Graphical Abstract Highlights d SARS-CoV-2-infected ferrets exhibit elevated body temperature and virus replication d SARS-CoV-2 is shed in nasal washes, saliva, urine and feces d SARS-CoV-2 is effectively transmitted to naive ferrets by direct contact d SARS-CoV-2 infection leads acute bronchiolitis in infected ferrets
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-1β-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-1β-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.
BackgroundFrom May to July 2015, the Republic of Korea experienced the largest outbreak of Middle East respiratory syndrome (MERS) outside the Arabian Peninsula. A total of 186 patients, including 36 deaths, had been diagnosed with MERS-coronavirus (MERS-CoV) infection as of September 30th, 2015.Materials and MethodsWe obtained information of patients who were confirmed to have MERS-CoV infection. MERS-CoV infection was diagnosed using real-time reverse-transcriptase polymerase chain reaction assay.ResultsThe median age of the patients was 55 years (range, 16 to 86). A total of 55.4% of the patients had one or more coexisting medical conditions. The most common symptom was fever (95.2%). At admission, leukopenia (42.6%), thrombocytopenia (46.6%), and elevation of aspartate aminotransferase (42.7%) were observed. Pneumonia was detected in 68.3% of patients at admission and developed in 80.8% during the disease course. Antiviral agents were used for 74.7% of patients. Mechanical ventilation, extracorporeal membrane oxygenation, and convalescent serum were employed for 24.5%, 7.1%, and 3.8% of patients, respectively. Older age, presence of coexisting medical conditions including diabetes or chronic lung disease, presence of dyspnea, hypotension, and leukocytosis at admission, and the use of mechanical ventilation were revealed to be independent predictors of death.ConclusionThe clinical features of MERS-CoV infection in the Republic of Korea were similar to those of previous outbreaks in the Middle East. However, the overall mortality rate (20.4%) was lower than that in previous reports. Enhanced surveillance and active management of patients during the outbreak may have resulted in improved outcomes.
Memory T cells contribute to rapid viral clearance during re-infection, but the longevity and differentiation of SARS-CoV-2-specific memory T cells remain unclear. Here we conduct ex vivo assays to evaluate SARS-CoV-2-specific CD4+ and CD8+ T cell responses in COVID-19 convalescent patients up to 317 days post-symptom onset (DPSO), and find that memory T cell responses are maintained during the study period regardless of the severity of COVID-19. In particular, we observe sustained polyfunctionality and proliferation capacity of SARS-CoV-2-specific T cells. Among SARS-CoV-2-specific CD4+ and CD8+ T cells detected by activation-induced markers, the proportion of stem cell-like memory T (TSCM) cells is increased, peaking at approximately 120 DPSO. Development of TSCM cells is confirmed by SARS-CoV-2-specific MHC-I multimer staining. Considering the self-renewal capacity and multipotency of TSCM cells, our data suggest that SARS-CoV-2-specific T cells are long-lasting after recovery from COVID-19, thus support the feasibility of effective vaccination programs as a measure for COVID-19 control.
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