in CKD Patients Vaccinated With CoronaVac

Background: Chronic Kidney Disease (CKD) has emerged as one of the major risk factors to a worse outcome in COVID19 (C19) patients. Vaccination became the main prevention policy against virus spread among individuals, apart from other measures, like using face masks and social distancing;however, CKD patients are a sensitive population excluded from many trials when eGFR are below 30 mL/min. C19 pandemic as never before, became possible vaccine development in a record time. CoronaVac, a live inactivated virus vaccine, was the main immunizing agent used in Brazil in the first wave of vaccination. Apart its safety and efficacy, there was no specific dose and regimen to immunosuppressed patients and advanced CKD population. The aim of this study was evaluate the SarsCov2 antibodies response after the full dose regimen of CoronaVac immunizing agent in CKD patients. Method(s): It is a cross sectional study conducted in Brazil during C19 second wave. Patients with stage 4 and 5 CKD were included with matched controls. Patients that received a full dosage regimen of CoronaVac, 2 shots of 0.5 mL (600 units of inactivated virus) with a 4 week interval were included. Total Sars-Cov2 antibodies and Spike antibodies were dosed after 12 weeks of the 2 dose CoronaVac regimen received. Siemens ADVIA Centaur essays were used to determine antibodies levels and a cut off superior to 0.05 U/mL was considered positive. Descriptive analysis were made to show data with their central tendency characteristics. Qualitative data were described with their proportions and to non-normality inference, Mann-Whitney was used. The alpha level accepted was 5%. Result(s): The study included 41 individuals in total: 19 patients with stage 4 and 5 CKD and 21 matched controls without renal disease. The mean age in the CKD group was 71,68 years (+/-7,79) and 72,95 years (+/-9,86) in control group. Male and female individuals were equal among groups. Total SarsCov2 antibodies levels were 4,32 U/mL (+/-4,16) in CKD group and 6,21 U/mL (+/-4,51) in controls with no statistical significance (p=0.46). Spike antibodies levels were 10,47 U/mL (+/-32,41) in CKD group and 10,35 U/mL (+/-28,34) in controls with a p=0.09 between groups using Mann-Whitney non parametric test. Conclusion(s): In conclusion, CKD patients developed adequate levels of antibodies against C19 with CoronaVac full dosage regimen in Brazil after a 3 month period.

Cardiac troponin and AKI in COVID-19 sepsis-related patients

Background: The COVID-19 pandemic become the major reason of hospitalization of patients in ICU worldwide. AKI is a major disease and continue closely related with sepsis and COVID-19 infection. Cardiac injury is frequent in patients with septic schock and higher levels of cardiac troponin are expected in AKI patients however whether this is related with a poor outcome in the pandemic scenario still remain unknown. The objective of the study was evaluate the impact of the occurrence of AKI and cardiac troponin levels in patients with severe SARS-CoV-2 infection and their major outcomes Methods: We conducted an observational study during COVID-19 pandemic in 2020 first wave outbreak in Brazil. The research was approved by IRB and patients of a Sao Paulo major public hospital. The main inclusion criteria were the occurrence of COVID-19 infection confirmed by oropharyngeal swab in the last 3 days of admission and the need of permanence of at least 3 days. Patients with a poorer expectancy of survival in the next 24 hours of inclusion were not considered elegible. Blood sample at admission was used to confirm sepsis and AKI and the patients were followed daily untill discharge of the unit or dead. AKI occurrence was seen as the rise of serum creatinine happened according KDIGO AKI guideline. Patients were divided in groups regarding the development of AKI and major outcome (mechanical ventilation or dead) Results: A total of 86 patients with sepsis were included. Female patients represented 58.3% of the sample. About 96,51% of the patients had at admission a level of d-dimer above 500 ng and 77,91% of patients had a cardiac troponin I above 20 ng in AKI patients group with a p level 0f 0,003. About 44 patients had AKI due to COVID-19 sepsis related by admission in the ICU Median serum creatinine at admission was 2.44 mg/dL (1.64-4.02). There was a higher proportion of patients in mechanical ventilation with development of AKI after admission (14) than those without AKI during the whole hospitalization (11) with a p of 0,299 The mortality of patients with higher cardiac troponin were significantly higher in AKI patients than the non AKI patients. Conclusions: IIn patients with COVID-19 sepsis related disease, there is a positive correlation between AKI and higher levels of cardiac troponin and higher days with mechanical ventilation.