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Widespread activation of MCs coinciding with lung pathology in NHPs.

(A) Cynomolgus macaques were infected intratracheally with SARS-CoV-2 and monitored for 21 days prior to necropsy. (B) Viral detection was determined by PCR at regular intervals post-infection in swabs from multiple mucosal tissues, lung lavage, and nasal rinses. All NHPs were positive for SARS-CoV-2 infection multiple days after inoculation. (C) Abnormal findings related to lung tissue observed at the time of necropsy were recorded and effected all animals. (D) Images of NHP lungs at the time of necropsy show areas of hemorrhaging and necrotic spots on the lung surface. Boxed region is enlarged. (E) Histological assessment of lung tissues by H&E staining shows hemorrhaging of the tissue and free RBCs within the lung alveolar spaces. (F) Inset corresponding to the boxed region of panel H. (G) Some RBCs in the tissue proximal to a blood vessel are indicated by arrows and cellular infiltrates are circled. (H) Multiple examples of degranulating or hypogranulated MCs are provided, observed in toluidine blue stained lung tissue sections. The MCs are enlarged in the red-outlined insets. For (I-K), lung sections were stained for MC heparin to indicate the location of MC granules (green) and DAPI to identify cellular nuclei and tissue structures. MCs are indicated with red arrows. (I) MCs were observed degranulating in the lung of SARS-CoV-2 infected primates in sections of a biopsy of lung tissue that did not have overt hemorrhaging visible on the lung surface at necropsy. (J) MCs appear more densely packed in the lung biopsy from a hemorrhagic lobe of the lung and again, degranulation is observed based on staining for MC-heparin. (K) Images of degranulating MCs are presented at higher magnification.