Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S. Research Support, U.S. Gov't, Non-P.H.S. Research Support, Non-U.S. Gov't Epublish 2 citations
PubMed: 39339912 DOI: 10.3390/v16091436
SARS-CoV-2 Variants from Long-Term, Persistently Infected Immunocompromised Patients Have Altered Syncytia Formation, Temperature-Dependent Replication, and Serum Neutralizing Antibody Escape.
Viruses 16(9)
Authors: Camille Wouters, Jaiprasath Sachithanandham, Elgin Akin, Lisa Pieterse, Amary Fall, Thao T Truong, Jennifer Dien Bard, Rebecca Yee, David J Sullivan, Heba H Mostafa, Andrew Pekosz
Affiliations
- W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
- Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA.
- Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.
- Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
- Department of Pathology, The George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USA.
Abstract
SARS-CoV-2 infection of immunocompromised individuals often leads to prolonged detection of viral RNA and infectious virus in nasal specimens, presumably due to the lack of induction of an appropriate adaptive immune response. Mutations identified in virus sequences obtained from persistently infected patients bear signatures of immune evasion and have some overlap with sequences present in variants of concern. We characterized virus isolates obtained greater than 100 days after the initial COVID-19 diagnosis from two COVID-19 patients undergoing immunosuppressive cancer therapy, wand compared them to an isolate from the start of the infection. Isolates from an individual who never mounted an antibody response specific to SARS-CoV-2 despite the administration of convalescent plasma showed slight reductions in plaque size and some showed temperature-dependent replication attenuation on human nasal epithelial cell culture compared to the virus that initiated infection. An isolate from another patient-who did mount a SARS-CoV-2 IgM response-showed temperature-dependent changes in plaque size as well as increased syncytia formation and escape from serum-neutralizing antibodies. Our results indicate that not all virus isolates from immunocompromised COVID-19 patients display clear signs of phenotypic change, but increased attention should be paid to monitoring virus evolution in this patient population.
MeSH
Sars-Cov-2, Serum, Virology, Antibodies, Neutralizing, Covid-19, Giant Cells, Viruses, Immunocompromised Host, Severe Acute Respiratory Syndrome-Related Coronavirus, Temperature, Infections