[Objectives]To investigate the clinical effect of Yinhuang Qingfei capsules in the treatment of asymptomatic and mild/common severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.[Methods]A total of 362...[Objectives]To investigate the clinical effect of Yinhuang Qingfei capsules in the treatment of asymptomatic and mild/common severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.[Methods]A total of 362 patients with SARS-CoV-2 infection were divided into the treatment group with 242 patients and control group with 120 patients according to their treatment regimen.The patients in the control group were given standard treatment regimen and those in the treatment group were given Yinhuang Qingfei capsules in addition to the treatment in the control group.The two groups were observed in terms of average length of hospital stay,mean time for nucleic acid clearance,TCM syndrome score,and progression to severe/critical illness,and clinical outcome was compared between the two groups.[Results]There was a significant difference in the overall response rate between the treatment group and the control group[97.52%(236/242)vs 95.00%(114/120),P<0.05].Compared with the control group,the treatment group had significantly shorter length of hospital stay and time for nucleic acid clearance(P<0.05).After 7 days of treatment,both groups had a significant change in TCM syndrome score,and there was a significant difference in TCM syndrome score between the two groups(P<0.05);after 15 days of treatment,both groups had a TCM syndrome score of 0.Progression to severe/critical illness was not observed in either group.[Conclusions]Compared with the standard treatment regimen alone,standard treatment regimen combined with Yinhuang Qingfei capsules can effectively shorten the length of hospital stay and time for nucleic acid clearance and improve TCM symptoms in patients with asymptomatic and mild/common SARS-CoV-2 infection.展开更多
The liver has many significant functions,such as detoxification,the urea cycle,gluconeogenesis,and protein synthesis.Systemic diseases,hypoxia,infections,drugs,and toxins can easily affect the liver,which is extremely...The liver has many significant functions,such as detoxification,the urea cycle,gluconeogenesis,and protein synthesis.Systemic diseases,hypoxia,infections,drugs,and toxins can easily affect the liver,which is extremely sensitive to injury.Systemic infection of severe acute respiratory syndrome coronavirus 2 can cause liver damage.The primary regulator of intracellular pH in the liver is the Na+/H+exchanger(NHE).Physiologically,NHE protects hepatocytes from apoptosis by making the intracellular pH alkaline.Severe acute respiratory syndrome coronavirus 2 increases local angiotensin II levels by binding to angiotensinconverting enzyme 2.In severe cases of coronavirus disease 2019,high angiotensin II levels may cause NHE overstimulation and lipid accumulation in the liver.NHE overstimulation can lead to hepatocyte death.NHE overstimulation may trigger a cytokine storm by increasing proinflammatory cytokines in the liver.Since the release of proinflammatory cytokines such as interleukin-6 increases with NHE activation,the virus may indirectly cause an increase in fibrinogen and D-dimer levels.NHE overstimulation may cause thrombotic events and systemic damage by increasing fibrinogen levels and cytokine release.Also,NHE overstimulation causes an increase in the urea cycle while inhibiting vitamin D synthesis and gluconeogenesis in the liver.Increasing NHE3 activity leads to Na+loading,which impairs the containment and fluidity of bile acid.NHE overstimulation can change the gut microbiota composition by disrupting the structure and fluidity of bile acid,thus triggering systemic damage.Unlike other tissues,tumor necrosis factor-alpha and angiotensin II decrease NHE3 activity in the intestine.Thus,increased luminal Na+leads to diarrhea and cytokine release.Severe acute respiratory syndrome coronavirus 2-induced local and systemic damage can be improved by preventing virus-induced NHE overstimulation in the liver.展开更多
The current corona virus disease 2019 outbreak caused by severe acute respiratory syndrome coronavirus 2 started in Wuhan,China in December 2019 and has put the world on alert.To safeguard Chinese citizens and to stre...The current corona virus disease 2019 outbreak caused by severe acute respiratory syndrome coronavirus 2 started in Wuhan,China in December 2019 and has put the world on alert.To safeguard Chinese citizens and to strengthen global health security,China has made great efforts to control the epidemic.Many in the global community have joined China to limit the epidemic.However,discrimination and prejudice driven by fear or misinformation have been flowing globally,superseding evidence and jeopardizing the anti-severe acute respiratory syndrome coronavirus 2 efforts.We analyze this phenomenon and its underlying causes and suggest practical solutions.展开更多
Background Both population-level epidemiological data and individual-level biological data are needed to control the coronavirus disease 2019(COVID-19)pandemic.Population-level data are widely available and efforts to...Background Both population-level epidemiological data and individual-level biological data are needed to control the coronavirus disease 2019(COVID-19)pandemic.Population-level data are widely available and efforts to combat COVID-19 have generated proliferate data on the biology and immunoresponse to the causative pathogen,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).However,there remains a paucity of systemized data on this subject.Objective In this review,we attempt to extract systemized data on the biology and immuno-response to SARS-CoV-2 from the most up-to-date peer-reviewed studies.We will focus on the biology of the virus and immunological variations that are key for determining long-term immunity,transmission potential,and prognosis.Data Sources and Methods Peer-reviewed articles were sourced from the PubMed database and by snowballing search of selected publications.Search terms included:“Novel Coronavirus”OR“COVID-19”OR“SARS-CoV-2”OR“2019-nCoV”AND“Immunity”OR“Immune Response”OR“Antibody Response”OR“Immunologic Response”.Studies published from December 31,2019 to December 31,2020 were included.To ensure validity,papers in pre-print were excluded.Results Of 2889 identified papers,36 were included.Evidence from these studies suggests early seroconversion in patients infected with SARS-CoV-2.Antibody titers appear to markedly increase two weeks after infection,followed by a plateau.A more robust immune response is seen in patients with severe COVID-19 as opposed to mild or asymptomatic presentations.This trend persists with regard to the length of antibody maintenance.However,overall immunity appears to wane within two to three months post-infection.Conclusion Findings of this study indicate that immune responses to SARS-CoV-2 follow the general pattern of viral infection.Immunity generated through natural infection appears to be short,suggesting a need for long-term efforts to control the pandemic.Antibody testing will be essential to gauge the epidemic and inform decision-making on effective strategies for treatment and prevention.Further research is needed to illustrate immunoglobulin-specific roles and neutralizing antibody activity.展开更多
Aim: To detect risk and preventive factors associated with the Omicron variant infection in university students, a combination of a web-based survey and multivariate logistic regression analysis was introduced as the ...Aim: To detect risk and preventive factors associated with the Omicron variant infection in university students, a combination of a web-based survey and multivariate logistic regression analysis was introduced as the front-line initiatives by the school health practitioners. Design: Questionnaire survey. Methods: The school-wide web-based questionnaire survey was conducted among our university students as a part of the annual health check-up in April, 2023. The positive outcome was confined to the first symptomatic COVID-19 onset during the Omicron variant outbreak. Results: In this self-administered survey, risk or protective associations were merely estimated statistically in university students (n = 5406). In measured factors, karaoke and club/group activities could maintain the statistical significance in adjusted odds ratios (ORs) as relative risk factors, and science course, measles/ rubella (MR) vaccination, and COVID-19 vaccination remained as relative protective factors in adjusted OR analyses. Club/group activities with member gathering and karaoke sing-along sessions in university students may frequently have WHO’s three Cs. These risk factors are still important topics for the infection control of COVID-19 in university students. Together with some recent reports from other researchers, the significant protective role of MR vaccine in our survey warrants further clinical investigation. If the breakthrough infection continuously constitutes the majority of infection, real data in test-negative case-control or web-based questionnaire design continue to be important for statistical analysis to determine the minimal requirement of our strategies which may be equivalent to or replace COVID-19 vaccines.展开更多
Background:Immunocompromised individuals have an increased risk of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection and severe outcomes,but we pay less attention to these people.Athymic nude mice a...Background:Immunocompromised individuals have an increased risk of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection and severe outcomes,but we pay less attention to these people.Athymic nude mice are a murine strain with a spontaneous deficiency of the Foxn1 gene,which can result in thymic degeneration or its absence,leading to immunosuppression and a decrease in the number of T cells,and are widely used in preclinical evaluations of disease in immunocompromised populations.Methods:We investigated the protection of the coronavirus disease 2019(COVID-19)inactivated vaccine(CoronaVac)against the infection of wild-type SARS-CoV-2(WH-09)or Omicron variant utilizing a hybrid-type nude-hACE2 mouse model.Results:Compared with nude-hACE2/W mice,the viral load in the brain and lung tissue of nude-hACE2 mice(nude-hACE2/WV)infected with WH-09 after vaccination significantly decreased,and the histopathological changes were also reduced.The viral load in the brain and lung tissue of nude-hACE2 mice(nude-hACE2/OV)infected with the Omicron variant after vaccination was lower than that in nude-hACE2/O,but histopathological symptoms did not improve significantly.Conclusion:CoronaVac provides some protection against infection of both WH-09 and the Omicron variant in the nude-hACE2 mice.Our findings aimed to provide a reference for vaccination against SARS-CoV-2 in immunocompromised populations.展开更多
Objective:The novel coronavirus(severe acute respiratory syndrome coronavirus 2)has been spreading worldwide since December 2019,posing a serious danger to human health and socioeconomic development.A large number of ...Objective:The novel coronavirus(severe acute respiratory syndrome coronavirus 2)has been spreading worldwide since December 2019,posing a serious danger to human health and socioeconomic development.A large number of clinical trials have revealed that coronavirus disease 2019(COVID-19)results in multi-organ damage including the urogenital system.This study aimed to explore the potential mechanisms of genitourinary damage associated with COVID-19 infection through bioinformatics and molecular simulation analysis.Methods:We used multiple publicly available databases to explore the expression patterns of angiotensin-converting enzyme 2(ACE2),transmembrane serine protease 2(TMPRSS2),and CD147 in major organs in the healthy and disease-specific populations,particularly the genitourinary organs.Single-cell RNA sequencing was used to analyze the cell-specific expression patterns of ACE2,TMPRSS2,CD147,cytokine receptors,and cytokine interacting proteins in genitourinary organs,such as the bladder,kidney,prostate,and testis.Additionally,gene set enrichmentanalysis was used to investigate the relationship between testosterone levels and COVID-19 vulnerability in patients with prostate cancer.Results:The results revealed that ACE2,TMPRSS2,and CD147 were highly expressed in normal urogenital organs.Then,they were also highly expressed in multiple tumors and chronic kidney diseases.Additionally,ACE2,TMPRSS2,and CD147 were significantly expressed in a range of cells in urogenital organs according to single-cell RNA sequencing.Cytokine receptors and cytokine interacting proteins,especially CCL2,JUN,and TIMP1,were commonly highly expressed in urogenital organs.Finally,gene set enrichment analysis results showed that high testosterone levels in prostate cancer patients were significantly related to the JAK-STAT signaling pathway and the Toll-like receptor signaling pathway which were associated with COVID-19.Conclusion:Our study provides new insights into the potential mechanisms of severe acute respiratory syndrome coronavirus 2 damage to urogenital organs from multiple perspectives,which may draw the attention of urologists to COVID-19 and contribute to the development of targeted drugs.展开更多
Increasing evidence reports a greater incidence of stroke in patients with coronavirus disease 2019(COVID-19)than in the non-COVID-19 population and suggests that severe acute respiratory syndrome coronavirus 2(SARS-C...Increasing evidence reports a greater incidence of stroke in patients with coronavirus disease 2019(COVID-19)than in the non-COVID-19 population and suggests that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection represents a risk factor for thromboembolic and acute ischemic stroke.Elderly people have higher risk factors for acute ischemic stroke or embolic vascular events,and advanced age is strongly associated with severe COVID-19 and death.We reported,instead,a case of an ischemic stroke in a young woman during her hospitalization for COVID-19-related pneumonia.A 29-year-old woman presented to the emergency department of the First Affiliated Hospital,Zhejiang University School of Medicine with progressive respiratory distress associated with a 2-day history of fever,nausea,and vomiting.The patient was transferred to the intensive care unit(ICU),where she underwent tracheostomy for mechanical ventilation due to her severe clinical condition and very low arterial partial pressure of oxygen.The nasopharyngeal swab test confirmed SARS-CoV-2 infection.Laboratory tests revealed neutrophilic leukocytosis,prolonged prothrombin time,and elevated D-dimer and fibrinogen levels.Left hemiplegia was reported 18 days later during her stay in the ICU after discontinuation of the sedative medications.Central facial palsy on the left side,dysarthria,and facial droop were present,with complete paralysis of the ipsilateral upper and lower limbs.Computed tomography(CT)of the head and magnetic resonance imaging of the brain confirmed the presence of lesions in the right hemisphere affecting the territories of the anterior and middle cerebral arteries,consistent with ischemic stroke.Pulmonary and splenic infarcts were also found after CT of the chest.The age of the patient and the absence of serious concomitant cardiovascular diseases place the emphasis on the capacity of SARS-CoV-2 infection to be an independent cerebrovascular risk factor.Increased levels of D-dimer and positivity forβ2-glycoprotein antibody could confirm the theory of endothelial activation and hypercoagulability,but other mechanisms-still under discussion-should not be excluded.展开更多
Objective:To evaluate the efficacy and safety of Huashi Baidu Granules(HSBD)in treating patients with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron variant.Methods:A single-center retrospective co...Objective:To evaluate the efficacy and safety of Huashi Baidu Granules(HSBD)in treating patients with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron variant.Methods:A single-center retrospective cohort study was conducted during COVID-19 Omicron epidemic in the Mobile Cabin Hospital of Shanghai New International Expo Center from April 1st to May 23rd,2022.All COVID-19 patients with asymptomatic or mild infection were assigned to the treatment group(HSBD users)and the control group(non-HSBD users).After propensity score matching in a 1:1 ratio,496 HSBD users of treatment group were matched by propensity score to 496 non-HSBD users.Patients in the treatment group were administrated HSBD(5 g/bag)orally for 1 bag twice a day for 7 consecutive days.Patients in the control group received standard care and routine treatment.The primary outcomes were the negative conversion time of nucleic acid and negative conversion rate at day 7.Secondary outcomes included the hospitalized days,the time of the first nucleic acid negative conversion,and new-onset symptoms in asymptomatic patients.Adverse events(AEs)that occurred during the study were recorded.Further subgroup analysis was conducted in vaccinated(378 HSBD users and 390 non-HSBD users)and unvaccinated patients(118 HSBD users and 106 non-HSBD users).Results:The median negative conversion time of nucleic acid in the treatment group was significantly shortened than the control group[3 days(IQR:2-5 days)vs.5 days(IQR:4-6 days);P<0.01].The negative conversion rate of nucleic acid in the treatment group were significantly higher than those in the control group at day 7(91.73%vs.86.90%,P=0.014).Compared with the control group,the hospitalized days in the treatment group were significantly reduced[10 days(IQR:8-11 days)vs.11 days(IQR:10.25-12 days);P<0.01].The time of the first nucleic acid negative conversion had significant differences between the treatment and control groups[3 days(IQR:2-4 days)vs.5 days(IQR:4-6 days);P<0.01].The incidence of new-onset symptoms including cough,pharyngalgia,expectoration and fever in the treatment group were lower than the control group(P<0.05 or P<0.01).In the vaccinated patients,the median negative conversion time and hospitalized days were significantly shorter than the control group after HSDB treatment[3days(IQR:2-5days)vs.5 days(IQR:4-6 days),P<0.01;10 days(IQR:8-11 days)vs.11 days(IQR:10-12 days),P<0.01].In the unvaccinatedpatients,HSBD treatment efficiently shorten the median negative conversion time and hospitalized days[4 days(IQR:2-6 days)vs.5 days(IQR:4-7 days),P<0.01;10.5 days(IQR:8.75-11 days)vs.11.0 days(IQR:10.75-13 days);P<0.01].No serious AEs were reported during the study.Conclusion:HSBD treatment significantly shortened the negative conversion time of nuclear acid,the length of hospitalization,and the time of the first nucleic acid negative conversion in patients infectedwith SARS-COV-2Omicronvariant(Trial registry No.ChiCTR2200060472).展开更多
The continuous emergence of new severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants meansthere is a need to explore additional strategies to develop broad-spectrum vaccines or therapeutics for individu...The continuous emergence of new severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants meansthere is a need to explore additional strategies to develop broad-spectrum vaccines or therapeutics for individuals remaining at risk of coronavirus disease 2019(COVID-19).Neutralizing monoclonal antibody(mAb)that binds to theconserved S2 subunit of the SARS-CoV-2 spike(S)protein alone,or in combination with mAb that binds to the receptor-binding domain(RBD)of S protein,might be effective in eliciting protection from infection by a variety of SARS-CoV2 variants.Using high-throughput single-cell immunoglobulin sequencing of B cells from COVID-19-convalescent donors,we identified a high-affinity S2-specific mAb-39,that could inhibit original SARS-CoV-2 strain,Omicron BA.1,BA.2.86,BA.4,BA.5,and EG.5.1 S protein-mediated membrane fusion,leading to the neutralization of these pseudoviralinfections.Moreover,mAb-39 could also improve the neutralizing activity of anti-RBD antibody against the highlyneutralization-resistant Omicron variants.Molecular docking and point mutation analyses revealed that mAb-39 recognized epitopes within the conserved upstream region of the heptad repeat 2(HR2)motif of the S2 subunit.Collectively,these findings demonstrate that targeting the conserved upstream region of the HR2 motif(e.g.,using mAbs)provides anovel strategy for preventing the infection of SARS-CoV-2 and its variants.展开更多
基金Supported by the Science and Medicine Joint Fund Project of Natural Science Foundation of Hunan Province(2022JJ80001).
文摘[Objectives]To investigate the clinical effect of Yinhuang Qingfei capsules in the treatment of asymptomatic and mild/common severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.[Methods]A total of 362 patients with SARS-CoV-2 infection were divided into the treatment group with 242 patients and control group with 120 patients according to their treatment regimen.The patients in the control group were given standard treatment regimen and those in the treatment group were given Yinhuang Qingfei capsules in addition to the treatment in the control group.The two groups were observed in terms of average length of hospital stay,mean time for nucleic acid clearance,TCM syndrome score,and progression to severe/critical illness,and clinical outcome was compared between the two groups.[Results]There was a significant difference in the overall response rate between the treatment group and the control group[97.52%(236/242)vs 95.00%(114/120),P<0.05].Compared with the control group,the treatment group had significantly shorter length of hospital stay and time for nucleic acid clearance(P<0.05).After 7 days of treatment,both groups had a significant change in TCM syndrome score,and there was a significant difference in TCM syndrome score between the two groups(P<0.05);after 15 days of treatment,both groups had a TCM syndrome score of 0.Progression to severe/critical illness was not observed in either group.[Conclusions]Compared with the standard treatment regimen alone,standard treatment regimen combined with Yinhuang Qingfei capsules can effectively shorten the length of hospital stay and time for nucleic acid clearance and improve TCM symptoms in patients with asymptomatic and mild/common SARS-CoV-2 infection.
文摘The liver has many significant functions,such as detoxification,the urea cycle,gluconeogenesis,and protein synthesis.Systemic diseases,hypoxia,infections,drugs,and toxins can easily affect the liver,which is extremely sensitive to injury.Systemic infection of severe acute respiratory syndrome coronavirus 2 can cause liver damage.The primary regulator of intracellular pH in the liver is the Na+/H+exchanger(NHE).Physiologically,NHE protects hepatocytes from apoptosis by making the intracellular pH alkaline.Severe acute respiratory syndrome coronavirus 2 increases local angiotensin II levels by binding to angiotensinconverting enzyme 2.In severe cases of coronavirus disease 2019,high angiotensin II levels may cause NHE overstimulation and lipid accumulation in the liver.NHE overstimulation can lead to hepatocyte death.NHE overstimulation may trigger a cytokine storm by increasing proinflammatory cytokines in the liver.Since the release of proinflammatory cytokines such as interleukin-6 increases with NHE activation,the virus may indirectly cause an increase in fibrinogen and D-dimer levels.NHE overstimulation may cause thrombotic events and systemic damage by increasing fibrinogen levels and cytokine release.Also,NHE overstimulation causes an increase in the urea cycle while inhibiting vitamin D synthesis and gluconeogenesis in the liver.Increasing NHE3 activity leads to Na+loading,which impairs the containment and fluidity of bile acid.NHE overstimulation can change the gut microbiota composition by disrupting the structure and fluidity of bile acid,thus triggering systemic damage.Unlike other tissues,tumor necrosis factor-alpha and angiotensin II decrease NHE3 activity in the intestine.Thus,increased luminal Na+leads to diarrhea and cytokine release.Severe acute respiratory syndrome coronavirus 2-induced local and systemic damage can be improved by preventing virus-induced NHE overstimulation in the liver.
文摘The current corona virus disease 2019 outbreak caused by severe acute respiratory syndrome coronavirus 2 started in Wuhan,China in December 2019 and has put the world on alert.To safeguard Chinese citizens and to strengthen global health security,China has made great efforts to control the epidemic.Many in the global community have joined China to limit the epidemic.However,discrimination and prejudice driven by fear or misinformation have been flowing globally,superseding evidence and jeopardizing the anti-severe acute respiratory syndrome coronavirus 2 efforts.We analyze this phenomenon and its underlying causes and suggest practical solutions.
文摘Background Both population-level epidemiological data and individual-level biological data are needed to control the coronavirus disease 2019(COVID-19)pandemic.Population-level data are widely available and efforts to combat COVID-19 have generated proliferate data on the biology and immunoresponse to the causative pathogen,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).However,there remains a paucity of systemized data on this subject.Objective In this review,we attempt to extract systemized data on the biology and immuno-response to SARS-CoV-2 from the most up-to-date peer-reviewed studies.We will focus on the biology of the virus and immunological variations that are key for determining long-term immunity,transmission potential,and prognosis.Data Sources and Methods Peer-reviewed articles were sourced from the PubMed database and by snowballing search of selected publications.Search terms included:“Novel Coronavirus”OR“COVID-19”OR“SARS-CoV-2”OR“2019-nCoV”AND“Immunity”OR“Immune Response”OR“Antibody Response”OR“Immunologic Response”.Studies published from December 31,2019 to December 31,2020 were included.To ensure validity,papers in pre-print were excluded.Results Of 2889 identified papers,36 were included.Evidence from these studies suggests early seroconversion in patients infected with SARS-CoV-2.Antibody titers appear to markedly increase two weeks after infection,followed by a plateau.A more robust immune response is seen in patients with severe COVID-19 as opposed to mild or asymptomatic presentations.This trend persists with regard to the length of antibody maintenance.However,overall immunity appears to wane within two to three months post-infection.Conclusion Findings of this study indicate that immune responses to SARS-CoV-2 follow the general pattern of viral infection.Immunity generated through natural infection appears to be short,suggesting a need for long-term efforts to control the pandemic.Antibody testing will be essential to gauge the epidemic and inform decision-making on effective strategies for treatment and prevention.Further research is needed to illustrate immunoglobulin-specific roles and neutralizing antibody activity.
文摘Aim: To detect risk and preventive factors associated with the Omicron variant infection in university students, a combination of a web-based survey and multivariate logistic regression analysis was introduced as the front-line initiatives by the school health practitioners. Design: Questionnaire survey. Methods: The school-wide web-based questionnaire survey was conducted among our university students as a part of the annual health check-up in April, 2023. The positive outcome was confined to the first symptomatic COVID-19 onset during the Omicron variant outbreak. Results: In this self-administered survey, risk or protective associations were merely estimated statistically in university students (n = 5406). In measured factors, karaoke and club/group activities could maintain the statistical significance in adjusted odds ratios (ORs) as relative risk factors, and science course, measles/ rubella (MR) vaccination, and COVID-19 vaccination remained as relative protective factors in adjusted OR analyses. Club/group activities with member gathering and karaoke sing-along sessions in university students may frequently have WHO’s three Cs. These risk factors are still important topics for the infection control of COVID-19 in university students. Together with some recent reports from other researchers, the significant protective role of MR vaccine in our survey warrants further clinical investigation. If the breakthrough infection continuously constitutes the majority of infection, real data in test-negative case-control or web-based questionnaire design continue to be important for statistical analysis to determine the minimal requirement of our strategies which may be equivalent to or replace COVID-19 vaccines.
基金the National Key Research and Development Project of China,Grant/Award Number:2020YFA0707600。
文摘Background:Immunocompromised individuals have an increased risk of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection and severe outcomes,but we pay less attention to these people.Athymic nude mice are a murine strain with a spontaneous deficiency of the Foxn1 gene,which can result in thymic degeneration or its absence,leading to immunosuppression and a decrease in the number of T cells,and are widely used in preclinical evaluations of disease in immunocompromised populations.Methods:We investigated the protection of the coronavirus disease 2019(COVID-19)inactivated vaccine(CoronaVac)against the infection of wild-type SARS-CoV-2(WH-09)or Omicron variant utilizing a hybrid-type nude-hACE2 mouse model.Results:Compared with nude-hACE2/W mice,the viral load in the brain and lung tissue of nude-hACE2 mice(nude-hACE2/WV)infected with WH-09 after vaccination significantly decreased,and the histopathological changes were also reduced.The viral load in the brain and lung tissue of nude-hACE2 mice(nude-hACE2/OV)infected with the Omicron variant after vaccination was lower than that in nude-hACE2/O,but histopathological symptoms did not improve significantly.Conclusion:CoronaVac provides some protection against infection of both WH-09 and the Omicron variant in the nude-hACE2 mice.Our findings aimed to provide a reference for vaccination against SARS-CoV-2 in immunocompromised populations.
文摘Objective:The novel coronavirus(severe acute respiratory syndrome coronavirus 2)has been spreading worldwide since December 2019,posing a serious danger to human health and socioeconomic development.A large number of clinical trials have revealed that coronavirus disease 2019(COVID-19)results in multi-organ damage including the urogenital system.This study aimed to explore the potential mechanisms of genitourinary damage associated with COVID-19 infection through bioinformatics and molecular simulation analysis.Methods:We used multiple publicly available databases to explore the expression patterns of angiotensin-converting enzyme 2(ACE2),transmembrane serine protease 2(TMPRSS2),and CD147 in major organs in the healthy and disease-specific populations,particularly the genitourinary organs.Single-cell RNA sequencing was used to analyze the cell-specific expression patterns of ACE2,TMPRSS2,CD147,cytokine receptors,and cytokine interacting proteins in genitourinary organs,such as the bladder,kidney,prostate,and testis.Additionally,gene set enrichmentanalysis was used to investigate the relationship between testosterone levels and COVID-19 vulnerability in patients with prostate cancer.Results:The results revealed that ACE2,TMPRSS2,and CD147 were highly expressed in normal urogenital organs.Then,they were also highly expressed in multiple tumors and chronic kidney diseases.Additionally,ACE2,TMPRSS2,and CD147 were significantly expressed in a range of cells in urogenital organs according to single-cell RNA sequencing.Cytokine receptors and cytokine interacting proteins,especially CCL2,JUN,and TIMP1,were commonly highly expressed in urogenital organs.Finally,gene set enrichment analysis results showed that high testosterone levels in prostate cancer patients were significantly related to the JAK-STAT signaling pathway and the Toll-like receptor signaling pathway which were associated with COVID-19.Conclusion:Our study provides new insights into the potential mechanisms of severe acute respiratory syndrome coronavirus 2 damage to urogenital organs from multiple perspectives,which may draw the attention of urologists to COVID-19 and contribute to the development of targeted drugs.
文摘Increasing evidence reports a greater incidence of stroke in patients with coronavirus disease 2019(COVID-19)than in the non-COVID-19 population and suggests that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection represents a risk factor for thromboembolic and acute ischemic stroke.Elderly people have higher risk factors for acute ischemic stroke or embolic vascular events,and advanced age is strongly associated with severe COVID-19 and death.We reported,instead,a case of an ischemic stroke in a young woman during her hospitalization for COVID-19-related pneumonia.A 29-year-old woman presented to the emergency department of the First Affiliated Hospital,Zhejiang University School of Medicine with progressive respiratory distress associated with a 2-day history of fever,nausea,and vomiting.The patient was transferred to the intensive care unit(ICU),where she underwent tracheostomy for mechanical ventilation due to her severe clinical condition and very low arterial partial pressure of oxygen.The nasopharyngeal swab test confirmed SARS-CoV-2 infection.Laboratory tests revealed neutrophilic leukocytosis,prolonged prothrombin time,and elevated D-dimer and fibrinogen levels.Left hemiplegia was reported 18 days later during her stay in the ICU after discontinuation of the sedative medications.Central facial palsy on the left side,dysarthria,and facial droop were present,with complete paralysis of the ipsilateral upper and lower limbs.Computed tomography(CT)of the head and magnetic resonance imaging of the brain confirmed the presence of lesions in the right hemisphere affecting the territories of the anterior and middle cerebral arteries,consistent with ischemic stroke.Pulmonary and splenic infarcts were also found after CT of the chest.The age of the patient and the absence of serious concomitant cardiovascular diseases place the emphasis on the capacity of SARS-CoV-2 infection to be an independent cerebrovascular risk factor.Increased levels of D-dimer and positivity forβ2-glycoprotein antibody could confirm the theory of endothelial activation and hypercoagulability,but other mechanisms-still under discussion-should not be excluded.
基金Supported by Traditional Chinese Medicine Emergency Project on Novel Coronavirus-Infected Pneumonia of State Administration of Traditional Chinese Medicine (No. 2022ZYLCYJ05-4)Shanghai Key Clinical Specialty Project (No. shslczdzk04401)+1 种基金National Traditional Chinese Medicine Emergency Medical Rescue Base Construction Project [No. ZY(2021-2023)-0101-01]National Traditional Chinese Medicine Multidisciplinary Cross Innovation Team Project (No. ZYYCXTD-D-202203)
文摘Objective:To evaluate the efficacy and safety of Huashi Baidu Granules(HSBD)in treating patients with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron variant.Methods:A single-center retrospective cohort study was conducted during COVID-19 Omicron epidemic in the Mobile Cabin Hospital of Shanghai New International Expo Center from April 1st to May 23rd,2022.All COVID-19 patients with asymptomatic or mild infection were assigned to the treatment group(HSBD users)and the control group(non-HSBD users).After propensity score matching in a 1:1 ratio,496 HSBD users of treatment group were matched by propensity score to 496 non-HSBD users.Patients in the treatment group were administrated HSBD(5 g/bag)orally for 1 bag twice a day for 7 consecutive days.Patients in the control group received standard care and routine treatment.The primary outcomes were the negative conversion time of nucleic acid and negative conversion rate at day 7.Secondary outcomes included the hospitalized days,the time of the first nucleic acid negative conversion,and new-onset symptoms in asymptomatic patients.Adverse events(AEs)that occurred during the study were recorded.Further subgroup analysis was conducted in vaccinated(378 HSBD users and 390 non-HSBD users)and unvaccinated patients(118 HSBD users and 106 non-HSBD users).Results:The median negative conversion time of nucleic acid in the treatment group was significantly shortened than the control group[3 days(IQR:2-5 days)vs.5 days(IQR:4-6 days);P<0.01].The negative conversion rate of nucleic acid in the treatment group were significantly higher than those in the control group at day 7(91.73%vs.86.90%,P=0.014).Compared with the control group,the hospitalized days in the treatment group were significantly reduced[10 days(IQR:8-11 days)vs.11 days(IQR:10.25-12 days);P<0.01].The time of the first nucleic acid negative conversion had significant differences between the treatment and control groups[3 days(IQR:2-4 days)vs.5 days(IQR:4-6 days);P<0.01].The incidence of new-onset symptoms including cough,pharyngalgia,expectoration and fever in the treatment group were lower than the control group(P<0.05 or P<0.01).In the vaccinated patients,the median negative conversion time and hospitalized days were significantly shorter than the control group after HSDB treatment[3days(IQR:2-5days)vs.5 days(IQR:4-6 days),P<0.01;10 days(IQR:8-11 days)vs.11 days(IQR:10-12 days),P<0.01].In the unvaccinatedpatients,HSBD treatment efficiently shorten the median negative conversion time and hospitalized days[4 days(IQR:2-6 days)vs.5 days(IQR:4-7 days),P<0.01;10.5 days(IQR:8.75-11 days)vs.11.0 days(IQR:10.75-13 days);P<0.01].No serious AEs were reported during the study.Conclusion:HSBD treatment significantly shortened the negative conversion time of nuclear acid,the length of hospitalization,and the time of the first nucleic acid negative conversion in patients infectedwith SARS-COV-2Omicronvariant(Trial registry No.ChiCTR2200060472).
基金funded bythe National Natural Science Foundation of China(81972753,32170712,and 32170937)R&D Program of Guangzhou National Laboratory(SRPG22-003)+6 种基金the China Postdoctoral Science Foundation(2019M663093)Prevention and Control ofCOVID-2019 Research Program in University of GuangdongProvince(2020KZDZX1176)the Science and TechnologyProgram of Guangdong Province,China(2020A1515110410and 2021A1515010917)the Guangdong Medical Scienceand Technology Research Foundation(A2021336)ShenzhenKey Laboratory Foundation(ZDSYS20200811143757022)theShenzhen Science and Technology Basic Research Program(JCYJ20180507182203049 and JCYJ20230807142815034)and the Shenzhen University(SZU)Top Ranking Project(86000000210).
文摘The continuous emergence of new severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants meansthere is a need to explore additional strategies to develop broad-spectrum vaccines or therapeutics for individuals remaining at risk of coronavirus disease 2019(COVID-19).Neutralizing monoclonal antibody(mAb)that binds to theconserved S2 subunit of the SARS-CoV-2 spike(S)protein alone,or in combination with mAb that binds to the receptor-binding domain(RBD)of S protein,might be effective in eliciting protection from infection by a variety of SARS-CoV2 variants.Using high-throughput single-cell immunoglobulin sequencing of B cells from COVID-19-convalescent donors,we identified a high-affinity S2-specific mAb-39,that could inhibit original SARS-CoV-2 strain,Omicron BA.1,BA.2.86,BA.4,BA.5,and EG.5.1 S protein-mediated membrane fusion,leading to the neutralization of these pseudoviralinfections.Moreover,mAb-39 could also improve the neutralizing activity of anti-RBD antibody against the highlyneutralization-resistant Omicron variants.Molecular docking and point mutation analyses revealed that mAb-39 recognized epitopes within the conserved upstream region of the heptad repeat 2(HR2)motif of the S2 subunit.Collectively,these findings demonstrate that targeting the conserved upstream region of the HR2 motif(e.g.,using mAbs)provides anovel strategy for preventing the infection of SARS-CoV-2 and its variants.