MOLECULAR EPIDEMIOLOGY of the COVID-19 PANDEMIC in CHICAGO

ABSTRACT

Background: The greater Chicagoland area has recorded over 10,000 COVID-related deaths and nearly 600,000 cases since the start of the COVID-19 pandemic in March of 2020. SARS-CoV-2, the causative agent of COVID-19, has continually changed over that time, with some variants evolving to become more transmissible or more resistant to neutralizing antibody responses. Methods: To better understand how viral genetic variation has contributed to differences in COVID-19 pathogenesis and patient outcome, we established a biobank of residual diagnostic samples from adult patients who tested positive for COVID-19 in a PCR-based test at Northwestern Memorial Hospital. Thus far, we have collected samples from 6448 out-patients and 632 in-patients. Of these, we have performed whole genome sequencing and viral load calculations on 1373 samples. Clinical and demographic information, including composite measures of disease severity, were extracted from available electronic health records. These data were assessed for longitudinal patterns and for specific association with viral lineage. Results: We found that the early epidemic in March of 2020 was defined by three distinct lineages reflecting the outbreaks in China (19B/A), Washington state (19B/A.1), and New York state (19A/B.1). By November of 2020, we saw a large increase in the number of confirmed cases, dominated by the 20G clade. This lineage remained predominant until March of 2021, when the Alpha and Gamma variants of concern became more established. These were recently supplanted by the Delta variant, which now accounts for over 90% of Chicago cases. At the height of the pandemic in November of 2020, case counts peaked at over 5000 cases per day, but hospitalizations, ICU admissions, and deaths over this period remained flat. Statistical testing revealed that the predominant clade at that time, 20G, was associated with better outcomes and less severe disease as measured by clinical measures of patient deterioration, even when controlling for patient demographics. These results suggest that a viral variant associated with less severe disease was predominant in late 2020 before the emergence of the more transmissible variants of concern. Conclusion: Current work is being done to determine if the less severe outcomes associated with this clade also contributed to more asymptomatic transmission, potentially contributing to the high case counts recorded over this period. These data emphasize the need for continued genomic surveillance of SARS-CoV-2 to character.