Clinical and molecular characterization of COVID-19 hospitalized patients

Abstract

Clinical and molecular characterization by Whole Exome Sequencing (WES) is reported in 35 COVID-19 patients attending the University Hospital in Siena, Italy, from April 7 to May 7, 2020. Eighty percent of patients required respiratory assistance, half of them being on mechanical ventilation. Fiftyone percent had hepatic involvement and hyposmia was ascertained in 3 patients. Searching for common genes by collapsing methods against 150 WES of controls of the Italian population failed to give straightforward statistically significant results with the exception of two genes. This result is not unexpected since we are facing the most challenging common disorder triggered by environmental factors with a strong underlying heritability (50%). The lesson learned from Autism-Spectrum-Disorders prompted us to re-analyse the cohort treating each patient as an independent case, following a Mendelian-like model. We identified for each patient an average of 2.5 pathogenic mutations involved in virus infection susceptibility and pinpointing to one or more rare disorder(s). To our knowledge, this is the first report on WES and COVID-19. Our results suggest a combined model for COVID-19 susceptibility with a number of common susceptibility genes which represent the favorite background in which additional host private mutations may determine disease progression.

The Role of Immunogenetics in COVID-19

“…11p15.5) was associated with influenza severity and mortality, and faster progression of HIV infection towards AIDS [ 125 , 126 , 127 , 128 ]. As regards COVID-19, the rs12252 (C) allele is considered a risk variant [ 120 ], especially as regards the homozygosity for the C allele, i.e., the (CC) genotype, in symptomatic cases [ 118 , 129 ]. As discussed in the previous sections, the adoption of uniform criteria to describe disease severity and the careful choice of the compared groups/populations are essential in order to obtain reproducible results.…”

“…By whole exome sequencing and unbiased collapsing gene analysis, an Italian study identified PRKRA as one of the two protective genes (see below) comparing hospitalized COVID-19 patients with controls of unknown status. In this context, the deleterious variant was more frequent in COVID-19 patients than in controls [ 120 ].…”

“…More studies are necessary to deepen these results, also establishing a causal relationship between expression of chemokine receptors and history of the SARS-CoV-2 infection. Supporting this urgency, an Italian study focused on hospitalized COVID-19 patients looking for variants involved in viral infection, susceptibility or protection by whole exome sequencing; the authors detected variant rs1799864 of C-C Motif Chemokine Receptor 2 (CCR2) in 8 out of 35 patients and rs1800940 of CCR5 (both associated with protection against HIV) in 1 out of 35 patients [ 120 , 152 , 153 ]. Furthermore, in lung tissues, transcriptome-wide association demonstrated that predicted low levels of CXCR6 together with low expression of CCCR3 and high expression of CCR2 are associated with severe COVID-19 (defined as admission to critical care) vs. controls [ 117 , 154 ].…”

“…Expression of lysosomal localized Lysosomal Protein Transmembrane 4 β ( LAPTM4B in 8q22.1), a lysosomal regulator of autophagy and an essential partner for endosomal transporters is finely regulated, since its overexpression causes enlargement of lysosomes [ 26 , 196 , 197 , 198 , 199 ]. LAPTM4B is the second gene identified by an Italian study for which deleterious variants were reported at higher frequencies in COVID-19 patients than in controls ( Table 3 ) [ 120 ].…”

Covid-19 in Chile. The experience of a Regional reference Center. Preliminary report

“…Currently there is little information on the clinical presentation of and outcomes in Latin America, especially in hospitalized patients (6)(7)(8)(9). This could contrast with that reported in countries of the northern hemisphere, which have dissimilar features on demographic, economic, cultural, healthcare systems and/or mitigation strategies issues (10)(11)(12)(13)(14)(15)(16)(17)(18)(19). We present this preliminary report on a cohort of patients during the first wave in a southern region in Chile detailing clinical features and outcomes in a reference center.…”