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Hypogammaglobulinemia and Sars-CoV-2 Viraemia Determine COVID-19 Severity in Patients with Haematological Malignancies

Coronavirus infection itself, rather than cytokine storm, lead to severe and lethal COVID-19 in patients with haematological malignancies
16 Jul 2021
COVID-19 and Cancer
Haematological Malignancies

Dr Jean-Marie Michot and colleagues from the Gustave Roussy in Villejuif, France investigated clinical factors associated with higher risk for severe COVID-19 in patients with haematological malignancies. They wrote on 12 July 2021 in the Annals of Oncology that the coronavirus infection itself, rather than cytokine storm, lead to severe and lethal COVID-19 in these patients. The study findings suggest that hypogammaglobulinemia and Sars-CoV-2 viraemia are two relevant determinants of COVID-19 severity in this patient population. 

The study team analyzed characteristics of all patients with haematological malignancies admitted to their hospital for COVID-19 from March to November 2020. In total, 51 adult patients with lymphoma, acute leukaemia, myeloma or other types of haematological malignancies were included in the analysis; from those, 24 (47%) had progressed to severe COVID-19. 

Patients who progressed to severe COVID-19 had at hospital admission significantly lower gammaglobulin levels in the serum (p = 0.0312) and tended to have more advanced age (64.7 versus 57.6 years; p = 0.0503). Lymphopenia was not significantly associated with increased risk of developing severe COVID-19. 

By linear logistic regression, hypogammaglobulinemia remained the most significant factor associated with progression to severe COVID-19. The severity of COVID-19 negatively correlated with serum gammaglobulins by the correlation Pearson statistics method (r = -0.43; p = 0.0018). The intensity of viral replication was higher in patients with hypogammaglobulinemia ≤ 6 g/L (p = 0.0033) and duration of virus carrier status in nasopharyngeal swabs tended to be prolonged in patients with severe COVID-19. 

The study team then retrospectively assessed Sars-CoV-2 viraemia in 21 patients by RT-PCR in whole blood and 10 patients had detectable viraemia (42%) at hospital admission. Viraemia was associated with a relative risk of progression to severe COVID-19 (p = 0.0019) and COVID-19 death (p = 0.0351). Furthermore, viraemia was more often present in patients with haematological malignancy as compared with patients with solid tumours (47.6% versus 18.2%; p = 0.0099). 

The authors stated that in patients with haematological malignancies, spread of the SARS-CoV-2 virus related to humoral immunosuppression, rather than cytokine storm, drives the COVID-19 severity. They commented that corticosteroids or anti-cytokines drugs such as anti-IL-6 receptor therapies may worsen immunosuppression and should be used with caution in humoral immunocompromised patients. Therapeutics supporting immunity against Sars-CoV-2, such as hyperimmune convalescent plasma, deserves to be investigated for immunocompromised patients. 


Michot JM, Hueso T, Ibrahimi N, et al. Severe COVID-19 in patients with hematological cancers presenting with viremia. Annals of Oncology; Published online 12 July 2021. DOI: https://doi.org/10.1016/j.annonc.2021.07.002

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