The effect of COVID-19 on Blood Smear Morphology


COVID-19, a potentially severe infection, is caused by the highly-infectious virus SARS-CoV-2. Since first being detected in Wuhan, China in November 2019 SARS-CoV-2 has proliferated and spread all over the world resulting in the COVID-19 pandemic – the most significant since the 1918 H1N1 (“Spanish Flu”) pandemic. The severity of COVID-19 infection in people varies greatly depending on the age and co-morbidity status, with haematology health of particularly significance. Younger people with no co-morbidies typically have asymptomatic or mild infections with lose of taste and smell, a dry cough and/or mild fever. Older patients and/or patients with co-morbidies, such as diabetes, malignancy, obesity or dementia, are more likely to have severe and potentially fatal COVID-19 infections. High fever and other flu-like symptoms, pneumonia and hyperinflammatory reactions are typical for more severe COVID-19 cases and can result in acute respiratory distress and multiple organ failure. In the UK over 200,000 patients have tested positive for COVID-19 after being hospitalised and over 60,000 patients have died after testing COVID-19 positive.

It is typical for the blood smear morphology of patients to be affected significantly when they are presenting with severe viral infection due to the massive co-ordinated response of immune blood cells, such as lymphocytes, neutrophils and platelets. Detailing the specifics of these changes is important in understanding both how the viral infection, in this case COVID-19, is provoking the immune system and which therapeutic interventions could be effective.

The effect of COVID-19 on lymphocyte morphology

Lymphocytes contribute to the immune response against viral infections by producing interferon, a key signalling protein in the inflammatory response. Interferon production results in antiviral changes to gene expression and encourages polyclonal antibody production. Patients admitted for severe COVID-19 infection show normal to lower presence of lymphocytes in their blood smear morphology with lymphopenia correlating with worse outcomes. There is a significant presence (6.9% of total lymphocytes) of atypical lymphocytes with wide heterogeneity, this is likely due to increased and rapid proliferation of lymphocytes during viral COVID-19 infection.

Other morphological changes include

  • Cytoplasmic pod formation
  • Presence of large granular lymphocytes
  • Increase in cytoplasmic volume
  • Nucleus changes including nucleoli, chromatin condensation and indented nuclei

The effect of COVID-19 on neutrophil morphology

Neutrophils have a significant role in combating viral infections; phagocytising antigenic materials, initiating antiviral signalling pathways, producing antiviral materials and cytokines and encouraging the development of adaptive, virus-specific T cells. It is typical for neutrophils to proliferate (neutrophilia) during viral infections, and the COVID-19 blood smear morphology shows this is no different after SARS-CoV-2 infection.

Neutrophil absolute counts universally increased for the first few days of COVID-19 infection and typically reduced a week after infection. The neutrophil morphology showed widespread abnormalities including large cytoplasmic and nuclear granulation. Granulation in neutrophils store a plethora of antimicrobial (including antiviral) peptides, enzymes and chemicals – including acids. Finding such granulated neutrophils is indicative of a large phagocytotic response from the immune system to COVID-19.

Other morphological changes include

  • Cytopemiac vacuolation
  • Nucleus changes e.g. C or ring-shaped, aberrant nuclear projections
  • Elongated nucleoplasm

The most severe and often fatal cases of COVID-19 do not show a drop in the neutrophil absolute count a week after infection and has been correlated to worse patient outcomes. Neutrophil extracellular traps (NETs) are a mechanism to limit microbial spread by releasing the contents of the neutrophils granules into the infected extracellular environment. However NETs in severe COVID-19 infections have been linked to contributing to acute respiratory distress.

The effect of COVID-19 on platelet morphology

Platelets act as sentinels in the immune systems response to potential viral infections by expressing pattern recognition receptors (PRRs). These PPRs recognise a range of viral antigens and when these antigens are detected, encourage inflammation and an immune response. Platelets also have a limited role in producing and releasing antimicrobial materials.

COVID-19 blood smear platelet morphology typically demonstrates a mild reduction in the number of platelets (thrombocytopenia), however platelets been shown to increase in number (thrombocytosis) in some patients. In both cases, platelets have shown abnormal morphologies with larger cell sizes and hyperchromatic nuclei after COVID-19 infection. The impact of platelets on the immune systems COVID-19 response is under-researched, but a COVID-19 blood smear morphology showing thrombocytopenia is associated with worse patient outcomes.

Other changes

Red cell fragments, or schistocytes, have also been reported in patients with severe COVID-19. When found in significant numbers, schistocytes indicate microangiopathic haemolytic anaemia.

Monocytopenia can accomponty COVID-19 infection and monocytes may show prominent cytoplasmic vacuolisation, granulation and nuclear blebbing.

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