Diagnostic Performance, Stability, and Usability of Self-Collected Combo Swabs and Saliva for Coronavirus Disease 2019 Diagnosis: A Case-Control Study.

BACKGROUND: Self-sampling procedures to detect severe acute respiratory syndrome coronavirus 2 is important for patients who have difficulty visiting the hospital and may decrease the burden for health care workers (HCWs). The objective of this study was to evaluate the diagnostic performance, stability and usability of self-collected nasal and oral combo swabs and saliva specimens. MATERIALS AND METHODS: We conducted a case-control study with 50 patients with coronavirus disease 2019 (COVID-19) and 50 healthy volunteers from March, 2021 to June, 2021. We performed real-time reverse-transcription polymerase chain reaction to compare the diagnostic performance of self-collected specimens using positive percent agreements (PPAs). RESULTS: The PPAs between self-collected and HCW-collected specimens were 77.3 - 81.0% and 80.5 -86.7% for the combo swabs and saliva specimens, respectively. The PPAs increased to 88.9 - 89.2% and 81.2 - 82.1% with a cycle threshold value ≤30. CONCLUSION: The diagnostic performance of self sampling was comparable to that of HCW sampling in patients with high viral loads and may thus assist in the early diagnosis of COVID-19.

Effectiveness of Regdanvimab at Preventing the Need for Oxygen Therapy in Patients with Mild-to-Moderate COVID-19: A Retrospective Cohort Study.

BACKGROUND: Monoclonal antibodies are a treatment option for patients with mild-to-moderate coronavirus disease (COVID-19). We investigated the effectiveness of regdanvimab, an anti-severe acute respiratory syndrome coronavirus-2 monoclonal antibody approved in Korea, in the treatment of patients with mild-to-moderate COVID-19. MATERIALS AND METHODS: Medical records of patients who were admitted to a COVID-19 designated hospital during the study period of February 1 to June 31 and met the indications for administration of regdanvimab were reviewed to assess baseline characteristics and clinical outcomes such as supplemental oxygen requirements, mortality, and length of hospitalization. Multivariable logistic regression analysis was conducted to identify factors associated with requiring supplemental oxygen. Subgroup analysis was performed according to the presence of pneumonia confirmed on a chest X-ray. RESULTS: Three hundred ninety-eight COVID-19 patients were included in the study, and 65 (16.3%) of them were administered regdanvimab. The proportion of patients requiring supplemental oxygen was significantly lower in the regdanvimab group than in the control group (6.2% vs. 20.1%, P = 0.007). There was no significant difference in mortality (0% vs. 1.5%, P >0.999) and the length of hospitalization (median: 10 days vs. 10 days, P = 0.267) between two groups. The multivariable analysis demonstrated that administration of regdanvimab was independently associated with lower oxygen supplement [odds ratio (OR): 0.20, 95% confidence interval (CI): 0.06 - 0.55, P = 0.004] after adjustment of potential risk factors related to supplemental oxygen including age, sex, chest X-ray abnormality, and underlying chronic kidney disease. Among the patients with pneumonia radiologically, administration of regdanvimab was also associated with lower risk of oxygen supplement (OR: 0.13, 95% CI: 0.02 - 0.46, P = 0.007). CONCLUSION: Regdanvimab use was related to lower need for supplemental oxygen in patients with mild-to-moderate COVID-19 for the indications for administration of regdanvimab.

Abnormality in the NK-cell population is prolonged in severe COVID-19 patients.

BACKGROUND: Our understanding of adaptive immune responses in patients with coronavirus disease 2019 (COVID-19) is rapidly evolving, but information on the innate immune responses by natural killer (NK) cells is still insufficient. OBJECTIVE: We aimed to examine the phenotypic and functional status of NK cells and their changes during the course of mild and severe COVID-19. METHODS: We performed RNA sequencing and flow cytometric analysis of NK cells from patients with mild and severe COVID-19 at multiple time points in the course of the disease using cryopreserved PBMCs. RESULTS: In RNA-sequencing analysis, the NK cells exhibited distinctive features compared with healthy donors, with significant enrichment of proinflammatory cytokine-mediated signaling pathways. Intriguingly, we found that the unconventional CD56dimCD16neg NK-cell population expanded in cryopreserved PBMCs from patients with COVID-19 regardless of disease severity, accompanied by decreased NK-cell cytotoxicity. The NK-cell population was rapidly normalized alongside the disappearance of unconventional CD56dimCD16neg NK cells and the recovery of NK-cell cytotoxicity in patients with mild COVID-19, but this occurred slowly in patients with severe COVID-19. CONCLUSIONS: The current longitudinal study provides a deep understanding of the NK-cell biology in COVID-19.

PD-1-Expressing SARS-CoV-2-Specific CD8+ T Cells Are Not Exhausted, but Functional in Patients with COVID-19.

Memory T cell responses have been demonstrated in COVID-19 convalescents, but ex vivo phenotypes of SARS-CoV-2-specific T cells have been unclear. We detected SARS-CoV-2-specific CD8+ T cells by MHC class I multimer staining and examined their phenotypes and functions in acute and convalescent COVID-19. Multimer+ cells exhibited early differentiated effector-memory phenotypes in the early convalescent phase. The frequency of stem-like memory cells was increased among multimer+ cells in the late convalescent phase. Cytokine secretion assays combined with MHC class I multimer staining revealed that the proportion of interferon-γ (IFN-γ)-producing cells was significantly lower among SARS-CoV-2-specific CD8+ T cells than those specific to influenza A virus. Importantly, the proportion of IFN-γ-producing cells was higher in PD-1+ cells than PD-1- cells among multimer+ cells, indicating that PD-1-expressing, SARS-CoV-2-specific CD8+ T cells are not exhausted, but functional. Our current findings provide information for understanding of SARS-CoV-2-specific CD8+ T cells elicited by infection or vaccination.

Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19.

Although most SARS-CoV-2-infected individuals experience mild coronavirus disease 2019 (COVID-19), some patients suffer from severe COVID-19, which is accompanied by acute respiratory distress syndrome and systemic inflammation. To identify factors driving severe progression of COVID-19, we performed single-cell RNA-seq using peripheral blood mononuclear cells (PBMCs) obtained from healthy donors, patients with mild or severe COVID-19, and patients with severe influenza. Patients with COVID-19 exhibited hyper-inflammatory signatures across all types of cells among PBMCs, particularly up-regulation of the TNF/IL-1ß-driven inflammatory response as compared to severe influenza. In classical monocytes from patients with severe COVID-19, type I IFN response co-existed with the TNF/IL-1ß-driven inflammation, and this was not seen in patients with milder COVID-19. Interestingly, we documented type I IFN-driven inflammatory features in patients with severe influenza as well. Based on this, we propose that the type I IFN response plays a pivotal role in exacerbating inflammation in severe COVID-19.