1097. A Prospective Evaluation of SARS-CoV-2 Shedding and Evolution in Immunocompromised Hosts During the Omicron Period — IVY Network, 5 U.S. States, April 11, 2022 – February 1, 2023

BACKGROUND: Prolonged SARS-CoV-2 infections in immunocompromised hosts may predict or source the emergence of highly mutated variants of concern. The types of immunosuppression placing patients at highest risk for prolonged infection and associated intra-host viral evolution remain unclear. [Figure: see text] [Figure: see text] METHODS: Adults aged ≥18 years were enrolled and followed at 5 hospitals in the Investigating Respiratory Viruses in the Acutely Ill (IVY) Network from 4/11/2022 – 2/1/2023. Eligible patients were SARS-CoV-2-positive by RT-qPCR in the previous 14 days and had an immunocompromising condition, including malignancy, solid organ or hematopoietic stem cell transplant (SOT/HSCT), autoimmune/autoinflammatory condition on immunosuppression, AIDS, or primary immunodeficiency. Nasal specimens were collected and tested by RT-qPCR every 2–4 weeks until negative in 2 consecutive specimens. All specimens underwent viral culture and whole genome sequencing. A Cox proportional hazards model was used to assess factors associated with prolonged infection. [Figure: see text] RESULTS: 150 patients were enrolled with the following conditions: B cell malignancy or anti-B cell therapy (n=18), SOT/HSCT (n=59), AIDS (n=5), non-B cell malignancy (n=23), and autoimmune/autoinflammatory (n=45, Table 1). 37 (25%) were RT-qPCR-positive and 11 (7%) were culture-positive ≥21 days after infection onset. Patients with B cell dysfunction had prolonged infection compared to those with autoimmune/autoinflammatory conditions (aHR 0.28, 95% CI 0.14–0.58) (Figures 1, 2). The within-host evolutionary rate was similar in prolonged (≥ 21 days) and shorter (< 21 days) infections (Figure 3). Consensus spike mutations were identified in 4 individuals who were RT-qPCR-positive ≥ 56 days; 68% were in the receptor-binding domain (RBD) (Figures 4, 5). The common spike mutations in this analysis were rare (< 2%) in global circulation. [Figure: see text] [Figure: see text] [Figure: see text] CONCLUSION: In this prospective cohort of immunocompromised patients during the Omicron variant period, prolonged SARS-CoV-2 infections were uncommon. While the within-host evolutionary rates are similar between prolonged and shorter infections, individuals with infections lasting ≥ 56 days accumulated mutations in the spike protein. These appear distinct from those seen globally. [Figure: see text] Bisected squares indicate more than one genomic mutation produced the same amino acid mutation. RBD is highlighted in gray. DISCLOSURES: Emily T. Martin, PhD, MPH, Merck: Grant/Research Support Natasha B. Halasa, MD, MPH, Merck: Grant/Research Support|Quidell: Grant/Research Support|Quidell: donation of kits|Sanofi: Grant/Research Support|Sanofi: vaccine support Carlos G. Grijalva, MD, MPH, AHRQ: Grant/Research Support|CDC: Grant/Research Support|FDA: Grant/Research Support|Merck: Advisor/Consultant|NIH: Grant/Research Support|Syneos Health: Grant/Research Support Adam S. Lauring, MD, PhD, Roche: Advisor/Consultant|Sanofi: Advisor/Consultant