In a single-institution study reported in a letter to the editor in The New England Journal of Medicine, Aydillo et al found that SARS-CoV-2 RNA could be detected in patients with COVID-19 receiving immunosuppressive treatment for cancer for as long as 78 days after the onset of virus symptoms. The authors also found that viable virus could be grown in culture at up to 61 days after symptom onset.
As stated by the investigators, “Detection of replication-competent SARS-CoV-2 is the most reliable indicator of contagiousness. Although the duration of live-virus shedding is well-characterized in immunocompetent patients with COVID-19, little is known about how long immunocompromised patients are contagious.”
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The study included 20 immunocompromised patients infected with COVID-19 diagnosed between March 10 and April 20, 2020, at Memorial Sloan Kettering Cancer Center, including 18 patients who received hematopoietic stem cell transplants or chimeric antigen receptor (CAR) T-cell therapy and 2 patients with lymphoma. Of the 20 patients, 15 were receiving active treatment or chemotherapy, and 11 had severe COVID-19.
Cell cultures were used to detect viable virus in serially collected respiratory samples, with live virus being isolated in Vero cells and genetic variants being identified by whole-genome sequencing of nasopharyngeal and cultured specimens.
A total of 57 respiratory samples (56 nasopharyngeal and 1 sputum) were serially collected and analyzed by quantitative reverse-transcriptase polymerase chain reaction; 18 isolates were cultured in vitro; all samples and isolates underwent viral RNA isolation; and 37 samples and 18 isolates underwent whole-genome sequencing.
Viral RNA was detected for up to 78 days after onset of symptoms (interquartile range = 24–64 days).
Viable virus was detected in 10 (71%) of 14 nasopharyngeal samples that were available from the first day of laboratory testing. Subsequent samples from five patients grew virus in culture for 8, 17, 25, 26, and 61 days after symptom onset. Of the three patients with virus persisting for longer than 20 days, two had received allogeneic hematopoietic stem cell transplants and one had received CAR T-cell therapy within the previous 6 months, with all remaining seronegative for antibodies to viral nucleoprotein.
On whole-genome sequencing, viral reads were detected in all samples and showed ≥ 95% complete SARS-CoV-2 genomes in 37 nasopharyngeal samples obtained from 17 patients and each of 18 cultured specimens.
“Patients with profound immunosuppression after undergoing hematopoietic stem cell transplantation or receiving cellular therapies may shed viable SARS-CoV-2 for at least 2 months. The current guidelines for COVID-19 isolation precautions may need to be revised for immunocompromised patients.”— Aydillo et al
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Serial sample genomes were obtained from 11 patients up to 63 days after onset of symptoms. Each patient was infected by a distinct virus, and no major changes were detected in the consensus sequences of the original serial specimens or cultured isolates, with these findings indicating persistent infection.
The investigators concluded, “Patients with profound immunosuppression after undergoing hematopoietic stem cell transplantation or receiving cellular therapies may shed viable SARS-CoV-2 for at least 2 months. The current guidelines for COVID-19 isolation precautions may need to be revised for immunocompromised patients.”
Disclosure: The study was supported by the National Cancer Institute, Jack and Dorothy Byrne Foundation, National Institute of Allergy and Infectious Diseases, and others. For full disclosures of the study authors, visit nejm.org.