Humoral and Cellular Immune Responses After a 3-dose Course of mRNA-1273 COVID-19 Vaccine in Kidney Transplant Recipients: A Prospective Cohort Study.

In kidney transplant recipients, there is discordance between the development of cellular and humoral response after vaccination against SARS-CoV-2. We sought to determine the interplay between the 2 arms of adaptive immunity in a 3-dose course of mRNA-1273 100 µg vaccine. Methods: Humoral (IgG/IgM) and cellular (N- and S-ELISpot) responses were studied in 117 kidney and 12 kidney-pancreas transplant recipients at the following time points: before the first dose, 14 d after the second dose' and before and after the third dose, with a median of 203 and 232 d after the start of the vaccination cycle, respectively. Results: After the second dose, 26.7% of naive cases experienced seroconversion. Before the third dose and in the absence of COVID-19, this percentage increased to 61.9%. After the third dose, seroconversion occurred in 80.0% of patients. Naive patients who had at any time point a detectable positivity for S-ELISpot were 75.2% of the population, whereas patients who maintained S-ELISpot positivity throughout the study were 34.3%. S-ELISpot positivity at 42 d was associated with final seroconversion (odds ratio' 3.14; 95% confidence interval' 1.10-8.96; P = 0.032). Final IgG titer was significantly higher in patients with constant S-ELISpot positivity (P < 0.001). Conclusions: A substantial proportion of kidney transplant recipients developed late seroconversion after 2 doses. Cellular immunity was associated with the development of a stronger humoral response.

Multicentre, randomised, open-label, phase IV-III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: study protocol for the SAFO trial.

INTRODUCTION: Methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is a frequent condition, with high mortality rates. There is a growing interest in identifying new therapeutic regimens able to reduce therapeutic failure and mortality observed with the standard of care of beta-lactam monotherapy. In vitro and small-scale studies have found synergy between cloxacillin and fosfomycin against S. aureus. Our aim is to test the hypothesis that cloxacillin plus fosfomycin achieves higher treatment success than cloxacillin alone in patients with MSSA bacteraemia. METHODS: We will perform a superiority, randomised, open-label, phase IV-III, two-armed parallel group (1:1) clinical trial at 20 Spanish tertiary hospitals. Adults (≥18 years) with isolation of MSSA from at least one blood culture ≤72 hours before inclusion with evidence of infection, will be randomly allocated to receive either cloxacillin 2 g/4-hour intravenous plus fosfomycin 3 g/6-hour intravenous or cloxacillin 2 g/4-hour intravenous alone for 7 days. After the first week, sequential treatment and total duration of antibiotic therapy will be determined according to clinical criteria by the attending physician.Primary endpoints: (1) Treatment success at day 7, a composite endpoint comprising all the following criteria: patient alive, stable or with improved quick-Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA at day 7. (2) Treatment success at test of cure (TOC) visit: patient alive and no isolation of MSSA in blood culture or at another sterile site from day 8 until TOC (12 weeks after randomisation).We assume a rate of treatment success of 74% in the cloxacillin group. Accepting alpha risk of 0.05 and beta risk of 0.2 in a two-sided test, 183 subjects will be required in each of the control and experimental groups to obtain statistically significant difference of 12% (considered clinically significant). ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Ethics Committee of Bellvitge University Hospital (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), and is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders. TRIAL REGISTRATION NUMBER: The protocol has been approved by AEMPS with the Trial Registration Number EudraCT 2018-001207-37. ClinicalTrials.gov Identifier: NCT03959345; Pre-results.

Clinical characteristics, risk factors, and incidence of symptomatic coronavirus disease 2019 in a large cohort of adults living with HIV: a single-center, prospective observational study.

BACKGROUND: It is unclear how characteristics, risk factors, and incidence of coronavirus disease 2019 (COVID-19) in people living with HIV (PLWH) differ from the general population. METHODS: Prospective observational single-center cohort study of adult PLWH reporting symptoms of COVID-19. We assessed clinical characteristics, risk factors for COVID-19 diagnosis and severity, and standardized incidence rate ratio for COVID-19 cases in PLWH cohort and in Barcelona. RESULTS: From 1 March 2020 to 10 May 2020, 53 out of 5683 (0.9% confidence interval 0.7-1.2%) PLWH were diagnosed with COVID-19. Median age was 44 years, CD4 T cells were 618/µl and CD4/CD8 was 0.90. All but two individuals were virologically suppressed. Cough (87%) and fever (82%) were the most common symptoms. Twenty-six (49%) were admitted, six (14%) had severe disease, four (8%) required ICU admission, and two (4%) died. Several laboratory markers (lower O2 saturation and platelets, and higher leukocytes, creatinine, lactate dehydrogenase, C reactive protein, procalcitonin, and ferritin) were associated with COVID-19 severity. No HIV or antiretroviral-related factors were associated with COVID-19 diagnosis or severity. Standardized incidence rate ratios of confirmed or confirmed/probable COVID-19 in PLWH were 38% (95% confidence interval 27-52%, P < 0.0001) and 33% (95% confidence interval 21-50%, P < 0.0001), respectively relative to the general population. CONCLUSION: PLWH with COVID-19 did not differ from the rest of the HIV cohort. Clinical presentation, severity rate, and mortality were not dependent on any HIV-related or antiretroviral-related factor. COVID-19 standardized incidence rate was lower in PLWH than in the general population. These findings should be confirmed in larger multicenter cohort studies.