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Tracking SARS-CoV-2 Spike Protein Mutations in the United States (January 2020-March 2021) Using a Statistical Learning Strategy.

ABSTRACT: The emergence and establishment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of interest (VOIs) and variants of concern (VOCs) highlight the importance of genomic surveillance. We propose a statistical learning strategy (SLS) for identifying and spatiotemporally tracking potentially relevant Spike protein mutations. We analyzed 167,893 Spike protein sequences from coronavirus disease 2019 (COVID-19) cases in the United States (excluding 21,391 sequences from VOI/VOC strains) deposited at GISAID from 19 January 2020 to 15 March 2021. Alignment against the reference Spike protein sequence led to the identification of viral residue variants (VRVs), i.e., residues harboring a substitution compared to the reference strain. Next, generalized additive models were applied to model VRV temporal dynamics and to identify VRVs with significant and substantial dynamics (false discovery rate q-value < 0.01; maximum VRV proportion >10% on at least one day). Unsupervised learning was then applied to hierarchically organize VRVs by spatiotemporal patterns and identify VRV-haplotypes. Finally, homology modeling was performed to gain insight into the potential impact of VRVs on Spike protein structure. We identified 90 VRVs, 71 of which had not previously been observed in a VOI/VOC, and 35 of which have emerged recently and are durably present. Our analysis identified 17 VRVs ~91 days earlier than their first corresponding VOI/VOC publication. Unsupervised learning revealed eight VRV-haplotypes of four VRVs or more, suggesting two emerging strains (B1.1.222 and B.1.234). Structural modeling supported a potential functional impact of the D1118H and L452R mutations. The SLS approach equally monitors all Spike residues over time, independently of existing phylogenic classifications, and is complementary to existing genomic surveillance methods.

SUBMITTER: Zhao LP

PROVIDER: S-EPMC8777887 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionThe emergence of novel SARS-CoV-2 has caused a pandemic of Coronavirus Disease 19 (COVID-19) which has spread exponentially worldwide. A robust surveillance system is essential for correct estimation of the disease burden and containment of the pandemic. We evaluated the performance of COVID-19 case-based surveillance system in FCT, Nigeria and assessed its key attributes.MethodsWe used a cross-sectional study design, comprising a survey, key informant interview, record review and secondary data analysis. A self-administered, semi-structured questionnaire was administered to key stakeholders to assess the attributes and process of operation of the surveillance system using CDC's Updated Guidelines for Evaluation of Public Health Surveillance System 2001. Data collected alongside surveillance data from March 2020 to January 2021 were analyzed and summarized using descriptive statistics.ResultsOut of 69,338 suspected cases, 12,595 tested positive with RT-PCR with a positive predictive value (PPV) of 18%. Healthcare workers were identified as high-risk group with a prevalence of 23.5%. About 82% respondents perceived the system to be simple, 85.5% posited that the system was flexible and easily accommodates changes, 71.4% reported that the system was acceptable and expressed willingness to continue participation. Representativeness of the system was 93%, stability 40%, data quality 56.2% and timeliness 45.5%, estimated result turnaround time (TAT) was suboptimal.ConclusionThe system was found to be useful, simple, flexible, sensitive, acceptable, with good representativeness but the stability, data quality and timeliness was poor. The system meets initial surveillance objectives but rapid expansion of sample collection and testing sites, improvement of TAT, sustainable funding, improvement of electronic database, continuous provision of logistics, supplies and additional trainings are needed to address identified weaknesses, optimize the system performance and meet increasing need of case detection in the wake of rapidly spreading pandemic. More risk-group persons should be tested to improve surveillance effectiveness.

Project description:BackgroundIn the United States, Coronavirus Disease 2019 (COVID-19) deaths are captured through the National Notifiable Disease Surveillance System and death certificates reported to the National Vital Statistics System (NVSS). However, not all COVID-19 deaths are recognized and reported because of limitations in testing, exacerbation of chronic health conditions that are listed as the cause of death, or delays in reporting. Estimating deaths may provide a more comprehensive understanding of total COVID-19-attributable deaths.MethodsWe estimated COVID-19 unrecognized attributable deaths, from March 2020-April 2021, using all-cause deaths reported to NVSS by week and six age groups (0-17, 18-49, 50-64, 65-74, 75-84, and ≥85 years) for 50 states, New York City, and the District of Columbia using a linear time series regression model. Reported COVID-19 deaths were subtracted from all-cause deaths before applying the model. Weekly expected deaths, assuming no SARS-CoV-2 circulation and predicted all-cause deaths using SARS-CoV-2 weekly percent positive as a covariate were modelled by age group and including state as a random intercept. COVID-19-attributable unrecognized deaths were calculated for each state and age group by subtracting the expected all-cause deaths from the predicted deaths.FindingsWe estimated that 766,611 deaths attributable to COVID-19 occurred in the United States from March 8, 2020-May 29, 2021. Of these, 184,477 (24%) deaths were not documented on death certificates. Eighty-two percent of unrecognized deaths were among persons aged ≥65 years; the proportion of unrecognized deaths were 0•24-0•31 times lower among those 0-17 years relative to all other age groups. More COVID-19-attributable deaths were not captured during the early months of the pandemic (March-May 2020) and during increases in SARS-CoV-2 activity (July 2020, November 2020-February 2021).InterpretationEstimating COVID-19-attributable unrecognized deaths provides a better understanding of the COVID-19 mortality burden and may better quantify the severity of the COVID-19 pandemic.FundingNone.

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Tracking SARS-CoV-2 Spike Protein Mutations in the United States (January 2020-March 2021) Using a Statistical Learning Strategy.

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