The complete blood count with WBC differential was performed with an XT-2000i hematologic analyzer (Sysmex Co., Kobe) for all samples. These tests were performed as part of routine clinical care. The blood tests included a complete blood count with white blood cell (WBC) differential, lactase dehydrogenase (LDH), total bilirubin (T-Bil), urea nitrogen (UN), creatinine and C-reactive protein (CRP). The comorbidities included hypertension, diabetes mellitus, chronic heart disease, chronic obstructive pulmonary disease (COPD), chronic kidney disease, coronary vascular disease, cerebrovascular disease and malignancy. We also inquired the day the symptoms had started, which was designated the day of the onset of disease. The symptoms included fever (defined as temperature ≥ 37.5☌), upper respiratory symptoms (sore throat, rhinorrhea and nasal congestion), lower respiratory symptoms (cough, sputum and dyspnea), constitutional symptoms (fatigue, myalgia, arthralgia, headache and chills), olfactory or taste dysfunction, and loose stool. The collected data were demographics, symptoms before admission, comorbidities, blood test results, radiographic findings, treatment after admission and the clinical course. We collected the clinical data pertaining to the enrolled patients from the medical records at Kashiwa Municipal Hospital. Therefore, we investigated the relationship between atypical lymphocytes and the clinical course of COVID-19 and aimed to demonstrate the clinical significance of that relationship in the present study. Such information would be useful for estimating the clinical course of COVID-19. However, there is limited information about the time course of the number or proportion of atypical lymphocytes in the peripheral blood. A retrospective analysis surveying data from patients’ first visits demonstrated that a positive result on a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) was related to a significantly higher prevalence of atypical lymphocytes than a negative PCR result, and another study comparing COVID-19 patients hospitalized in the intensive care unit (ICU) and non-ICU wards indicated that atypical lymphocytes were associated with a milder clinical course of the disease. However, few studies have reported the clinical significance of atypical lymphocytes in COVID-19 patients. It may reflect the disease pathophysiology and provide important information about the diagnosis or prognosis of the disease. Several studies have shown that atypical lymphocytes have also been found in the peripheral blood and bronchoalveolar lavage (BAL) samples of COVID-19 patients. The clinical characteristics hinder its prompt diagnosis and the prediction of the clinical course of the disease, and many efforts to clarify the characteristics of this disease have been made.Ītypical lymphocytes are large lymphocytes with varied morphology in the peripheral blood of patients with several viral infections, such as Epstein-Barr virus infection, cytomegalovirus infection, rubella, Hantavirus infection, viral hepatitis and HIV infection. COVID-19 has a broad spectrum of manifestations, ranging from asymptomatic cases or cases of mild symptoms similar to those of the common cold to cases of severe respiratory disease with systemic inflammation and thrombosis. Since the first report in December 2019, there have been approximately 149 million cases of COVID-19 and approximately 3 million related deaths worldwide as of Ap. URL of the funder is The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist.Ĭoronavirus disease 2019 (COVID-19), an emerging disease caused by a coronavirus, has imposed a substantial health burden worldwide. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: All relevant data are within the manuscript and its Supporting Information files.įunding: This study is funded by Japan Agency for Medical Research and Development. Received: JAccepted: OctoPublished: November 12, 2021Ĭopyright: © 2021 Sugihara et al. PLoS ONE 16(11):Įditor: Baochuan Lin, Defense Threat Reduction Agency, UNITED STATES (2021) Atypical lymphocytes in the peripheral blood of COVID-19 patients: A prognostic factor for the clinical course of COVID-19. Citation: Sugihara J, Shibata S, Doi M, Shimmura T, Inoue S, Matsumoto O, et al.
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