ABSTRACT
Background: During the COVID-19 pandemic, a phenomenon emerged in which some patients with severe disease were critically ill and could not be discharged from the ICU even though they exhibited negative viral tests. In general, continuous negative viral tests are thought to indicate that the virus has been cleared from the body and that the patients can be considered "recovered". However, because these patients were still critically ill, they obviously had not truly recovered from the disease. We sought to investigate why these patients were still critically ill even though they exhibited negative viral tests by analyzing the gene expression profiles of their peripheral immune cells using transcriptome sequencing. Methods: Fourteen severe COVID-19 patients with at least 3 negative virus tests but were still in critical ill and could not be discharged from the ICU were enrolled. Blood samples from 14 patients and 5 healthy donors were collected. Total RNA was extracted from nucleated cells for RNA-Sequencing. FeatureCounts v1.5.0-p3 was used to count the reads numbers mapped to each gene. Results: All enrolled patients, regardless of changes in genes related to different symptoms and inflammatory responses, showed universally and severely decreased expression of adaptive immunity-related genes, especially those related to T/B cell arms and HLA molecules, and that these patients exhibited long-term secondary infections. This adaptive immune suppression is unlikely due to classic immune checkpoint molecules such as PD-1 or long-term use of glucocorticoids but may be caused by an unknown mechanism that has not yet been discovered. Conclusions: Our findings strongly suggest that an initial recovery of these severe COVID-19 patients, as indicated by negative viral tests, may not indicate actual recovery. They still suffer from secondary infections for a long period of time because of severe adaptive immunosuppression and need to receive a variety of antibiotics, antifungal drugs, or combination therapies. Appropriate methods should be used to detect their adaptive immune function, and appropriate immunotherapy that can activate the adaptive immune response should be developed. Trial registration: Not applicable (this study does not involve intervention on human participants).
Subject(s)
COVID-19ABSTRACT
Background Data regarding critical care for patients with severe COVID-19 are limited. We aimed to describe the clinical course, multi-strategy management, and respiratory support usage for the severe COVID-19 at the provincial level. Methods Using data from Sichuan Provincial Department of Health and the multicentre cohort study, all microbiologically confirmed COVID-19 patients in Sichuan who met the national severe criteria were included and followed-up from the day of inclusion (D1), until discharge, death, or the end of the study. Findings Out of 539 COVID-19 patients, 81 severe cases (15.0%) were identified. The median (IQR) age was 50 (39-65) years, 37% were female, and 53.1% had chronic comorbidities. All severe cases were identified before requiring mechanical ventilation and treated in the intensive care units (ICUs), among whom 51 (63.0%) were treated in provisional ICUs and 77 patients (95.1%) were admitted by D1. On D1, 76 (93.8%) were administered by respiratory support, including 55 (67.9%) by conventional oxygen therapy (COT), 8 (9.9%) by high-flow nasal cannula (HFNC) and 13 (16.0%) by non-invasive ventilation (NIV). By D28, 53 (65.4%) were discharged, three (3.7%) were deceased, and 25 (30.9%) were still hospitalized. COT, administered to 95.1% of the patients, was the most commonly used respiratory support and met 62.7% of the respiratory support needed, followed by HFNC (19.3%), NIV ventilation (9.4%) and IV 8.5%. Interpretation The multi-strategy management for severe COVID-19 patients including early identification and timely critical care may contribute to the low case-fatailty. Preparation of sufficient conventional oxygen equipment should be prioritized.