Antibody-Dependent Enhancement (ADE) and the role of complement system in disease pathogenesis.

Antibody-dependent enhancement (ADE) has been associated with severe disease outcomes in several viral infections, including respiratory infections. In vitro and in vivo studies showed that antibody-response to SARS-CoV and MERS-CoV could exacerbate infection via ADE. Recently in SARS CoV-2, the in vitro studies and structural analysis shows a risk of disease severity via ADE. This phenomenon is partially attributed to non-neutralizing antibodies or antibodies at sub-neutralizing levels. These antibodies result in antigen-antibody complexes' deposition and propagation of a chronic inflammatory process that destroys affected tissues. Further, antigen-antibody complexes may enhance the internalization of the virus into cells through the Fc gamma receptor (FcγR) and lead to further virus replication. Thus, ADE occur via two mechanisms; 1. Antibody mediated replication and 2. Enhanced immune activation. Antibody-mediated effector functions are mainly driven by complement activation, and the first complement in the cascade is complement 1q (C1q) which binds to the virus-antibody complex. Reports say that deficiency in circulating plasma levels of C1q, an independent predictor of mortality in high-risk patients, including diabetes, is associated with severe viral infections. Complement mediated ADE is reported in several viral infections such as dengue, West Nile virus, measles, RSV, Human immunodeficiency virus (HIV), and Ebola virus. This review discusses ADE in viral infections and the in vitro evidence of ADE in coronaviruses. We outline the mechanisms of ADE, emphasizing the role of complements, especially C1q in the outcome of the enhanced disease.

Antibiotic prescription patterns for upper respiratory tract infections in the outpatient Qatari population in the private sector.

BACKGROUND: Antibiotics are often inappropriately prescribed for upper respiratory tract infections (URTIs) in developed countries. Data on the proportion of inappropriate prescriptions are lacking from the Middle East and other developing countries. METHODS: Health insurance claims for all antibiotics prescribed for URTIs in the private sector in the State of Qatar between May 2014 and December 2015 were retrieved. During the study period, health insurance was limited to Qatari nationals. Topical antibiotics were excluded. Data on the prescriber's specialty, as listed with the licensing authority, were also retrieved. Diagnoses were classified as appropriate or inappropriate based on the likelihood of a bacterial etiology that may warrant antibiotic use. RESULTS: A total of 75 733 claims were made during the study period. Of these, 41 556 (55%) were for an appropriate indication, while 34 177 (45%) were for an inappropriate indication. The most common antibiotic classes prescribed were cephalosporins (43% of claims; 44% inappropriate), penicillins (28% of claims; 44% inappropriate), macrolides (19% of claims; 52% inappropriate), and fluoroquinolones (9% of claims; 40% inappropriate). Nearly 5% of antibiotics were prescribed in intravenous formulations. The most common prescribers were General/Family Practice physicians (53% of claims; 50% inappropriate), followed by Pediatrics (18.6% of claims; 36% inappropriate) and Internal Medicine (14.1% of claims; 44% inappropriate). CONCLUSIONS: There is a high rate of inappropriate antibiotic prescription for acute URTIs in the private health care sector in the State of Qatar. Further studies are needed to determine the population-based rates across the country. Interventions to decrease inappropriate use in such settings are urgently needed.