We measured plasma and/or serum antibody responses to the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2 in 343 North American patients infected with SARS-CoV-2 (of which 93% required hospitalization) up to 122 days after symptom onset and compared them to responses in 1548 individuals whose blood samples were obtained prior to the pandemic. After setting seropositivity thresholds for perfect specificity (100%), we estimated sensitivities of 95% for IgG, 90% for IgA, and 81% for IgM for detecting infected individuals between 15 and 28 days after symptom onset. While the median time to seroconversion was nearly 12 days across all three isotypes tested, IgA and IgM antibodies against RBD were short-lived with median times to seroreversion of 71 and 49 days after symptom onset. In contrast, anti-RBD IgG responses decayed slowly through 90 days with only 3 seropositive individuals seroreverting within this time period. IgG antibodies to SARS-CoV-2 RBD were strongly correlated with anti-S neutralizing antibody titers, which demonstrated little to no decrease over 75 days since symptom onset. We observed no cross-reactivity of the SARS-CoV-2 RBD-targeted antibodies with other widely circulating coronaviruses (HKU1, 229 E, OC43, NL63). These data suggest that RBD-targeted antibodies are excellent markers of previous and recent infection, that differential isotype measurements can help distinguish between recent and older infections, and that IgG responses persist over the first few months after infection and are highly correlated with neutralizing antibodies.
Background: Variable health literacy and genetic knowledge may pose significant challenges to engaging the general public in personal genomics, specifically with respect to promoting risk comprehension and healthy behaviors. Methods: We are conducting a multistage study of individual responses to genomic risk information for Type 2 diabetes mellitus. A total of 300 individuals were recruited from the general public in Durham, North Carolina: 60% self-identified as White; 70% female; and 65% have a college degree. As part of the baseline survey, we assessed genetic knowledge and attitudes toward genetic testing. Results: Scores of factual knowledge of genetics ranged from 50% to 100% (average = 84%), with significant differences in relation to racial groups, the education level, and age. Scores were significantly higher on questions pertaining to the inheritance and causes of disease (mean score 90%) compared to scientific questions (mean score 77.4%). Scores on the knowledge survey were significantly higher than scores from European populations. Participants' perceived knowledge of the social consequences of genetic testing was significantly lower than their perceived knowledge of the medical uses of testing. More than half agreed with the statement that testing may affect a person's ability to obtain health insurance (51.3%) and 16% were worried about the consequences of testing for chances of finding a job. Conclusions: Despite the relatively high educational status and genetic knowledge of the study population, we find an imbalance of knowledge between scientific and medical concepts related to genetics as well as between the medical applications and societal consequences of testing, suggesting that more effort is needed to present the benefits, risks, and limitations of genetic testing, particularly, at the social and personal levels, to ensure informed decision making.
BACKGROUND Characterizing the humoral immune response to SARS-CoV-2 and developing accurate serologic assays are needed for diagnostic purposes and estimating population-level seroprevalence. METHODS We measured the kinetics of early antibody responses to the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2 in a cohort of 259 symptomatic North American patients infected with SARS-CoV-2 (up to 75 days after symptom onset) compared to antibody levels in 1548 individuals whose blood samples were obtained prior to the pandemic. RESULTS Between 14-28 days from onset of symptoms, IgG, IgA, or IgM antibody responses to RBD were all accurate in identifying recently infected individuals, with 100% specificity and a sensitivity of 97%, 91%, and 81% respectively. Although the estimated median time to becoming seropositive was similar across isotypes, IgA and IgM antibodies against RBD were short-lived with most individuals estimated to become seronegative again by 51 and 47 days after symptom onset, respectively. IgG antibodies against RBD lasted longer and persisted through 75 days post-symptoms. IgG antibodies to SARS-CoV-2 RBD were highly correlated with neutralizing antibodies targeting the S protein. No cross-reactivity of the SARS-CoV-2 RBD-targeted antibodies was observed with several known circulating coronaviruses, HKU1, OC 229 E, OC43, and NL63. CONCLUSIONS Among symptomatic SARS-CoV-2 cases, RBD-targeted antibodies can be indicative of previous and recent infection. IgG antibodies are correlated with neutralizing antibodies and are possibly a correlate of protective immunity.
It is anticipated that as the range of drugs for which pharmacogenetic testing becomes available expands, primary care physicians (PCPs) will become major users of these tests. To assess their training, familiarity, and attitudes toward pharmacogenetic testing in order to identify barriers to uptake that may be addressed at this early stage of test use, we conducted a national survey of a sample of PCPs. Respondents were mostly white (79%), based primarily in community-based primary care (81%) and almost evenly divided between family medicine and internal medicine. The majority of respondents had heard of PGx testing and anticipated that these tests are or would soon become a valuable tool to inform drug response. However, only a minority of respondents (13%) indicated they felt comfortable ordering PGx tests and almost a quarter reported not having any education about pharmacogenetics. CONCLUSIONS Our results indicate that primary care practitioners envision a major role for themselves in the delivery of PGx testing but recognize their lack of adequate knowledge and experience about these tests. Development of effective tools for guiding PCPs in the use of PGx tests should be a high priority.
there would be a small difference in the rate of neonatal sepsis, although not statistically significant, with a relative risk of 0.66, absolute risk difference of 1.4%, and a number needed to treat of 71. The authors conclude by stating that there is sufficient evidence to support EM of PPROM in the late preterm period.Unfortunately, if we had no existing policy, that might be true. However, most facilities have existing policies of delivery of women with PPROM in the late preterm period, most at 34 weeks' gestation. The current study should not push providers to change their policy for 3 reasons. One, they do not demonstrate any improvement over the current policy of IoL from EM. Two, the study was certainly not powered to demonstrate safety of EM with regard to stillbirth, abruption, or cord prolapse. Finally, the study's one positive finding was a greater risk of clinical chorioamnionitis in the EM arm.So, I would hold steady with my current PPROM management schema. The good news is that the Australian study is funded to recruit more than 1800 women, which will more than triple the data from recent studies and more than double the total data in the existing literature. With that study completed in the future, our answers regarding the short-term outcomes using modern data should be answered. Hopefully, both these authors and the Australians will conduct long-term neonatal follow-up for developmental, behavioral, and scholastic performance outcomes.VABC) ABSTRACTWith the expansion of drugs available for pharmacogenetic (PGx) testing, primary care physicians (PCPs) will likely become major users of these tests. Pharmacogenetics uses genetic tests to determine the proper and optimal pharmaceutical therapy for an individual patient with the goal of reducing adverse reactions and improving drug efficacy. Because implementation of PGx testing has been slow, this national survey of a sample of PCPs was undertaken to assess their training, familiarity with, and attitudes toward PGx testing and to identify barriers to test use. Primary care physicians were asked about their willingness and readiness to use PGx testing, desirable test properties, and relevant factors for using such tests.Survey questions were based on a literature review and focus groups of health professionals. After a pretest survey was completed by a panel of PCPs, the final survey had 6 major parts with 101 questions. The survey sample was obtained from the AMA Physician Masterfile through Direct Medical Data. Inclusion criteria were board certification in either family medicine or internal medicine but not in a subspecialty, licensed to practice in their state of residence, and graduated between 1970 and 2003. A total of 4000 names were randomly selected from 47,348 internists and 47,179 family medicine practitioners. Data were collected from a mailed survey invitation and questionnaire. Of 3045 confirmed names and addresses, 597 completed the survey, 3 were not eligible, and 2445 did not respond, for a cooperation rate of 20% (597/3042).When PCPs...
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