On March 29, 2021, this report was posted as an MMWR Early Release on the MMWR website (https://www.cdc.gov/mmwr)Messenger RNA (mRNA) BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccines have been shown to be effective in preventing symptomatic COVID-19 in randomized placebo-controlled Phase III trials (1,2); however, the benefits of these vaccines for preventing asymptomatic and symptomatic SARS-CoV-2 (the virus that causes COVID-19) infection, particularly when administered in real-world conditions, is less well understood. Using prospective cohorts of health care personnel, first responders, and other essential and frontline workers* in eight U.S. locations during December 14, 2020-March 13, 2021, CDC routinely tested for SARS-CoV-2 infections every week regardless of symptom status and at the onset of symptoms consistent with COVID-19-associated illness. Among 3,950 participants with no previous laboratory documentation of SARS-CoV-2 infection, 2,479 (62.8%) received both recommended mRNA doses and 477 (12.1%) received only one dose of mRNA vaccine. † Among unvaccinated participants, 1.38 SARS-CoV-2 infections were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) per 1,000 person-days. § In contrast, among fully immunized (≥14 days after second dose) persons, 0.04 infections per 1,000 person-days were reported, and among partially immunized (≥14 days after first dose and * Occupational categories: primary health care personnel (physicians, physician assistants, nurse practitioners, and dentists), other allied health care personnel (nurses, therapists, technicians, medical assistants, orderlies, and all other persons providing clinical support in inpatient or outpatient settings), first responders (firefighters, law enforcement, corrections, and emergency medical technicians), other essential and frontline workers (workers in hospitality, delivery, and retail; teachers; and all other occupations that require contact within 3 feet of the public, customers, or coworkers as a routine part of their job). † An additional five participants received the Janssen COVID-19 vaccine (Johnson & Johnson), resulting in 2,961 vaccinated participants. § Person-days is an estimate of the time-at-risk (to SARS-CoV-2 infection) that each participant contributed to the study.

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BACKGROUND: Information is limited on messenger RNA (mRNA) BNT162b2 (Pfizer–BioNTech) and mRNA–1273 (Moderna) COVID–19 vaccine effectiveness (VE) in preventing SARS–CoV–2 infection or attenuating disease when administered in real–world conditions. METHODS: Prospective cohorts of 3,975 healthcare personnel, first responders, and other essential and frontline workers completed weekly SARS–CoV–2 testing during December 14 2020—April 10 2021. Self–collected mid–turbinate nasal swabs were tested by qualitative and quantitative reverse–transcription—polymerase–chain–reaction (RT–PCR). VE was calculated as 100%× (1−hazard ratio); adjusted VE was calculated using vaccination propensity weights and adjustments for site, occupation, and local virus circulation . RESULTS: SARS–CoV–2 was detected in 204 (5.1%) participants; 16 were partially (≥14 days post–dose–1 to 13 days after dose–2) or fully (≥14 days post–dose–2) vaccinated, and 156 were unvaccinated; 32 with indeterminate status (<14 days after dose–1) were excluded. Adjusted mRNA VE of full vaccination was 91% (95% confidence interval [CI]=76%—97%) against symptomatic or asymptomatic SARS–CoV–2 infection; VE of partial vaccination was 81% (95% CI=64%–90%). Among partially or fully vaccinated participants with SARS–CoV–2 infection, mean viral RNA load (Log10 copies/mL) was 40% lower (95% CI=16%–57%), the risk of self–reported febrile COVID–19 was 58% lower (Risk Ratio=0.42, 95% CI=0.18–0.98), and 2.3 fewer days (95% CI=0.8–3.7) were spent sick in bed compared to unvaccinated infected participants. CONCLUSIONS: Authorized mRNA vaccines were highly effective among working–age adults in preventing SARS–CoV–2 infections when administered in real–world conditions and attenuated viral RNA load, febrile symptoms, and illness duration among those with breakthrough infection despite vaccination.

Apolipoprotein (Apo) E is one of the five main types of blood lipoproteins (A–E). It is synthesized primarily in the liver and brain and helps in transporting lipids from one place to another as well as facilitates the clearing of dietary fats, such as triglycerides, from the blood. The ApoE gene exists in three different forms: E2, E3 and E4. E3 is considered to be the normal form. Variants of the ApoE gene have been associated with various diseases. Developing an assay for the genotyping of ApoE variants for use both in clinical and large cohort based association settings would be extremely valuable and would require the use of a platform that has high-throughput capabilities and is highly accurate. Here we describe an assay for the simultaneous genotyping of the ApoE variants in a single bi-plex reaction and a single well using the matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry and the homogeneous mass-extend (hME) technology. The assay is robust, highly accurate and suitable for both clinical applications and for the genotyping of large disease cohorts. Moreover, the prevalence of ApoE variants in a cohort of Caucasians from the central Wisconsin area is outlined.

ABSTRACT:No major susceptibility genes for sporadically occurring congenital vertebral malformations (CVM) in humans have been identified to date. Body patterning genes whose mutants cause axial skeletal anomalies in mice are candidates for human CVM susceptibility. T (also known as Brachyury) and TBX6 are critical genes needed to establish mesodermal identity. We hypothesized that mutations in T and/or TBX6 contribute to the pathogenesis of human CVMs. The complete T and TBX6 coding regions, splice junctions, and proximal 500 bp of the promoters were sequenced in 50 phenotyped patients with CVM. Three unrelated patients with sacral agenesis, Klippel-Feil syndrome, and multiple cervical and thoracic vertebral malformations were heterozygous for a c.1013C>T substitution, resulting in a predicted Ala338Val missense alteration in exon 8. A clinically unaffected parent of each patient also harbored the substitution, but the variant did not occur in an ethnically diverse, 443-person reference population. The c.1013C>T variant is significantly associated with CVM (p < 0.001). Alanine 338 shows moderate conservation across species, and valine at this position has not been reported in any species. A fourth patient harbored a c.908-8C>T variant in intron 7. This previously unreported variant was tested in 347 normal control subjects, and 11 heterozygotes and 2 T/T individuals were found. No TBX6 variants were identified. We infer that the c.1013C>T substitution is pathogenic and represents the first report of an association between a missense mutation in the T gene and the occurrence of sporadic CVMs in humans. It is uncertain whether the splice junction variant increases CVM risk. TBX6 mutations do not seem to be associated with CVM. We hypothesize that epistatic interactions between T and other developmental genes and the environment modulate the phenotypic consequences of T variants.

BackgroundThere is a lack of knowledge regarding the frequency of disease associated polymorphisms in populations and population attributable risk for many populations remains unknown. Factors that could affect the association of the allele with disease, either positively or negatively, such as race, ethnicity, and gender, may not be possible to determine without population based allele frequencies.Here we used a panel of 51 polymorphisms previously associated with at least one disease and determined the allele frequencies within the entire Personalized Medicine Research Project population based cohort. We compared these allele frequencies to those in dbSNP and other data sources stratified by race. Differences in allele frequencies between self reported race, region of origin, and sex were determined.ResultsThere were 19544 individuals who self reported a single racial category, 19027 or (97.4%) self reported white Caucasian, and 11205 (57.3%) individuals were female. Of the 11,208 (57%) individuals with an identifiable region of origin 8337 or (74.4%) were German.41 polymorphisms were significantly different between self reported race at the 0.05 level. Stratification of our Caucasian population by self reported region of origin revealed 19 polymorphisms that were significantly different (p = 0.05) between individuals of different origins. Further stratification of the population by gender revealed few significant differences in allele frequencies between the genders.ConclusionsThis represents one of the largest population based allele frequency studies to date. Stratification by self reported race and region of origin revealed wide differences in allele frequencies not only by race but also by region of origin within a single racial group. We report allele frequencies for our Asian/Hmong and American Indian populations; these two minority groups are not typically selected for population allele frequency detection. Population wide allele frequencies are important for the design and implementation of studies and for determining the relevance of a disease associated polymorphism for a given population.

c Anaplasmosis and ehrlichiosis are emerging tick-borne diseases with clinically similar presentations caused by closely related pathogens. Currently, laboratories rely predominantly on blood smear analysis (for the detection of intracellular morulae) and on serologic tests, both of which have recognized limitations, for diagnostic purposes. We compared the performance of a published real-time PCR assay that incorporates melt curve analysis to differentiate Anaplasma and Ehrlichia species with blood smear and serologic methods in an upper Midwest population. Overall, 38.5% of the specimens selected for evaluation had one or more tests that were positive for anaplasmosis. The PCR positivity for all specimens was maximal (21.2%; 29/137) during the early acute phase of illness (0 to 4 days since illness onset) and significantly less frequent (11.5%; 20/174) during later phases (>4 days since illness onset). All positive specimens were Anaplasma phagocytophilum; no Ehrlichia species were identified. The realtime PCR detected 100% of infections that were detected by blood smear analysis (14/14) and broadened the detection window from a maximum of 14 days for smear positivity to 30 days for PCR. Additional infections were detected by real-time PCR in 12.9% (11/85) of smear-negative patients. There was poor agreement between the real-time PCR assay and serologic test results: 19.8% (19/96) and 13.7% (29/212) of seropositive and -negative patients, respectively, were PCR positive. Seropositivity increased with increasing days of illness, demonstrating that serologic detection methods are best utilized during presumed convalescence. Our results indicate that the optimal performance and utilization of laboratory tests for the diagnosis of anaplasmosis require knowledge regarding time of symptom onset or days of illness.

The genome-wide association study (GWAS) is a powerful approach for studying the genetic complexities of human disease. Unfortunately, GWASs often fail to identify clinically significant associations and describing function can be a challenge. GWAS is a phenotype-to-genotype approach. It is now possible to conduct a converse genotype-to-phenotype approach using extensive electronic medical records to define a phenome. This approach associates a single genetic variant with many phenotypes across the phenome and is called a phenome-wide association study (PheWAS). The majority of PheWASs conducted have focused on variants identified previously by GWASs. This approach has been efficient for rediscovering gene-disease associations while also identifying pleiotropic effects for some single-nucleotide polymorphisms (SNPs). However, the use of SNPs identified by GWAS in a PheWAS is limited by the inherent properties of the GWAS SNPs, including weak effect sizes and difficulty when translating discoveries to function. To address these challenges, we conducted a PheWAS on 105 presumed functional stop-gain and stop-loss variants genotyped on 4235 Marshfield Clinic patients. Associations were validated on an additional 10 640 Marshfield Clinic patients. PheWAS results indicate that a nonsense variant in ARMS2 (rs2736911) is associated with age-related macular degeneration (AMD). These results demonstrate that focusing on functional variants may be an effective approach when conducting a PheWAS.