C oronaviruses are a family of RNA viruses whose large genomes, propensity for mutation, and frequent recombination events have resulted in a diversity of strains and species that are capable of rapid adaptation to new hosts and ecologic environments (1). This viral plasticity has garnered widespread concern because of zoonotic potential and the consequences of new emergence events in both human and animal populations. The emergence of a new strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease (COVID-19) has once again demonstrated the role of the family Coronaviridae in causing human disease outbreaks. SARS-CoV-2, a novel betacoronavirus, was identifi ed in human patients from Wuhan, China, during December 2019 and has resulted in a global pandemic, an unprecedented public health emergency, and untold economic and societal repercussions worldwide. Similar to the 2002-2003 severe acute respiratory syndrome (SARS) epidemic, a live animal market where hundreds of animal species were sold is suspected to be associated with the emergence or early spread of COVID-19 in humans (2). Although COVID-19 is novel in the breadth of the human outbreak, several pathogenic alphacoronaviruses and betacoronaviruses have shown similar patterns of emergence. As early as the 1930s, coronaviruses pathogenic to livestock, companion animals, and laboratory animals were identifi ed (3). During the 1960s, 2 human coronaviruses, HCoV-229E and HCoV-OC43, were detected in patients who had common colds (4,5). Although it is speculated that HCoV-OC43 might also have emerged through a global pandemic in the late 1800s (6), the 2002-2003 SARS outbreak is the fi rst known global epidemic caused by a coronavirus. The SARS epidemic triggered research within this viral family (3). This research led to detection of 2 new human coronaviruses, HCoV-NL63 and HCoV-HKU1 (7,8). HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1 are now accepted as globally endemic common cold species that are typically associated with mild-to-moderate respiratory illness. In 2012, the most deadly human coronavirus to date was detected in the Arabian Peninsula: Middle East respiratory syndrome coronavirus (MERS-CoV) (9). A cumulative body of research on these and other coronaviruses has shown that most alphacoronaviruses and betacoronaviruses infecting humans have come from animal hosts and that both historic patterns and coronavirus biology establish an urgent ongoing threat to human and animal health (10).

Previous work has shown that non-invasive optical measurement of low cerebral blood flow (CBF) is an acute biomarker of poor long-term cognitive outcome after repetitive mild traumatic brain injury (rmTBI). Herein, we explore the relationship between acute cerebral blood flow and underlying neuroinflammation. Specifically, because neuroinflammation is a driver of secondary injury after TBI, we hypothesized that both glial activation and inflammatory signaling are associated with acute CBF and, by extension, with long-term cognitive outcome after rmTBI. To test this hypothesis, cortical CBF was non-invasively measured in anesthetized mice 4h after 3 repetitive closed head injuries spaced once-daily, at which time brains were collected. Right hemispheres were fixed for immunohistochemical staining for glial activation markers Iba1 and GFAP while left hemispheres were used to quantify Iba1 and GFAP expression via Western blot as well as 32 cytokines and 21 phospho-proteins in the MAPK, PI3K/Akt, and NF-κB pathways using a Luminex multiplexed immunoassay. N=8/7 injured/sham C57/black-6 adult male mice were studied. Within the injured group, CBF inversely correlated with Iba1 expression (R=−0.86, p<0.01). Further, partial least squares regression analysis revealed significant correlations between CBF and expression of multiple pro-inflammatory cytokines, including RANTES and IL-17. Finally, within the injured group, phosphorylation of specific signals in the MAPK and NF-κB intracellular signaling pathways (e.g., p38 MAPK and NF-κB) were significantly positively correlated with Iba1. In total, our data indicate that acute cerebral blood flow after rmTBI is a biomarker of underlying neuroinflammatory pathology.

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OBJECTIVE To characterize clinical and epidemiologic features of SARS-CoV-2 in companion animals detected through both passive and active surveillance in the US. ANIMALS 204 companion animals (109 cats, 95 dogs) across 33 states with confirmed SARS-CoV-2 infections between March 2020 and December 2021. PROCEDURES Public health officials, animal health officials, and academic researchers investigating zoonotic SARS-CoV-2 transmission events reported clinical, laboratory, and epidemiologic information through a standardized One Health surveillance process developed by the CDC and partners. RESULTS Among dogs and cats identified through passive surveillance, 94% (n = 87) had reported exposure to a person with COVID-19 before infection. Clinical signs of illness were present in 74% of pets identified through passive surveillance and 27% of pets identified through active surveillance. Duration of illness in pets averaged 15 days in cats and 12 days in dogs. The average time between human and pet onset of illness was 10 days. Viral nucleic acid was first detected at 3 days after exposure in both cats and dogs. Antibodies were detected starting 5 days after exposure, and titers were highest at 9 days in cats and 14 days in dogs. CLINICAL RELEVANCE Results of the present study supported that cats and dogs primarily become infected with SARS-CoV-2 following exposure to a person with COVID-19, most often their owners. Case investigation and surveillance that include both people and animals are necessary to understand transmission dynamics and viral evolution of zoonotic diseases like SARS-CoV-2.