Aerosol delivery of SARS-CoV-2 human monoclonal antibodies in macaques limits viral replication and lung pathology.

Passively administered monoclonal antibodies (mAbs) given before or after viral infection can prevent or blunt disease. Here, we examine the efficacy of aerosol mAb delivery to prevent infection and disease in rhesus macaques inoculated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant via intranasal and intratracheal routes. SARS-CoV-2 human mAbs or a human mAb directed to respiratory syncytial virus (RSV) are nebulized and delivered using positive airflow via facemask to sedated macaques pre- and post-infection. Nebulized human mAbs are detectable in nasal, oropharyngeal, and bronchoalveolar lavage (BAL) samples. SARS-CoV-2 mAb treatment significantly reduces levels of SARS-CoV-2 viral RNA and infectious virus in the upper and lower respiratory tracts relative to controls. Reductions in lung and BAL virus levels correspond to reduced BAL inflammatory cytokines and lung pathology. Aerosolized antibody therapy for SARS-CoV-2 could be effective for reducing viral burden and limiting disease severity.

Early-life behavioral features are associated with chronic emesis in rhesus macaques (Macaca mulatta).

Chronic emesis (CE) is a poorly understood condition in human and nonhuman primates that negatively impacts the quality of life. Early identification of risk factors for the development of CE is likely to improve the ability to manage CE cases successfully and is, therefore, desirable. Using a case-control study, we reviewed the necropsy records of the California National Primate Research Center and identified 24 animals with recorded CE, defined as five or more incidents of emesis in 1 month. A group of 89 healthy rhesus macaques (Macaca mulatta), comparable in age and percent time housed indoors, was similarly identified. Next, we investigated the association between the occurrence of CE during later stages of life after infancy and the behavioral temperament scores attained in infancy, age, sex, birth location, rearing condition, history of self-injurious behavior (SIB), and the number of lifetime sedation events. Our analysis revealed that CE was associated with degrees of temperament constructs obtained in infancy (data was available for n = 113), such as Confidence (odds ratio (OR) = 0.45, 95% CI: 0.18, 1.08, p = 0.07), Gentleness (OR = 0.47, 95% CI: 0.23, 0.96, p = 0.03), Nervousness (OR = 2.04, 95% CI: 0.98, 4.23, p = 0.05), and Vigilance (OR = 0.36, 95% CI: 015, 0.87, p = 0.02), suggesting that CE is linked to behavioral phenomenon measured in early life, long before it becomes a medical concern. Our data suggest that CE was positively correlated with a history of SIB (OR 4.26, 95% CI: 0.98, 18.47, p = 0.04). Accurate prediction of CE can then assist behavioral and colony management professionals in making informed decisions regarding the care of animals at risk of developing CE. Moreover, the novel information we reported here could have valuable implications in human medicine, where gastrointestinal distress is a common complaint affecting a person's quality of life.