A Micronized Electrostatic Precipitator Respirator Effectively Removes Ambient SARS-CoV-2 Bioaerosols (preprint)

Rationale Inhalation of ambient SARS-CoV-2-containing bioaerosols leads to infection and pandemic airborne transmission in susceptible populations. Filter-based respirators effectively reduce exposure but complicate normal respiration through breathing zone pressure differential and are therefore impractical for long-term use. Objectives We tested the comparative effectiveness of a prototyped micronized electrostatic precipitator (mEP) to a filter-based respirator (N95) in the removal of viral bioaerosols from a simulated inspired air stream. Methods Each respirator was tested within a 16-liter environmental chamber housed within a Class III biological safety cabinet within biosafety level 3 containment. SARS-CoV-2 containing bioaerosols were generated into the chamber, drawn by vacuum through each respirator, and physical particle removal and viral genomic RNA were measured distal to the breathing zone of each device. Measurement and Main Results The mEP respirator removed particles (96.5±0.4%) approximating efficiencies of the N95 (96.9±0.6%). The mEP respirator similarly decreased SARS-CoV-2 viral RNA (99.792%) when compared to N95 removal (99.942%) as a function of particle removal from the airstream distal to the breathing zone of each respirator. Conclusions The mEP respirator approximated performance of a filter-based N95 respirator for particle removal and viral RNA as a constituent of the SARS-CoV-2 bioaerosols generated for this evaluation. In practice, the mEP respirator would provide equivalent protection from ambient infectious bioaerosols as the N95 respirator without undue pressure drop to the wearer, thereby facilitating long-term use in an unobstructed breathing configuration.

Myeloid cell-driven nonregenerative pulmonary scarring is conserved in multiple nonhuman primate species regardless of SARS-CoV-2 infection modality (preprint)

The novel coronavirus SARS-CoV-2 has caused a worldwide pandemic resulting in widespread efforts in development of animal models that recapitulate human disease for evaluation of medical countermeasures, and to dissect COVID-19 immunopathogenesis. We tested whether route of experimental infection substantially changes COVID-19 disease characteristics in two species (Macaca mulatta; rhesus macaques; RM, Chlorocebus atheiops; African green monkeys; AGM) of nonhuman primates. Species-specific cohorts of RM and AGM Rhesus macaques (Macaca mulatta, RMs) and African green monkeys (Chlorocebus aethiops, AGMs) were experimentally infected with homologous SARS-CoV-2 by either direct mucosal instillation or small particle aerosol in route-discrete subcohorts. Both species demonstrated equivalent infection initially by either exposure route although the magnitude and duration of viral loading was greater in AGMs than that of the RM. Clinical onset was nearly immediate (+1dpi) in mucosally-exposed cohorts whereas aerosol-infected animals began to show signs +7dpi. Myeloid cell responses indicative of the development of pulmonary scarring and extended lack of regenerative capacity in the pulmonary compartment was a conserved pathologic response in both species by either exposure modality. This pathological commonality may be useful in future anti-fibrosis therapeutic evaluations and expands our understanding of how SARS-CoV-2 infection leads to ARDS and functional lung damage.

The pigtail macaque (Macaca nemestrina) model of COVID-19 reproduces diverse clinical outcomes and reveals new and complex signatures of disease (preprint)

The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 disease, has killed over four million people worldwide as of July 2021 with infections rising again due to the emergence of highly transmissible variants. Animal models that faithfully recapitulate human disease are critical for assessing SARS-CoV-2 viral and immune dynamics, for understanding mechanisms of disease, and for testing vaccines and therapeutics. Pigtail macaques (PTM, Macaca nemestrina) demonstrate a rapid and severe disease course when infected with simian immunodeficiency virus (SIV), including the development of severe cardiovascular symptoms that are pertinent to COVID-19 manifestations in humans. We thus proposed this species may likewise exhibit severe COVID-19 disease upon infection with SARS-CoV-2. Here, we extensively studied a cohort of SARS-CoV-2-infected PTM euthanized either 6- or 21-days after respiratory viral challenge. We show that PTM demonstrate largely mild-to-moderate COVID-19 disease. Pulmonary infiltrates were dominated by T cells, including CD4+ T cells that upregulate CD8 and express cytotoxic molecules, as well as virus-targeting T cells that were predominantly CD4+. We also noted increases in inflammatory and coagulation markers in blood, pulmonary pathologic lesions, and the development of neutralizing antibodies. Together, our data demonstrate that SARS-CoV-2 infection of PTM recapitulates important features of COVID-19 and reveals new immune and viral dynamics and thus may serve as a useful animal model for studying pathogenesis and testing vaccines and therapeutics.