Immune reconstitution and severity of COVID‐19 among hematopoietic cell transplant recipients

Abstract

Coronavirus disease 2019 , secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide pandemic, presenting unprecedented challenges to health-care providers and systems. 1 The immunopathogenesis of COVID-19 is intriguing as it involves virus-driven tissue damage intertwined with an uncontrolled inflammatory response, contributing to severity of disease, acute respiratory distress syndrome (ARDS), and multiple organ failure. 2 Hematopoietic cell transplant (HCT) recipients are severely immunocompromised, with increased risk of severe COVID-19 secondary to the myeloablative conditioning regimens, organ damage, and possible immune recovery leading to an exuberant inflammatory reaction. A comprehensive approach to manage HCT recipients with COVID-19 at different stages after HCT (pre-engraftment, early and late post-engraftment) is lacking in terms of the potential role of early or pre-emptive antiviral use and/or immunomodulators that may improve clinical outcomes. In this brief report, we present two patients with COVID-19 pneumonia that occurred during the pre-engraftment period after HCT at our comprehensive cancer center. Additionally, we review the previously reported cases of COVID-19 in adults HCT recipients until December 31st, 2020, for whom sufficient data were available. [3][4][5][6][7][8][9][10][11][12][13]

Autologous hematopoietic stem cell transplantation with concomitant SARS-CoV-2 infection

“…So far, only three adult COVID-19 cases have been described in HSCT recipients in the pre-engraftment phase (Table 1 ) [ 8 , 9 ]. This is possibly due to stringent measures taken by transplant centers to prevent SARS-CoV-2 infections in this highly vulnerable patient population [ 10 ].…”

“…Cases presented include our case with testicular non-seminomatous germ cell tumor (NSGCT), one patient with Acute Myeloid Leukemia (AML), one patient with Acute Lymphoid Leukemia (ALL), one patient with Chronic Lymphocytic Leukemia (CLL) and one patient with Multiple myeloma (MM). Patients received either reduced intensity conditioning (RIC) or myeloablative conditioning (MAC) before undergoing allogeneic (allo) or autologous (auto) hematopoietic stem cell transplantation (HSCT) Reference Age (yrs) Gender Underlying malignancy Type of HSCT Intensity of conditioning regimen Day of COVID-19 diagnosis in relation to HSCT COVID related treatment Need of respiratory support Outcome Presented case 33 m NSGCT auto MAC day − 4 Remdesivir None Survived Kannelopoulos et al [ 8 ] 64 m AML allo RIC day + 6 Hyroxychloroquine No details provided Survived Malek et al [ 9 ] 61 m MM auto MAC day + 3 Tocilizumab, dexamethasone None Survived Malek et al [ 9 ] 69 m CLL allo RIC day + 13 Convalescent plasma, tocilizumab, anakinra, remdesivir, corticosteroids Mechanical ventilation Deceased …”

COVID-19 in the context of autologous hematopoietic stem cell transplantation for a patient with autoimmune disease

“…The mortality rate in the HCT setting appears to be higher than in the general population, probably in relation to profound immunosuppression or because of the long exposure to immune-modulating and immune-compromising therapies (such as rituximab and dexamethasone) used to treat our patients [9] .…”

“…To the best of our knowledge 3 cases were previously reported of COVID-19 in the context of ASCT [8] , [9] , [10] , none were recorded in an autoimmune disease setting. Our case may show the impact of COVID-19 on ASCT recipients during the period of immune reconstitution.…”

Delayed Immune Reconstitution Inflammatory Syndrome in an Immunosuppressed Patient With SARS-CoV-2

“…Some types of IRIS and severe COVID-19 have been described in patients who received hematopoietic cell transplants during the pre-engraftment period and at the time of immune reconstitution [8] . However, the most similar case report to ours was published by Mertens et al [9] .…”