COVID-19 in Patients with Hematologic Malignancies: Clinical Manifestations, Persistence, and Immune Response

Abstract

<b><i>Background:</i></b> The clinical presentation of coronavirus disease 19 (COVID-19) is the result of intricate interactions between the novel coronavirus and the immune system. In patients with hematologic malignancies (HM), these interactions dramatically change the clinical course and outcomes of COVID-19. <b><i>Summary:</i></b> Patients with HM and COVID-19 are at an increased risk for prolonged viral shedding, more protracted and severe presentation, and death, even when compared to other immunocompromised hosts. HM (e.g., multiple myeloma, chronic lymphocytic leukemia) and anticancer treatments (e.g., anti-CD20 agents) that impair humoral immunity markedly increase the risk of severe COVID-19 as well as protracted viral shedding and possibly longer infectivity. Cytokine release syndrome (CRS) is an important player in the pathophysiology of severe and fatal COVID-19. Treatments targeting specific cytokines involved in CRS such as interleukin-6 and Janus kinase have proven beneficial in COVID-19 patients but were not assessed specifically in HM patients. Although neutropenia (as well as neutrophilia) was associated with increased COVID-19 mortality, granulocyte colony-stimulating factors were not beneficial in patients with COVID-19 and may have been associated with worse outcomes. Decreased levels of T lymphocytes and especially decreased CD4+ counts, and depletion of CD8+ lymphocytes, are a hallmark of severe COVID-19, and even more so among patients with HM, underlying the important role of T-helper dysfunction in severe COVID-19. In HM patients with intact cellular immunity, robust T-cell responses may compensate for an impaired humoral immune system. Further prospective studies are needed to evaluate the mechanisms of severe COVID-19 among patients with HM and assess the efficacy of new immunomodulating COVID-19 treatments in this population. <b><i>Key Messages:</i></b> Understanding the immunopathology of COVID-19 has greatly benefited from the previous research in patients with HM. So far, no COVID-19 treatments were properly evaluated in patients with HM. Patients with HM should be included in future RCTs assessing treatments for COVID-19.

The unique presentation of SARS-CoV-2 Infection in patients with B-cell depletion: definition of ‘persistent inflammatory sero-negative COVID’

“…Hence, persistent viral shedding and seronegativity are insufficient to explain this condition. [ 4 , 7 ] There is growing evidence that these patients have an abnormal/dysregulated T cell response [ 8 , 9 ]. This abnormal T cell function leads to a hyper inflammatory response which does not lead to eradication of the virus.…”

Dual antiviral therapy in haematological patients with protracted SARS‐CoV‐2 infection

“…Haematological patients with SARS-CoV-2 infection exhibit higher mortality rate and more severe clinical presentation when compared to other immunocompromised subjects, 1 especially if chemotherapy has been administered in the previous 3 months. 2 Haematological treatment may be delayed until COVID-19 resolution.…”

“…9 Due to protracted COVID-19 and haematological disease progression for chemotherapy delay, an off-label combination of remdesivir and nirmatrelvir/ritonavir was proposed to haematological patients with protracted COVID-19 or with persistent viral positivity needing chemotherapy. Dual antiviral therapy was chosen to minimize the risk of viral resistance, as greater intrahost viral diversity was observed in patients with impaired CD8+ T-cell immunity, 1 and viral resistance has been previously described in immunocompromised subjects with persistent viral replication. 10 Six patients with protracted SARS-CoV-2 infection were treated from November 2022 to February 2023.…”

Hematological Aspects of COVID-19

“…Most prolonged shedding has been described among patients treated with anti CD-20, chimeric antigen receptor T cell, or hematopoietic stem cells transplant recipients. Inter-actions between COVID-19 and the specific components of the immune system are described, with discussion regarding the effect of various drugs used to treat hematological malignancies [2].…”

“…Gur et al [2] discuss the unique clinical characteristics of COVID-19 in patients with hematological malignancy. These include a protracted disease course, with prolonged viral shedding and possibly longer infectivity.…”