The pathophysiology of the haematological manifestations of COVID-19 : a review

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the coronavirus disease 2019 (COVID-19) it causes, are associated with several haematological abnormalities which manifest as some of the clinical syndromes seen in COVID-19. The main organ affected by COVID-19 is the lung, where an intense inflammatory response occurs in the alveoli and the lung vasculature. This may result in severely compromised gaseous exchange consistent with acute respiratory disease syndrome (ARDS). Multiple organ failure and death may ensue. The extent to which SARS-CoV-2 directly affects erythroid, granulocytic and monocytic progenitors is unknown, however related Coronaviridae have previously been shown to infect megakaryocytes and their progenitors. Furthermore, SARS-CoV-2 may directly infect lymphocytes or monocytes causing the production of cytokines and chemokines, which then cause lymphocyte death and lymphopenia. The quantitative changes seen in monocytes and granulocytes are at least partly due to the marked increase in various cytokines also called the “cytokine storm” and the downstream effects of these cytokines. A COVID-19-associated coagulopathy (CAC) may occur, which ranges from a mild derangement of laboratory haemostatic tests, through to sepsis-induced coagulopathy (SIC), and later, frank disseminated intravascular coagulation (DIC). The most common and devastating haemostatic abnormality is widespread thrombosis, which is associated with severe lung inflammation, hypoxia and death. COVID-19 is associated with immune perturbation states namely, immune thrombocytopenia (ITP), Guillain-Barré syndrome, the anti-phospholipid syndrome and a Kawasaki-like syndrome in children. The pathophysiology of the haematological abnormalities seen in COVID-19 is briefly reviewed in this article.

Hematological findings in adult patients with SARS CoV‐2 infection at Tygerberg Hospital Cape Town South Africa

“…5,9,36 Anemia could develop during the course of COVID-19 either due to direct SARS-CoV-2 infection, iatrogenic blood loss during admission, or dysregulation of iron metabolism. 5,7 Unlike other studies, Hb level, RDW and MCHC were not associated with worse outcome in our cohort. 36,37 COVID-19 is associated with clinically significant coagulopathy termed CAC.…”

“…3,6,35 Changes in platelet count in COVID-19 can be due to several reasons including the effect of cytokines, inhibition of platelet production by SARS-CoV2 infection, platelet consumption in COVID-19-associated lung damage and associated-thrombosis, and the effect of therapeutic agents. 7 Using platelet count as a predictor of COVID-19 severity has shown contradicting findings. 22,27 In early SARS-CoV2 infection, platelet counts have not correlated with the outcome which probably explains the normal platelet count in this cohort.…”

“…[4][5][6] The correlation between early changes in hematological parameters and disease outcome, is under active investigation. 4,5,[7][8][9] Hematological changes reported include changes in full blood count (FBC) parameters, abnormal morphological characteristics of blood cells on peripheral blood smear examination and derangement of hemostatic parameters, referred to as COVID-19-associated coagulopathy (CAC). 4,7,10 FBC findings associated with SARS-CoV-2 infection include anemia, neutrophilia, lymphopenia, monocytosis, eosinopenia, mild thrombocytopenia, and less frequently thrombocytosis.…”

“…4,7,10 FBC findings associated with SARS-CoV-2 infection include anemia, neutrophilia, lymphopenia, monocytosis, eosinopenia, mild thrombocytopenia, and less frequently thrombocytosis. 2,4,5,7,9 Lymphopenia, increased platelet-to-lymphocyte ratio, increased neutrophil-to-lymphocyte ratio (NLR), low B lymphocytes, low CD8-positive T lymphocytes, and elevated CD4/CD8 ratio have been associated with adverse disease outcomes. [11][12][13] Changes reported on peripheral blood smears are predominantly nonspecific features seen in infective/inflammatory states.…”

“…4,5,[7][8][9] Hematological changes reported include changes in full blood count (FBC) parameters, abnormal morphological characteristics of blood cells on peripheral blood smear examination and derangement of hemostatic parameters, referred to as COVID-19-associated coagulopathy (CAC). 4,7,10 FBC findings associated with SARS-CoV-2 infection include anemia, neutrophilia, lymphopenia, monocytosis, eosinopenia, mild thrombocytopenia, and less frequently thrombocytosis. 2,4,5,7,9 Lymphopenia, increased platelet-to-lymphocyte ratio, increased neutrophil-to-lymphocyte ratio (NLR), low B lymphocytes, low CD8-positive T lymphocytes, and elevated CD4/CD8 ratio have been associated with adverse disease outcomes.…”