key: cord-0706819-xp0w2wn9
authors: Kaya, Hiroyasu; Usuda, Daisuke
title: Duration from onset to discharge is longer in COVID‐19 patients with low blood regulatory T‐cell counts
date: 2021-10-21
journal: J Med Virol
DOI: 10.1002/jmv.27401
sha: 13fc4c64a82d13993cd9c560e482d6b9f3f235cb
doc_id: 706819
cord_uid: xp0w2wn9

nan

To the Editor,

We read with interest the article by Rahimzadeh et al. 1 They observed a trend toward decreasing regulatory T-cell (T reg) levels in severe coronavirus disease 2019 (COVID-19) patients. We also studied the relationship between T reg in peripheral blood and severity of COVID-19, and believe that T reg is important in the progression of COVID-19 cases from serious to very severe.

Severe COVID-19 patients show various immunological abnormalities, including T-cell reduction and cytokine release syndrome. Previous reports have suggested a correlation between abnormalities in T reg and the autoimmune system. 2,3 Single cell-level mechanisms for T-cell dysregulation in severe COVID-19 have already been shown. 4 We performed a prospective observational study at Toyama Prefectural Central Hospital, in Japan. The research participants included 29 patients with positive results for SARS-CoV-2 RNA (11 wild-types, 17 alpha variants, 1 delta variant) between November 1, 2020 and July 30, 2021. We chose the first 29 consecutive patients with pneumonia at admission. The primary outcome was the duration in days from onset to discharge. Typically, patients were discharged approximately 10 days from the onset and 3 days from the improvement of fever or respiratory symptoms by rule, although hospitalization was prolonged on a case-by-case basis. We collected the following baseline, demographic, clinical, laboratory characteristics, treatment, and outcome data: age, sex, peripheral T reg counts (CD4-positive, CD25-positive, and CD127-negative cells) by flow cytometry (BML, Inc.) on admission, 5 complications of pneumonia, and use of oxygen therapy. The cut-off value for the T reg count was determined by receiver operating characteristic (ROC) curve analysis. We applied univariate and multivariate analysis to compare each of the characteristics and outcome data. Patients were allocated into two groups on the basis of the following cut-off values: Group A, patients with low T reg levels (<13/μl) and pneumonia; Group B, patients with high T reg level (≥13/μl) and pneumonia. Comparison of the two groups for the duration from onset to discharge was performed using the Kaplan-Meier method for comparison of disease severity. EZR version 1.54 was used for all statistical analyses. 6 First, the optimal cut-off for the regulatory T-cell count was determined as 13/μl by ROC curve analysis. The mean T reg count of patients with severe pneumonia (as determined by the need for oxygen therapy) and without severe pneumonia were 18.9 and 23.3, respectively. The mean T reg count of patients with severe pneumonia tended to be lower, although the difference between the groups was not significant. Age ≥65 years, sex, variant type, and low T reg level (<13/μl) did not correlate significantly with complications of severe pneumonia in univariate analyses. These categories were therefore removed from this model on multivariate logistic regression analysis. However, the T reg count of one patient with high blood T reg count on admission and severe pneumonia decreased before intubation (from 33 to 10.8/μl). If more such cases are evaluated or the timing of T reg examination is changed, we might find a significant correlation between low T reg level and complications of severe pneumonia. Furthermore, the onset to discharge duration in Group Awas significantly longer in comparison with Group B (Figure 1 ). The median duration in COVID-19 patients with pneumonia and low T reg count was 19 days, while that in COVID-19 patients with pneumonia and high T reg count was 17 days.

Our data suggested that peripheral blood T reg levels on admission are associated with severe pneumonia requiring oxygen therapy, but not with pneumonia without oxygen therapy. The difference in median days from onset to discharge between pneumonia patients with low T reg and

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