Phylogenetic Analysis and Comparative Genomics of SARS-CoV-2 from Survivor and Non-survivor COVID-19 Patients in Cordoba, Argentina

Background: The SARS-CoV-2 virus is responsible for the COVID-19 pandemic. To better understand the evolution of SARS-CoV-2 early in the pandemic in the Province of Cordoba, Argentina, we performed a comparative genomic analysis of SARS-CoV-2 strains detected in survivors and non-survivors of COVID-19. We also carried out an epidemiological study to find a possible association between the symptoms and comorbidities of these patients with their clinical outcomes.

Results: A representative sampling was performed in different cities in the Province of Cordoba. Ten and nine complete SARS-CoV-2 genomes were obtained by next-generation sequencing of nasopharyngeal specimens from non-survivors and survivors, respectively. Phylogenetic and phylodynamic analyses revealed multiple introductions of the most common lineages in South America, including B.1, B.1.1.1, B.1.499, and N.3. Fifty-six mutations were identified, with 14% of those in common between the non-survivor and survivor groups. Specific SARS-CoV-2 mutations for survivors constituted 25% whereas for non-survivors they were 41% of the repertoire, indicating partial selectivity. The non-survivors' variants showed higher diversity in 9 genes, with a majority in Nsp3, while the survivors' variants were detected in 5 genes, with a higher incidence in the Spike protein. At least one comorbidity was present in 60% of non-survivor patients and 33% of survivors. Age 75-85 years (p = 0.018) and hospitalization (p = 0.019) were associated with non-survivor patients. Related to the most common symptoms, the prevalence of fever was similar in both groups, while dyspnea was more frequent among non-survivors and cough among survivors.

Conclusions: This study describes the association of clinical characteristics with the clinical outcomes of survivors and non-survivors of COVID-19 patients, and the specific mutations found in the genome sequences of SARS-CoV-2 in each patient group. Future research on the functional characterization of novel mutations should be performed to understand the role of these variations in SARS-CoV-2 pathogenesis and COVID-19 disease outcomes. These results add new genomic data to better understand the evolution of the SARS-CoV-2 variants that spread in Argentina during the first wave of the COVID-19 pandemic.