First case of persistent pancytopenia associated with SARS-CoV-2 bone marrow infiltration in an immunocompromised patient

A 53-year-old man was referred from an intensive care unit for acute respiratory distress, pancytopenia and cytokine release syndrome. His symptoms had begun 3 weeks earlier with anosmia, ageusia, cough, fever and dyspnea. He had a medical history of mantle-cell lymphoma diagnosed in 2017, and was in complete remission following autologous bone marrow transplant in 2018 and nine-monthly maintenance infusions of anti-CD20 monoclonal antibody (last infusion 42 days before his symptoms appeared). Blood tests showed pancytopenia (hemoglobin 7.9 g/dl, leukocytes 0.8 G/l and platelets 48 G/l) and elevated inflammatory markers (C-reactive protein 235 mg/l, fibrinogen >10 g/l, ferritin 8106 ng/ml and D-dimers 1132 ng/ml). Coronavirus disease 2019 (COVID-19) tests by semiquantitative severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) reverse transcription-PCR (RT-PCR) revealed negative findings in nasopharyngeal swab samples, but positive findings in bronchoalveolar lavage fluid, blood [cycle threshold (Ct) value = 30] and bone marrow aspiration samples. Other microbiological examination results were negative. Bone marrow aspiration revealed neither hemophagocytosis features nor viral infection except SARS-CoV-2. Flow cytometry analysis of circulating leukocytes revealed the absence of circulating B lymphocytes, a result of the repeated anti-CD20 antibody infusions, and a low T-lymphocyte count (0.447 G/l). Serum protein electrophoresis revealed gamma globulin level of 3 g/l (versus 4.9 g/l 6 months before). Thoracic CT scan showed bilateral patchy ground-glass opacities. Upon admission, he received two successive infusions of tocilizumab (8 mg/kg) and an infusion of polyvalent immunoglobulins (400 mg/kg). He required respiratory support with noninvasive ventilation and high-flow oxygen therapy for 7 days. Clinical evolution was gradually favorable over 2 weeks, with apyrexia, reduced oxygen requirements and normalized inflammatory biomarker levels. However, at 45 days after admission, SARS-CoV-2 RT-PCR test results remained positive in blood (Ct value = 35) and bone marrow. Moreover, SARS-CoV-2 serological testing detected no antiviral immunoglobulin G, while pancytopenia persisted.

If respiratory complications are the most common clinical presentation of severe COVID-19, hematological involvement as described here and persistent viremia are not published in the literature.^{1 , 2} Therefore, SARS-CoV-2 RT-PCR should be performed in blood and bone marrow aspiration in case of pancytopenia associated with typical COVID-19 symptoms, especially in case of secondary humoral immunodeficiency. Among the many therapeutic options under investigation, including antiviral drugs, we suggest that convalescent plasma could be useful in patients with COVID-19 infection and concurrent persistent B-cell immunodeficiency; we will consider this approach for our patient.3, 4, 5