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Hot Topics of the Day|PHGKB
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08/03/2022

Hot Topics of the Day are picked by experts to capture the latest information and publications on public health genomics and precision health for various diseases and health topics. Sources include published scientific literature, reviews, blogs and popular press articles.

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Association of Receiving a Fourth Dose of the BNT162b Vaccine With SARS-CoV-2 Infection Among Health Care Workers in Israel.
Cohen Matan J et al. JAMA network open 2022 8 (8) e2224657

Was there a benefit of vaccinating health care workers with a fourth dose of BNT162b2 vaccine during the Omicron variant outbreak of the COVID-19 pandemic? In this multicenter cohort study of 29?611 health care workers in Israel, the breakthrough infection rate among those who received 4 doses was 6.9% compared with 19.8% in those who received 3 doses.

Covid-19: is omicron less lethal than delta?
Lorenzo-Redondo Ramon et al. BMJ (Clinical research ed.) 2022 8 o1806

Neutralization of SARS-CoV-2 Omicron sublineages by 4 doses of mRNA vaccine
X Xie et al, BIORXIV, July 29, 2022

In sera from 2- 3- and 4-dose vaccinees in the US with and without BA.1 breakthrough, vaccine plus prior BA.1 better neutralized Omicron VOCs than 4-doses with no infection. Neutralization titers were similar for 2- and 3-doses post breakthrough and were 1.4, 4.8, 3.1, 4.1, 4.9, and 3.9x higher for WA1/2020, BA.1-, BA.2-, BA.212.1-, BA.3-, and BA.4/5, respectively, for 2-dose and breakthroughs vs 4 doses only.

Coronaviruses exploit a host cysteine-aspartic protease for replication
H Chu et al, Nature, August 3, 2022

We show that a cysteine-aspartic protease of the apoptosis cascade, caspase-6, serves as an important host factor for efficient coronavirus replication. We demonstrate that caspase-6 cleaves coronavirus nucleocapsid (N) proteins, generating N fragments that serve as interferon (IFN) antagonists, thus facilitating virus replication.

Heart disease after COVID: what the data say
SM Sidik, Nature, August 2, 2022

Some studies suggest that the risk of cardiovascular problems, such as a heart attack or stroke, remains high even many months after a SARS-CoV-2 infection clears up. Researchers are starting to pin down the frequency of these issues and what is causing the damage.

Cardiovascular safety of COVID-19 vaccines in real-world studies: a systematic review and meta-analysis
Y Chang et al, MEDRXIV, August 2, 2022

Association of SARS-CoV-2 BA.4/BA.5 Omicron lineages with immune escape and clinical outcome
JA Lewnard et al, MEDRXIV, August 2, 2022

Development, testing and validation of a SARS-CoV-2 multiplex panel for detection of the five major variants of concern on a portable PCR platform
BJ Stanhope et al, MEDRXIV, August 2, 2022

We have created a panel of four triplex RT-qPCR assays targeting 12 mutations to detect and differentiate all five variants of concern: Alpha, Beta, Gamma, Delta and Omicron. We also developed an expanded pentaplex assay that can reliably distinguish among the major sublineages (BA.1-BA.5) of Omicron. In silico, analytical and clinical testing of the variant panel indicate the assays have a sensitivity and specificity of >95%. This variant panel can be used as a Research Use Only screening tool for triaging SARS-CoV-2 positive samples prior to whole genome sequencing.

Limited induction of lung-resident memory T cell responses against SARS-CoV-2 by mRNA vaccination
DKJ Pieren et al, MEDRXIV, August 2, 2022

Metabolic control by the microbiome.
Cox Timothy O et al. Genome medicine 2022 7 (1) 80

We review the interactions between the metabolic activities of the microbiome and the systemic metabolism of the host. The concept that the endocrine system includes more than just the host component enables the rational design of exogenous interventions that shape human metabolism. An improved mechanistic understanding of the metabolic microbiome-host interaction may therefore pioneer actionable microbiota-based diagnostics or therapeutics

Universal screening for familial hypercholesterolemia in 2 populations.
Sustar Ursa et al. Genetics in medicine : official journal of the American College of Medical Genetics 2022 8

In Europe, >2 million individuals with familial hypercholesterolemia (FH) are currently undiagnosed. Effective screening strategies for FH diagnosis in childhood are urgently needed. We assessed the overall performances of 2 different FH screening programs in children: universal screening program with opt-out and opt-in type participation. Our study suggests that universal 3-step FH screening approach in children enabled detection of most children and their parents in every generation screened at reasonable costs. Opt-out screening strategy might be preferable over opt-in screening strategy.

Comprehensive genomic and epigenomic analysis in cancer of unknown primary guides molecularly-informed therapies despite heterogeneity.
Möhrmann Lino et al. Nature communications 2022 8 (1) 4485

The benefit of molecularly-informed therapies in cancer of unknown primary (CUP) is unclear. Here, we use comprehensive molecular characterization by whole genome/exome, transcriptome and methylome analysis in 70 CUP patients to reveal substantial mutational heterogeneity with TP53, MUC16, KRAS, LRP1B and CSMD3 being the most frequently mutated known cancer-related genes.

Diagnostic accuracy of telemedicine for detection of surgical site infection: a systematic review and meta-analysis
R Lathan et al, NPJ Digital Medicine, August 3, 2022

Summary sensitivity and specificity was 87.8% (95% CI, 68.4–96.1) and 96.8% (95% CI 93.5–98.4) respectively. The overall surgical site infection (SSI) rate was 5.6%. Photograph methods had lower sensitivity and specificity at 63.9% (95% CI 30.4–87.8) and 92.6% (95% CI, 89.9–94.5). Telemedicine is highly specific for SSI diagnosis is highly specific, giving rise to great potential for utilisation excluding SSI.

Circulating tumor DNA to guide rechallenge with panitumumab in metastatic colorectal cancer: the phase 2 CHRONOS trial.
Sartore-Bianchi Andrea et al. Nature medicine 2022 8

The primary endpoint of the trial was met; and, of 27 enrolled patients, eight (30%) achieved partial response and 17 (63%) disease control, including two unconfirmed responses. These clinical results favorably compare with standard third-line treatments and show that interventional liquid biopsies can be effectively and safely exploited in a timely manner to guide anti-EGFR rechallenge therapy with panitumumab in patients with mCRC.


Disclaimer: Articles listed in Hot Topics of the Day are selected by Public Health Genomics Branch to provide current awareness of the scientific 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 Clips, 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.
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