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      Determining Gaps in Publicly Shared SARS-CoV-2 Genomic Surveillance Data by Analysis of Global Submissions

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          Abstract

          Viral genomic surveillance has been a critical source of information during the COVID-19 pandemic, but publicly available data can be sparse, concentrated in wealthy countries, and often made public weeks or months after collection. We used publicly available viral genomic surveillance data submitted to GISAID and GenBank to examine sequencing coverage and lag time to submission during 2020–2021. We compared publicly submitted sequences by country with reported infection rates and population and also examined data based on country-level World Bank income status and World Health Organization region. We found that as global capacity for viral genomic surveillance increased, international disparities in sequencing capacity and timeliness persisted along economic lines. Our analysis suggests that increasing viral genomic surveillance coverage worldwide and decreasing turnaround times could improve timely availability of sequencing data to inform public health action.

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          The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application

          Background: A novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in China in December 2019. There is limited support for many of its key epidemiologic features, including the incubation period for clinical disease (coronavirus disease 2019 [COVID-19]), which has important implications for surveillance and control activities. Objective: To estimate the length of the incubation period of COVID-19 and describe its public health implications. Design: Pooled analysis of confirmed COVID-19 cases reported between 4 January 2020 and 24 February 2020. Setting: News reports and press releases from 50 provinces, regions, and countries outside Wuhan, Hubei province, China. Participants: Persons with confirmed SARS-CoV-2 infection outside Hubei province, China. Measurements: Patient demographic characteristics and dates and times of possible exposure, symptom onset, fever onset, and hospitalization. Results: There were 181 confirmed cases with identifiable exposure and symptom onset windows to estimate the incubation period of COVID-19. The median incubation period was estimated to be 5.1 days (95% CI, 4.5 to 5.8 days), and 97.5% of those who develop symptoms will do so within 11.5 days (CI, 8.2 to 15.6 days) of infection. These estimates imply that, under conservative assumptions, 101 out of every 10 000 cases (99th percentile, 482) will develop symptoms after 14 days of active monitoring or quarantine. Limitation: Publicly reported cases may overrepresent severe cases, the incubation period for which may differ from that of mild cases. Conclusion: This work provides additional evidence for a median incubation period for COVID-19 of approximately 5 days, similar to SARS. Our results support current proposals for the length of quarantine or active monitoring of persons potentially exposed to SARS-CoV-2, although longer monitoring periods might be justified in extreme cases. Primary Funding Source: U.S. Centers for Disease Control and Prevention, National Institute of Allergy and Infectious Diseases, National Institute of General Medical Sciences, and Alexander von Humboldt Foundation.
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            The effect of travel restrictions on the spread of the 2019 novel coronavirus (COVID-19) outbreak

            Motivated by the rapid spread of COVID-19 in Mainland China, we use a global metapopulation disease transmission model to project the impact of travel limitations on the national and international spread of the epidemic. The model is calibrated based on internationally reported cases, and shows that at the start of the travel ban from Wuhan on 23 January 2020, most Chinese cities had already received many infected travelers. The travel quarantine of Wuhan delayed the overall epidemic progression by only 3 to 5 days in Mainland China, but has a more marked effect at the international scale, where case importations were reduced by nearly 80% until mid February. Modeling results also indicate that sustained 90% travel restrictions to and from Mainland China only modestly affect the epidemic trajectory unless combined with a 50% or higher reduction of transmission in the community.
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              Ongoing global and regional adaptive evolution of SARS-CoV-2

              Understanding the ongoing evolution of SARS-CoV-2 is essential to control and ultimately end the pandemic. We analyzed more than 300,000 SARS-CoV-2 genomes available as of January 2021 and demonstrate adaptive evolution of the virus that affects, primarily, multiple sites in the spike and nucleocapsid protein. Selection appears to act on combinations of mutations in these and other SARS-CoV-2 genes. Evolution of the virus is accompanied by ongoing adaptive diversification within and between geographic regions. This diversification could substantially prolong the pandemic and the vaccination campaign, in which variant-specific vaccines are likely to be required. Understanding the trends in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution is paramount to control the COVID-19 pandemic. We analyzed more than 300,000 high-quality genome sequences of SARS-CoV-2 variants available as of January 2021. The results show that the ongoing evolution of SARS-CoV-2 during the pandemic is characterized primarily by purifying selection, but a small set of sites appear to evolve under positive selection. The receptor-binding domain of the spike protein and the region of the nucleocapsid protein associated with nuclear localization signals (NLS) are enriched with positively selected amino acid replacements. These replacements form a strongly connected network of apparent epistatic interactions and are signatures of major partitions in the SARS-CoV-2 phylogeny. Virus diversity within each geographic region has been steadily growing for the entirety of the pandemic, but analysis of the phylogenetic distances between pairs of regions reveals four distinct periods based on global partitioning of the tree and the emergence of key mutations. The initial period of rapid diversification into region-specific phylogenies that ended in February 2020 was followed by a major extinction event and global homogenization concomitant with the spread of D614G in the spike protein, ending in March 2020. The NLS-associated variants across multiple partitions rose to global prominence in March to July, during a period of stasis in terms of interregional diversity. Finally, beginning in July 2020, multiple mutations, some of which have since been demonstrated to enable antibody evasion, began to emerge associated with ongoing regional diversification, which might be indicative of speciation.
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                Author and article information

                Journal
                Emerg Infect Dis
                Emerg Infect Dis
                EID
                Emerging Infectious Diseases
                Centers for Disease Control and Prevention
                1080-6040
                1080-6059
                December 2022
                : 28
                : Suppl 1
                : S85-S92
                Affiliations
                [1]Centers for Disease Control and Prevention, Atlanta, Georgia, USA
                Author notes
                Address for correspondence: Elizabeth C. Ohlsen, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Mailstop E-92, Atlanta, GA 30329-4027, USA; email: rhu4@ 123456cdc.gov
                Article
                22-0780
                10.3201/eid2813.220780
                9745223
                36502409
                846ed0d1-356c-4fe8-8085-7fc118078969
                Copyright @ 2022

                Emerging Infectious Diseases is a publication of the U.S. Government. This publication is in the public domain and is therefore without copyright. All text from this work may be reprinted freely. Use of these materials should be properly cited.

                History
                Categories
                Surveillance, Information, and Laboratory Systems
                Surveillance, Information, and Laboratory Systems
                Determining Gaps in Publicly Shared SARS-CoV-2 Genomic Surveillance Data by Analysis of Global Submissions

                Infectious disease & Microbiology
                sars-cov-2,viral surveillance,pandemic,covid-19,coronavirus disease,severe acute respiratory syndrome coronavirus 2,viruses,respiratory infections,zoonoses,vaccine-preventable diseases

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