Background 24The COVID-19 pandemic caused by SARS-CoV-2 coronavirus threatens global public 25 health. Currently, neutralizing antibodies (NAbs) versus this virus are expected to 26 correlate with recovery and protection of this disease. However, the characteristics of 27 these antibodies have not been well studied in association with the clinical 28 manifestations in patients. 30 Methods 31Plasma collected from 175 COVID-19 recovered patients with mild symptoms were 32 screened using a safe and sensitive pseudotyped-lentiviral-vector-based neutralization 33 assay. Spike-binding antibody in plasma were determined by ELISA using RBD, S1, 34 and S2 proteins of SARS-CoV-2. The levels and the time course of SARS-CoV-2-35 specific NAbs and the spike-binding antibodies were monitored at the same time. 36 37 Findings 38 SARS-CoV-2 NAbs were unable to cross-reactive with SARS-CoV virus. SARS-CoV-39 2-specific NAbs were detected in patients from day 10-15 after the onset of the disease 40 and remained thereafter. The titers of NAb among these patients correlated with the 41 spike-binding antibodies targeting S1, RBD, and S2 regions. The titers of NAbs were 42 variable in different patients. Elderly and middle-age patients had significantly higher 43 plasma NAb titers (P<0.0001) and spike-binding antibodies (P=0.0003) than young 44 patients. Notably, among these patients, there were ten patients whose NAb titers were 45 under the detectable level of our assay (ID50: < 40); while in contrast, two patients, 46 showed very high titers of NAb, with ID50 :15989 and 21567 respectively. The NAb 47 titers were positive correlated with plasma CRP levels but negative correlated with the 48 lymphocyte counts of patients at the time of admission, indicating an association 49 between humoral response and cellular immune response.50 51 Interpretation 52The variations of SARS-CoV-2 specific NAbs in recovered COVID-19 patients may 53 raise the concern about the role of NAbs on disease progression. The correlation of 54 NAb titers with age, lymphocyte counts, and blood CRP levels suggested that the 55 interplay between virus and host immune response in coronavirus infections should be 56 further explored for the development of effective vaccine against SARS-CoV-2 virus. 57 Furthermore, titration of NAb is helpful prior to the use of convalescent plasma for 58 prevention or treatment. Sciences 64 65 66 67 All rights reserved. No reuse allowed without permission.

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The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens global public health. The association between clinical characteristics of the virus and neutralizing antibodies (NAbs) against this virus have not been well studied. OBJECTIVE To examine the association between clinical characteristics and levels of NAbs in patients who recovered from COVID-19.

In the Acknowledgements section of this Article, the grant number 'SQ2019FY010009' should have been '2019FY101500'; this has been corrected online.

bioRxiv preprint 2 Emerging and re-emerging infectious diseases, such as SARS, MERS, Zika and highly 25 pathogenic influenza present a major threat to public health 1-3 . Despite intense research 26 effort, how, when and where novel diseases appear are still the source of considerable 27 uncertainly. A severe respiratory disease was recently reported in the city of Wuhan, 28 Hubei province, China. At the time of writing, at least 62 suspected cases have been 29 reported since the first patient was hospitalized on December 12 nd 2019. Epidemiological 30 investigation by the local Center for Disease Control and Prevention (CDC) suggested 31 that the outbreak was associated with a sea food market in Wuhan. We studied seven 32 patients who were workers at the market, and collected bronchoalveolar lavage fluid 33 (BALF) from one patient who exhibited a severe respiratory syndrome including fever, 34 dizziness and cough, and who was admitted to Wuhan Central Hospital on December 35 26 th 2019. Next generation metagenomic RNA sequencing 4 identified a novel RNA virus 36 from the family Coronaviridae designed WH-Human-1 coronavirus (WHCV). 37 Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that 38 WHCV was most closely related (89.1% nucleotide similarity similarity) to a group of 39 Severe Acute Respiratory Syndrome (SARS)-like coronaviruses (genus Betacoronavirus, 40 subgenus Sarbecovirus) previously sampled from bats in China and that have a history 41 of genomic recombination. This outbreak highlights the ongoing capacity of viral spill-42 over from animals to cause severe disease in humans. 43 44 Seven patients, comprising five men and two women, were hospitalized at the Central 45 : bioRxiv preprint 3 patients was 43, ranging from 31 to 70 years old. The clinical characteristics of the patients 47 are shown in Table 1. Fever and cough were the most common symptoms. All patients had 48 fever with body temperatures ranging from 37.2 o C to 40 o C. Patients 1, 2, 5, 6 and 7 had 49 cough, while patients 1, 2 and 7 presented with severe cough with phlegm at onset of illness. 50 Patients 4 and 5 also complained of chest tightness and dyspnea. Patients 1, 3, 4 and 6 51 experienced dizziness and patient 3 felt weakness. No neurological symptoms were observed 52 in any of the patients. Bacterial culture revealed the presence of Streptococcus bacteria in 53 throat swabs from patients 3, 4 and 7. Combination antibiotic, antiviral and glucocorticoid 54 therapy were administered. Unfortunately, patient 1 and 4 showed respiratory failure: patient 55 1 was given high flow noninvasive ventilation, while patient 4 was provided with nasal/face 56 mask ventilation (Table 1). 57Epidemiological investigation by the Wuhan CDC revealed that all the suspected cases 58 were linked to individuals working in a local indoor seafood market. Notably, in addition to 59 fish and shell fish, a variety of live wild animals including hedgehogs, badgers, snakes, and 60 birds (turtledoves) were available for sale in th...

Rapid proliferation is one of the critical characteristics of breast cancer. However, the underlying regulatory mechanism of breast cancer cell proliferation is largely unclear. The present study indicated that sevoflurane, one of inhalational anesthetics, could significantly suppress breast cancer cell proliferation by arresting cell cycle at G1 phase. Notably, the rescue experiment indicated that miR-203 was upregulated by sevoflurane and mediated the function of sevoflurane on suppressing the breast cancer cell proliferation. The present study indicated the function of the sevoflurane/miR-203 signaling pathway on regulating breast cancer cell proliferation. These results provide mechanistic insight into how the sevoflurane/miR-203 signaling pathway supresses proliferation of breast cancer cells, suggesting the sevoflurane/miR-203 pathway may be a potential target in the treatment of breast cancer.

Antibody-dependent enhancement (ADE) has been reported in several virus infections including dengue fever virus, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronavirus infection. To study whether ADE is involved in COVID-19 infections, in vitro pseudotyped SARS-CoV-2 entry into Raji cells, K562 cells, and primary B cells mediated by plasma from recovered COVID-19 patients were employed as models. The enhancement of SARS-CoV-2 entry into cells was more commonly detected in plasma from severely-affected elderly patients with high titers of SARS-CoV-2 spike protein-specific antibodies. Cellular entry was mediated via the engagement of FcγRII receptor through virus-cell membrane fusion, but not by endocytosis. Peptide array scanning analyses showed that antibodies which promote SARS-CoV-2 infection targeted the variable regions of the RBD domain. To further characterize the association between the spike-specific antibody and ADE, an RBD-specific monoclonal antibody (7F3) was isolated from a recovered patient, which potently inhibited SARS-Cov-2 infection of ACE-2 expressing cells and also mediated ADE in Raji cells. Site-directed mutagenesis the spike RBD domain reduced the neutralization activity of 7F3, but did not abolish its binding to the RBD domain. Structural analysis using cryo-electron microscopy (Cryo-EM) revealed that 7F3 binds to spike proteins at a shift-angled pattern with one up and two down RBDs, resulting in partial overlapping with the receptor binding motif (RBM), while a neutralizing monoclonal antibody that lacked ADE activity binds to spike proteins with three up RBDs, resulting in complete overlapping with RBM. Our results revealed that ADE mediated by SARS-CoV-2 spike-specific antibodies could result from binding to the receptor in slightly different pattern from antibodies mediating neutralizations. Studies on ADE using antibodies from recovered patients via cell biology and structural biology technology could be of use for developing novel therapeutic and preventive measures for control of COVID-19 infection.

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