Antibody and memory B-cell immunity in a heterogeneously SARS-CoV-2 infected and vaccinated population (preprint)

Global population immunity to SARS-CoV-2 is accumulating through heterogenous combinations of infection and vaccination. Vaccine distribution in low- and middle-income countries has been variable and reliant on diverse vaccine platforms. We studied B-cell immunity in Mexico, a middle-income country where five different vaccines have been deployed to populations with high SARS-CoV-2 incidence. Levels of antibodies that bound a stabilized prefusion spike trimer, neutralizing antibody titers and memory B-cell expansion correlated with each other across vaccine platforms. Nevertheless, the vaccines elicited variable levels of B-cell immunity, and the majority of recipients had undetectable neutralizing activity against the recently emergent omicron variant. SARS-CoV-2 infection, experienced prior to or after vaccination potentiated B-cell immune responses and enabled the generation of neutralizing activity against omicron and SARS-CoV for all vaccines in nearly all individuals. These findings suggest that broad population immunity to SARS-CoV-2 will eventually be achieved, but by heterogenous paths

Role of Tissue Inhibitor of Metalloproteinases-2 and Insulin Like Growth Factor Binding Protein 7 for Early Recognition of Acute Kidney Injury in Critically Ill COVID-19 Patients (preprint)

Background: A high proportion of critically ill patients with COVID-19 develop acute kidney injury (AKI) and die. Early recognition of subclinical AKI could contribute to AKI prevention. Therefore, this study was aimed at exploring the role of the urinary biomarkers NGAL and [TIMP-2]•[IGFBP7] for early detection of AKI in this population. Methods: : This prospective, longitudinal cohort study included critically ill COVID-19 patients without AKI at study entry. Urine samples were collected on admission to critical care areas for determination of NGAL and [TIMP-2]•[IGFBP7] concentrations. Demographic information, comorbidities, clinical and laboratory data were recorded. The study outcomes were development of AKI and mortality during hospitalization. Comparisons of individuals who developed AKI during hospitalization vs. those without AKI were made using chi-squared test for categorical variables and Mann-Whitney U for continuous variables. Urinary biomarkers and their cutoff values were selected based on the highest sensitivity, specificity and area under the receiver-operating characteristics curve with 95% confidence intervals for prediction of AKI. Selected biomarkers and cutoffs were used in the Kaplan-Meier survival analyses for the time to AKI. Logistic regression analysis was used to identify the association between relevant covariates with AKI and mortality. For all analyses, two-sided P values £0.05 were considered statistically significant. Results: : Of the 51 individuals studied, 25 developed AKI during hospitalization (49%). The risk factors for AKI were male gender (HR=7.57, 95% CI: 1.28-44.8; p=0.026) and [TIMP-2]•[IGFBP7] ³ 0.2 (ng/ml) 2 /1000 (HR=7.23 , 95% CI: 0.99-52.4; p=0.050). Mortality during hospitalization was significantly higher in the group with AKI than in the group without AKI (p=0.004). Persistent AKI was a risk factor for mortality (HR=7.42, 95% CI: 1.04-53.04; p=0.046). Conclusions: : The combination of [TIMP-2]•[IGFBP7], together with clinical information, were useful for identification of subclinical AKI in critically ill COVID-19 patients. The role of additional biomarkers and their possible combinations for detection of AKI in critically ill COVID-19 patients remains to be explored in large clinical trials.

Acute kidney injury in patients with severe COVID-19 in Mexico (preprint)

Introduction: Some patients with COVID-19 pneumonia present systemic disease involving multiple systems. There is limited information about the clinical characteristics and events leading to acute kidney injury (AKI). We described the factors associated with the development of AKI and explored the relation of AKI and mortality in Mexican population with severe COVID-19. Methods: We retrospectively reviewed the medical records of individuals with severe pneumonia caused by SARS-CoV-2 hospitalized at the largest third-level reference institution for COVID-19 care in Mexico between March and April 2020. Demographic information, comorbidities, clinical and laboratory data, dates of mechanical ventilation and hospitalization, mechanical-ventilator settings and use of vasoactive drugs were recorded. Results: Of 99 patients studied, 58 developed AKI (58.6%). The group with AKI had higher body mass index (p=0.0003) and frequency of obesity (p=0.001); a higher requirement of invasive mechanical ventilation (p=0.008) and vasoactive drugs (p=0.004); greater levels of serum creatinine (p<0.001) and D-dimer on admission (p<0.001); and lower lymphocyte counts (p=0.001) than the non-AKI group. The multivariate analysis indicated that risk factors for AKI were obesity (adjusted hazard ratio (HR)=2.71, 95% confidence interval (CI)=1.33-5.51, p=0.005); higher serum creatinine (HR=1.44, CI=1.02-2.02, p=0.035) and D-dimer levels on admission (HR=1.14, CI=1.06-1.23, p<0.001). In-hospital mortality was higher in the AKI group than in the non-AKI group (65.5% vs. 14.6%; p=0.001). Conclusions: AKI was common in our cohort of patients with severe COVID-19 and it was associated with mortality. The risk factors for AKI were obesity, elevated creatinine levels and higher D-dimer levels on admission. Key words: Acute kidney injury; AKI; acute renal failure; COVID-19; SARS-CoV-2.