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Fig 1.

Representative atypical lymphocytes in the peripheral blood of COVID-19 patients.

All images are of May-Giemsa-stained peripheral blood smears. (A, B) Atypical lymphocytes with condensed chromatin, deep basophilic cytoplasm and eccentric nuclei. (C, D) Atypical lymphocytes with abundant pale cytoplasm and indented nuclei, resembling Downey II cells.

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Fig 2.

Distribution of the fractions of atypical lymphocytes.

The number of patients in each fraction of atypical lymphocytes is shown. Each patient was classified according to their peak value. Numbers above bars indicate the actual counts of each fraction.

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Fig 3.

First appearance of atypical lymphocytes after disease onset.

Patients were counted according to the day of the first identification of atypical lymphocytes after disease onset. The total number of patients who had atypical lymphocytes in their peripheral blood was 51. The median value was eight days.

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Table 1.

Patient characteristics.

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Fig 4.

Comparison of dates on which pneumonia and atypical lymphocytes appeared.

(A) Difference between the days on which radiographic evidence of pneumonia and atypical lymphocytes were detected in each patient. Total number of patients was 41. Bars represent the difference for each patient in days and are arranged in ascending order. A negative value (blue bar) indicates that the radiographic evidence of pneumonia appeared first, and a positive value (orange bar) indicates that atypical lymphocytes appeared first. (B) Beeswarm plot of the first day of detection. The bold dotted line indicates the median, and the thin dotted lines indicate the upper and lower quantiles. * p < 0.0001 by Wilcoxon rank-sum test.

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Table 2.

Comparison of laboratory values.

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Fig 5.

Clinical courses of representative patients who received supplemental oxygen.

Abbreviations: LyC, lymphocyte count; ALyC, atypical lymphocyte count. (A-D) Time course of lymphocyte count (yellow diamond), atypical lymphocyte count (blue circle) and amount of supplemental oxygen (gray bar) in representative patients. The number above the gray bar demonstrates the amount of oxygen in liters per minute, and double-headed arrows indicate the period of data collection for each patient. (A) A patient who improved after atypical lymphocytes were detected. (B) A patient who had already stopped oxygen therapy when atypical lymphocytes appeared. (C) A patient whose condition worsened after atypical lymphocytes appeared. (D) A patient who worsened when the presence of atypical lymphocytes was detected. This patient was admitted to the ICU on day 8. (E) Proportion of patients in each clinical category. A–D correspond to the categories mentioned above.

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Fig 6.

Comparison of clinical indices among clinical courses.

(A) Comparison of the date on which atypical lymphocytes appeared. (B) Comparison of the peak fraction of atypical lymphocytes. (C) Comparison of the peak number of atypical lymphocytes. Each plot indicates a patient in a group. No significant differences were detected among groups by one-way ANOVA.

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