Peripheral Blood Examination Findings in SARS-CoV-2 Infection

Alia Nazarullah, MD; Christine Liang, MD; Andrew Villarreal, MLS; Russell A. Higgins, MD; Daniel D. Mais, MD


Am J Clin Pathol. 2020;154(3):319-329. 

In This Article


The 12 COVID-19 cases included 7 men and 5 women, with an age range of 25 to 100 years (mean, 55 years). The patients presented predominantly with respiratory symptoms (11/12) and fever (6/12) Table 1. Most patients had comorbidities at presentation, which included hypertension (3/12), asthma (3/12), HIV/AIDS (2/12), bacterial infections (2/12), malignancy (1/12), chronic kidney disease (1/12), and diabetes (1/12). Both patients with HIV/AIDS had less than 20 RNA copies/mL by PCR. Seven patients (58%) were admitted directly to the intensive care unit and required mechanical ventilation, of which 2 patients (16%) died. The demographics and symptoms in the control group were similar Table 2. The 10 patients in the control group included 8 men and 2 women, with an age range of 27 to 77 years (mean, 56 years). The comorbidities in this group of patients included bacterial infections (7/10), malignancy (3/10), hypertension (2/10), diabetes (2/10), HIV/AIDS (1/10), renal disease (1/10), congestive heart failure (1/10), and chronic obstructive pulmonary disease (1/10). Two patients (20%) required mechanical ventilation and died in this group.

Among the COVID-19 patients, CBCs revealed anemia in 5 cases (mean hemoglobin, 12.5 g/dL; range, 10–16.1 g/dL), leukocytosis in 4 cases (mean, 7.3 × 103/μL; range, 3.9–35.6 × 103/μL), thrombocytosis in 1 case, and thrombocytopenia in 1 case. Absolute lymphopenia was present in 2 cases; one of them had HIV/AIDS. Absolute neutrophilia was seen in 6 cases (mean, 9.24 × 103/μL; range, 2.3–32.6 × 103/μL). Absolute monocyte count was low in 1 patient and within reference ranges in others. Absolute eosinophil count was within reference ranges in all patients. The control group showed CBC findings similar to the COVID-19 group; however, absolute lymphopenia was present in 6 control group patients as compared to only 2 COVID-19 patients (P < .05).

Peripheral blood smear review showed presence of APHA in all COVID-19 cases, with 50% of cases (6/12) having over 10% pelgeroid neutrophils, 25% cases (3/12) having 5% to 10%, and the remaining 25% cases (3/12) having less than 5%. Monolobate neutrophils were noted in 50% of COVID-19 cases (6/12). Rare neutrophils showed prominent apoptotic changes. In contrast, the control group showed APHA in 50% of cases (P < .05), and in 4 of 5 of these cases, pelgeroid cells comprised less than 5% of neutrophils. Notably, monolobate neutrophils were not present in any of the control cases. Morphologic findings in granulocytes are illustrated in Image 1A, Image 1B, Image 1C, and Image 1D. Two patients with HIV/AIDS had APHA greater than 10%; however, both patients had less than 20 HIV RNA copies/mL detected by PCR. None of these patients had a history of myeloid neoplasms. Review of outpatient medications revealed no definite evidence of medications reported to be associated with APHA. Inpatient medications were not pertinent, as the peripheral blood studied were drawn during hospital admission.

Image 1.

Morphologic findings in peripheral smears in coronavirus disease 2019 patients (Wright stain, ×100). A, Acquired Pelger-Huët anomaly. B, Monolobate neutrophil. C, Apoptotic neutrophil. D, Left shift to blast stage. E, Atypical lymphocyte with irregular nuclear contours. F, Plasmacytoid lymphocyte. G, Downey type I lymphocyte. H, Downey type II lymphocyte. I, Downey type III lymphocyte. J, Large granular lymphocyte.

In only a minority of COVID-19 cases did granulocytes show prominent toxic changes. In 1 severely ill patient with multifocal pneumonia and respiratory failure, the peripheral smear showed leukoerythroblastosis and toxic changes in greater than 10% neutrophils. The patient died soon after. In the remaining 11 cases, toxic changes were present in less than 10% of granulocytes. However, granulocytic left shift was a prominent feature in a majority of cases (8/12). Among the cases with left shift, 62% of cases (5/8) showed left shift to metamyelocyte/myelocyte stage, 25% of cases (2/8) showed presence of circulating bands, and the 1 case described above with leukoerythroblastosis showed rare circulating blasts (<1% blasts). In the control group, 6 of 10 cases showed extensive toxic changes and granulocytic left shift; however, most of those cases also had concurrent bacterial infections.

All COVID-19 cases showed varying types of atypical lymphocytes, albeit constituting less than 10% of lymphocytes in the majority of cases Image 1E, Image 1F, Image 1G, Image 1H, Image 1I, and Image 1J. The most common and least specific type of reactive lymphocyte, the Downey type II lymphocyte, was noted in all cases; however, it constituted less than 10% of lymphocytes in all cases. Large granular lymphocytes were noted in 11 of 12 cases, but only 1 case showed mildly increased numbers of LGLs comprising greater than 10% of lymphocytes. Plasmacytoid lymphocytes were noted in 9 of 12 cases, Downey type III lymphocytes in 5 of 12 cases, and Downey type I lymphocytes in 2 of 12 cases, with each individually comprising less than 10% of total lymphocytes. Rare atypical lymphocytes with markedly irregular nuclear contours and scant to moderate basophilic cytoplasm were noted in 7 of 12 cases but comprised less than 5% of total lymphocytes in each case. Plasmacytoid lymphocytes were seen in greater frequency in COVID-19 patients, compared to controls (P < .05), although they constituted less than 10% of lymphocytes in all cases. Otherwise, the control group had a comparable qualitative and quantitative spectrum of atypical lymphocytes, except 1 case of infectious mononucleosis.

Of the 12 cases, flow cytometric studies for lymphocyte subsets were performed in 7 cases. This included 2 patients with HIV/AIDS; however, both patients had less than 20 HIV RNA copies/mL detected by PCR. Decreases in absolute numbers of CD3+ T-cells, CD4+ T-cells, and CD8+ T-cells were identified in 6, 5, and 3 cases respectively. B cells and NK cells were enumerated only in 4 cases, of which the majority showed absolute counts in normal ranges. One case had a low B-cell count and another case had a low NK-cell count. Although the numbers are too few to draw meaningful comparisons, cytopenia of CD3+ T cells appears to be a common finding. All patients with decreased T cells required mechanical ventilation. The control group only had flow cytometry performed in 1 case.