Assessment of Virological Contributions to COVID-19 Outcomes in a Longitudinal Cohort of Hospitalized Adults

Abstract

While several demographic and clinical correlates of Coronavirus Disease 2019 (COVID-19) outcome have been identified, their relationship to virological and immunological parameters remain poorly defined. To address this, we performed longitudinal collection of nasopharyngeal swabs and blood samples from a cohort of 58 hospitalized adults with COVID-19. Samples were assessed for SARS-CoV-2 viral load, viral genotype, viral diversity, and antibody titer. Demographic and clinical information, including patient blood tests and several composite measures of disease severity, were extracted from electronic health records. Several factors, including male sex, higher age, higher body mass index, higher 4C Mortality score, and elevated lactate dehydrogenase levels were associated with ICU admission. Of all measured parameters, only the retrospectively calculated median Deterioration Index score was significantly associated with death. While quantitative PCR cycle threshold (Ct) values and genotype of SARS-CoV-2 were not significantly associated with outcome, Ct value did correlate positively with C-reactive protein levels and negatively with D-dimer, lymphocyte count, and antibody titer. Intra-host viral genetic diversity remained constant through disease course and resulted in changes in viral genotype in some participants. Ultimately, these results suggest worse outcomes are driven by immune dysfunction rather than by viral load and that SARS-CoV-2 evolution in hospital settings is relatively constant over time.

Sequencing during Times of Change: Evaluating SARS-CoV-2 Clinical Samples during the Transition from the Delta to Omicron Wave

“…We report that no single mutation was identified to be specific to, or associated with, severe disease. Our report supports previous findings that known factors such as age over 60, immunosuppression, and other co-morbidities previously identified including diabetes and high body mass have been reported to be more significantly associated with disease severity than any specific SARS-CoV-2 VOC [ 34 , 48 , 49 , 50 , 51 , 52 ].…”

“…We report low cycle threshold (Ct) values for these patients, suggesting high levels of virus replication ( Supplemental Table S1 ). We also found agreement with other findings that older age, (e.g., >60) was a statistically significant factor correlated with severe disease outcomes [ 34 , 49 , 51 , 52 , 55 ]. We identified both Delta and Omicron lineages in hospitalized patients ( Figure 2 A).…”

Heterogeneity of neutrophils and inflammatory responses in patients with COVID-19 and healthy controls

“…The progression of ARDS during severe COVID-19 disease, as well as other severe respiratory viral infections, continues despite patients already having cleared the viral infection in the majority of cases, especially in immunocompetent hosts ( 44 ). It is during this period when the host is transitioning either to recovery or persistent inflammation that the outcome of infection is determined.…”

Within-host genetic diversity of SARS-CoV-2 in the context of large-scale hospital-associated genomic surveillance

“…Previously, similar observations had been hinted at in smaller studies comparing cancer patients with healthcare workers, comparing mildly and severely ill patients, and examining minor variants in samples from patients of different ages 27–29 . Studies in which patients were longitudinally sampled have shown fluctuating numbers of minor variants over time, with little directional trend 9,30 . Combined with our data, this suggests that within-host diversity is temporally dynamic, but in the aggregate is more likely to be high in more severely ill patients.…”