ABSTRACT
Objective and design: The heterogeneity of response to SARS-COV-2 infection is directly linked to the individual genetic background. Genetic variants of inflammasome related genes have been pointed as risk factors for several inflammatory sterile and infectious disease. In the group of inflammasome receptors, NLRP1 stand out as a good novel candidate as severity factor for Covid-19 disease. Methods: To address this question, we performed an association study of NLRP1, DPP9, CARD8, IL1B and IL18 single nucleotide variants (SNVs) in a cohort of 945 Covid-19 patients. Results: The NLRP1 p.Leu155His in the linker region, target of viral protease, was significantly associated to Covid-19 severity, which could contribute to the excessive cytokine release reported in severe cases.
Subject(s)
COVID-19ABSTRACT
INTRODUCTIONCOVID-19 convalescent plasma (CCP) transfusion has emerged in the past months as an alternative approach to treat pneumonia cases of SARS-CoV-2. Current evidence regarding characteristics of the plasma product, the titer of neutralizing antibodies (nAbs) in the transfused units, time to onset of intervention, and impact of nAbs produced by the patient are limited and heterogeneous. MATERIAL AND METHODSWe describe the preliminary results of 104 patients with severe pneumonia due to SARS-CoV-2 transfused with CCP at three medical centers in Brazil. All enrolled patients were transfused with doses between 200 mL through 600mL of ABO compatible CCP on days 0-2 after enrolment. Clinical parameters were monitored and nAbs titration was performed using the cytopathic effect-based virus neutralization test with SARS-CoV-2 (GenBank MT126808.1). RESULTSForty-one patients achieved clinical improvement on day 14, and multivariable logistic regression showed that nAbs T (from CCP units transfused) (p= 0.001), nAbs P0 (on day of enrolment) (p=0.009) and use of other supportive therapies (p<0.001) were associated with higher odds for this clinical improvement. Considering ICU length of stay (LOS) and length of mechanical ventilation, in our analysis, nAbs P0 were associated with a significant reduction in ICU LOS (p=0.018) and duration of mechanical ventilation (p<0.001). Administration of CCP after 10 days of symptom onset was associated with increases in ICU length of stay (p<0.001). DISCUSSION/CONCLUSIONDespite the study limitations, our data have shown an association between patients previously acquired nAbs and clinical outcomes. The potential value of timely administration of CCP transfusion before day 10 of disease onset was demonstrated and nAbsP0, but not nAbsT, were associated with ICU LOS, and duration of mechanical ventilation on the improvement of clinical outcomes was also demonstrated. In conclusion, we consider these data are useful parameters to guide future CPP transfusion strategies to COVID-19.