Association of the Interleukin 1B-31*C Proinflammatory Allele with the Severity of COVID-19 Patients: A Preliminary Report.

Individuals with no known comorbidities or risk factors may develop severe coronavirus disease 2019 (COVID-19). The present study assessed the effect of certain host polymorphisms and viral lineage on the severity of COVID-19 among hospitalized patients with no known comorbidities in Mexico. The analysis included 117 unrelated hospitalized patients with COVID-19. Patients were stratified by whether they required intensive care unit (ICU) admission: the ICU group (n = 40) and non-ICU group (n = 77). COVID-19 was diagnosed on the basis of a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription-polymerase chain reaction (RT-PCR) assay and clinical and radiographic criteria. The presence of the IL1B-31 (T/C) polymorphism was determined for all patients using PCR and nucleotide sequencing. Genotyping of the IL-4 (-590, T/C) and IL-8 (-251, T/A) polymorphisms was performed by the amplification refractory mutation system-PCR method. Genotyping of IL1-RN was performed using PCR. Viral genome sequencing was performed using the ARTIC Network amplicon sequencing protocol using a MinION. Logistic regression analysis identified the carriage of IL-1 B*-31 *C as an independent potential risk factor (odds ratio [OR] = 3.1736, 95% confidence interval [CI] = 1.0748-9.3705, p = 0.0366) for ICU admission and the presence of IL-RN*2 as a protective factor (OR = 0.4371, 95% CI = 0.1935-0.9871, p = 0.0465) against ICU admission. Under the codominant model, the CC genotype of IL1B-31 significantly increased the risk of ICU admission (OR: 6.38, 95% CI: 11.57-25.86, p < 0.024). The IL1B-31 *C-IL-4-590 *T haplotype increased the risk of ICU admission (OR = 2.53, 95% CI = 1.02-6.25, p = 0.047). The 42 SARS-CoV-2 genomes sequenced belonged to four clades, 20A-20D. No association was detected between SARS-CoV-2 clades and ICU admission or death. Thus, in patients with no known comorbidities or risk factors, the IL1B-31*C proinflammatory allele was observed to be associated with the risk of ICU admission owing to COVID-19.

Seroprevalence of Anti-SARS-CoV-2 Antibodies in Blood Donors from Nuevo Leon State, Mexico, during 2020: A Retrospective Cross-Sectional Evaluation.

The progression and distribution of the SARS-CoV-2 pandemic are continuously changing over time and can be traced by blood donors' serological survey. Here, we investigated the seroprevalence of anti-SARS-CoV-2 antibodies in blood donors in Nuevo Leon, Mexico during 2020 as a strategy for the rapid evaluation of the spread of SARS-CoV-2 and asymptomatic case detection. We collected residual plasma samples from blood donors who attended two regional donation centers from January to December of 2020 to identify changes in anti-SARS-CoV-2 IgG prevalence. Plasma samples were analyzed on the Abbott Architect instrument using the commercial Abbott SARS-CoV-2 IgG chemiluminescent assay. We found a total of 99 reactive samples from 2068 analyzed plasma samples, resulting in a raw prevalence of 4.87%. Donors aged 18-49 years were more likely to be seropositive compared to those aged >50 years (p < 0.001). Weekly seroprevalence increased from 1.8% during the early pandemic stage to 27.59% by the end of the year. Prevalence was 1.46-fold higher in females compared to males. Case geographical mapping showed that Monterrey city recorded the majority of SARS-CoV-2 cases. These results show that there is a growing trend of seroprevalence over time associated with asymptomatic infection that is unnoticed under the current epidemiological surveillance protocols.

Whole-exome sequencing in three children with sporadic Blau syndrome, one of them co-presenting with recurrent polyserositis.

Blau syndrome (BS) is a rare, chronic autoinflammatory disease with onset before age 4 and mainly characterised by granulomatous arthritis, recurrent uveitis, and skin rash. Sporadic (also known as early-onset sarcoidosis) or familial BS is caused by gain-of-function mutations in the NOD2 gene, which encodes for a multi-task protein that plays a crucial role in the innate immune defense. We report on three Mexican patients clinically diagnosed with BS who exhibited a likely pathogenic variant in NOD2 as revealed by whole-exome sequencing (WES) and Sanger sequencing: two variants (c.1000 C > T/p.Arg334Trp and c.1538 T > C/p.Met513Thr) lie in the ATP/Mg2+ binding site, whereas the other (c.3019dupC/p.Leu1007ProfsTer2) introduces a premature stop codon disrupting the last LRR domain (LRR9) formation; all three variants are consistent with gain-of-function changes. Interestingly, all these patients presented concomitant likely pathogenic variants in other inflammatory disease-related genes, i.e. TLR10, PRR12, MEFV and/or SLC22A5. Although the clinical presentation in these patients included the BS diagnostic triad, overall it was rather heterogeneous. It is plausible that this clinical variability depends partly on the patients' genetic background as suggested by our WES results. After this molecular diagnosis and given the absence of NOD2 mutations (demonstrated in two trios) and related symptoms in the respective parents (confirmed in all trios), patients 1 and 2 were considered to have sporadic BS, while patient 3, a sporadic BS-recurrent polyserositis compound phenotype. Altogether, our observations and findings underscore the overlapping among inflammatory diseases and the importance of determining the underlying genetic cause by high-throughput methods. Likewise, this study further reinforces a pathogenic link between the here found NOD2 variants and BS and envisages potential additive effects from other loci in these, and probably other patients.