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COVID-19 GPH|COVID-19 Genomics and Precision Public Health Weekly Update|PHGKB
Publication Date: Feb 25, 2021
Pathogen and Human Genomics Studies

A genomic region associated with protection against severe COVID-19 is inherited from Neandertals.
Zeberg Hugo et al. Proceedings of the National Academy of Sciences of the United States of America 2021 03 (9) >

Using data from the GenOMICC consortium, we show that a haplotype at a region on chromosome 12 associated with requiring intensive care when infected with the virus is inherited from Neandertals. This region encodes proteins that activate enzymes that are important during infections with RNA viruses. In contrast to the previously described Neandertal haplotype that increases the risk for severe COVID-19, this Neandertal haplotype is protective against severe disease
High throughput detection and genetic epidemiology of SARS-CoV-2 using COVIDSeq next-generation sequencing.
Bhoyar Rahul C et al. PloS one 2021 (2) e0247115>
The rapid emergence of coronavirus disease 2019 (COVID-19) as a global pandemic affecting millions of individuals globally has necessitated sensitive and high-throughput approaches for the diagnosis, surveillance, and determining the genetic epidemiology of SARS-CoV-2. In the present study, we used the COVIDSeq protocol, which involves multiplex-PCR, barcoding, and sequencing of samples for high-throughput detection and deciphering the genetic epidemiology of SARS-CoV-2.
Emergence in late 2020 of multiple lineages of SARS-CoV-2 Spike protein variants affecting amino acid position 677.
Hodcroft Emma B et al. medRxiv : the preprint server for health sciences 2021 Feb >
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S) plays critical roles in host cell entry. Non-synonymous substitutions affecting S are not uncommon and have become fixed in a number of SARS-CoV-2 lineages. A subset of such mutations enable escape from neutralizing antibodies or are thought to enhance transmission through mechanisms such as increased affinity for the cell entry receptor, angiotensin-converting enzyme 2 (ACE2).
Genomic Evidence of SARS-CoV-2 Reinfection Involving E484K Spike Mutation, Brazil.
Nonaka Carolina K V et al. Emerging infectious diseases 2021 Feb (5) >
Uncertainty remains about how long the protective immune responses against severe acute respiratory syndrome coronavirus 2 persists, and suspected reinfection in recovered patients has been reported. We describe a case of reinfection from distinct virus lineages in Brazil harboring the E484K mutation, a variant associated with escape from neutralizing antibodies
Viral genetic sequencing identifies staff transmission of COVID-19 is important in a community hospital outbreak
J Masoli et al, MEDRXIV, February 19, 2021>
Following multiple symptomatic cases within a two-week period, all staff and patients were screened by RT-PCR and staff subsequently had serology tests. Findings Thirty staff (25%) and 16 patients (62%) tested positive for COVID-19. Genomic sequencing data showed significant overlap of viral haplotypes in staff who had overlapping shift patterns
SARS-CoV-2 variant evolution in the United States: High accumulation of viral mutations over time likely through serial Founder Events and mutational bursts
RN Tasakis et al, BIORXIV, February 19,2021>
Our study focuses on a representative set of sequences from the United States throughout 2020 and early 2021. We show that the driving force behind the variants of public health concern, is widespread infection and superspreader events. In particular, we show accumulation of mutations over time with little loss from genetic drift, including in the Spike region, which could be problematic for vaccines and therapies.
Interleukin-3 is a predictive marker for severity and outcome during SARS-CoV-2 infections.
Bénard Alan et al. Nature communications 2021 02 (1) 1112>
In a prospective multicentric study, we identify IL-3 as an independent prognostic marker for the outcome during SARS-CoV-2 infections. Specifically, low plasma IL-3 levels is associated with increased severity, viral load, and mortality during SARS-CoV-2 infections. Patients with severe COVID-19 exhibit also reduced circulating plasmacytoid dendritic cells (pDCs) and low plasma IFNa and IFN? levels when compared to non-severe COVID-19 patients
Acquisition of the L452R mutation in the ACE2-binding interface of Spike protein triggers recent massive expansion of SARS-Cov-2 variants
V Tchesnokova et al, BIORXIV, February 22, 2021>
Ee investigated genetic variations in a 414-583 amino acid region of the Spike protein, across a subset of 570 nasopharyngeal samples isolated between April 2020 and February 2021, from Washington, California, Arizona, Colorado, Minnesota and Illinois. We found that samples isolated since November have an increased number of amino acid mutations in the region, with L452R being the dominant mutation. This mutation is associated with multiple outbreaks.
Estimating the spreading and dominance of SARS-CoV-2 VOC 202012/01 (lineage B.1.1.7) across Europe
N Gozzi et al, MEDRXIV, February 23, 2021>
We develop a two strain,compartmental model to assess the spreading potential of the B.1.1.7 variant across several European countries. The model accounts for B.1.1.7 introductions from the UK and different locations, as well as local mitigation policies in the time period 2020/09-2021/02. In the case of an increase of transmissibility of 50%, the B.1.1.7 variant has the potential to become dominant in all investigated areas by the end of March 2021.
Wastewater Monitoring of SARS-CoV-2 from Acute Care Hospitals Identifies Nosocomial Transmission and Outbreaks
N Acosta et al, MEDRXIV, February 23, 2021>
SARS-CoV-2 has been detected in wastewater and its abundance correlated with community COVID-19 cases, hospitalizations and deaths. We sought to use wastewater-based detection of SARS-CoV-2 to assess the epidemiology of SARS-CoV-2 in hospitals. Methods: Between August and December 2020, twice-weekly wastewater samples from three tertiary-care hospitals (totalling >2100 dedicated inpatient beds) were collected.
No higher infectivity but immune escape of SARS-CoV-2 501Y.V2 variants
Q Li et al, Cell, February 23, 2021>
The 501Y.V2 variants of SARS-CoV-2 containing multiple mutations in Spike are now dominant in South Africa and are rapidly spreading to other countries. Here, experiments with 18 pseudotyped viruses showed that the 501Y.V2 variants do not confer increased infectivity in multiple cell types except for murine ACE2-overexpressing cells, where a substantial increase in infectivity was observed.
Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine induced sera
D Zhou et al, Cell, February 23, 2021>
We describe a structure-function analysis of B.1.351 using a large cohort of convalescent and vaccinee serum samples. The receptor binding domain mutations provide tighter ACE2 binding and widespread escape from monoclonal antibody neutralization largely driven by E484K although K417N and N501Y act together against some important antibody classes. In a number of cases it would appear that convalescent and some vaccine serum offers limited protection against this variant.
BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting
N Dagan et al, NEJM, February 24, 2021>
In this study, data from Israel’s largest health care organization were used to evaluate the effectiveness of the BNT162b2 mRNA vaccine. Estimated vaccine effectiveness for the study outcomes at days 14 through 20 after the first dose and at 7 or more days after the second dose was as follows: for documented infection, 46% and 92% for symptomatic Covid-19, 57% and 94% for hospitalization, 74% and 87% and for severe disease, 62% and 92%, respectively.

Non-Genomics Precision Health Studiess

A deep learning integrated radiomics model for identification of coronavirus disease 2019 using computed tomography.
Zhang Xiaoguo et al. Scientific reports 2021 02 (1) 3938

We retrospectively collected CT images of 386 patients (129 with COVID-19 and 257 with other community-acquired pneumonia) from three medical centers to train and externally validate the developed models. A pre-trained DL algorithm was utilized to automatically segment infected lesions (ROIs) on CT images which were used for feature extraction. Five feature selection methods and four machine learning algorithms were utilized to develop radiomics models.
Accuracy of Smartphone Integrated Pulse Oximetry Meets Full FDA Clearance Standards for Clinical Use.
SH Browne et al, MEDRXIV, February 18, 2021
This is the first report of smartphone derived pulse oximetry measurements that meet full FDA/ISO accuracy certification requirements. Both Samsung S9 and S10 contain the same integrated pulse oximeter, thus over 100 million smartphones in current global circulation could be used to obtain clinically accurate spot SpO2 measurements to support at home assessment of COVID-19 patients.
Population subgroup differences in the use of a COVID-19 chatbot
LC Schubel et al, NPJ DIgital Medicine, February 19, 2021
COVID-19 chatbots are widely used to screen for symptoms and disseminate information about the virus, yet little is known about the population subgroups that interact with this technology and the specific features that are used. An analysis of 1,000,740 patients invited to use a COVID-19 chatbot, 69,451 (6.94%) of which agreed to participate, shows differences in chatbot feature use by gender, race, and age.
When Could the United States Reach Herd Immunity? It’s Complicated.
M Conlen et al, NY Times, February 20, 2021
A comprehensive overview of the COVID-19 literature: A machine learning-based bibliometric analysis.
Abd-Alrazaq Alaa et al. Journal of medical Internet research 2020 Nov
We used the COVID-19 Open Research Dataset (CORD-19) that consists of large number of articles related to all coronaviruses. We used machine learning method to analyze most relevant COVID-19 related articles and extracted most prominent topics. Specifically, we used clustering algorithm to group articles based on similarity of their abstracts to identify the research hotspots and current research directions. We have made our software accessible to the community via GitHub.
Discriminant Accuracy of the SOFA Score for Determining the Probable Mortality of Patients With COVID-19 Pneumonia Requiring Mechanical Ventilation.
Raschke Robert A et al. JAMA 2021 Feb
The SOFA score comprises 0 to 4 points assigned to each of 6 organ systems based on ratio of Pao2 to fraction inspired oxygen, Glasgow Coma Scale score, mean arterial pressure, serum creatinine level, bilirubin level, and platelet count. The SOFA score ranges from 0 to 24 points and higher scores indicate worse organ function.
CovidCTNet: an open-source deep learning approach to diagnose covid-19 using small cohort of CT images
Y Jahaveri et al, NPJ Digital Medicine, February 18, 2021
CovidCTNet is designed to work with heterogeneous and small sample sizes independent of the CT imaging hardware. To facilitate the detection of Covid-19 globally and assist radiologists and physicians in the screening process, we are releasing all algorithms and model parameter details as open-source.
Real-time analysis of a mass vaccination effort via an Artificial Intelligence platform confirms the safety of FDA-authorized COVID-19 vaccines
R McMurry et al, MEDRXIV, February 23, 2021
Curation from large-scale electronic health records (EHRs) allows for near real-time safety evaluations that were not previously possible. Here, we advance context- and sentiment-aware deep neural networks over the multi-state Mayo Clinic enterprise (Minnesota, Arizona, Florida, Wisconsin) for automatically curating the adverse effects mentioned by physicians in over 108,000 EHR clinical notes between December 1st 2020 to February 8th 2021.

News, Reviews and Commentaries

A universal coronavirus vaccine

WC Koff et al, Science, February 19, 2021

SARS-CoV-2 is rapidly adapting to humans, and other novel coronaviruses are mutating, recombining, and replicating in bats and other animal species, positioning to jump species sometime in the future. If we choose to wait for the next coronavirus to emerge, it may be too late, as it was with COVID-19. Creating the tools for preventing the next coronavirus pandemic is within our means.
When Could the United States Reach Herd Immunity? It’s Complicated.

M Conlen et al, NY Times, February 20, 2021
How Variants Complicate Everything

S Srinivasan et al, FiveThirtyEight, February 19, 2021
The Smartphone Pandemic: How Big Tech and public health authorities partner in the digital response to Covid-19.

Storeng Katerini Tagmatarchi et al. Global public health 2021 Feb 1-17

We discuss three main domains of public health action in which private technology companies and public health authorities have converged: contact-tracing, epidemic modelling and public health communication to manage the 'infodemic' of misinformation about the new coronavirus.
Could mutations of SARS-CoV-2 suppress diagnostic detection?

Ascoli Carl A et al. Nature biotechnology 2021 Feb
Stop variants by stopping the spread

CDC COVID Data Tracker Weekly Review, February 19, 2021

Viruses change (or mutate) all the time. While most changes do not affect how the virus behaves, every time a virus makes a copy of itself (or replicates) it has the potential to produce a variant virus that can spread more easily, cause more severe disease, or resist the body’s ability to fight them naturally or with vaccination. The best way to stop new variants from emerging is to stop the virus from spreading within our communities.
Evaluation of saliva as a complementary technique to the diagnosis of COVID-19: a systematic review.

Sagredo-Olivares K et al. Medicina oral, patologia oral y cirugia bucal 2021 Feb

Saliva samples analyzed by RT-qPCR, reverse transcription isothermal amplification (RT-LAMP), spectroscopy, and enzyme-linked immunosorbent assay (ELISA) offer high sensitivity to detect SARS-CoV-2 in the early stages of the disease and among asymptomatic patients as compared to nasopharyngeal swab RT-qPCR. In addition, the self-collection of saliva offers the possibility of receiving telemedicine instructions to carry out the test, reducing the risk of contagion.
Multisystem inflammatory syndrome in pediatric COVID-19 patients: a meta-analysis.

Toraih Eman A et al. World journal of pediatrics : WJP 2021 Feb

Analysis of 15 articles (318 COVID-19 patients) revealed that although many patients presented with the typical multisystem inflammatory syndrome in pediatrics, Kawasaki-like features as fever (82.4%), polymorphous maculopapular exanthema (63.7%), oral mucosal changes (58.1%), conjunctival injections (56.0%), edematous extremities (40.7%), and cervical lymphadenopathy (28.5%), atypical gastrointestinal (79.4%) and neurocognitive symptoms (31.8%) were also common.
Insights from SARS-CoV-2 sequences.

Martin Michael A et al. Science (New York, N.Y.) 2021 01 (6528) 466-467
Contact-tracing apps help reduce COVID infections, data suggest Evaluations find apps are useful, but would benefit from better integration into health-care systems.

D Lewis, Nature News, February 22,2 021
Trials of retooled vaccines for variants could take months: U.S. FDA

M Erman, Reuters, February 22, 2021
Methodological Approach for Wastewater Based Epidemiological Studies for SARS-CoV-2

H Kopperi et al, MEDRXIV, February 22, 2021

Post COVID-19 outbreak, wastewater-based epidemiology (WBE) studies as surveillance system is becoming an emerging interest due to its functional advantage as tool for early warning signal and to catalyze effective disease management strategies based on the community diagnosis.
Can COVID vaccines stop transmission? Scientists race to find answers Controlling the pandemic will require shots that prevent viral spread, but that feature is difficult to measure.

S Mallapaty, Nature News, February 19, 2021
Superspreading drives the COVID pandemic — and could help to tame it Uneven transmission of the SARS-CoV-2 coronavirus has had tragic consequences — but also offers clues for how best to target control measures.

D Lewis, Nature News, February 23, 2021
Report Outlines Strategy for Surveillance of Emerging Coronavirus Variants

J Stephenson et al, JAMA Health Forum, February 23, 2021
Adoption of COVID-19 Contact Tracing Apps: A Balance Between Privacy and Effectiveness.

Seto Emily et al. Journal of medical Internet research 2021 2
One Year of SARS-CoV-2 Evolution

A Wu et al, Cell, March 2021

Since the outbreak of SARS-CoV-2, the etiologic agent of the COVID-19 pandemic, the viral genome has acquired numerous mutations with the potential to increase transmission. One year after its emergence, we now further analyze emergent SARS-CoV-2 genome sequences in an effort to understand the evolution of this virus.
Studies Examine Variant Surging in California, and the News Isn’t Good Two studies confirm that a new coronavirus mutant in California is more contagious, although the scale of its threat is unclear.

C Zimmer, NY Times, February 23, 2021
Preliminary Survey Results Highlight Impact of COVID-19 on Rare Disease Community

M Macaluso, Rare Diseases Clinical Research Network, February 2021

A preliminary analysis of more than 3,400 responses to a recent survey of people living with rare diseases and their caregivers is shedding new light on their experiences during the novel coronavirus (COVID-19) pandemic. 71 responses indicated a positive COVID-19 diagnosis, a significant number of respondents were uncertain of their infection status due to difficulties accessing testing. Most who reported COVID-19 infection experienced a mild infection.
Researchers find worrying new coronavirus variant in New York City

M Fox, February 25,2021
Research in the Context of a Pandemic.

Lane H Clifford et al. The New England journal of medicine 2020 7 (8) 755-757

About Weekly Scan

This weekly update contains the latest information and publications on the impact of genomics and precision health technologies on the investigation and control of COVID-19. Items are selected by staff from the CDC Office of Genomics and Precision Public Health daily from the COVID-19 GPH.

Disclaimer: Articles listed in the Public Health Knowledge Base are selected by the CDC Office of Public Health Genomics to provide current awareness of the literature and news. Inclusion in the update does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article's methods or findings. CDC and DHHS assume no responsibility for the factual accuracy of the items presented. The selection, omission, or content of items does not imply any endorsement or other position taken by CDC or DHHS. Opinion, findings and conclusions expressed by the original authors of items included in the update, or persons quoted therein, are strictly their own and are in no way meant to represent the opinion or views of CDC or DHHS. References to publications, news sources, and non-CDC Websites are provided solely for informational purposes and do not imply endorsement by CDC or DHHS.