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1.
Nat Commun ; 13(1): 1012, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1709629

ABSTRACT

Mitigation of SARS-CoV-2 transmission from international travel is a priority. We evaluated the effectiveness of travellers being required to quarantine for 14-days on return to England in Summer 2020. We identified 4,207 travel-related SARS-CoV-2 cases and their contacts, and identified 827 associated SARS-CoV-2 genomes. Overall, quarantine was associated with a lower rate of contacts, and the impact of quarantine was greatest in the 16-20 age-group. 186 SARS-CoV-2 genomes were sufficiently unique to identify travel-related clusters. Fewer genomically-linked cases were observed for index cases who returned from countries with quarantine requirement compared to countries with no quarantine requirement. This difference was explained by fewer importation events per identified genome for these cases, as opposed to fewer onward contacts per case. Overall, our study demonstrates that a 14-day quarantine period reduces, but does not completely eliminate, the onward transmission of imported cases, mainly by dissuading travel to countries with a quarantine requirement.


Subject(s)
COVID-19/prevention & control , Communicable Diseases, Imported/prevention & control , Quarantine/legislation & jurisprudence , SARS-CoV-2/genetics , COVID-19/epidemiology , COVID-19/transmission , Communicable Diseases, Imported/epidemiology , Communicable Diseases, Imported/transmission , Contact Tracing , England/epidemiology , Genome, Viral/genetics , Genomics , Health Impact Assessment , Humans , SARS-CoV-2/classification , Travel/legislation & jurisprudence , Travel-Related Illness
2.
Nat Commun ; 13(1): 751, 2022 02 08.
Article in English | MEDLINE | ID: covidwho-1684022

ABSTRACT

Understanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.


Subject(s)
COVID-19/epidemiology , COVID-19/transmission , SARS-CoV-2/genetics , Universities , COVID-19/prevention & control , COVID-19/virology , Contact Tracing , Genome, Viral/genetics , Genomics , Humans , Phylogeny , RNA, Viral/genetics , Risk Factors , SARS-CoV-2/classification , SARS-CoV-2/isolation & purification , Students , United Kingdom/epidemiology , Universities/statistics & numerical data
3.
Mol Biol Evol ; 39(3)2022 03 02.
Article in English | MEDLINE | ID: covidwho-1672233

ABSTRACT

Identifying linked cases of infection is a critical component of the public health response to viral infectious diseases. In a clinical context, there is a need to make rapid assessments of whether cases of infection have arrived independently onto a ward, or are potentially linked via direct transmission. Viral genome sequence data are of great value in making these assessments, but are often not the only form of data available. Here, we describe A2B-COVID, a method for the rapid identification of potentially linked cases of COVID-19 infection designed for clinical settings. Our method combines knowledge about infection dynamics, data describing the movements of individuals, and evolutionary analysis of genome sequences to assess whether data collected from cases of infection are consistent or inconsistent with linkage via direct transmission. A retrospective analysis of data from two wards at Cambridge University Hospitals NHS Foundation Trust during the first wave of the pandemic showed qualitatively different patterns of linkage between cases on designated COVID-19 and non-COVID-19 wards. The subsequent real-time application of our method to data from the second epidemic wave highlights its value for monitoring cases of infection in a clinical context.


Subject(s)
COVID-19 , SARS-CoV-2 , Hospitals , Humans , Pandemics , Retrospective Studies , SARS-CoV-2/genetics
4.
Lancet Microbe ; 3(2): e151-e158, 2022 02.
Article in English | MEDLINE | ID: covidwho-1440435

ABSTRACT

We reviewed all genomic epidemiology studies on COVID-19 in long-term care facilities (LTCFs) that had been published to date. We found that staff and residents were usually infected with identical, or near identical, SARS-CoV-2 genomes. Outbreaks usually involved one predominant cluster, and the same lineages persisted in LTCFs despite infection control measures. Outbreaks were most commonly due to single or few introductions followed by a spread rather than a series of seeding events from the community into LTCFs. The sequencing of samples taken consecutively from the same individuals at the same facilities showed the persistence of the same genome sequence, indicating that the sequencing technique was robust over time. When combined with local epidemiology, genomics allowed probable transmission sources to be better characterised. The transmission between LTCFs was detected in multiple studies. The mortality rate among residents was high in all facilities, regardless of the lineage. Bioinformatics methods were inadequate in a third of the studies reviewed, and reproducing the analyses was difficult because sequencing data were not available in many facilities.


Subject(s)
COVID-19 , COVID-19/epidemiology , Disease Outbreaks , Genomics , Humans , Long-Term Care , SARS-CoV-2/genetics
5.
Elife ; 102021 08 24.
Article in English | MEDLINE | ID: covidwho-1371047

ABSTRACT

SARS-CoV-2 is notable both for its rapid spread, and for the heterogeneity of its patterns of transmission, with multiple published incidences of superspreading behaviour. Here, we applied a novel network reconstruction algorithm to infer patterns of viral transmission occurring between patients and health care workers (HCWs) in the largest clusters of COVID-19 infection identified during the first wave of the epidemic at Cambridge University Hospitals NHS Foundation Trust, UK. Based upon dates of individuals reporting symptoms, recorded individual locations, and viral genome sequence data, we show an uneven pattern of transmission between individuals, with patients being much more likely to be infected by other patients than by HCWs. Further, the data were consistent with a pattern of superspreading, whereby 21% of individuals caused 80% of transmission events. Our study provides a detailed retrospective analysis of nosocomial SARS-CoV-2 transmission, and sheds light on the need for intensive and pervasive infection control procedures.


The COVID-19 pandemic, caused by the SARS-CoV-2 virus, presents a global public health challenge. Hospitals have been at the forefront of this battle, treating large numbers of sick patients over several waves of infection. Finding ways to manage the spread of the virus in hospitals is key to protecting vulnerable patients and workers, while keeping hospitals running, but to generate effective infection control, researchers must understand how SARS-CoV-2 spreads. A range of factors make studying the transmission of SARS-CoV-2 in hospitals tricky. For instance, some people do not present any symptoms, and, amongst those who do, it can be difficult to determine whether they caught the virus in the hospital or somewhere else. However, comparing the genetic information of the SARS-CoV-2 virus from different people in a hospital could allow scientists to understand how it spreads. Samples of the genetic material of SARS-CoV-2 can be obtained by swabbing infected individuals. If the genetic sequences of two samples are very different, it is unlikely that the individuals who provided the samples transmitted the virus to one another. Illingworth, Hamilton et al. used this information, along with other data about how SARS-CoV-2 is transmitted, to develop an algorithm that can determine how the virus spreads from person to person in different hospital wards. To build their algorithm, Illingworth, Hamilton et al. collected SARS-CoV-2 genetic data from patients and staff in a hospital, and combined it with information about how SARS-CoV-2 spreads and how these people moved in the hospital . The algorithm showed that, for the most part, patients were infected by other patients (20 out of 22 cases), while staff were infected equally by patients and staff. By further probing these data, Illingworth, Hamilton et al. revealed that 80% of hospital-acquired infections were caused by a group of just 21% of individuals in the study, identifying a 'superspreader' pattern. These findings may help to inform SARS-CoV-2 infection control measures to reduce spread within hospitals, and could potentially be used to improve infection control in other contexts.


Subject(s)
COVID-19/epidemiology , COVID-19/transmission , Disease Outbreaks/statistics & numerical data , Hospitals/statistics & numerical data , Female , Humans , Male , Middle Aged , Retrospective Studies
6.
Genome Biol ; 22(1): 196, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1295478

ABSTRACT

In response to the ongoing SARS-CoV-2 pandemic in the UK, the COVID-19 Genomics UK (COG-UK) consortium was formed to rapidly sequence SARS-CoV-2 genomes as part of a national-scale genomic surveillance strategy. The network consists of universities, academic institutes, regional sequencing centres and the four UK Public Health Agencies. We describe the development and deployment of CLIMB-COVID, an encompassing digital infrastructure to address the challenge of collecting and integrating both genomic sequencing data and sample-associated metadata produced across the COG-UK network.


Subject(s)
Cloud Computing , Genomics/organization & administration , SARS-CoV-2/genetics , COVID-19/epidemiology , Epidemiological Monitoring , Genome, Viral , Humans , Sequence Analysis, DNA , United Kingdom , User-Computer Interface , Whole Genome Sequencing
7.
Nat Rev Microbiol ; 19(7): 409-424, 2021 07.
Article in English | MEDLINE | ID: covidwho-1253944

ABSTRACT

Although most mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome are expected to be either deleterious and swiftly purged or relatively neutral, a small proportion will affect functional properties and may alter infectivity, disease severity or interactions with host immunity. The emergence of SARS-CoV-2 in late 2019 was followed by a period of relative evolutionary stasis lasting about 11 months. Since late 2020, however, SARS-CoV-2 evolution has been characterized by the emergence of sets of mutations, in the context of 'variants of concern', that impact virus characteristics, including transmissibility and antigenicity, probably in response to the changing immune profile of the human population. There is emerging evidence of reduced neutralization of some SARS-CoV-2 variants by postvaccination serum; however, a greater understanding of correlates of protection is required to evaluate how this may impact vaccine effectiveness. Nonetheless, manufacturers are preparing platforms for a possible update of vaccine sequences, and it is crucial that surveillance of genetic and antigenic changes in the global virus population is done alongside experiments to elucidate the phenotypic impacts of mutations. In this Review, we summarize the literature on mutations of the SARS-CoV-2 spike protein, the primary antigen, focusing on their impacts on antigenicity and contextualizing them in the protein structure, and discuss them in the context of observed mutation frequencies in global sequence datasets.


Subject(s)
COVID-19/virology , Immune Evasion , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/classification , Amino Acids/chemistry , Amino Acids/genetics , Antigenic Variation/genetics , Antigenic Variation/physiology , COVID-19/immunology , COVID-19/prevention & control , COVID-19/transmission , COVID-19 Vaccines/immunology , COVID-19 Vaccines/standards , Epitopes/chemistry , Epitopes/genetics , Epitopes/immunology , Humans , Immune Evasion/genetics , Mutation , Protein Conformation , SARS-CoV-2/classification , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology
9.
Elife ; 102021 03 02.
Article in English | MEDLINE | ID: covidwho-1112865

ABSTRACT

COVID-19 poses a major challenge to care homes, as SARS-CoV-2 is readily transmitted and causes disproportionately severe disease in older people. Here, 1167 residents from 337 care homes were identified from a dataset of 6600 COVID-19 cases from the East of England. Older age and being a care home resident were associated with increased mortality. SARS-CoV-2 genomes were available for 700 residents from 292 care homes. By integrating genomic and temporal data, 409 viral clusters within the 292 homes were identified, indicating two different patterns - outbreaks among care home residents and independent introductions with limited onward transmission. Approximately 70% of residents in the genomic analysis were admitted to hospital during the study, providing extensive opportunities for transmission between care homes and hospitals. Limiting viral transmission within care homes should be a key target for infection control to reduce COVID-19 mortality in this population.


Subject(s)
COVID-19/epidemiology , COVID-19/transmission , Nursing Homes , SARS-CoV-2/genetics , Aged, 80 and over , COVID-19/virology , Disease Outbreaks , England/epidemiology , Female , Humans , Infectious Disease Transmission, Patient-to-Professional , Infectious Disease Transmission, Professional-to-Patient , Male , Polymorphism, Single Nucleotide , Sequence Analysis , Time Factors
10.
PLoS One ; 16(1): e0245532, 2021.
Article in English | MEDLINE | ID: covidwho-1045570

ABSTRACT

BACKGROUND: Understanding the T cell response to SARS-CoV-2 is critical to vaccine development, epidemiological surveillance and disease control strategies. This systematic review critically evaluates and synthesises the relevant peer-reviewed and pre-print literature published from 01/01/2020-26/06/2020. METHODS: For this systematic review, keyword-structured literature searches were carried out in MEDLINE, Embase and COVID-19 Primer. Papers were independently screened by two researchers, with arbitration of disagreements by a third researcher. Data were independently extracted into a pre-designed Excel template and studies critically appraised using a modified version of the MetaQAT tool, with resolution of disagreements by consensus. Findings were narratively synthesised. RESULTS: 61 articles were included. 55 (90%) studies used observational designs, 50 (82%) involved hospitalised patients with higher acuity illness, and the majority had important limitations. Symptomatic adult COVID-19 cases consistently show peripheral T cell lymphopenia, which positively correlates with increased disease severity, duration of RNA positivity, and non-survival; while asymptomatic and paediatric cases display preserved counts. People with severe or critical disease generally develop more robust, virus-specific T cell responses. T cell memory and effector function has been demonstrated against multiple viral epitopes, and, cross-reactive T cell responses have been demonstrated in unexposed and uninfected adults, but the significance for protection and susceptibility, respectively, remains unclear. CONCLUSION: A complex pattern of T cell response to SARS-CoV-2 infection has been demonstrated, but inferences regarding population level immunity are hampered by significant methodological limitations and heterogeneity between studies, as well as a striking lack of research in asymptomatic or pauci-symptomatic individuals. In contrast to antibody responses, population-level surveillance of the T cell response is unlikely to be feasible in the near term. Focused evaluation in specific sub-groups, including vaccine recipients, should be prioritised.


Subject(s)
COVID-19/pathology , Lymphopenia/pathology , SARS-CoV-2/physiology , T-Lymphocytes/pathology , COVID-19/complications , COVID-19/immunology , COVID-19/virology , Host-Pathogen Interactions , Humans , Immunity, Cellular , Lymphopenia/etiology , Lymphopenia/immunology , Lymphopenia/virology , SARS-CoV-2/immunology , T-Lymphocytes/immunology , T-Lymphocytes/virology
11.
PLoS One ; 15(12): e0244126, 2020.
Article in English | MEDLINE | ID: covidwho-1004459

ABSTRACT

BACKGROUND: Progress in characterising the humoral immune response to Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) has been rapid but areas of uncertainty persist. Assessment of the full range of evidence generated to date to understand the characteristics of the antibody response, its dynamics over time, its determinants and the immunity it confers will have a range of clinical and policy implications for this novel pathogen. This review comprehensively evaluated evidence describing the antibody response to SARS-CoV-2 published from 01/01/2020-26/06/2020. METHODS: Systematic review. Keyword-structured searches were carried out in MEDLINE, Embase and COVID-19 Primer. Articles were independently screened on title, abstract and full text by two researchers, with arbitration of disagreements. Data were double-extracted into a pre-designed template, and studies critically appraised using a modified version of the Public Health Ontario Meta-tool for Quality Appraisal of Public Health Evidence (MetaQAT) tool, with resolution of disagreements by consensus. Findings were narratively synthesised. RESULTS: 150 papers were included. Most studies (113 or 75%) were observational in design, were based wholly or primarily on data from hospitalised patients (108, 72%) and had important methodological limitations. Few considered mild or asymptomatic infection. Antibody dynamics were well described in the acute phase, up to around three months from disease onset, but the picture regarding correlates of the antibody response was inconsistent. IgM was consistently detected before IgG in included studies, peaking at weeks two to five and declining over a further three to five weeks post-symptom onset depending on the patient group; IgG peaked around weeks three to seven post-symptom onset then plateaued, generally persisting for at least eight weeks. Neutralising antibodies were detectable within seven to 15 days following disease onset, with levels increasing until days 14-22 before levelling and then decreasing, but titres were lower in those with asymptomatic or clinically mild disease. Specific and potent neutralising antibodies have been isolated from convalescent plasma. Cross-reactivity but limited cross-neutralisation with other human coronaviridae was reported. Evidence for protective immunity in vivo was limited to small, short-term animal studies, showing promising initial results in the immediate recovery phase. CONCLUSIONS: Literature on antibody responses to SARS-CoV-2 is of variable quality with considerable heterogeneity of methods, study participants, outcomes measured and assays used. Although acute phase antibody dynamics are well described, longer-term patterns are much less well evidenced. Comprehensive assessment of the role of demographic characteristics and disease severity on antibody responses is needed. Initial findings of low neutralising antibody titres and possible waning of titres over time may have implications for sero-surveillance and disease control policy, although further evidence is needed. The detection of potent neutralising antibodies in convalescent plasma is important in the context of development of therapeutics and vaccines. Due to limitations with the existing evidence base, large, cross-national cohort studies using appropriate statistical analysis and standardised serological assays and clinical classifications should be prioritised.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , Antibody Formation , COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/blood , COVID-19/immunology , Cross Reactions , Female , Humans , Male , SARS-CoV-2/immunology , SARS-CoV-2/metabolism
12.
Influenza Other Respir Viruses ; 15(1): 3-6, 2021 01.
Article in English | MEDLINE | ID: covidwho-695884

ABSTRACT

Point-of-care tests (POCTs) offer considerable potential for improving clinical and public health management of COVID-19 by providing timely information to guide decision-making, but data on real-world performance are in short supply. Besides SARS-CoV-2-specific tests, there is growing interest in the role of surrogate (non-specific) tests such as FebriDx, a biochemical POCT which can be used to distinguish viral from bacterial infection in patients with influenza-like illnesses. This short report assesses what is currently known about FebriDx performance across settings and populations by comparison with some of the more intensively evaluated SARS-CoV-2-specific POCTs. While FebriDx shows some potential in supporting triage for early-stage infection in acute care settings, this is dependent on SARS-CoV-2 being the most likely cause for influenza-like illnesses, with reduction in discriminatory power when COVID-19 case numbers are low, and when co-circulating viral respiratory infections become more prevalent during the autumn and winter. Too little is currently known about its performance in primary care and the community to support use in these contexts, and further evaluation is needed. Reliable SARS CoV2-specific POCTs-when they become available-are likely to rapidly overtake surrogates as the preferred option given the greater specificity they provide.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , Point-of-Care Testing , SARS-CoV-2 , COVID-19/prevention & control , Humans
13.
Lancet Infect Dis ; 20(11): 1263-1272, 2020 11.
Article in English | MEDLINE | ID: covidwho-643826

ABSTRACT

BACKGROUND: The burden and influence of health-care associated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is unknown. We aimed to examine the use of rapid SARS-CoV-2 sequencing combined with detailed epidemiological analysis to investigate health-care associated SARS-CoV-2 infections and inform infection control measures. METHODS: In this prospective surveillance study, we set up rapid SARS-CoV-2 nanopore sequencing from PCR-positive diagnostic samples collected from our hospital (Cambridge, UK) and a random selection from hospitals in the East of England, enabling sample-to-sequence in less than 24 h. We established a weekly review and reporting system with integration of genomic and epidemiological data to investigate suspected health-care associated COVID-19 cases. FINDINGS: Between March 13 and April 24, 2020, we collected clinical data and samples from 5613 patients with COVID-19 from across the East of England. We sequenced 1000 samples producing 747 high-quality genomes. We combined epidemiological and genomic analysis of the 299 patients from our hospital and identified 35 clusters of identical viruses involving 159 patients. 92 (58%) of 159 patients had strong epidemiological links and 32 (20%) patients had plausible epidemiological links. These results were fed back to clinical, infection control, and hospital management teams, leading to infection-control interventions and informing patient safety reporting. INTERPRETATION: We established real-time genomic surveillance of SARS-CoV-2 in a UK hospital and showed the benefit of combined genomic and epidemiological analysis for the investigation of health-care associated COVID-19. This approach enabled us to detect cryptic transmission events and identify opportunities to target infection-control interventions to further reduce health-care associated infections. Our findings have important implications for national public health policy as they enable rapid tracking and investigation of infections in hospital and community settings. FUNDING: COVID-19 Genomics UK funded by the Department of Health and Social Care, UK Research and Innovation, and the Wellcome Sanger Institute.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Cross Infection/epidemiology , Cross Infection/prevention & control , Infection Control/methods , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19 , Child , Child, Preschool , Coronavirus Infections/virology , Cross Infection/virology , England/epidemiology , Female , Genome, Viral/genetics , Hospitals, University , Humans , Infant , Infant, Newborn , Male , Middle Aged , Patient Safety , Phylogeny , Pneumonia, Viral/virology , Polymerase Chain Reaction/methods , Polymorphism, Single Nucleotide , Prospective Studies , SARS-CoV-2 , Whole Genome Sequencing/methods , Young Adult
14.
JAMA ; 324(8): 782-793, 2020 Aug 25.
Article in English | MEDLINE | ID: covidwho-639851

ABSTRACT

IMPORTANCE: The coronavirus disease 2019 (COVID-19) pandemic, due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease. This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19. OBSERVATIONS: SARS-CoV-2 is spread primarily via respiratory droplets during close face-to-face contact. Infection can be spread by asymptomatic, presymptomatic, and symptomatic carriers. The average time from exposure to symptom onset is 5 days, and 97.5% of people who develop symptoms do so within 11.5 days. The most common symptoms are fever, dry cough, and shortness of breath. Radiographic and laboratory abnormalities, such as lymphopenia and elevated lactate dehydrogenase, are common, but nonspecific. Diagnosis is made by detection of SARS-CoV-2 via reverse transcription polymerase chain reaction testing, although false-negative test results may occur in up to 20% to 67% of patients; however, this is dependent on the quality and timing of testing. Manifestations of COVID-19 include asymptomatic carriers and fulminant disease characterized by sepsis and acute respiratory failure. Approximately 5% of patients with COVID-19, and 20% of those hospitalized, experience severe symptoms necessitating intensive care. More than 75% of patients hospitalized with COVID-19 require supplemental oxygen. Treatment for individuals with COVID-19 includes best practices for supportive management of acute hypoxic respiratory failure. Emerging data indicate that dexamethasone therapy reduces 28-day mortality in patients requiring supplemental oxygen compared with usual care (21.6% vs 24.6%; age-adjusted rate ratio, 0.83 [95% CI, 0.74-0.92]) and that remdesivir improves time to recovery (hospital discharge or no supplemental oxygen requirement) from 15 to 11 days. In a randomized trial of 103 patients with COVID-19, convalescent plasma did not shorten time to recovery. Ongoing trials are testing antiviral therapies, immune modulators, and anticoagulants. The case-fatality rate for COVID-19 varies markedly by age, ranging from 0.3 deaths per 1000 cases among patients aged 5 to 17 years to 304.9 deaths per 1000 cases among patients aged 85 years or older in the US. Among patients hospitalized in the intensive care unit, the case fatality is up to 40%. At least 120 SARS-CoV-2 vaccines are under development. Until an effective vaccine is available, the primary methods to reduce spread are face masks, social distancing, and contact tracing. Monoclonal antibodies and hyperimmune globulin may provide additional preventive strategies. CONCLUSIONS AND RELEVANCE: As of July 1, 2020, more than 10 million people worldwide had been infected with SARS-CoV-2. Many aspects of transmission, infection, and treatment remain unclear. Advances in prevention and effective management of COVID-19 will require basic and clinical investigation and public health and clinical interventions.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections , Pandemics , Pneumonia, Viral , Betacoronavirus/isolation & purification , COVID-19 , COVID-19 Testing , COVID-19 Vaccines , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Coronavirus Infections/therapy , Coronavirus Infections/transmission , Global Health , Health Status Disparities , Hospital Mortality , Humans , Lung/diagnostic imaging , Lung/pathology , Oxygen Inhalation Therapy , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , Pneumonia, Viral/transmission , Prognosis , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2 , Viral Vaccines
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