COVID-19 has prematurely ended many lives, particularly among the oldest Americans, but the pandemic has also had an indirect effect on health and non-COVID mortality among the working-age population, who have suffered the brunt of the economic consequences. This analysis quantifies the changes in mortality for selected causes of death during the COVID-19 pandemic up to December 31, 2020, and investigates whether the levels of excess mortality varied by age group. The data comprise national-level monthly death counts by age group and selected causes of death from January 1999 to December 2020 combined with annual mid-year population estimates over the same period. A negative binomial regression model was used to estimate monthly cause-specific excess mortality during 2020 controlling for the pre-pandemic mortality patterns by age, calendar year, and season. To determine whether excess mortality varied by age, we tested interactions between broad age groups and dichotomous indicators for the pre-pandemic (Januease in mortality from external causes, which was evident even during January-February 2020. Exploratory analyses suggest that drug-related mortality may be driving the early rise in external mortality. The growth in drug overdoses well before there was any hint of a pandemic suggests it is probably not solely an indirect effect of COVID-19, although the pandemic may have exacerbated the problem.
  Mass vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is on-going in the United States with vaccines approved for emergency use by the FDA. Each vaccine can induce spike-specific antibodies (Abs) with virus-neutralizing activities; however, the Fc-mediated Ab activities have received little attention. Moreover, while plasma/serum Abs are commonly studied, scant information is available about Abs in the respiratory mucosa, the site of SARS-CoV-2 transmission.
 
  Plasma and saliva were collected from mRNA vaccine recipients and convalescent coronavirus disease 2019 (COVID-19) patients. Antigen-specific total Ig and Ig isotypes were measured. In addition to virus neutralization, Fc-mediated activities were investigated, including antibody-dependent cellular phagocytosis (ADCP) and complement deposition.
 
  Similar to infection, vaccination stimulated spike-specific Ab responses detected in plasma and saliva, with IgG1 as the dominant isotype.  https://www.selleckchem.com/products/Zileuton.html  Interestingly, vaccination produced greater IgG2, IgG3, and IgG4 responses and higher ratios of (IgG1+IgG3)/(IgG2+IgG4) than infection. Moreover, while plasma neutralization and ADCP potencies were comparable in vaccinated and convalescent individuals, vaccine-induced plasma Abs elicited stronger complement binding and activation.
 
  Compared with natural infection, mRNA vaccines induced a greater array of IgG subtypes against spike in saliva and plasma. The vaccine-induced Abs were also more potent in mediating complement activation.
 Compared with natural infection, mRNA vaccines induced a greater array of IgG subtypes against spike in saliva and plasma. The vaccine-induced Abs were also more potent in mediating complement activation.The durability of circulating neutralizing antibody (nAb) responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and their boosting by vaccination remains to be defined. We show that outpatient and hospitalized SARS-CoV-2 seropositive individuals mount a robust neutralizing antibody (nAb) response that peaks at days 23 and 27 post-symptom onset, respectively. Although nAb titers remained higher in hospitalized patients, both study groups showed long-lasting nAb responses that can persist for up to 12 months after natural infection. These nAb responses in previously seropositive individuals can be significantly boosted through immunization with two doses of the CoronaVac (Sinovac) or one dose of the BNT162b2 (BioNTech/Pfizer) vaccines, suggesting a substantial induction of B cell memory responses. Noteworthy, three obese previously seropositive individuals failed to mount a booster response upon vaccination, warranting further studies in this population. Immunization of naïve individuals with two doses of the CoronaVac vaccine or one dose of the BNT162b2 vaccine elicited similar levels of nAbs compared to seropositive individuals 4.2 to 13.3 months post-infection with SARS-CoV-2. Thus, this preliminary evidence suggests that both, seropositive and naïve individuals, require two doses of CoronaVac to ensure the induction of robust nAb titers.
  Evidence has shown that a large proportion of SARS-CoV-2 infected individuals do not experience symptomatic disease. Owing to its critical role in immune response, we hypothesized that variation in the 
  (HLA) loci may underly asymptomatic infection.
 
  We enrolled 29,947 individuals registered in the National Marrow Donor Program for whom high-resolution 
  genotyping data were available in a smartphone-based study designed to track COVID-19 symptoms and outcomes. Among 21,893 individuals who completed the baseline survey, our discovery (N=640) and replication (N=788) cohorts were comprised of self-identified White subjects who reported a positive test result for SARS-CoV-2. We tested for association of five 
  loci ( 
  ) with asymptomatic vs. symptomatic infection.
 
  was significantly increased in asymptomatic individuals in the discovery cohort compared to symptomatic (OR = 2.45; 95%CI 1.38-4.24, 
  = 0.0016, 
  
  = 0.048), and we reproduced this association in the replication cohort (OR= 2.32; 95%CI = 1.10-4.43, 
  = 0.017). We found robust association of 
  in the combined dataset (OR=2.40 95% CI = 1.54-3.64; 
  = 5.67 ×10 
  ) and observed that homozygosity of this allele increases more than eight times the chance of remaining asymptomatic after SARS-CoV-2 infection (OR = 8.58, 95%CI = 1.74-34.43, 
  = 0.003). Finally, we demonstrated the association of 
  with asymptomatic SARS-Cov-2 infection is enhanced by the presence of 
  .
 
  is strongly associated with asymptomatic infection with SARS-CoV-2 and is likely to be involved in the mechanism underlying early viral clearance.
 HLA-B*1501 is strongly associated with asymptomatic infection with SARS-CoV-2 and is likely to be involved in the mechanism underlying early viral clearance.