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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IMPORTANCE Data about the risk of SARS-CoV-2 infection among children compared with adults are needed to inform COVID-19 risk communication and prevention strategies, including COVID-19 vaccination policies for children. OBJECTIVE To compare incidence rates and clinical characteristics of SARS-CoV-2 infection among adults and children and estimated household infection risks within a prospective household cohort.

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.

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Physiological cardiac hypertrophy, in response to stimuli such as exercise, is considered adaptive and beneficial. In contrast, pathological cardiac hypertrophy that arises in response to pathological stimuli such as unrestrained high blood pressure and oxidative or metabolic stress is maladaptive and may precede heart failure. We found that the transcript encoding DNA-damage-inducible transcript 4-like (DDiT4L) was expressed in murine models of pathological cardiac hypertrophy, but not in those of physiological cardiac hypertrophy. In cardiomyocytes, DDiT4L localized to early endosomes and promoted stress-induced autophagy through a process involving mechanistic target of rapamycin complex 1 (mTORC1). Exposing cardiomyocytes to various types of pathological stress increased the abundance of DDiT4L, which inhibited mTORC1 but activated mTORC2 signaling. Mice with conditional cardiac-specific overexpression of DDiT4L had mild systolic dysfunction, increased baseline autophagy, reduced mTORC1 activity, and increased mTORC2 activity, all of which were reversed by suppression of transgene expression. Genetic suppression of autophagy also reversed cardiac dysfunction in these mice. Our data showed that DDiT4L may be an important transducer of pathological stress to autophagy through mTOR signaling in the heart and that DDiT4L could be therapeutically targeted in cardiovascular diseases in which autophagy and mTOR signaling play a major role.

Background-Since influenza often presents non-specifically in infancy, we aimed to assess the extent to which existing respiratory surveillance platforms might underestimate the frequency of severe influenza disease among infants.Methods-The Influenza and Respiratory Syncytial Virus in Infants (IRIS) study was a prospective observational study done at four hospitals in Albania, Jordan, Nicaragua, and the Philippines. We included acutely ill infants aged younger than 1 year admitted to hospital within 10 days or less of illness onset during two influenza seasons (2015-16 and 2016-17) in Albania, Jordan, and Nicaragua, and over a continuous 34 week period in the Philippines. We assessed the frequency of influenza virus infections by real-time RT-PCR (rRT-PCR) and serology. The main study outcome was seroconversion, defined as convalescent antibody titres more than or equal to four-fold higher than acute sera antibody titres, and convalescent antibody titres of 40 or higher. Seroconverison was confirmed by haemagglutination inhibition assay for influenza A viruses, and by hemagglutination inhibition assay and microneutralisation for influenza B viruses.Findings-Between June 27, 2015, and April 21, 2017, 3634 acutely ill infants were enrolled, of whom 1943 were enrolled during influenza seasons and had complete acute-convalescent pairs and thus were included in the final analytical sample. Of the 1943 infants, 94 (5%) were influenzapositive by both rRT-PCR and serology, 58 (3%) were positive by rRT-PCR-only, and 102 (5%) were positive by serology only. Seroconversion to at least one of the influenza A or B viruses was observed among 196 (77%) of 254 influenza-positive infants. Of the 254 infants with influenza virus, 84 (33%) only had non-respiratory clinical discharge diagnoses (eg, sepsis, febrile seizures, dehydration, or other non-respiratory viral illness). A focus on respiratory diagnoses and rRT-PCR-confirmed influenza underdetects influenza-associated hospital admissions among infants by a factor of 2•6 (95% CI 2•0-3•6). Findings were unchanged when syndromic severe acute respiratory infection criteria were applied instead of clinical diagnosis. Interpretation-If the true incidence of laboratory-confirmed influenza-associated hospital admissions among infants is at least twice that of previous estimates, this substantially increases the global burden of severe influenza and expands our estimates of the preventive value of maternal and infant influenza vaccination programmes.