ACE-2-like enzymatic activity is associated with immunoglobulin in COVID-19 patients.

Many mechanisms responsible for COVID-19 pathogenesis are well-established, but COVID-19 includes features with unclear pathogenesis, such as autonomic dysregulation, coagulopathies, and high levels of inflammation. The receptor for the SARS-CoV-2 spike protein receptor-binding domain (RBD) is angiotensin-converting enzyme 2 (ACE2). We hypothesized that some COVID-19 patients may develop antibodies that have a negative molecular image of RBD sufficiently similar to ACE2 to yield ACE2-like catalytic activity-ACE2-like abzymes. To explore this hypothesis, we studied patients hospitalized with COVID-19 who had plasma samples available obtained about 7 days after admission. ACE2 is a metalloprotease that requires Zn2+ for activity. However, we found that the plasma from some patients studied could specifically cleave a synthetic ACE2 peptide substrate, even though the plasma samples were collected using disodium EDTA anticoagulant. When we spiked plasma with synthetic ACE2, no ACE2 substrate cleavage activity was observed unless Zn2+ was added or the plasma was diluted to decrease EDTA concentration. After processing samples by 100 kDa size exclusion columns and protein A/G adsorption, which depleted immunoglobulin by >99.99%, the plasma samples did not cleave the ACE2 substrate peptide. The data suggest that some patients with COVID-19 develop antibodies with abzyme-like activity capable of cleaving synthetic ACE2 substrate. Since abzymes can exhibit promiscuous substrate specificities compared to the enzyme whose active site image they resemble, and since proteolytic cascades regulate many physiologic processes, anti-RBD abzymes may contribute to some otherwise obscure COVID-19 pathogenesis. IMPORTANCE: We provide what we believe to be the first description of angiotensin-converting enzyme 2 (ACE2)-like enzymatic activity associated with immunoglobulin in COVID-19 patients. COVID-19 includes many puzzling clinical features that have unclear pathogenesis, including a hyperinflammatory state, abnormalities of the clotting cascade, and blood pressure instability. We hypothesized that some patients with COVID-19 patients may produce antibodies against SARS-CoV-2 with enzymatic activity, or abzymes, that target important proteolytic regulatory cascades. The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein binds ACE2 on the surface of the future host cell. This means that the RBD has a negative molecular image of ACE2. We hypothesized that some antibodies produced against the RBD would have, in turn, a negative molecular image of the RBD sufficiently similar to ACE2 to have ACE2-like catalytic activity. In other words, some anti-RBD antibodies would be ACE2-like abzymes. Abzymes elicited by SARS-CoV-2 infection have the potential to affect host physiology.

The impact of air pollution on asthma: clinical outcomes, current epidemiology, and health disparities.

INTRODUCTION: Air pollution has been shown to have a significant impact on morbidity and mortality of respiratory illnesses including asthma. AREAS COVERED: Outdoor air pollution consists of a mixture of individual pollutants including vehicle traffic and industrial pollution. Studies have implicated an array of individual components of air pollution, with PM2.5, NO2, SO2, and ozone being the most classically described, and newer literature implicating other pollutants such as black carbon and volatile organic compounds. Epidemiological and cohort studies have described incidence and prevalence of pollution-related asthma and investigated both acute and chronic air pollution exposure as they relate to asthma outcomes. There is an increasing body of literature tying disparities in pollution exposure to clinical outcomes. In this narrative review, we assessed the published research investigating the association of pollution with asthma outcomes, focusing on the adult population and health care disparities. EXPERT OPINION: Pollution has multiple deleterious effects on respiratory health but there is a lack of data on individualized pollution monitoring, making it difficult to establish a temporal relationship between exposure and symptoms, thereby limiting our understanding of safe exposure levels. Future research should focus on more personalized monitoring and treatment plans for mitigating exposure.