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Title: Examining viral pathogen evolution and spread through genomic data
Abstract: This work makes use of viral genomic data to examine the evolution and spread of the virus SARS-CoV-2 at multiple scales: from the virus present in individual patients over time to its introduction and transmission within a large university community.
Before e-infection with SARS-CoV-2 was a commonly known phenomenon, genomic data produced in the course of this work identified a case of reinfection in an immunosuppressed organ transplant recipient, distinguishing a second period of positivity and symptomatic COVID-19 as a new infection. The viral genomes from this later period were found to be derived phylogenetically from viral genomes sampled from other cases occurring in the surrounding region rather than from the genome of the initial period of positivity, indicating independent re-exposure in the community and subsequent reinfection. This was the first genomically-informed report of SARS-CoV-2 reinfection in a solid organ transplant recipient, the findings of which retain clinical relevance for the care of other immunocompromised individuals who may be vulnerable to reinfection with SARS-CoV-2, and highlight the importance of routine viral diagnostic testing of organ transplant recipients during periods of high pathogen transmission in the community.
The investigative approach employed for the single case was then applied systematically to a cohort of more than 1500 patients of Massachusetts General Hospital with medical records noting that each had a repeat positive test for SARS-CoV-2 more than 45 days after an initial positive. Viral genomic sequencing was attempted for all available retained specimens with a standardized qRT-PCR cycle threshold <32. The patients were classified using genomic data and clinical and viral load-based assessments into three distinct groups: cases where data were supportive of reinfection, cases where data were supportive of persistent RNA detection, and cases which could not be conclusively classified. Reinfection and persistent RNA detection were both identified, though conclusive classification of either was uncommon due to the challenge of producing longitudinal sequence data for each patient given the inherent variability in viral load during and following infection. The clinical and genomic assessments were compared, and it was found that clinical assessment alone failed to identify approximately one third of reinfection cases, a finding with implications for which cases are considered "active" infections as well as the allocation of therapeutics and private hospital rooms.
An additional study examined COVID-19 cases occurring at a large public university, taking a multi-modal approach to understanding the transmission of the virus and risk of infection. Viral genomic sequencing of residual material from genomic tests was used to identify a number of introductions to the campus community, and the subsequent size of descendant clusters. The phylogenetic case clusters were compared to connections reported by cases as close contacts, and to links inferred from physical proximity, as determined by nearby contemporaneous Wi-Fi network access. The interaction patterns of individuals were compared. The relative risk of infection was compared for various demographic groups, including team sports and residential dormitories. Viral-genomic variation observed through sequencing of wastewater effluent was compared with viral variation detected among clinical cases at the university and within the broader region.
Collectively, this work demonstrated the role viral genomic data can have during a pandemic in clinical care, pathogen surveillance, and public health.
Committee: Pardis Sabeti (Advisor) Colleen Cavanaugh (Chair), Michael Desai, and Jeremy Lubain (UMass Medical School)