Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Classic Maya Settlement and Politics in the Rosario Valley, Chiapas, Mexico. (Volumes I-Iii).

This study reports on and analyzes results of archaeological settlement survey in the Rosario Valley, Chiapas, Mexico. The area surveyed, just over 50 square kilometers, corresponds to the densely settled core of a small Late/Terminal Classic Period (A.D. 700 to 950) Maya polity, on the Maya Lowl and s' southwest edge. Estimated core population is 10,000 to 20,000 people, distributed over 198 sites. Settlement was very sparse in the periods preceding or following the Late/Terminal Classic Period. The Rosario polity was one of several in the Upper Grijalva Tributaries Region. These polities appear to have been colonial dependencies of larger Maya centers in the Usumacinta zone. The project's aim was to characterize ancient sociopolitical structure in the Late/Terminal Classic Period Rosario Valley through an analysis of settlement remains. The theoretical framework consisted of a set of closely related continua of variation along which the Rosario polity could be placed. The principal continua concerned: segmentary versus unitary political structure; pyramidal versus hierarchical politico-administrative structure; group versus individual political stratification; and mechanical versus organic economic solidarity. Archaeological measures were devised for charting the Rosario polity's position along each continuum. Basic analytical elements were measures of population (numbers of housemounds) and political importance (numbers and kinds of civic-ceremonial buildings). Analyses showed that the Rosario polity had a tendency towards unitary political structure on most archaeological measures. There was a more hierarchical than pyramidal form of politico-administrative structure. There was individual rather than group political stratification. and economic solidarity was more mechanical than organic. Additionally it was found that the layout of civic-ceremonial plazas at the capital site, Tenam Rosario, replicated in microcosmic form the territorial structure of the polity. Besides characterizing the entire Rosario polity, it was possible to characterize and compare its constituent territorial subdivisions. This revealed a good deal of internal variability. Ultimately it will be valuable to compare results from this case study to those from other completely surveyed portions of the Maya Lowl and s to arrive at an improved underst and ing of Classic Maya settlement and politics.Ph.D.ArchaeologyNative American studiesUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/160782/1/8600433.pd