In silico immune infiltration profiling combined with functional enrichment analysis reveals a potential role for naïve B cells as a trigger for severe immune responses in the lungs of COVID-19 patients.

COVID-19, caused by SARS-CoV-2, has rapidly spread to more than 160 countries worldwide since 2020. Despite tremendous efforts and resources spent worldwide trying to explore antiviral drugs, there is still no effective clinical treatment for COVID-19 to date. Approximately 15% of COVID-19 cases progress to pneumonia, and patients with severe pneumonia may die from acute respiratory distress syndrome (ARDS). It is believed that pulmonary fibrosis from SARS-CoV-2 infection further leads to ARDS, often resulting in irreversible impairment of lung function. If the mechanisms by which SARS-CoV-2 infection primarily causes an immune response or immune cell infiltration can be identified, it may be possible to mitigate excessive immune responses by modulating the infiltration and activation of specific targets, thereby reducing or preventing severe lung damage. However, the extent to which immune cell subsets are significantly altered in the lung tissues of COVID-19 patients remains to be elucidated. This study applied the CIBERSORT-X method to comprehensively evaluate the transcriptional estimated immune infiltration landscape in the lung tissues of COVID-19 patients and further compare it with the lung tissues of patients with idiopathic pulmonary fibrosis (IPF). We found a variety of immune cell subtypes in the COVID-19 group, especially naïve B cells were highly infiltrated. Comparison of functional transcriptomic analyses revealed that non-differentiated naïve B cells may be the main cause of the over-active humoral immune response. Using several publicly available single-cell RNA sequencing data to validate the genetic differences in B-cell populations, it was found that the B-cells collected from COVID-19 patients were inclined towards naïve B-cells, whereas those collected from IPF patients were inclined towards memory B-cells. Further differentiation of B cells between COVID-19 mild and severe patients showed that B cells from severe patients tended to be antibody-secreting cells, and gene expression showed that B cells from severe patients were similar to DN2 B cells that trigger extrafollicular response. Moreover, a higher percentage of B-cell infiltration seems associated with poorer clinical outcome. Finally, a comparison of several specific COVID-19 cases treated with targeted B-cell therapy suggests that appropriate suppression of naïve B cells might potentially be a novel strategy to alleviate the severe symptoms of COVID-19.

A Double Triage and Telemedicine Protocol to Optimize Infection Control in an Emergency Department in Taiwan During the COVID-19 Pandemic: Retrospective Feasibility Study.

BACKGROUND: Frontline health care workers, including physicians, are at high risk of contracting coronavirus disease (COVID-19) owing to their exposure to patients suspected of having COVID-19. OBJECTIVE: The aim of this study was to evaluate the benefits and feasibility of a double triage and telemedicine protocol in improving infection control in the emergency department (ED). METHODS: In this retrospective study, we recruited patients aged ≥20 years referred to the ED of the National Taiwan University Hospital between March 1 and April 30, 2020. A double triage and telemedicine protocol was developed to triage suggested COVID-19 cases and minimize health workers' exposure to this disease. We categorized patients attending video interviews into a telemedicine group and patients experiencing face-to-face interviews into a conventional group. A questionnaire was used to assess how patients perceived the quality of the interviews and their communication with physicians as well as perceptions of stress, discrimination, and privacy. Each question was evaluated using a 5-point Likert scale. Physicians' total exposure time and total evaluation time were treated as primary outcomes, and the mean scores of the questions were treated as secondary outcomes. RESULTS: The final sample included 198 patients, including 93 cases (47.0%) in the telemedicine group and 105 cases (53.0%) in the conventional group. The total exposure time in the telemedicine group was significantly shorter than that in the conventional group (4.7 minutes vs 8.9 minutes, P<.001), whereas the total evaluation time in the telemedicine group was significantly longer than that in the conventional group (12.2 minutes vs 8.9 minutes, P<.001). After controlling for potential confounders, the total exposure time in the telemedicine group was 4.6 minutes shorter than that in the conventional group (95% CI -5.7 to -3.5, P<.001), whereas the total evaluation time in the telemedicine group was 2.8 minutes longer than that in the conventional group (95% CI -1.6 to -4.0, P<.001). The mean scores of the patient questionnaire were high in both groups (4.5/5 to 4.7/5 points). CONCLUSIONS: The implementation of the double triage and telemedicine protocol in the ED during the COVID-19 pandemic has high potential to improve infection control.