Adjunctive viral cell culture supports treatment decision‐making in patients with secondary humoral immunodeficiency and persistent SARS‐CoV‐2 infection

• Published in: British Journal of Haematology Vol. 196; no. 5; pp. 1170 - 1174
• Main Authors: Pallett, Scott J. C., Wake, Rachel, Youngs, Jonathan, Pope, Cassie, Tan, Ngee Keong, Taylor, Joshua, Hawkins, Lois, Witney, Adam A., Laing, Kenneth G., Monahan, Irene M., Akay, Melek, Cox, Alison, Groppelli, Elisabetta, Kelleher, Peter, Miller, Paul, Bicanic, Tihana
• Format: Journal Article Web Resource
• Language: English
• Published: England John Wiley & Sons, Inc 01.03.2022; Blackwell Publishing Ltd; John Wiley and Sons Inc
• Subjects: Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cell culture; Cell Culture Techniques; Clinical Decision-Making; Correspondence; Correspondence‐COVID‐19; COVID-19 - complications; COVID-19 - immunology; COVID-19 - therapy; COVID‐19; Decision making; Female; Hematology; Humans; immune reconstitution; Immunity, Cellular - drug effects; Immunity, Humoral - drug effects; Immunocompromised Host; Immunodeficiency; Immunotherapy; lymphoma; Lymphoma, Non-Hodgkin - complications; Lymphoma, Non-Hodgkin - immunology; Lymphoma, Non-Hodgkin - therapy; recurrence; SARS-CoV-2 - immunology; SARS-CoV-2 - isolation & purification; SARS‐CoV‐2; Secondary Prevention; Severe acute respiratory syndrome coronavirus 2; COVID-19; recurrence; immune reconstitution; SARS-CoV-2; lymphoma
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/bjh.17957

Persistent Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) infection is observed among patients with haematological malignancy, conferring an increased mortality risk.1, 2 Persistent SARS-CoV-2 RNA detection from clinical samples may represent redundant fragmented RNA, replication-competent virus, or reinfection.3, 4 Given the role of the host immune response in viral clearance and COVID-19 immunopathogenesis,5, 6 distinguishing these scenarios is important for therapeutic decision-making (antiviral versus immunomodulatory) as well as preventing onward hospital transmission. Investigation was conducted as per current Public Health England guidelines, including infection specialist advice, in-house whole-genome sequencing (WGS) and immunological testing using both B-cell and T-cell assays (Data S1).8, 9 Additionally, in-house viral cell culture was conducted to assess for replication-competent virus (Data S1). In this case, viral cell culture results alongside WGS supported reactivation of symptomatic infection and led to the decision to treat with a full course of high-dose steroids and remdesivir. [...]administration of G-CSF therapy for supportive management of chemotherapy-induced neutropenia was highlighted as a possible risk for further symptomatic (fever, breathlessness) disease in the presence of infection with replication-competent SARS-CoV-2 virus. In addition to stimulating neutrophil proliferation and maturation, G-CSF reconstitutes immune mediators including the pro-inflammatory cytokines interleukin-1, tumour necrosis factor (TNF)-α and interleukin-6,6 which play a role in a maladaptive inflammatory response to SARS-CoV-2 infection.10 Furthermore, autopsy studies reveal aggregated neutrophils and neutrophil extracellular traps in lung tissue,11 induced by a mechanism that appears dependent on active SARS-CoV-2 viral replication.10 We therefore postulate that rising neutrophils following G-CSF therapy during active SARS-CoV-2 infection may have led to relapsing pneumonitis in this manner, clinically resembling paradoxical immune reconstitution inflammatory syndromes (IRIS; Fig 1B), occasionally seen with treatment initiation of HIV or tuberculosis,12, 13 with one such case reported.14 As with IRIS, treatment with steroids may have contributed to resolution of CRP and oxygen requirement (Fig 1) although timing of G-CSF alongside steroids is a confounding factor that makes further interpretation in this case difficult.