[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
To evaluate the role of murine fibrinogen like protein 2 (mfgl2) /fibroleukin in lung impairment in Severe acute respiratory syndrome (SARS), a murine SARS model induced by Murine hepatitis virus strain 3 (MHV-3) thro...To evaluate the role of murine fibrinogen like protein 2 (mfgl2) /fibroleukin in lung impairment in Severe acute respiratory syndrome (SARS), a murine SARS model induced by Murine hepatitis virus strain 3 (MHV-3) through trachea was established. Impressively, all the animals developed interstitial pneumonia with extensive hyaline membranes formation within alveoli, and presence of micro-vascular thrombosis in the pulmonary vessels. MHV-3 nucleocapsid gene transcripts were identified in multiple organs including lungs, spleen etc. As a representative proinflammatory gene, mfgl2 prothrombinase expression was evident in terminal and respiratory bronchioles, alveolar epithelia and infiltrated cells in the lungs associated with fibrin deposition and micro-vascular thrombosis. In summary, the established murine SARS model could mimic the pathologic characteristics of lungs in patients with SARS. Besides the physical damages due to virus replication in organs, the up-regulation of novel gene mfgl2 in lungs may play a vital role in the development of SARS associated lung damage.展开更多
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) is a truly novel, multifaceted disease that has negatively impacted the lives of many including the pregnant women. We present a 34-year-old pregnant patien...Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) is a truly novel, multifaceted disease that has negatively impacted the lives of many including the pregnant women. We present a 34-year-old pregnant patient at 35 weeks with SARS-COV-2 requiring emergent cesarean section under general endotracheal anesthesia and a prolonged postoperative course in the ICU with multiple end organ function derangement of this disease. After nearly 1 month, she was discharged home. Her baby did not have any manifestations of SARS-COV-2 and was able to go home after 5 days.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
The new coronavirus (SARS-CoV-2) broke out in Wuhan in China in December 2019, causing severe pneumonia and deaths, soon in March 2020, it reached pandemic level, affecting several countries including Brazil. The dise...The new coronavirus (SARS-CoV-2) broke out in Wuhan in China in December 2019, causing severe pneumonia and deaths, soon in March 2020, it reached pandemic level, affecting several countries including Brazil. The disease was named COVID-19, with characteristics of most infected having mild and moderate symptoms and a part severe symptom. The disease has already reached 158 ethnic groups, which have high vulnerability and limited access to health services. The objective is to investigate the clinical and spatial characteristics of Severe Acute Respiratory Syndrome of COVID-19 in the indigenous peoples of Brazil. It is an epidemiological, cross-sectional, analytical ecological study, based on data from the OpenDataSUS platform from 01/01/2020 to 31/08/2020. Profile variables, signs and symptoms and risk factors/comorbidities. The data were analyzed by Bioestat 5.3. There were 1,207 cases and 470 deaths. Profile: male gender (59.48%) means age 53 years. Signs and symptoms: fever (74.23%), cough (77.71%), sore throat (35.62%), dyspnea (69.34%), respiratory discomfort (62.80%), O<sub>2</sub> saturation < 95% (56.42%);and associated with mortality: dyspnea (80.0%) and O<sub>2</sub> saturation < 95% (69.36%). Risk factors and comorbidities (45.89%) were associated with deaths (54.04%). About comorbidities, chronic cardiovascular diseases represented (18.97%) and Diabetes Mellitus (18.97%), and associated with deaths: Chronic Cardiovascular Disease (24.46%). Being admitted to the ICU has a risk of death in (OR-3.96- < 0.0001-CI-2913/5383) followed by not being vaccinated against influenza (OR-1.85- < 0.0001-CI-1358/2528). The public and health policies of Brazil should be directed to control the dissemination of COVID-19 in this population, that COVID-19 evolves in the same intensity, however, the indigenous have vulnerabilities that can increase the impact of the pandemic in this population.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
The outbreak of coronavirus disease 2019(COVID-19)caused by the novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has become a pandemic.SARS-CoV-2 vaccination is currently being actively promoted worldw...The outbreak of coronavirus disease 2019(COVID-19)caused by the novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has become a pandemic.SARS-CoV-2 vaccination is currently being actively promoted worldwide as a promising measure to combat the pandemic.However,human immunodeficiency virus(HIV)-infected individuals who manifest varying degrees of immunodeficiency and chronic inflammation may require special consideration with regards to vaccine types and the timing of immunization depending on specific clinical situations.The present recommendation provides a reference for SARS-CoV-2 vaccination in HIV-infected patients.展开更多
Coronavirus disease 2019(COVID-19),caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has caused millions of infections and deaths worldwide since its emergence in December 2019.As there is litt...Coronavirus disease 2019(COVID-19),caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has caused millions of infections and deaths worldwide since its emergence in December 2019.As there is little or no natural immunity in the human population or specific anti-COVID-19 drugs,researchers from the government,academia and industry are developing vaccines at an unprecedented speed to halt the pandemic.In this review,the results of animal experiments and clinical trials on several vaccine technical platforms are summarized,and several challenges are also discussed to further promote the development,evaluation and application of vaccines during the challenging situation of the global pandemic.展开更多
In November 2002, a new disease-severe acute respiratory syndrome, or SARS-first emerged in Guangdong Province, China. Subsequently, it spread to more than 30 countries worldwide.1 The causative agent was identified t...In November 2002, a new disease-severe acute respiratory syndrome, or SARS-first emerged in Guangdong Province, China. Subsequently, it spread to more than 30 countries worldwide.1 The causative agent was identified to be a previously unknown member of the coronaviridae family, and was named SARS coronavirus (SARS-CoV). SARS coronavirus is a large, enveloped, positive-sense RNA virus. The genome is about 30 kb, which is predicted to contain 14 functional open reading frames (ORFs). Two large 5'-terminal ORFs (1a and 1b) encode the polymerases that are required for viral RNA synthesis. The remaining twelve ORFs encode four structural proteins [spike protein (S), envelope protein (E), membrane protein (M) and nucleocapsid protein (N)] and eight accessory proteins. Though the SARS-CoV genome is clear, a great deal more work will be required to develop an efficient vaccine and effective drugs. Neutralizing antibodies were detectable in the convalescent sera of SARS patients, and sera from recovered patients could be used to treat newly infected individuals. The data suggest that protective humoral immunity is achievable and that vaccines can be developed for prevention of SARS. In this article, we review and discuss progress towards development of a SARS vaccine.展开更多
Since the end of 2019,coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has spread worldwide.The RNA genome of SARS-CoV-2,which is highly infectious and prone to ra...Since the end of 2019,coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has spread worldwide.The RNA genome of SARS-CoV-2,which is highly infectious and prone to rapid mutation,encodes both structural and non-structural proteins.Vaccination is currently the only effective method to prevent COVID-19,and structural proteins are critical targets for vaccine development.Currently,many vaccines are in clinical trials or are already on the market.This review highlights ongoing advances in the design of prophylactic or therapeutic vaccines against COVID-19,including viral vector vaccines,DNA vaccines,RNA vaccines,live-attenuated vaccines,inactivated virus vaccines,recombinant protein vaccines and bionic nanoparticle vaccines.In addition to traditional inactivated virus vaccines,some novel vaccines based on viral vectors,nanoscience and synthetic biology also play important roles in combating COVID-19.However,many challenges persist in ongoing clinical trials.展开更多
Since June 2020,the re-emergence of coronavirus disease 2019(COVID-19)epidemics in parts of China was linked to the cold chain,which attracted extensive attention and heated discussions from the public.According to th...Since June 2020,the re-emergence of coronavirus disease 2019(COVID-19)epidemics in parts of China was linked to the cold chain,which attracted extensive attention and heated discussions from the public.According to the typical characteristics of these epidemics,we speculated a possible route of transmission from cold chain to human.A series of factors in the supply chain contributed to the epidemics if the cold chain were contaminated by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),such as temperature,humidity,personal hygiene/protection,and disinfection.The workers who worked in the cold chain at the receiving end faced a higher risk of being infected when they were not well protected.Facing the difficult situation,China put forward targeted and powerful countermeasures to block the cold chain-related risk.However,in the context of the unstable pandemic situation globally,the risk of the cold chain needs to be recognized and evaluated seriously.Hence,in this review,we reviewed the cold chain-related epidemics in China,analyzed the possible mechanisms,introduced the Chinese experience,and suggested coping strategies for the global epidemic prevention and control.展开更多
Background The rapid transmission and high mortality rate made severe acute respiratory syndrome (SARS) a global threat for which no efficacious therapy is available now. Without sufficient knowledge about the SARS c...Background The rapid transmission and high mortality rate made severe acute respiratory syndrome (SARS) a global threat for which no efficacious therapy is available now. Without sufficient knowledge about the SARS coronavirus (SARS-CoV), it is impossible to define the candidate for the anti-SARS targets. The putative non-structural protein 2 (nsp2) (3CL pro , following the nomenclature by Gao et al, also known as nsp5 in Snidjer et al) of SARS-CoV plays an important role in viral transcription and replication, and is an attractive target for anti-SARS drug development, so we carried on this study to have an insight into putative polymerase nsp2 of SARS-CoV Guangdong (GD) strain. Methods The SARS-CoV strain was isolated from a SARS patient in Guangdong, China, and cultured in Vero E6 cells. The nsp2 gene was amplified by reverse transcription-polymerase chain reaction (RT-PCR) and cloned into eukaryotic expression vector pCI-neo (pCI-neo/nsp2). Then the recombinant eukaryotic expression vector pCI-neo/nsp2 was transfected into COS-7 cells using lipofectin reagent to express the nsp2 protein. The expressive protein of SARS-CoV nsp2 was analyzed by 7% sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE). The nucleotide sequence and protein sequence of GD nsp2 were compared with that of other SARS-CoV strains by nucleotide-nucleotide basic local alignment search tool (BLASTN) and protein-protein basic local alignment search tool (BLASTP) to investigate its variance trend during the transmission. The secondary structure of GD strain and that of other strains were predicted by Garnier-Osguthorpe-Robson (GOR) Secondary Structure Prediction. Three-dimensional-PSSM Protein Fold Recognition (Threading) Server was employed to construct the three-dimensional model of the nsp2 protein.Results The putative polymerase nsp2 gene of GD strain was amplified by RT-PCR. The eukaryotic expression vector (pCI-neo/nsp2) was constructed and expressed the protein in COS-7 cells successfully. The result of sequencing and sequence comparison with other SARS-CoV strains showed that nsp2 gene was relatively conservative during the transmission and total five base sites mutated in about 100 strains investigated, three of which in the early and middle phases caused synonymous mutation, and another two base sites variation in the late phase resulted in the amino acid substitutions and secondary structure changes. The three-dimensional structure of the nsp2 protein was successfully constructed. Conclusions The results suggest that polymerase nsp2 is relatively stable during the phase of epidemic. The amino acid and secondary structure change may be important for viral infection. The fact that majority of single nucleotide variations (SNVs) are predicted to cause synonymous, as well as the result of low mutation rate of nsp2 gene in the epidemic variations, indicates that the nsp2 is conservative and could be a target for anti-SARS drugs. The three-dimensional structure result indicates that the nsp2 protein of GD strain is high homologous with 3CL pro of SARS-CoV urbani strain, 3CL pro of transmissible gastroenteritis virus and 3CL pro of human coronavirus 229E strain, which further suggests that nsp2 protein of GD strain possesses the activity of 3CL pro .展开更多
Background:Mitochondria have been shown to play vital roles during severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection and coronavirus disease 2019(COVID-19)development.Currently,it is unclear whether...Background:Mitochondria have been shown to play vital roles during severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection and coronavirus disease 2019(COVID-19)development.Currently,it is unclear whether mitochondrial DNA(mtDNA)variants,which define mtDNA haplogroups and determine oxidative phosphorylation performance and reactive oxygen species production,are associated with COVID-19 risk.Methods:A population-based case-control study was conducted to compare the distribution of mtDNA variations defining mtDNA haplogroups between healthy controls(n=615)and COVID-19 patients(n=536).COVID-19 patients were diagnosed based on molecular diagnostics of the viral genome by qPCR and chest X-ray or computed tomography scanning.The exclusion criteria for the healthy controls were any history of disease in the month preceding the study assessment.MtDNA variants defining mtDNA haplogroups were identified by PCR-RFLPs and HVS-I sequencing and determined based on mtDNA phylogenetic analysis using Mitomap Phylogeny.Student’s t-test was used for continuous variables,and Pearson’s chi-squared test or Fisher’s exact test was used for categorical variables.To assess the independent effect of each mtDNA variant defining mtDNA haplogroups,multivariate logistic regression analyses were performed to calculate the odds ratios(OR)and 95%confidence intervals(CI)with adjustments for possible confounding factors of age,sex,smoking and diseases(including cardiopulmonary diseases,diabetes,obesity and hypertension)as determined through clinical and radiographic examinations.Results:Multivariate logistic regression analyses revealed that the most common investigated mtDNA variations(>10%in the control population)at C5178 a(in NADH dehydrogenase subunit 2 gene,ND2)and A249 d(in the displacement loop region,D-loop)/T6392 C(in cytochrome c oxidase I gene,CO1)/G10310 A(in ND3)were associated with a reduced risk of severe COVID-19(OR=0.590,95%CI 0.428–0.814,P=0.001;and OR=0.654,95%CI 0.457–0.936,P=0.020,respectively),while A4833 G(ND2),A4715 G(ND2),T3394 C(ND1)and G5417 A(ND2)/C16257 a(D-loop)/C16261 T(D-loop)were related to an increased risk of severe COVID-19(OR=2.336,95%CI 1.179–4.608,P=0.015;OR=2.033,95%CI 1.242–3.322,P=0.005;OR=3.040,95%CI 1.522–6.061,P=0.002;and OR=2.890,95%CI 1.199–6.993,P=0.018,respectively).Conclusions:This is the first study to explore the association of mtDNA variants with individual’s risk of developing severe COVID-19.Based on the case–control study,we concluded that the common mtDNA variants at C5178 a and A249 d/T6392 C/G10310 A might contribute to an individual’s resistance to developing severe COVID-19,whereas A4833 G,A4715 G,T3394 C and G5417 A/C16257 a/C16261 T might increase an individual’s risk of developing severe COVID-19.展开更多
Severe Acute Respiratory Syndrome Coronavirus 1(SARS-CoV-1)infections almost always caused overt symptoms,so effective case and contact management enabled its effective eradication within months.However,Severe Acute R...Severe Acute Respiratory Syndrome Coronavirus 1(SARS-CoV-1)infections almost always caused overt symptoms,so effective case and contact management enabled its effective eradication within months.However,Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2)usually causes only mild symptoms,so transmission chains may grow to include several individuals before at least one index case becomes ill enough to self-report for diagnosis and care.Here,simple mathematical models were developed to evaluate the implications of delayed index case detection for retrospective contact tracing and management responses.Specifically,these simulations illustrate how:(1)Contact tracing and management may effectively contain most but not all large SARS-CoV-2 clusters arising at foci with high reproduction numbers because rapidly expanding transmission chains ensure at least one overtly symptomatic index case occurs within two viral generations a week or less apart.(2)However,lower reproduction numbers give rise to thinner transmission chains extending through longer sequences of non-reporting asymptomatic and paucisymptomatic individuals,often spanning three or more viral generations(2 weeks of transmission)before an overtly symptomatic index case occurs.(3)Consequently,it is not always possible to fully trace and contain such long,thin transmission chains,so the community transmission they give rise to is underrepresented in surveillance data.(4)Wherever surveillance systems are weak and/or transmission proceeds within population groups with lower rates of overt clinical symptoms and/or self-reporting,case and contact management effectiveness may be more severely limited,even at the higher reproduction numbers associated with larger outbreaks.(5)Because passive surveillance platforms may be especially slow to detect the thinner transmission chains that occur at low reproduction numbers,establishing satisfactory confidence of elimination may require that no confirmed cases are detected for two full months,throughout which presumptive preventative measures must be maintained to ensure complete collapse of undetected residual transmission.(6)Greater scope exists for overcoming these limitations by enhancing field surveillance for new suspected cases than by improving diagnostic test sensitivity.(7)While population-wide active surveillance may enable complete traceability and containment,this goal may also be achievable through enhanced passive surveillance for paucisymptomatic infections,combining readily accessible decentralized testing with population hypersensitization to self-reporting with mild symptoms.Containment and elimination of SARS-CoV-2 will rely far more upon presumptive,population-wide prevention measures than was necessary for SARS-CoV-1,necessitating greater ambition,political will,investment,public support,persistence and patience.Nevertheless,case and contact management may be invaluable for at least partially containing SARS-CoV-2 transmission,especially larger outbreaks,but only if enabled by sufficiently sensitive surveillance.Furthermore,consistently complete transmission chain containment may be enabled by focally enhanced surveillance around manageably small numbers of outbreaks in the end stages of successful elimination campaigns,so that their endpoints may be accelerated and sustained.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.
基金National 973 project of Chnia for SARS study (2003CB514112) Ministry of Education of China for SARS study (2003-18) National Science Fund for Distinguished Young Investigators (30225040,. 30123019).
文摘To evaluate the role of murine fibrinogen like protein 2 (mfgl2) /fibroleukin in lung impairment in Severe acute respiratory syndrome (SARS), a murine SARS model induced by Murine hepatitis virus strain 3 (MHV-3) through trachea was established. Impressively, all the animals developed interstitial pneumonia with extensive hyaline membranes formation within alveoli, and presence of micro-vascular thrombosis in the pulmonary vessels. MHV-3 nucleocapsid gene transcripts were identified in multiple organs including lungs, spleen etc. As a representative proinflammatory gene, mfgl2 prothrombinase expression was evident in terminal and respiratory bronchioles, alveolar epithelia and infiltrated cells in the lungs associated with fibrin deposition and micro-vascular thrombosis. In summary, the established murine SARS model could mimic the pathologic characteristics of lungs in patients with SARS. Besides the physical damages due to virus replication in organs, the up-regulation of novel gene mfgl2 in lungs may play a vital role in the development of SARS associated lung damage.
文摘Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) is a truly novel, multifaceted disease that has negatively impacted the lives of many including the pregnant women. We present a 34-year-old pregnant patient at 35 weeks with SARS-COV-2 requiring emergent cesarean section under general endotracheal anesthesia and a prolonged postoperative course in the ICU with multiple end organ function derangement of this disease. After nearly 1 month, she was discharged home. Her baby did not have any manifestations of SARS-COV-2 and was able to go home after 5 days.
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The new coronavirus (SARS-CoV-2) broke out in Wuhan in China in December 2019, causing severe pneumonia and deaths, soon in March 2020, it reached pandemic level, affecting several countries including Brazil. The disease was named COVID-19, with characteristics of most infected having mild and moderate symptoms and a part severe symptom. The disease has already reached 158 ethnic groups, which have high vulnerability and limited access to health services. The objective is to investigate the clinical and spatial characteristics of Severe Acute Respiratory Syndrome of COVID-19 in the indigenous peoples of Brazil. It is an epidemiological, cross-sectional, analytical ecological study, based on data from the OpenDataSUS platform from 01/01/2020 to 31/08/2020. Profile variables, signs and symptoms and risk factors/comorbidities. The data were analyzed by Bioestat 5.3. There were 1,207 cases and 470 deaths. Profile: male gender (59.48%) means age 53 years. Signs and symptoms: fever (74.23%), cough (77.71%), sore throat (35.62%), dyspnea (69.34%), respiratory discomfort (62.80%), O<sub>2</sub> saturation < 95% (56.42%);and associated with mortality: dyspnea (80.0%) and O<sub>2</sub> saturation < 95% (69.36%). Risk factors and comorbidities (45.89%) were associated with deaths (54.04%). About comorbidities, chronic cardiovascular diseases represented (18.97%) and Diabetes Mellitus (18.97%), and associated with deaths: Chronic Cardiovascular Disease (24.46%). Being admitted to the ICU has a risk of death in (OR-3.96- < 0.0001-CI-2913/5383) followed by not being vaccinated against influenza (OR-1.85- < 0.0001-CI-1358/2528). The public and health policies of Brazil should be directed to control the dissemination of COVID-19 in this population, that COVID-19 evolves in the same intensity, however, the indigenous have vulnerabilities that can increase the impact of the pandemic in this population.
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National Key Technologies R&D Program of China during the 13th Five-year Plan Period(2017ZX10202101)Medical Innovation Research Project of Science and Technology Innovation Action Plan of Shanghai Science and Technology Committee 2020(20Z11900900).
文摘The outbreak of coronavirus disease 2019(COVID-19)caused by the novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has become a pandemic.SARS-CoV-2 vaccination is currently being actively promoted worldwide as a promising measure to combat the pandemic.However,human immunodeficiency virus(HIV)-infected individuals who manifest varying degrees of immunodeficiency and chronic inflammation may require special consideration with regards to vaccine types and the timing of immunization depending on specific clinical situations.The present recommendation provides a reference for SARS-CoV-2 vaccination in HIV-infected patients.
基金supported by the National Key R&D Program of China(2020YFC0849700)the Program of Chinese Academy of Medicine Sciencethe Major Science and Technology Special Projects of Yunnan Province。
文摘Coronavirus disease 2019(COVID-19),caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has caused millions of infections and deaths worldwide since its emergence in December 2019.As there is little or no natural immunity in the human population or specific anti-COVID-19 drugs,researchers from the government,academia and industry are developing vaccines at an unprecedented speed to halt the pandemic.In this review,the results of animal experiments and clinical trials on several vaccine technical platforms are summarized,and several challenges are also discussed to further promote the development,evaluation and application of vaccines during the challenging situation of the global pandemic.
基金This research was supported by the Science Foundation for SARS ofGuangdong Province (No.2003Z3-E0461).
文摘In November 2002, a new disease-severe acute respiratory syndrome, or SARS-first emerged in Guangdong Province, China. Subsequently, it spread to more than 30 countries worldwide.1 The causative agent was identified to be a previously unknown member of the coronaviridae family, and was named SARS coronavirus (SARS-CoV). SARS coronavirus is a large, enveloped, positive-sense RNA virus. The genome is about 30 kb, which is predicted to contain 14 functional open reading frames (ORFs). Two large 5'-terminal ORFs (1a and 1b) encode the polymerases that are required for viral RNA synthesis. The remaining twelve ORFs encode four structural proteins [spike protein (S), envelope protein (E), membrane protein (M) and nucleocapsid protein (N)] and eight accessory proteins. Though the SARS-CoV genome is clear, a great deal more work will be required to develop an efficient vaccine and effective drugs. Neutralizing antibodies were detectable in the convalescent sera of SARS patients, and sera from recovered patients could be used to treat newly infected individuals. The data suggest that protective humoral immunity is achievable and that vaccines can be developed for prevention of SARS. In this article, we review and discuss progress towards development of a SARS vaccine.
基金supported by the National Natural Science Foundation of China(31900950)。
文摘Since the end of 2019,coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has spread worldwide.The RNA genome of SARS-CoV-2,which is highly infectious and prone to rapid mutation,encodes both structural and non-structural proteins.Vaccination is currently the only effective method to prevent COVID-19,and structural proteins are critical targets for vaccine development.Currently,many vaccines are in clinical trials or are already on the market.This review highlights ongoing advances in the design of prophylactic or therapeutic vaccines against COVID-19,including viral vector vaccines,DNA vaccines,RNA vaccines,live-attenuated vaccines,inactivated virus vaccines,recombinant protein vaccines and bionic nanoparticle vaccines.In addition to traditional inactivated virus vaccines,some novel vaccines based on viral vectors,nanoscience and synthetic biology also play important roles in combating COVID-19.However,many challenges persist in ongoing clinical trials.
基金the National Natural Science Foundation of China(42077398)the Program for HUST Academic Frontier Youth Team(2018QYTD12).
文摘Since June 2020,the re-emergence of coronavirus disease 2019(COVID-19)epidemics in parts of China was linked to the cold chain,which attracted extensive attention and heated discussions from the public.According to the typical characteristics of these epidemics,we speculated a possible route of transmission from cold chain to human.A series of factors in the supply chain contributed to the epidemics if the cold chain were contaminated by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),such as temperature,humidity,personal hygiene/protection,and disinfection.The workers who worked in the cold chain at the receiving end faced a higher risk of being infected when they were not well protected.Facing the difficult situation,China put forward targeted and powerful countermeasures to block the cold chain-related risk.However,in the context of the unstable pandemic situation globally,the risk of the cold chain needs to be recognized and evaluated seriously.Hence,in this review,we reviewed the cold chain-related epidemics in China,analyzed the possible mechanisms,introduced the Chinese experience,and suggested coping strategies for the global epidemic prevention and control.
文摘Background The rapid transmission and high mortality rate made severe acute respiratory syndrome (SARS) a global threat for which no efficacious therapy is available now. Without sufficient knowledge about the SARS coronavirus (SARS-CoV), it is impossible to define the candidate for the anti-SARS targets. The putative non-structural protein 2 (nsp2) (3CL pro , following the nomenclature by Gao et al, also known as nsp5 in Snidjer et al) of SARS-CoV plays an important role in viral transcription and replication, and is an attractive target for anti-SARS drug development, so we carried on this study to have an insight into putative polymerase nsp2 of SARS-CoV Guangdong (GD) strain. Methods The SARS-CoV strain was isolated from a SARS patient in Guangdong, China, and cultured in Vero E6 cells. The nsp2 gene was amplified by reverse transcription-polymerase chain reaction (RT-PCR) and cloned into eukaryotic expression vector pCI-neo (pCI-neo/nsp2). Then the recombinant eukaryotic expression vector pCI-neo/nsp2 was transfected into COS-7 cells using lipofectin reagent to express the nsp2 protein. The expressive protein of SARS-CoV nsp2 was analyzed by 7% sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE). The nucleotide sequence and protein sequence of GD nsp2 were compared with that of other SARS-CoV strains by nucleotide-nucleotide basic local alignment search tool (BLASTN) and protein-protein basic local alignment search tool (BLASTP) to investigate its variance trend during the transmission. The secondary structure of GD strain and that of other strains were predicted by Garnier-Osguthorpe-Robson (GOR) Secondary Structure Prediction. Three-dimensional-PSSM Protein Fold Recognition (Threading) Server was employed to construct the three-dimensional model of the nsp2 protein.Results The putative polymerase nsp2 gene of GD strain was amplified by RT-PCR. The eukaryotic expression vector (pCI-neo/nsp2) was constructed and expressed the protein in COS-7 cells successfully. The result of sequencing and sequence comparison with other SARS-CoV strains showed that nsp2 gene was relatively conservative during the transmission and total five base sites mutated in about 100 strains investigated, three of which in the early and middle phases caused synonymous mutation, and another two base sites variation in the late phase resulted in the amino acid substitutions and secondary structure changes. The three-dimensional structure of the nsp2 protein was successfully constructed. Conclusions The results suggest that polymerase nsp2 is relatively stable during the phase of epidemic. The amino acid and secondary structure change may be important for viral infection. The fact that majority of single nucleotide variations (SNVs) are predicted to cause synonymous, as well as the result of low mutation rate of nsp2 gene in the epidemic variations, indicates that the nsp2 is conservative and could be a target for anti-SARS drugs. The three-dimensional structure result indicates that the nsp2 protein of GD strain is high homologous with 3CL pro of SARS-CoV urbani strain, 3CL pro of transmissible gastroenteritis virus and 3CL pro of human coronavirus 229E strain, which further suggests that nsp2 protein of GD strain possesses the activity of 3CL pro .
基金supported by grants from the Special Project of Contingency Research for COVID-19(2020XGFYZR11)the Cultivating Project for Young Scholar at Hubei University of Medicine(2018QDJZR01)awarded to Dr.Fuyun Jithe Special Project of Contingency Research for COVID-19 at Hubei University of Medicine(2020XGFYZR03)。
文摘Background:Mitochondria have been shown to play vital roles during severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection and coronavirus disease 2019(COVID-19)development.Currently,it is unclear whether mitochondrial DNA(mtDNA)variants,which define mtDNA haplogroups and determine oxidative phosphorylation performance and reactive oxygen species production,are associated with COVID-19 risk.Methods:A population-based case-control study was conducted to compare the distribution of mtDNA variations defining mtDNA haplogroups between healthy controls(n=615)and COVID-19 patients(n=536).COVID-19 patients were diagnosed based on molecular diagnostics of the viral genome by qPCR and chest X-ray or computed tomography scanning.The exclusion criteria for the healthy controls were any history of disease in the month preceding the study assessment.MtDNA variants defining mtDNA haplogroups were identified by PCR-RFLPs and HVS-I sequencing and determined based on mtDNA phylogenetic analysis using Mitomap Phylogeny.Student’s t-test was used for continuous variables,and Pearson’s chi-squared test or Fisher’s exact test was used for categorical variables.To assess the independent effect of each mtDNA variant defining mtDNA haplogroups,multivariate logistic regression analyses were performed to calculate the odds ratios(OR)and 95%confidence intervals(CI)with adjustments for possible confounding factors of age,sex,smoking and diseases(including cardiopulmonary diseases,diabetes,obesity and hypertension)as determined through clinical and radiographic examinations.Results:Multivariate logistic regression analyses revealed that the most common investigated mtDNA variations(>10%in the control population)at C5178 a(in NADH dehydrogenase subunit 2 gene,ND2)and A249 d(in the displacement loop region,D-loop)/T6392 C(in cytochrome c oxidase I gene,CO1)/G10310 A(in ND3)were associated with a reduced risk of severe COVID-19(OR=0.590,95%CI 0.428–0.814,P=0.001;and OR=0.654,95%CI 0.457–0.936,P=0.020,respectively),while A4833 G(ND2),A4715 G(ND2),T3394 C(ND1)and G5417 A(ND2)/C16257 a(D-loop)/C16261 T(D-loop)were related to an increased risk of severe COVID-19(OR=2.336,95%CI 1.179–4.608,P=0.015;OR=2.033,95%CI 1.242–3.322,P=0.005;OR=3.040,95%CI 1.522–6.061,P=0.002;and OR=2.890,95%CI 1.199–6.993,P=0.018,respectively).Conclusions:This is the first study to explore the association of mtDNA variants with individual’s risk of developing severe COVID-19.Based on the case–control study,we concluded that the common mtDNA variants at C5178 a and A249 d/T6392 C/G10310 A might contribute to an individual’s resistance to developing severe COVID-19,whereas A4833 G,A4715 G,T3394 C and G5417 A/C16257 a/C16261 T might increase an individual’s risk of developing severe COVID-19.
基金GFK is supported by an AXA Research Chair award funded by the AXA Research Fund and the College of Science,Engineering and Food Science at University College Cork.
文摘Severe Acute Respiratory Syndrome Coronavirus 1(SARS-CoV-1)infections almost always caused overt symptoms,so effective case and contact management enabled its effective eradication within months.However,Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2)usually causes only mild symptoms,so transmission chains may grow to include several individuals before at least one index case becomes ill enough to self-report for diagnosis and care.Here,simple mathematical models were developed to evaluate the implications of delayed index case detection for retrospective contact tracing and management responses.Specifically,these simulations illustrate how:(1)Contact tracing and management may effectively contain most but not all large SARS-CoV-2 clusters arising at foci with high reproduction numbers because rapidly expanding transmission chains ensure at least one overtly symptomatic index case occurs within two viral generations a week or less apart.(2)However,lower reproduction numbers give rise to thinner transmission chains extending through longer sequences of non-reporting asymptomatic and paucisymptomatic individuals,often spanning three or more viral generations(2 weeks of transmission)before an overtly symptomatic index case occurs.(3)Consequently,it is not always possible to fully trace and contain such long,thin transmission chains,so the community transmission they give rise to is underrepresented in surveillance data.(4)Wherever surveillance systems are weak and/or transmission proceeds within population groups with lower rates of overt clinical symptoms and/or self-reporting,case and contact management effectiveness may be more severely limited,even at the higher reproduction numbers associated with larger outbreaks.(5)Because passive surveillance platforms may be especially slow to detect the thinner transmission chains that occur at low reproduction numbers,establishing satisfactory confidence of elimination may require that no confirmed cases are detected for two full months,throughout which presumptive preventative measures must be maintained to ensure complete collapse of undetected residual transmission.(6)Greater scope exists for overcoming these limitations by enhancing field surveillance for new suspected cases than by improving diagnostic test sensitivity.(7)While population-wide active surveillance may enable complete traceability and containment,this goal may also be achievable through enhanced passive surveillance for paucisymptomatic infections,combining readily accessible decentralized testing with population hypersensitization to self-reporting with mild symptoms.Containment and elimination of SARS-CoV-2 will rely far more upon presumptive,population-wide prevention measures than was necessary for SARS-CoV-1,necessitating greater ambition,political will,investment,public support,persistence and patience.Nevertheless,case and contact management may be invaluable for at least partially containing SARS-CoV-2 transmission,especially larger outbreaks,but only if enabled by sufficiently sensitive surveillance.Furthermore,consistently complete transmission chain containment may be enabled by focally enhanced surveillance around manageably small numbers of outbreaks in the end stages of successful elimination campaigns,so that their endpoints may be accelerated and sustained.