Atypical lymphocytes in the peripheral blood of COVID-19 patients: A prognostic factor for the clinical course of COVID-19

Abstract

Background Clinical observations have shown that there is a relationship between coronavirus disease 2019 (COVID-19) and atypical lymphocytes in the peripheral blood; however, knowledge about the time course of the changes in atypical lymphocytes and the association with the clinical course of COVID-19 is limited. Objective Our purposes were to investigate the dynamics of atypical lymphocytes in COVID-19 patients and to estimate their clinical significance for diagnosis and monitoring disease course. Materials and methods We retrospectively identified 98 inpatients in a general ward at Kashiwa Municipal Hospital from May 1st, 2020, to October 31st, 2020. We extracted data on patient demographics, symptoms, comorbidities, blood test results, radiographic findings, treatment after admission and clinical course. We compared clinical findings between patients with and without atypical lymphocytes, investigated the behavior of atypical lymphocytes throughout the clinical course of COVID-19, and determined the relationships among the development of pneumonia, the use of supplemental oxygen and the presence of atypical lymphocytes. Results Patients with atypical lymphocytes had a significantly higher prevalence of pneumonia (80.4% vs. 42.6%, p < 0.0001) and the use of supplemental oxygen (25.5% vs. 4.3%, p = 0.0042). The median time to the appearance of atypical lymphocytes after disease onset was eight days, and atypical lymphocytes were observed in 16/98 (16.3%) patients at the first visit. Atypical lymphocytes appeared after the confirmation of lung infiltrates in 31/41 (75.6%) patients. Of the 13 oxygen-treated patients with atypical lymphocytes, approximately two-thirds had a stable or improved clinical course after the appearance of atypical lymphocytes. Conclusion Atypical lymphocytes frequently appeared in the peripheral blood of COVID-19 patients one week after disease onset. Patients with atypical lymphocytes were more likely to have pneumonia and to need supplemental oxygen; however, two-thirds of them showed clinical improvement after the appearance of atypical lymphocytes.

Are atypical lymphocytes a new predictive factor in the development of COVID-19?

“…Similarly, Sugihara et al 10 demonstrated that atypical lymphocytes were frequently observed in patients with COVID-19. These authors pointed out that most patients included in the study had better clinical evolution when these atypical lymphocytes were present.…”

“…These authors pointed out that most patients included in the study had better clinical evolution when these atypical lymphocytes were present. The authors also pointed out that low numbers of CD8+ T lymphocytes were detected in patients with severe COVID-19 11 , suggesting a relationship between T cells and disease severity 10 , which is essential because a complex disease is expected to have a number of pathophysiological abnormalities. 12 also referred to the frequent observation of atypical lymphocytes in patients with COVID-19 and reported that this atypia is usually accompanied by lymphopenia.…”

Coronavirus disease 2019 (COVID‐19): Focus on peripheral blood cell morphology

“…In one study, atypical lymphocytes were present in 16% of patients at the first visit, while the median time for their appearance in most patients was 8 days, with a peak at day 9. 37 In a reported multivariate analysis, the presence of atypical lymphocytes, especially with lymphoplasmacytic features, was predictive of COVID‐19 positivity, 11 or was found to be valuable as an indication for reverse transcriptase polymerase chain reaction for SARS‐CoV‐2. 68 In only one study, was the proportion of atypical lymphocytes higher in non‐COVID‐19 ICU patients than in patients with COVID‐19.…”

“…It is reported in almost all morphological studies and considered heterogeneous by their authors. Such lymphoid cells are generically defined as atypical, 11 , 40 , 45 , 47 , 52 reactive, 16 , 22 , 37 , 48 , 49 activated, 46 , 50 variant 21 or pleomorphic, 25 , 44 and are similar to those seen in Epstein–Barr virus (EBV) and cytomegalovirus (CMV), 25 and other viral infections. 11 Such terminology variability and confusion is reflected in the PB cell nomenclature document published by the International Committee for Standardization in Haematology (ICSH).…”

“…We found 28 studies dealing with morphological alterations observed in groups of multiple COVID‐19 patients. Nine reported atypia of a single cell population: abnormal lymphocytes in seven, 31 , 32 , 33 , 34 , 35 , 36 , 37 atypical monocytes in one. 38 In all, 19 of these group studies detailed morphological abnormalities in multiple cell populations in patients with different phases of the disease (10 of them included control groups of healthy subjects or patients with non‐COVID‐19 inflammatory states) (Table 1 ).…”