Changes in the hematological cells ratios are associated with death in COVID-19 patients

The impaired hematological parameters have been identified as risk factors for critical illness and higher mortality rates in patients with COVID-19. The aim is to analyze the changes in hematological cells ratios and the relationship to death in COVID-19 patients. Method(s): A retrospective study in COVID-19 patients, classified according to the PaO2/FiO2 relation. The plateletto-lymphocyte ratio (PLR), neutrophil-to-lymphocyte (NLR), and monocyte-to-lymphocyte (MLR) were determined during hospitalization, and changes between four observations during hospitalization were analyzed. Of 780 patients included, 464 were discharged by improvement, and 316 died. From deaths, 26.4% were classified as mild or moderate and 14.1% as severe COVID-19 at admission. The PLR, NLR, and MLR values at admission were higher in patients who died than those who survived. The increase of PLR during later hospitalization stages was associated with death in patients with mild or moderate COVID-19 (OR= 2.22, p<0.001) and, in severe disease (OR= 2.01, p=0.004), a similar association showed the increase MLR (OR= 3.07, p<0.001, and OR= 2.2, p<0.001, respectively). Conversely, the increase in NLR from early stages was associated with death outcome;in early stages (OR= 1.54, p=0.024, and OR= 1.60, p=0.04, according to severity category). In late stages (OR= 3.72, p<0.001 and OR= 3.26, p<0.001, respectively). All models were adjusted by age and sex. The positive change on PLR, MLR, and NRL is associated with death regardless of severity at hospital admission;therefore, the monitoring during the hospitalization stay will be useful to patients' management.

Relevance of IFNAR2 variants in the mortality of patients with severe COVID-19

Background: The Interferon (IFN)-gamma pathway, including its receptor subunits (IFNAR1 and IFNAR2), is related to hyperinflammation and lower viral clearance in COVID-19. IFNAR2 and the soluble form of the protein have been associated with COVID-19 severity. Aim(s): We aimed to evaluate the association of the IFNAR2 rs2236757, rs1051393, rs3153, rs2834158, and rs2229207 with the clinical outcome (survivors and non-survivors) of patients with severe COVID-19. Method(s): The study included 1,136 patients (67% males, median 56 years old) with severe COVID-19, hospitalized in the Instituto Nacional de Enfermedades Respiratorias, a tertiary care hospital in Mexico. Variants were assessed using Taqman assays. The association study was performed using PLINK v2. Result(s): Four hundred and fifteen patients died during the hospital stay (36.5%). We found higher minor allele frequencies of the rs2236757, rs3153, and rs2834158 among non-survivors compared with survivors. The analyses of genotypes also showed associations of the dominant model for the three variants (Table 1). The rs2834158 was also associated with a logistic regression model adjusted for age (p= 0.038). Conclusion(s): IFNAR2 variants contribute to the genetic risk for mortality in patients with severe COVID-19. (Table Presented).

TNF, TNFRSF1A, and TNFRSF1B variants affect TNFR1 and TNFR2 levels in patients with severe COVID-19

Background: TNF and its receptors (TNFR1 and TNFR2) have been implicated in the severity of COVID-19. But it has not been explored the association of genetic variants with cytokine levels. Aim(s): We assessed the association of TNF (rs1800629, rs361525), TNFRSF1A (rs767455, rs1800693), and TNFRSF1B (rs1061622, rs3397) single nucleotide variants with TNF, TNFR1, and TNFR2 plasma levels in patients with severe COVID-19. Method(s): The study included 334 severe COVID-19 hospitalized patients in Mexico's Instituto Nacional de Enfermedades Respiratorias. Blood sampling was performed among the first seven days since patients' admission. Cytokine levels were determined using ELISA and Taqman assays for genotyping. Kruskal-Wallis test was performed in RStudio v.1.3.1073. Result(s): Patients with TT or GT genotype (TNFRSF1B rs1061622) exhibited higher sTNFR1 levels than those carrying GG (1,580 and 1,499 pg/ml vs 1,031 pg/mL). For TNF rs1800629 and rs361525 the higher TNFR2 levels were observed among patients homozygous for the common allele (rs1800629 GG=3,993 pg/mL vs AG+AA=2,881 pg/mL;rs361525 GG=3,996 pg/mL, AG=3,919 pg/mL, and AA=1,935 pg/mL). Higher levels of both receptors were related with more severe forms of COVID-19. Conclusion(s): TNFRSF1B rs1061622, and TNF rs1800629 and rs361525 affect the TNFR1 and TNFR2 levels implicated in the severity of COVID-19.

HLA Class I allele is associated with a lower risk to develop Post-COVID19 interstitial lung manifestations

Introduction: The HLA Class I genes codify crucial molecules in developing the immunological response against pathogenic agents such as SARS-CoV-2. We aimed to assess HLA-A alleles associated with COVID-19 subsequent pulmonary complications as interstitial lung manifestations (ILM). Material(s) and Method(s): 209 Mexican mestizo patients with a positive RT-PCR test for SARS-CoV-2 and confirmed clinical diagnosis of COVID-19 were included. The participants were monitored three months after the hospital discharge through tomography;They were divided into two groups, 1) patients who developed ILM post-COVID19 (n = 85) and 2) those patients without tomographic evidence of ILM (n = 124). The HLA-A locus was genotyped by endpoint PCR using Micro SSP Generic HLA Class I kits. The clinical and demographic variables were analyzed by SPSS software. The alleles and genotypes were analyzed by 2 x 2 contingency tables, the value of p was obtained by Yates' correction. Result(s): There is no significant difference in age, sex, BMI, hospitalization days, PAO2/FIO2, or invasive mechanical ventilation. The alleles HLA-A*02:01, *24:02, and *68:01 are the most frequent in both study groups, grouping more than 60% of the alleles identified. On the other hand, the frequency of the HLA-A*01:01 allele was decreased in the group with interstitial lung manifestations at 3 months of discharge, compared to the group without interstitial lung manifestations (p= 0.004, OR = 0.13, IC95% 0.03-0.58). There is no significant difference in the genotypic frequencies. Conclusion(s): Subjects carrying the HLA-A*01:01 allele have a lower risk of developing interstitial lung manifestations posterior from COVID-19.