Bone Marrow and Peripheral Blood Findings in Patients Infected by SARS-CoV-2

Cynthia K. Harris, MD; Yin P. Hung, MD, PhD; G. Petur Nielsen, MD; James R. Stone, MD, PhD; Judith A. Ferry, MD

Disclosures

Am J Clin Pathol. 2021;155(5):627-637. 

In This Article

Abstract and Introduction

Abstract

Objectives: Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with diverse clinical, including hematologic, abnormalities. We describe peripheral blood and bone marrow findings in deceased and living patients with COVID-19.

Methods: We examined bone marrows from 20 autopsies and 2 living patients with COVID-19 using H&E-stained slides and immunohistochemical stains. Clinical history and laboratory values were reviewed. HScore was calculated to estimate risk of hemophagocytic lymphohistocytosis (HLH).

Results: The deceased patients included 12 men and 8 women (aged 32 to >89 years; median, 63 years). Hematologic abnormalities included frequent neutrophilic leukocytosis, lymphopenia, anemia, and thrombocytopenia; one patient showed striking erythrocytosis. The bone marrows were all normocellular to hypercellular, most showing maturing trilineage hematopoiesis with myeloid left shift. In all 19 evaluable bone marrows, hemophagocytic histiocytes were identified. The HScore for secondary HLH ranged from 35 to 269 (median, 125; >169 in 5 patients). Coinfections were identified in 6 patients. In 2 living patients, bone marrow showed maturing trilineage hematopoiesis, including one showing few hemophagocytic histiocytes.

Conclusions: Peripheral blood from deceased patients with COVID-19 frequently showed neutrophilic leukocytosis, lymphopenia, and, rarely, secondary polycythemia; hemophagocytosis was common in their bone marrow. Consistent with other studies, we provide histopathologic evidence of secondary HLH development in patients with COVID-19.

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the agent that causes coronavirus disease 2019 (COVID-19), represents a severe and ongoing threat to public health worldwide.[1] Much focus on COVID-19, both clinically and histopathologically, has centered on patients with acute respiratory failure and corresponding diffuse alveolar damage of their lungs.[2,3] Although there is still much to learn regarding the pulmonary consequences of COVID-19, comparatively little is known about the effects of COVID-19 on other tissues. Several studies have described findings in the peripheral blood and/or bone marrow, but the spectrum of hematologic findings remains to be defined.[4–7]

Immune dysfunction has been implicated in the morbidity and mortality of affected patients.[8,9] Recent studies discussing the hyperinflammatory state of patients who test positive for COVID-19 have noted an overproduction of cytokines, which may correlate with secondary hemophagocytic lymphohistiocytosis (HLH).[8,9] Understanding changes in the bone marrow of affected individuals is of particular importance given these clinical concerns about HLH. In this report, we describe the hematologic and histopathologic findings in the bone marrow of 20 patients who died of COVID-19 and in 2 living patients infected by SARS-CoV-2. A striking finding at autopsy was the frequent presence of marrow hemophagocytosis.

processing....