ABSTRACT
While SARS-CoV-2 infection rates are declining, older adults remain vulnerable to severe disease with high mortality. Although there have been some studies on revealing different risk factors affecting the death of COVID-19 patients, such as bilirubin, organ failure, patient age, and underlying disease, they fail to provide a comprehensive analysis to reveal their relationships and interactive effects on the risk of death. Based on the demographic information, inspection indicators, and underlying diseases of 1917 patients (102 were dead) admitted to Xiangya Hospital over a 4-month period, we used the association rule mining method to identify the risk factors leading causes of death among elderly Omicron patients. Firstly, we used the Affinity Propagation clustering to extract key features such as blood parameters, liver function indicators, renal function indicators, coagulation function indicators, and underlying diseases affecting death from the dataset. Then, we applied the Apriori to obtain 7 groups of abnormal feature combinations with significant increments in mortality rate. The results showed a relationship between the number of abnormal feature combinations and mortality rates within different groups. For instance, patients with “C-reactive protein > 8 mg/L”, “neutrophils percentage > 75.0 %”, “lymphocytes percentage < 20 %”, and “albumin < 40 g/L” have a 2x mortality rate than the basic one. If the characteristics of “D-dimer > 0.5 mg/L” and “WBC > 9.5 * 10 9 /L” are continuously included in this foundation, the mortality rate can be increased to 3x or 4x. In addition, we also found that liver and kidney diseases significantly affect patient mortality. Given patients with liver and renal diseases associated with other abnormal features, their mortality rate can be as high as 100 %. These findings can support auxiliary diagnosis and treatment to, facilitate early intervention in patients, thereby reducing patient mortality.
Subject(s)
COVID-19 , Kidney Diseases , Multiple Organ Failure , DeathABSTRACT
BACKGROUND The impact of prior SARS-CoV-2 infection on postoperative recovery of patients who underwent liver resection for hepatocellular carcinoma (HCC) remains uncertain given the lack of sufficient evidence.AIM To investigate the impact of prior SARS-CoV-2 infection on postoperative recovery of patients who underwent liver resection for hepatocellular carcinoma (HCC).METHODS Patients who were pathologically diagnosed with HCC and underwent elective partial hepatectomy in Guangdong Provincial People’s Hospital between January 2022 and April 2023 were enrolled in this retrospective cohort study. The patients were divided into two groups based on their history of SARS-CoV-2 infection. Rehabilitation parameters, including postoperative liver function, incidence of complications, and hospitalization expenses, were compared between the two groups. Propensity score matching (PSM) was performed to reduce confounding bias.RESULTS We included 172 patients (58 with and 114 without prior SARS-CoV-2 infection) who underwent liver resection for HCC. No significant differences in the rehabilitation parameters were observed between the two groups. After PSM, 58 patients were selected from each group to form the new comparative groups. Similar results were obtained within the population after PSM.CONCLUSION Prior SARS-CoV-2 infection does not appear to affect postoperative rehabilitation, including liver function, postoperative complications, or hospitalization expenses among patients with HCC after elective partial hepatectomy.
Subject(s)
COVID-19 , Adenoma, Liver CellABSTRACT
Striking antibody evasion by emerging circulating SARS-CoV-2 variants drives the identification of broadly neutralizing antibodies (bNAbs). However, how a bNAb acquires increased neutralization breadth during antibody evolution is still elusive. Here, we identified a clonally-related antibody family from a convalescent individual. One of the members, XG005, exhibited potent and broad neutralizing activities against SARS-CoV-2 variants, while the other members showed significant reductions in neutralization breadth and potency, especially against the Omicron sublineages. Structural analysis visualizing the XG005-Omicron spike binding interface revealed how crucial somatic mutations endowed XG005 with greater neutralization potency and breadth. A single administration of XG005 with extended half-life, reduced antibody-dependent enhancement (ADE) effect, and increased antibody product quality, exhibited a high therapeutic efficacy in BA.2- and BA.5-challenged mice. Our results provided a natural example to show the importance of somatic hypermutation during antibody evolution for SARS-CoV-2 neutralization breadth and potency.
ABSTRACT
The contact and interaction of human is considered to be one of the important factors affecting the epidemic transmission, and it is critical to model the heterogeneity of individual activities in epidemiological risk assessment. In digital society, massive data makes it possible to implement this idea on large scale. Here, we use the mobile phone signaling to track the users’ trajectories and construct contact network to describe the topology of daily contact between individuals dynamically. We show the spatiotemporal contact features of about 7.5 million mobile phone users during the outbreak of COVID-19 in Shanghai, China. Furthermore, the individual feature matrix extracted from contact network enables us to carry out the extreme event learning and predict the regional transmission risk, which can be further decomposed into the risk due to the inflow of people from epidemic hot zones and the risk due to people close contacts within the observing area. This method is much more flexible and adaptive, and can be taken as one of the epidemic precautions with high efficiency and low cost.
Subject(s)
COVID-19ABSTRACT
The highly mutated and transmissible Omicron variant has provoked serious concerns over its decreased sensitivity to the current coronavirus disease 2019 (COVID-19) vaccines and evasion from most anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies (NAbs). In this study, we explored the possibility of combatting the Omicron variant by constructing bispecific antibodies based on non-Omicron NAbs. We engineered ten IgG-like bispecific antibodies with non-Omicron NAbs named GW01, 16L9, 4L12, and REGN10987 by fusing the single-chain variable fragments (scFvs) of two antibodies through a linker and then connecting them to the Fc region of IgG1. Surprisingly, eight out of ten bispecific antibodies showed high binding affinity to the Omicron receptor-binding domain (RBD) and exhibited extreme breadth and potency against pseudotyped SARS-CoV-2 variants of concern (VOCs) including Omicron, as well as authentic Omicron(+R346K) variants. Six bispecific antibodies containing the cross-NAb GW01 neutralized Omicron variant and retained their abilities to neutralize other sarbecoviruses. Bispecific antibodies inhibited Omicron infection by binding to the ACE2 binding site. A cryo-electron microscopy (cryo-EM) structure study of the representative bispecific antibody FD01 in complex with the Omicron spike (S) revealed 5 distinct trimers and one unique bi-trimer conformation. The structure and mapping analyses of 34 Omicron S variant single mutants elucidated that two scFvs of the bispecific antibody synergistically induced the RBD-down conformation into 3-RBD-up conformation, enlarged the interface area, accommodated the S371L mutation, improved the affinity between a single IgG and the Omicron RBD, and hindered ACE2 binding by forming bi-trimer conformation. Our study offers an important foundation for anti-Omicron NAb design. Engineering bispecific antibodies based on non-Omicron NAbs may provide an efficient solution to combat the Omicron variant.
Subject(s)
COVID-19 , Coronavirus InfectionsABSTRACT
Objective: To evaluate suicide risk, sleep quality and psychological status of patients with coronavirus disease 2019 (COVID-19) and analyze the factors contributing to a high suicide risk in these patients.
ABSTRACT
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 Fc{gamma}RII 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.
Subject(s)
Coronavirus Infections , Fever , Severe Acute Respiratory Syndrome , COVID-19ABSTRACT
Objective: The observational study was intended to explore the weight changes and risk factors of weight gain during the self-quarantine and find available methods to lose weight. Method: This was an online retrospective observational study investigating the weight changes before and after home confinement. A total of 530 participants completed the online questionnaire. diet, sleep, self-reported depression, disease history and exercise information possibly relating to weight changes were incorporated into the questionnaire. The differences among four groups (underweight, normal weight, overweight and obesity) in BMI change and weight change were compared, and the risk factors of weight gain was also analyzed by multiple linear regression analysis. Result: Participants were mostly between 21-50 years old, getting an average weight change of 0.82±3.31kg, and an average BMI change of 0.35 [-0.37, 1.00]. 43.77% of them gained weight by 2.99±2.29kg averagely. People with normal weight were easier to gain weight than obese group (p=0.001). There were differences in food intake (p<0.001), eating habits(p<0.001), taste preference (p=0.047), daily exercise step change(p=0.007), exercise (p=0.02) between non-weight gain group and weight gain group. The multiple linear regression revealed that weight gains were associated with sex (p=0.002), food intake (p=0.004), current daily exercise step (p=0.009) and self-reported depression (p=0.002) and weight loss was related to food intake (p=0.004) and pre-BMI (p=0.001). Conclusion: Eating irregularly, increasing food intake, self-reported depression and decreased daily steps were risk factors of weight gain, yet weight loss was related to decreased food intake and pre-BMI.
Subject(s)
COVID-19 , ObesityABSTRACT
Background: The COVID-19 pandemic caused by SARS-CoV-2 coronavirus threatens global public health. Currently, neutralizing antibodies (NAbs) versus this virus are expected to correlate with recovery and protection of this disease. However, the characteristics of these antibodies have not been well studied in association with the clinical manifestations in patients. Methods: Plasma collected from 175 COVID-19 recovered patients with mild symptoms were screened using a safe and sensitive pseudotyped-lentiviral-vector-based neutralization assay. Spike-binding antibody in plasma were determined by ELISA using RBD, S1, and S2 proteins of SARS-CoV-2. The levels and the time course of SARS-CoV-2-specific NAbs and the spike-binding antibodies were monitored at the same time. Findings: SARS-CoV-2 NAbs were unable to cross-reactive with SARS-CoV virus. SARS-CoV-2-specific NAbs were detected in patients from day 10-15 after the onset of the disease and remained thereafter. The titers of NAb among these patients correlated with the spike-binding antibodies targeting S1, RBD, and S2 regions. The titers of NAbs were variable in different patients. Elderly and middle-age patients had significantly higher plasma NAb titers (P<0·0001) and spike-binding antibodies (P=0·0003) than young patients. Notably, among these patients, there were ten patients whose NAb titers were under the detectable level of our assay (ID50: < 40); while in contrast, two patients, showed very high titers of NAb, with ID50 :15989 and 21567 respectively. The NAb titers were positive correlated with plasma CRP levels but negative correlated with the lymphocyte counts of patients at the time of admission, indicating an association between humoral response and cellular immune response. Interpretation: The variations of SARS-CoV-2 specific NAbs in recovered COVID-19 patients may raise the concern about the role of NAbs on disease progression. The correlation of NAb titers with age, lymphocyte counts, and blood CRP levels suggested that the interplay between virus and host immune response in coronavirus infections should be further explored for the development of effective vaccine against SARS-CoV-2 virus. Furthermore, titration of NAb is helpful prior to the use of convalescent plasma for prevention or treatment. Funding Statement: This work was supported by the National Major Science and Technology Projects of China (2017ZX10202102 and 2018ZX10301403), National Natural Science Foundation of China (31771008), Hundred Talent Program of Shanghai Municipal Health Commission (2018BR08), and Chinese Academy of Medical Sciences (2019PT350002). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The study was conducted under a clinical protocol approved by the Investigational Review Board in the Shanghai Public Health Clinical Center (Study number: YJ-2020-S021-01). All participants signed an informed consent approved by the IRB.
Subject(s)
COVID-19 , Coronavirus InfectionsABSTRACT
Background The COVID-19 pandemic caused by SARS-CoV-2 coronavirus threatens global public health. Currently, neutralizing antibodies (NAbs) versus this virus are expected to correlate with recovery and protection of this disease. However, the characteristics of these antibodies have not been well studied in association with the clinical manifestations in patients. Methods Plasma collected from 175 COVID-19 recovered patients with mild symptoms were screened using a safe and sensitive pseudotyped-lentiviral-vector-based neutralization assay. Spike-binding antibody in plasma were determined by ELISA using RBD, S1, and S2 proteins of SARS-CoV-2. The levels and the time course of SARS-CoV-2-specific NAbs and the spike-binding antibodies were monitored at the same time. Findings SARS-CoV-2 NAbs were unable to cross-reactive with SARS-CoV virus. SARS-CoV-2-specific NAbs were detected in patients from day 10-15 after the onset of the disease and remained thereafter. The titers of NAb among these patients correlated with the spike-binding antibodies targeting S1, RBD, and S2 regions. The titers of NAbs were variable in different patients. Elderly and middle-age patients had significantly higher plasma NAb titers (P<0.0001) and spike-binding antibodies (P=0.0003) than young patients. Notably, among these patients, there were ten patients whose NAb titers were under the detectable level of our assay (ID50: < 40); while in contrast, two patients, showed very high titers of NAb, with ID50 :15989 and 21567 respectively. The NAb titers were positive correlated with plasma CRP levels but negative correlated with the lymphocyte counts of patients at the time of admission, indicating an association between humoral response and cellular immune response. Interpretation The variations of SARS-CoV-2 specific NAbs in recovered COVID-19 patients may raise the concern about the role of NAbs on disease progression. The correlation of NAb titers with age, lymphocyte counts, and blood CRP levels suggested that the interplay between virus and host immune response in coronavirus infections should be further explored for the development of effective vaccine against SARS-CoV-2 virus. Furthermore, titration of NAb is helpful prior to the use of convalescent plasma for prevention or treatment. Funding Ministry of Science and Technology of China, National Natural Science Foundation of China, Shanghai Municipal Health Commission, and Chinese Academy of Medical Sciences
Subject(s)
Coronavirus Infections , Severe Acute Respiratory Syndrome , COVID-19ABSTRACT
From December 2019, the new coronavirus pneumonia (COVID-19) broke out in Wuhan, Hubei, and spread rapidly to the nationwide. On January 20, 2020, the National Health Committee classified COVID-19 pneumonia as one of B class infectious diseases and treated it as class A infectious disease. During the epidemic period, the routine diagnosis and treatment of tumor patients was affected with varying degrees. In this special period, we performed the superiority of the multi-disciplinary team of diagnosis and treatment, achieved accurate diagnosis and treatment of patients with hepatobiliary malignant tumors, provided support for these patients with limited medical resources, and helped them to survive during the epidemic period.On the basis of fully understanding the new coronavirus pneumonia, the treatment strategy should be changed timely during the epidemic, and more appropriate treatment methods should be adopted to minimize the adverse effect of the epidemic on tumor treatment.
ABSTRACT
Emerging and re-emerging infectious diseases, such as SARS, MERS, Zika and highly pathogenic influenza present a major threat to public health1-3. Despite intense research effort, how, when and where novel diseases appear are still the source of considerable uncertainly. A severe respiratory disease was recently reported in the city of Wuhan, Hubei province, China. At the time of writing, at least 62 suspected cases have been reported since the first patient was hospitalized on December 12nd 2019. Epidemiological investigation by the local Center for Disease Control and Prevention (CDC) suggested that the outbreak was associated with a sea food market in Wuhan. We studied seven patients who were workers at the market, and collected bronchoalveolar lavage fluid (BALF) from one patient who exhibited a severe respiratory syndrome including fever, dizziness and cough, and who was admitted to Wuhan Central Hospital on December 26th 2019. Next generation metagenomic RNA sequencing4 identified a novel RNA virus from the family Coronaviridae designed WH-Human-1 coronavirus (WHCV). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that WHCV was most closely related (89.1% nucleotide similarity similarity) to a group of Severe Acute Respiratory Syndrome (SARS)-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) previously sampled from bats in China and that have a history of genomic recombination. This outbreak highlights the ongoing capacity of viral spill-over from animals to cause severe disease in humans.