SARS-CoV-2 shedding dynamics and transmission in immunosuppressed patients.
Jee-Soo Lee, Ki Wook Yun, Hyeonju Jeong, Boram Kim, Man Jin Kim, Jae Hyeon Park, Ho Seob Shin, Hyeon Sae Oh, Hobin Sung, Myung Gi Song, Sung Im Cho, So Yeon Kim, Chang Kyung Kang, Pyoeng Gyun Choe, Wan Beom Park, Nam Joong Kim, Myoung-Don Oh, Eun Hwa Choi, Seungman Park, Taek Soo Kim, Jung-Hee Lee, Heungsup Sung, Sung Sup Park, Moon-Woo Seong
Author Information
Jee-Soo Lee: Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
Ki Wook Yun: Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea.
Hyeonju Jeong: Department of Internal Medicine, Gyeonggi Provincial Medical Center, Ansung Hospital, Anseong Gyeonggi-do, Republic of Korea.
Boram Kim: Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
Man Jin Kim: Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
Jae Hyeon Park: Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
Ho Seob Shin: Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
Hyeon Sae Oh: Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
Hobin Sung: Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
Myung Gi Song: Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
Sung Im Cho: Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
So Yeon Kim: Department of Laboratory Medicine, National Medical Center, Seoul, Republic of Korea.
Chang Kyung Kang: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Pyoeng Gyun Choe: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Wan Beom Park: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Nam Joong Kim: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Myoung-Don Oh: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Eun Hwa Choi: Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea.
Seungman Park: Department of Laboratory Medicine, Seegene Medical Foundation, Seoul, Republic of Korea.
Taek Soo Kim: Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
Jung-Hee Lee: Department of Haematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Heungsup Sung: Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Sung Sup Park: Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
Moon-Woo Seong: Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea. ORCID
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern have been emerging. However, knowledge of temporal and spatial dynamics of SARS-CoV-2 is limited. This study characterized SARS-CoV-2 evolution in immunosuppressed patients with long-term SARS-CoV-2 shedding for 73-250 days, without specific treatment. We conducted whole-genome sequencing of 27 serial samples, including 26 serial samples collected from various anatomic sites of two patients and the first positive sample from patient 2's mother. We analysed the intrahost temporal dynamics and genomic diversity of the viral population within different sample types. Intrahost variants emerging during infection showed diversity between individual hosts. Remarkably, N501Y, P681R, and E484K, key substitutions within spike protein, emerged during infection and became the dominant population. P681R, which had not yet been detected in the publicly available genome in Korea, appeared within patient 1 during infection. Mutually exclusive substitutions at residues R346 (R346S and R346I) and E484 (E484K and E484A) of spike protein and continuous turnover of these substitutions occurred. Unique genetic changes were observed in urine samples. A household transmission from patient 2 to his mother, at least 38 days after the diagnosis, was characterized. Viruses may differently mutate and adjust to the host selective pressure, which could enable the virus to replicate efficiently for fitness in each host. Intrahost variants could be candidate variants likely to spread to the population eventually. Our findings may provide new insights into the dynamics of SARS-CoV-2 in response to interactions between the virus and host.
