were collected and analyzed. The data of laboratory examinations, including peripheral lymphocyte subsets, were analyzed and compared between severe and non-severe patients. ResultsOf the 452 patients with COVID-19 recruited, 286 were diagnosed as severe infection. The median age was 58 years and 235 were male. The most common symptoms were fever, shortness of breath, expectoration, fatigue, dry cough and myalgia. Severe cases tend to have lower lymphocytes counts, higher leukocytes counts and neutrophil-lymphocyte-ratio (NLR), as well as lower percentages of monocytes, eosinophils, and basophils. Most of severe cases demonstrated elevated levels of infection-related biomarkers and inflammatory cytokines.The number of T cells significantly decreased, and more hampered in severe cases. Both helper T cells and suppressor T cells in patients withCOVID-19 were below normal levels, and lower level of helper T cells in severe group. The percentage of naïve helper T cells increased and memory helper T cells decreased in severe cases. Patients with COVID-19 also have lower level of regulatory T cells, and more obviously damaged in severe cases. Downloaded from https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciaa248/5803306 by guest on 30 March 2020 5 ConclusionsThe novel coronavirus might mainly act on lymphocytes, especially T lymphocytes.Surveillance of NLR and lymphocyte subsets is helpful in the early screening of critical illness, diagnosis and treatment of COVID-19.

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Background: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel batorigin CoV causing severe and fatal pneumonia in humans. Methods: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Jin Yin-tan Hospital of Wuhan, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. Results: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown b-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically 1 closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. Conclusion: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

The pandemic of COVID-19 caused by SARS-CoV-2 has posed serious threats to global health and economy, thus calling for the development of safe and effective vaccines. The receptor-binding domain (RBD) in the spike protein of SARS-CoV-2 is responsible for its binding to ACE2 receptor. It contains multiple dominant neutralizing epitopes and serves as an important antigen for the development of COVID-19 vaccines. Here, we showed that immunization of mice with a candidate subunit vaccine consisting of SARS-CoV-2 RBD and Fc fragment of human IgG, as an immunopotentiator, elicited high titer of RBD-speci c antibodies with robust neutralizing activity against both pseudotyped and live SARS-CoV-2 infections. The mouse antisera could also effectively neutralize infection by pseudotyped SARS-CoV-2 with several natural mutations in RBD and the IgG extracted from the mouse antisera could also show neutralization against pseudotyped SARS-CoV and SARS-related coronavirus (SARSr-CoV). Vaccination of human ACE2 transgenic mice with RBD-Fc could effectively protect mice from the SARS-CoV-2 challenge. These results suggest that SARS-CoV-2 RBD-Fc has good potential to be further developed as an effective and broad-spectrum vaccine to prevent infection of the current SARS-CoV-2 and its mutants, as well as future emerging SARSr-CoVs and re-emerging SARS-CoV. Background The outbreaks of severe acute respiratory syndrome (SARS) caused by SARS coronavirus (SARS-CoV) in 2002/2003 and those of middle east respiratory syndrome (MERS) caused by MERS coronavirus (MERS-CoV) in 2012 have highlighted the high zoonotic potential of emerging coronaviruses 1, 2. The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel coronavirus 2019 (2019-nCoV) 3 , which was also denoted as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 4 , or human coronavirus 2019 (HCoV-19) 5 , has resulted in more than 17 million con rmed cases and 0.66 million deaths in 216 countries, areas or territories (https://www.who.int/), endangering the global public health and economy and thus calling for the development of effective vaccines to protect at-risk populations. Currently, more than 150 COVID-19 vaccines are under development at different stages 6-9. Especially, a number of COVID-19 vaccines' phase 1/2 clinical trials have been completed, including the adenovirusvectored vaccines (Ad5-nCoV and ChAdOx1 nCoV-19) from CanSino 10 and Oxford University/AstraZeneca 11 , respectively; the mRNA vaccines (mRNA-1273 and BNT162b1) from Moderna 12 and P zer/BioNTech 13 , respectively; and the inactivated vaccines (PiCoVacc and BBIBP-CorV) from Sinovac 14 and Beijing Institute of Biological Products 15 , respectively (https://biorender.com/covid-vaccine-tracker/). Generally speaking, all these vaccines could induce antibodies speci c for spike (S) protein and receptor-binding domain (RBD), which neutralized pseudotyped and live SARS-CoV-2 infection. Some reports have shown that the neutralizing antibody titers are strongly correlated with RBD-binding IgG ...

IMPORTANCE Health care workers (HCWs) have high infection risk owing to treating patients with coronavirus disease 2019 (COVID-19). However, research on their infection risk and clinical characteristics is limited. OBJECTIVES To explore infection risk and clinical characteristics of HCWs with COVID-19 and to discuss possible prevention measures.

Background and Purpose White matter (WM) ischemic injury, a major neuropathological feature of cerebral small vessel diseases, is an important cause of vascular cognitive impairment in later life. The pathogenesis of demyelination following WM ischemic damage are often accompanied by microglial activation. Fingolimod (FTY720) was approved for the treatment of multiple sclerosis for its immunosuppression property. In this study, we evaluated the neuroprotective potential of FTY720 in a WM ischemia model. Methods Chronic WM ischemic injury model was induced by bilateral carotid artery stenosis (BCAS). Cognitive function, WM integrity, microglial activation and potential pathway involved in microglial polarization were assessed after BCAS. Results Disruption of WM integrity was characterized by demyelination in the corpus callosum and disorganization of Ranvier’s Nodes using Luxol Fast Blue staining, immunofluorescence staining and electron microscopy. In addition, radial maze test demonstrated that working memory performance was decreased at one-month post BCAS-induced injury. Interestingly, FTY720 could reduce cognitive decline and ameliorate the disruption of WM integrity. Mechanistically, cerebral hypoperfusion induced microglial activation, production of associated pro-inflammatory cytokines and priming of microglial polarization toward the M1 phenotype; whereas FTY720 attenuated microglia mediated neuroinflammation after WM ischemia and promoted oligodendrocytogenesis by shifting microglia toward M2 polarization. FTY720’s effect on microglial M2 polarization was largely suppressed by selective STAT3 blockade in vitro, revealing that FTY720-enabled shift of microglia from M1 to M2 polarization state was possibly mediated by STAT3 signaling. Conclusions Our study suggested that FTY720 might be a potential therapeutic drug targeting brain inflammation by skewing microglia toward M2 polarization after chronic cerebral hypoperfusion.

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Introduction Abnormal coagulation function has been demonstrated to be involved in the disease progression of COVID-19. However, the association between D-dimer levels and the severity of COVID-19 is not clear. The study was aimed to investigate the association between D-dimer levels and the severity of COVID-19 based on a cohort study and meta-analysis. Materials and methods Demographic and clinical data of all confirmed cases with COVID-19 on admission to Tongji Hospital from January 27 to March 5, 2020, were collected and analyzed, and coagulation function parameters were described and compared between patients with severe infection and those with non-severe infection. Cohort studies reporting risk estimates for the D-dimer and severity of COVID-19 association were searched and included to perform a meta-analysis. Results In our cohort study, patients with severe disease were more likely to exhibit dysregulated coagulation function, and a significantly higher D-dimer level (median 1.8 μg/ml [interquartile range 0.9–4.6] vs 0.5 [0.3–1.1], p < 0.001) was found in severe cases than the mild ones, on admission. In the meta-analysis of 13 cohort studies (including the current study), patients with severe disease had an increase in mean D-dimer value by 0.91 (95% confidence interval, 0.51–1.31, p < 0.001) μg/ml compared to those with non-severe disease, and odds of severe infection was associated with D-dimer greater than 0.5 μg/ml (odds ratio = 5.78, 95% confidence interval, 2.16–15.44, p < 0.001) on admission. Conclusions Patients with severe COVID-19 have a higher level of D-dimer than those with non-severe disease, and D-dimer greater than 0.5 μg/ml is associated with severe infection in patients with COVID-19.