Pancytopenia during SARS-CoV-2 infection

To the Editor,

The finding of pancytopenia in a patient should not be considered as a disease in itself but rather the sign of a disease that needs to be diagnosed. Among the various causes, viral infections stand out. The case reported is an example of a patient with pancytopenia secondary to SARS-CoV-2 infection.

A 77 year-old female referred from the nursing home to the emergency department due to a 4 day history of evening fever without any other associated symptoms. She did not have any history of interest, independent for basic daily life activities and without cognitive impairment. The physical examination revealed crackles in both lung bases and the chest X-ray showed bilateral infiltrates compatible with COVID. Unknown cause pancytopenia stood out in the lab results: 1730 leukocytes (neutropenia and lymphopenia of 760 in both series), 94,000 platelets and haemoglobin of 11.5 g/dl. An assessment by Haematology was requested, which carried out a smear test compatible with the infectious process: 45% of the segmented population with reinforced granulation and some hyposegmented forms with some band neutrophils, 44% small lymphocytes and some activated lymphocytes, 11% monocytes with abundant vacuoles. Given these findings, a was performed for SARS-CoV-2, which was positive and was admitted for respiratory monitoring and laboratory control. The patient did not wish to receive compassionate use treatment for COVID-19. A spontaneous laboratory improvement was observed after 48 h, with almost a complete recovery of parameters: 3060 leukocytes, 121,000 platelets, and haemoglobin of 12.5 g/dl. Given the clinical stability and laboratory improvement, it was decided to discharge her to her nursing home in a quarantine environment.

Among the possible causes of pancytopenia,¹ such as drug-induced bone marrow toxicity, tumour or autoimmune processes, it is worth highlighting viral infections. There are multiple known viral infections causing pancytopenia, including human immunodeficiency virus, parvovirus B19, cytomegalovirus or Epstein–Barr virus.

Pancytopenia is classified as central (if there is a decrease in hematopoietic cells in the bone marrow) or peripheral (if there is cell destruction or sequestration). In the case of a viral infection, the etiological mechanism is bone marrow aplasia, which is caused by various mechanisms.

King and Goodell² classified 4 different mechanisms by which viral infections can affect hematopoietic stem cells. The first of these is produced by the direct action of the virus that triggers changes in the expression of intracellular factors with the ability to manipulate cellular pathways or even cause the interruption of host cell translation. The second of them takes place through the direct recognition of a pathogen: through various pathogen-associated molecular pattern (PAMPs), hematopoietic cells give rise to the activation of different pattern recognition receptors (PRR) and cause changes in the expression of the chemokine receptor until apoptosis induction. The third of them focuses on the overproduction of inflammatory cytokines. This mechanism results in hematopoietic failure due to depletion that rapidly returns to quiescence after the initial response. Finally, although the link between the bone marrow microenvironment and haematopoiesis is difficult to define, it is well known that stromal cells play an important role in signalling haematopoiesis induction. These 4 scenarios are not mutually exclusive.

Hemophagocytic lymphohistiocytosis (HLH)³ is a rare hyperinflammatory syndrome characterized by uncontrolled macrophage and lymphocyte activation and a life-threatening cytokine storm, accompanied by pancytopenia among other complications. Among the infectious triggers, viral infection is the most common, either as a primary infection or after reactivation in immunocompromised patients. It may be that our patient presented HLH in relation to primary infection by SARS-CoV-2, but without being a risk factor for severe disease as has been raised in other published cases.⁴ The fact that the same virus can lead to different manifestations in the hematopoietic series in different patients points to the existence of a genetic basis for an aberrant immune activation which it is still unknown.

We are still in the process of investigating haematological abnormalities due to COVID-19.⁵ More studies are needed to determine if this new virus associates notable differences in the mechanisms that produce pancytopenia compared to other viruses.