Commemoration and Emotional Sustenance: A Text Analysis of Students' Motivations Behind Online Mourning of Dr Li Wenliang.

As one of the first doctors issued a protective warning to the public, Dr. Li Wenliang was known as "whistleblower" of COVID-19 pandemic. After his death of COVID-19, students entered to his Sina Weibo to display their condolences and sorrow. We conduct text analysis and sentiment classification to investigate the motivation behind online mourning for Dr. Li among students on Sina Weibo. Our results indicate that, a) there always more than one motivation behind online mourning exists in each time period. b) continuing connection and semi-interaction with the deceased is the main motivation when students mourn online. c) there exists positive correlation between the influence of the deceased and the motivation--sharing information with the community of fans and creating social support in a time of loss and social support. d) the motivation--honoring the dead and expressing sadness and resentment can gradually lose over time.

The characteristics and predictive role of lymphocyte subsets in COVID-19 patients.

OBJECTIVE: To investigate the characteristics and predictive roles of lymphocyte subsets in COVID-19 patients. METHOD: We evaluated lymphocyte subsets and other clinical features of COVID-19 patients, and analyzed their potential impacts on COVID-19 outcomes. RESULTS: 1. Lymphocyte subset counts in the peripheral blood of patients with COVID-19 were significantly reduced, especially in patients with severe disease. 2. In patients with non-severe disease, the time from symptom onset to hospital admission was positively correlated with total T cell counts. 3. Among COVID-19 patients who did not reach the composite endpoint, lymphocyte subset counts were higher than in patients who had reached the composite endpoint. 4. The Kaplan-Meier survival curves showed significant differences in COVID-19 patients, classified by the levels of total, CD8+, and CD4+ T cells at admission. CONCLUSION: Our study showed that total, CD8+, and CD4+ T cell counts in patients with COVID-19 were significantly reduced, especially in patients with severe disease. Lower T lymphocyte subsets were significantly associated with a higher occurrence of composite endpoint events. These subsets may help identify patients with a high risk of composite endpoint events.

A mathematical model to assess the impact of testing and isolation compliance on the transmission of COVID-19.

The COVID-19 pandemic has ravaged global health and national economies worldwide. Testing and isolation are effective control strategies to mitigate the transmission of COVID-19, especially in the early stage of the disease outbreak. In this paper, we develop a deterministic model to investigate the impact of testing and compliance with isolation on the transmission of COVID-19. We derive the control reproduction number R C , which gives the threshold for disease elimination or prevalence. Using data from New York State in the early stage of the disease outbreak, we estimate R C = 7.989 . Both elasticity and sensitivity analyses show that testing and compliance with isolation are significant in reducing R C and disease prevalence. Simulation reveals that only high testing volume combined with a large proportion of individuals complying with isolation have great impact on mitigating the transmission. The testing starting date is also crucial: the earlier testing is implemented, the more impact it has on reducing the infection. The results obtained here would also be helpful in developing guidelines of early control strategies for pandemics similar to COVID-19.

Dynamics of disease characteristics and viral RNA decay in patients with asymptomatic and mild infections during the Omicron wave in Shanghai, China: A retrospective cohort study.

OBJECTIVES: Asymptomatic infections and mild diseases were more common during the Omicron outbreak in Shanghai, China in 2022. This study aimed to assess the characteristics and viral RNA decay between patients with asymptomatic and mild infections. METHODS: A total of 55,111 patients infected with SARS-CoV-2 who were quarantined in the National Exhibition & Convention Center (Shanghai) Fangcang shelter hospital within 3 days after diagnosis from April 9 to May 23, 2022 were enrolled. The kinetics of cycle threshold (Ct) values of reverse transcription-polymerase chain reaction were assessed. The influencing factors for disease progression and the risk factors for the viral RNA shedding time (VST) were investigated. RESULTS: On admission, 79.6% (43,852/55,111) of the cases were diagnosed with asymptomatic infections, and 20.4% were mild diseases. However, 78.0% of initially asymptomatic subjects developed mild diseases at the follow-up. The final proportion of asymptomatic infections was 17.5%. The median time of symptom onset, the duration of symptoms, and the VST were 2 days, 5 days, and 7 days, respectively. Female, age 19-40 years, underlying comorbidities with hypertension and diabetes, and vaccination were associated with higher risks of progressing to mildly symptomatic infections. In addition, mildly symptomatic infections were found to be associated with prolonged VST compared with asymptomatic infections. However, the kinetics of viral RNA decay and dynamics of Ct values were similar among asymptomatic subjects, patients with asymptomatic-to-mild infection, and patients with mild infection. CONCLUSION: A large proportion of initially diagnosed asymptomatic Omicron infections is in the presymptomatic stage. The Omicron infection has a much shorter incubation period and VST than previous variants. The infectivity of asymptomatic infections and mildly symptomatic infections with Omicron is similar.

Outcome of COVID-19 Infection in Patients With Multiple Sclerosis Who Received Disease-Modifying Therapies: A Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: A systematic review and meta-analysis was performed of the outcome of Coronavirus disease 2019 (COVID-19) infection in patients with multiple sclerosis (MS) who received disease-modifying therapies (DMTs). METHODS: Relevant studies published before November 2022 in the PubMed, Cochrane Library, Chinese National Knowledge Infrastructure, and Web of Science databases were retrieved using the following search expression: ("multiple sclerosis" OR "MS") AND ("DMT" OR "disease modifying therapies") AND ("COVID-19"). Two authors independently screened the articles and extracted the data. Qualitative analyses and a meta-analysis constituted 22 of the 794 retrieved articles. Differences in the hospitalization and mortality rates were used as the main measures of efficacy, and the meta-analysis was performed using RevMan software. RESULTS: 22 clinical trials were selected. The hospitalization rate was lower in the 3,216 patients who received DMTs than in the 774 patients who did not receive any treatment, with a moderate effect size of 0.43 (p<0.00001). The mortality rate was also lower among patients with MS treated using DMTs than in controls (odds ratio [OR]=0.19, 95% confidence interval [CI]=0.13-0.27, p<0.00001). The hospitalization rates for COVID-19 infection in patients with MS treated with anti-CD20 therapy also increased markedly (OR=3.32, 95% CI=2.63-4.20, p<0.00001). However, there was no significant difference between patients with MS who did and did not receive DMTs. CONCLUSIONS: In summary, the application of DMTs was found to be valuable for patients with MS infected with COVID-19. However, more clinical studies are needed to determine the use of anti-CD20 drugs in patients with MS during the COVID-19 pandemic.

TIMELESS is a key gene mediating thrombogenesis in COVID-19 and antiphospholipid syndrome.

Abnormal coagulation and increased risk of thrombosis are some of the symptoms associated with COVID-19 severity. Anti-phospholipid antibodies (aPLs) present in critically ill COVID-19 patients contribute to systemic thrombosis. The aim of this study was to identify key common genes to characterize genetic crosstalk between COVID-19 and antiphospholipid syndrome (APS) using bioinformatics analysis and explore novel mechanisms of immune-mediated thrombosis in critically ill COVID-19 patients. The transcriptome data of mononuclear cells from severe COVID-19 patients and APS patients were evaluated to obtain the common genes. The protein-protein interaction network and cytoHubba module analysis in Cytoscape software were used to find the associated hinge genes and hub genes. Among the common differentially expressed genes, TIMELESS depletion was identified only in patients with severe COVID-19 and not in patients with mild COVID-19, and it was validated with the GSE159678 dataset. Functional analyses using gene ontology terms and the Kyoto Encyclopedia of Genes and Genomes pathway suggested that TIMELESS might contribute to the production of antiphospholipid antibody and thrombosis in both COVID-19 and APS patients. The potential role of TIMELESS and autophagy genes in momonuclear cells were further investigated, and GSK3B was found to be associated with TIMELESS. Autophagy targeting agents have a therapeutic potential against COVID-19 and thrombogenesis in APS, which may be related to the role of autophagy genes in the modification of circadian clock proteins. Interference with TIMELESS and other genes associated with it to regulate autoantibody expression may be a potential strategy for immunotherapy against thrombogenesis in severe COVID-19 patients.

Epidemiological characteristics and pathological changes of primary glomerular diseases.

OBJECTIVE: By analyzing the pathological characteristics and clinical data of renal biopsy in our hospital in the past 20 years, to further understand the epidemic characteristics and pathological changes of primary glomerular disease, and to provide regional data for the big data of kidney disease in my country. METHODS: A retrospective analysis of 9448 patients with primary glomerular disease who were hospitalized in our hospital from January 1, 2000 to December 31, 2019, aged 18 years or older, and undergoing renal biopsy. Divided every 5 years into a group, a total of 4 groups (first group 2000.1.1-2004.12.31, second groups 2005.1.1-2009.12.31; third groups 2010.1.1-2014.12.31, fourth groups 2015.1.1-2019.12.31). RESULTS: ① There were more males than females, and male: female vs 1.53:1. The proportion of men in the past five years has increased compared with the previous 15 years. ② Mostly middle-aged, with a median age of 41.39 years old. The age is increasing over time. There are differences between the four groups, P <0.001; ③ The most common clinical manifestations are nephrotic syndrome, followed by chronic glomerulonephritis. Occult glomerulonephritis, the proportion of patients with nephrotic syndrome increases over time, first to fourth group (40.08%< 42.64% < 47.08%< 53.69%); ④ The most common pathology type from 2000 to 2009 was mesangial proliferative glomerulonephritis. IgA nephropathy was the most common type from 2010 to 2014, but the proportion of membranous nephropathy increased year by year, and it became the most common pathological type from 2015 to 2019; ⑤ The clinical and pathological manifestations of different genders are different, but there is no statistical difference. CONCLUSION: In the past 20 years, the primary glomerular disease is mainly middle-aged. There are more men than women. The most common type of clinical manifestation is nephrotic syndrome. The pathological type is mesangial proliferative glomerulonephritis. Over time, the average age is increasing, and the proportion of patients with renal syndrome is increasing. IgA nephropathy is the most common pathological type from 2010 to 2014, and membranous nephropathy has become the main pathological type in the past 5 years.

Uncovering the genetic links of SARS-CoV-2 infections on heart failure co-morbidity by a systems biology approach.

AIMS: The co-morbidities contribute to the inferior prognosis of COVID-19 patients. Recent reports suggested that the higher co-morbidity rate between COVID-19 and heart failure (HF) leads to increased mortality. However, the common pathogenic mechanism between them remained elusive. Here, we aimed to reveal underlying molecule mechanisms and genetic correlation between COVID-19 and HF, providing a new perspective on current clinical management for patients with co-morbidity. METHODS: The gene expression profiles of HF (GSE26887) and COVID-19 (GSE147507) were retrieved from the GEO database. After identifying the common differentially expressed genes (|log2FC| > 1 and adjusted P < 0.05), integrated analyses were performed, namely, enrichment analyses, protein-protein interaction network, module construction, critical gene identification, and functional co-expression analysis. The performance of critical genes was validation combining hierarchical clustering, correlation, and principal component analysis in external datasets (GSE164805 and GSE9128). Potential transcription factors and miRNAs were obtained from the JASPER and RegNetwork repository used to construct co-regulatory networks. The candidate drug compounds in potential genetic link targets were further identified using the DSigDB database. RESULTS: The alteration of 12 genes was identified as a shared transcriptional signature, with the role of immune inflammatory pathway, especially Toll-like receptor, NF-kappa B, chemokine, and interleukin-related pathways that primarily emphasized in response to SARS-CoV-2 complicated with HF. Top 10 critical genes (TLR4, TLR2, CXCL8, IL10, STAT3, IL1B, TLR1, TP53, CCL20, and CXCL10) were identified from protein-protein interaction with topological algorithms. The unhealthy microbiota status and gut-heart axis in co-morbidity were identified as potential disease roads in bridging pathogenic mechanism, and lipopolysaccharide acts as a potential marker for monitoring HF during COVID-19. For transcriptional and post-transcriptional levels, regulation networks tightly coupling with both disorders were constructed, and significant regulator signatures with high interaction degree, especially FOXC1, STAT3, NF-κB1, miR-181, and miR-520, were detected to regulate common differentially expressed genes. According to genetic links targets, glutathione-based antioxidant strategy combined with muramyl dipeptide-based microbe-derived immunostimulatory therapies was identified as promising anti-COVID-19 and anti-HF therapeutics. CONCLUSIONS: This study identified shared transcriptomic and corresponding regulatory signatures as emerging therapeutic targets and detected a set of pharmacologic agents targeting genetic links. Our findings provided new insights for underlying pathogenic mechanisms between COVID-19 and HF.

Build a tourism "operating in epidemic" mode that is compatible with normalized epidemic prevention and control

The global outbreak of the new crown epidemic, because the RO value of the virus is as high as 1.4 to 2.5, its spread rate is increasing exponentially, and its impact on human society is unprecedented. This means that the new coronavirus will have a high probability of long-term existence and coexist with humans in the future. Some experts predict two long-term forms of the new coronavirus: First, the new coronavirus has the potential to transform into a seasonal plague, just like the flu.

Physiological characteristics, geochemical properties and hydrological variables influencing pathogen migration in subsurface system: What we know or not?

The global outbreak of coronavirus infectious disease-2019 (COVID-19) draws attentions in the transport and spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in aerosols, wastewater, surface water and solid wastes. As pathogens eventually enter the subsurface system, e.g., soils in the vadose zone and groundwater in the aquifers, they might survive for a prolonged period of time owing to the uniqueness of subsurface environment. In addition, pathogens can transport in groundwater and contaminate surrounding drinking water sources, possessing long-term and concealed risks to human society. This work critically reviews the influential factors of pathogen migration, unravelling the impacts of pathogenic characteristics, vadose zone physiochemical properties and hydrological variables on the migration of typical pathogens in subsurface system. An assessment algorithm and two rating/weighting schemes are proposed to evaluate the migration abilities and risks of pathogens in subsurface environment. As there is still no evidence about the presence and distribution of SARS-CoV-2 in the vadose zones and aquifers, this study also discusses the migration potential and behavior of SARS-CoV-2 viruses in subsurface environment, offering prospective clues and suggestions for its potential risks in drinking water and effective prevention and control from hydrogeological points of view.

Establishment of Routine Clinical Indicators-Based Nomograms for Predicting the Mortality in Patients With COVID-19.

This study aimed to establish and validate the nomograms to predict the mortality risk of patients with coronavirus disease 2019 (COVID-19) using routine clinical indicators. This retrospective study included a development cohort enrolled 2,119 hospitalized patients with COVID-19 and a validation cohort included 1,504 patients with COVID-19. The demographics, clinical manifestations, vital signs, and laboratory tests of the patients at admission and outcome of in-hospital death were recorded. The independent factors associated with death were identified by a forward stepwise multivariate logistic regression analysis and used to construct the two prognostic nomograms. The nomogram 1 was a full model to include nine factors identified in the multivariate logistic regression and nomogram 2 was built by selecting four factors from nine to perform as a reduced model. The nomogram 1 and nomogram 2 showed better performance in discrimination and calibration than the Multilobular infiltration, hypo-Lymphocytosis, Bacterial coinfection, Smoking history, hyper-Tension and Age (MuLBSTA) score in training. In validation, nomogram 1 performed better than nomogram 2 for calibration. We recommend the application of nomogram 1 in general hospitals which provide robust prognostic performance though more cumbersome; nomogram 2 in the out-patient, emergency department, and mobile cabin hospitals, which depend on less laboratory examinations to make the assessment more convenient. Both the nomograms can help the clinicians to identify the patients at risk of death with routine clinical indicators at admission, which may reduce the overall mortality of COVID-19.

Early kidney injury predicts disease progression in patients with COVID-19: a cohort study.

BACKGROUND: The receptor of severe respiratory syndrome coronavirus 2 (SARS-CoV-2), angiotensin-converting enzyme 2, is more abundant in kidney than in lung tissue, suggesting that kidney might be another important target organ for SARS-CoV-2. However, our understanding of kidney injury caused by Coronavirus Disease 2019 (COVID-19) is limited. This study aimed to explore the association between kidney injury and disease progression in patients with COVID-19. METHODS: A retrospective cohort study was designed by including 2630 patients with confirmed COVID-19 from Huoshenshan Hospital (Wuhan, China) from 1 February to 13 April 2020. Kidney function indexes and other clinical information were extracted from the electronic medical record system. Associations between kidney function indexes and disease progression were analyzed using Cox proportional-hazards regression and generalized linear mixed model. RESULTS: We found that estimated glomerular filtration rate (eGFR) and creatinine clearance (Ccr) decreased in 22.0% and 24.0% of patients with COVID-19, respectively. Proteinuria was detected in 15.0% patients and hematuria was detected in 8.1% of patients. Hematuria (HR 2.38, 95% CI 1.50-3.78), proteinuria (HR 2.16, 95% CI 1.33-3.51), elevated baseline serum creatinine (HR 2.84, 95% CI 1.92-4.21) and blood urea nitrogen (HR 3.54, 95% CI 2.36-5.31), and decrease baseline eGFR (HR 1.58, 95% CI 1.07-2.34) were found to be independent risk factors for disease progression after adjusted confounders. Generalized linear mixed model analysis showed that the dynamic trajectories of uric acid was significantly related to disease progression. CONCLUSION: There was a high proportion of early kidney function injury in COVID-19 patients on admission. Early kidney injury could help clinicians to identify patients with poor prognosis at an early stage.

Fasting plasma glucose and glucose fluctuation are associated with COVID-19 prognosis regardless of pre-existing diabetes.

AIMS: We aimed to investigate the role of Fasting Plasma Glucose (FPG) and glucose fluctuation in the prognosis of COVID-19 patients stratified by pre-existing diabetes. METHODS: The associations of FPG and glucose fluctuation indexes with prognosis of COVID-19 in 2,642 patients were investigated by multivariate Cox regression analysis. The primary outcome was in-hospital mortality; the secondary outcome was disease progression. The longitudinal changes of FPG over time were analyzed by the latent growth curve model in COVID-19 patients stratified by diabetes and severity of COVID-19. RESULTS: We found FPG as an independent prognostic factor of overall survival after adjustment for age, sex, diabetes and severity of COVID-19 at admission (HR: 1.15, 95% CI: 1.06-1.25, P = 1.02 × 10-3). Multivariate logistic regression analysis indicated that the standard deviation of blood glucose (SDBG) and largest amplitude of glycemic excursions (LAGE) were also independent risk factors of COVID-19 progression (P = 0.03 and 0.04, respectively). The growth trajectory of FPG over the first 3 days of hospitalization was steeper in patients with critical COVID-19 in comparison to moderate patients. CONCLUSIONS: Hyperglycemia and glucose fluctuation were adverse prognostic factors of COVID-19 regardless of pre-existing diabetes. This stresses the importance of glycemic control in addition to other therapeutic management.

Major Characteristics of Severity and Mortality in Diabetic Patients With COVID-19 and Establishment of Severity Risk Score.

Objectives: Diabetes is a risk factor for poor COVID-19 prognosis. The analysis of related prognostic factors in diabetic patients with COVID-19 would be helpful for further treatment of such patients. Methods: This retrospective study involved 3623 patients with COVID-19 (325 with diabetes). Clinical characteristics and laboratory tests were collected and compared between the diabetic group and the non-diabetic group. Binary logistic regression analysis was applied to explore risk factors associated in diabetic patients with COVID-19. A prediction model was built based on these risk factors. Results: The risk factors for higher mortality in diabetic patients with COVID-19 were dyspnea, lung disease, cardiovascular diseases, neutrophil, PLT count, and CKMB. Similarly, dyspnea, cardiovascular diseases, neutrophil, PLT count, and CKMB were risk factors related to the severity of diabetes with COVID-19. Based on these factors, a risk score was built to predict the severity of disease in diabetic patients with COVID-19. Patients with a score of 7 or higher had an odds ratio of 7.616. Conclusions: Dyspnea is a critical clinical manifestation that is closely related to the severity of disease in diabetic patients with COVID-19. Attention should also be paid to the neutrophil, PLT count and CKMB levels after admission.

Inflammation characteristics and anti-inflammation treatment with tocilizumab of severe/critical COVID-19 patients: A retrospective cohort study.

The efficacy of tocilizumab on the prognosis of severe/critical COVID-19 patients is still controversial so far. We aimed to delineate the inflammation characteristics of severe/critical COVID-19 patients and determine the impact of tocilizumab on hospital mortality. Here, we performed a retrospective cohort study which enrolled 727 severe or critical inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Huoshenshan Hospital (Wuhan, China), among which 50 patients received tocilizumab. This study confirmed that most recovered patients manifested relatively normal inflammation levels at admission, whereas most of the deceased cases presented visibly severe inflammation at admission and even progressed into extremely aggravated inflammation before their deaths, proved by some extremely high concentrations of interleukin-6, procalcitonin, C-reactive protein and neutrophil count. Moreover, based on the Cox proportional-hazards models before or after propensity score matching, we demonstrated that tocilizumab treatment could lessen mortality by gradually alleviating excessive inflammation and meanwhile continuously enhancing the levels of lymphocytes within 14 days for severe/critical COVID-19 patients, indicating potential effectiveness for treating COVID-19.

Risk stratification scores for hospitalization duration and disease progression in moderate and severe patients with COVID-19.

BACKGROUND: During outbreak of Coronavirus Disease 2019 (COVID-19), healthcare providers are facing critical clinical decisions based on the prognosis of patients. Decision support tools of risk stratification are needed to predict outcomes in patients with different clinical types of COVID-19. METHODS: This retrospective cohort study recruited 2425 patients with moderate or severe COVID-19. A logistic regression model was used to select and estimate the factors independently associated with outcomes. Simplified risk stratification score systems were constructed to predict outcomes in moderate and severe patients with COVID-19, and their performances were evaluated by discrimination and calibration. RESULTS: We constructed two risk stratification score systems, named as STPCAL (including significant factors in the prediction model: number of clinical symptoms, the maximum body temperature during hospitalization, platelet count, C-reactive protein, albumin and lactate dehydrogenase) and TRPNCLP (including maximum body temperature during hospitalization, history of respiratory diseases, platelet count, neutrophil-to-lymphocyte ratio, creatinine, lactate dehydrogenase, and prothrombin time), to predict hospitalization duration for moderate patients and disease progression for severe patients, respectively. According to STPCAL score, moderate patients were classified into three risk categories for a longer hospital duration: low (Score 0-1, median = 8 days, with less than 20.0% probabilities), intermediate (Score 2-6, median = 13 days, with 30.0-78.9% probabilities), high (Score 7-9, median = 19 days, with more than 86.5% probabilities). Severe patients were stratified into three risk categories for disease progression: low risk (Score 0-5, with less than 12.7% probabilities), intermediate risk (Score 6-11, with 18.6-69.1% probabilities), and high risk (Score 12-16, with more than 77.9% probabilities) by TRPNCLP score. The two risk scores performed well with good discrimination and calibration. CONCLUSIONS: Two easy-to-use risk stratification score systems were built to predict the outcomes in COVID-19 patients with different clinical types. Identifying high risk patients with longer stay or poor prognosis could assist healthcare providers in triaging patients when allocating limited healthcare during COVID-19 outbreak.

Elevated Exhaustion Levels of NK and CD8+ T Cells as Indicators for Progression and Prognosis of COVID-19 Disease.

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) induced Coronavirus Disease 2019 (COVID-19) has posed a global threat to public health. The immune system is crucial in defending and eliminating the virus and infected cells. However, immune dysregulation may result in the rapid progression of COVID-19. Here, we evaluated the subsets, phenotypic and functional characteristics of natural killer (NK) and T cells in patients with COVID-19 and their associations with disease severity. Methods: Demographic and clinical data of COVID-19 patients enrolled in Wuhan Union Hospital from February 25 to February 27, 2020, were collected and analyzed. The phenotypic and functional characteristics of NK cells and T cells subsets in circulating blood and serum levels of cytokines were analyzed via flow cytometry. Then the LASSO logistic regression model was employed to predict risk factors for the severity of COVID-19. Results: The counts and percentages of NK cells, CD4+ T cells, CD8+ T cells and NKT cells were significantly reduced in patients with severe symptoms. The cytotoxic CD3-CD56dimCD16+ cell population significantly decreased, while the CD3-CD56dimCD16- part significantly increased in severe COVID-19 patients. More importantly, elevated expression of regulatory molecules, such as CD244 and programmed death-1 (PD-1), on NK cells and T cells, as well as decreased serum cytotoxic effector molecules including perforin and granzyme A, were detected in patients with COVID-19. The serum IL-6, IL-10, and TNF-α were significantly increased in severe patients. Moreover, the CD3-CD56dimCD16- cells were screened out as an influential factor in severe cases by LASSO logistic regression. Conclusions: The functional exhaustion and other subset alteration of NK and T cells may contribute to the progression and improve the prognosis of COVID-19. Surveillance of lymphocyte subsets may in the future enable early screening for signs of critical illness and understanding the pathogenesis of this disease.

The structure-activity relationship of the interactions of SARS-CoV-2 spike glycoproteins with glucuronomannan and sulfated galactofucan from Saccharina japonica.

The SARS-CoV-2 spike glycoproteins (SGPs) and human angiotensin converting enzyme 2 (ACE2) are the two key targets for the prevention and treatment of COVID-19. Host cell surface heparan sulfate (HS) is believed to interact with SARS-CoV-2 SGPs to facilitate host cell entry. In the current study, a series of polysaccharides from Saccharina japonica were prepared to investigate the structure-activity relationship on the binding abilities of polysaccharides (oligosaccharides) to pseudotype particles, including SARS-CoV-2 SGPs, and ACE2 using surface plasmon resonance. Sulfated galactofucan (SJ-D-S-H) and glucuronomannan (Gn) displayed strongly inhibited interaction between SARS-CoV-2 SGPs and heparin while showing negligible inhibition of the interaction between SARS-CoV-2 SGPs and ACE2. The IC50 values of SJ-D-S-H and Gn in blocking heparin SGP binding were 27 and 231 nM, respectively. NMR analysis showed that the structure of SJ-D-S-H featured with a backbone of 1, 3-linked α-L-Fucp residues sulfated at C4 and C2/C4 and 1, 3-linked α-L-Fucp residues sulfated at C4 and branched with 1, 6-linked ß-D-galacto-biose; Gn had a backbone of alternating 1, 4-linked ß-D-GlcAp residues and 1, 2-linked α-D-Manp residues. The sulfated galactofucan and glucuronomannan showed strong binding ability to SARS-CoV-2 SGPs, suggesting that these polysaccharides might be good candidates for preventing and/or treating SARS-CoV-2.