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SARS-CoV-2 virus has infected more than 92 million people worldwide resulting in the Coronavirus disease 2019 (COVID-19). Using a rhesus macaque model of SARS-CoV-2 infection, we have characterized the transcriptional signatures induced in the lungs of juvenile and old macaques following infection. Genes associated with Interferon (IFN) signaling, neutrophil degranulation and innate immune pathways are significantly induced in macaque infected lungs, while pathways associated with collagen formation are downregulated, as also seen in lungs of macaques with tuberculosis. In COVID-19, increasing age is a significant risk factor for poor prognosis and increased mortality. Type I IFN and Notch signaling pathways are significantly upregulated in lungs of juvenile infected macaques when compared with old infected macaques. These results are corroborated with increased peripheral neutrophil counts and neutrophil lymphocyte ratio in older individuals with COVID-19 disease. Together, our transcriptomic studies have delineated disease pathways that improve our understanding of the immunopathogenesis of COVID-19.

The human infection of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a public health emergency of international concern that has caused more than 16.8 million new cases and 662,000 deaths as of July 30, 2020. Although coronavirus disease 2019 (COVID-19), which is associated with this virus, mainly affects the lungs, recent evidence from clinical and pathological studies indicates that this pathogen has a broad infective ability to spread to extrapulmonary tissues, causing multiorgan failure in severely ill patients. In this regard, there is increasing preoccupation with the neuroinvasive potential of SARS-CoV-2 due to the observation of neurological manifestations in COVID-19 patients. This concern is also supported by the neurotropism previously documented in other human coronaviruses, including the 2002-2003 SARS-CoV-1 outbreak. Hence, in the current review article, we aimed to summarize the spectrum of neurological findings associated with COVID-19, which include signs of peripheral neuropathy, myopathy, olfactory dysfunction, meningoencephalitis, Guillain-Barré syndrome, and neuropsychiatric disorders. Furthermore, we analyze the mechanisms underlying such neurological sequela and discuss possible therapeutics for patients with neurological findings associated with COVID-19. Finally, we describe the host-and pathogen-specific factors that determine the tissue tropism of SARS-CoV-2 and possible routes employed by the virus to invade the nervous system from a pathophysiological and molecular perspective. In this manner, the current manuscript contributes to increasing the current understanding of the neurological aspects of COVID-19 and the impact of the current pandemic on the neurology field.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is a global health threat with the potential to cause severe disease manifestations in the lungs. Although COVID-19 has been extensively characterized clinically, the factors distinguishing SARS-CoV-2 from other respiratory viruses are unknown. Here, we compared the clinical, histopathological, and immunological characteristics of patients with COVID-19 and pandemic influenza A(H1N1). We observed a higher frequency of respiratory symptoms, increased tissue injury markers, and a histological pattern of alveolar pneumonia in pandemic influenza A(H1N1) patients. Conversely, dry cough, gastrointestinal symptoms and interstitial lung pathology were observed in COVID-19 cases. Pandemic influenza A(H1N1) was characterized by higher levels of IL-1RA, TNF-α, CCL3, G-CSF, APRIL, sTNF-R1, sTNF-R2, sCD30, and sCD163. Meanwhile, COVID-19 displayed an immune profile distinguished by increased Th1 (IL-12, IFN-γ) and Th2 (IL-4, IL-5, IL-10, IL-13) cytokine levels, along with IL-1β, IL-6, CCL11, VEGF, TWEAK, TSLP, MMP-1, and MMP-3. Our data suggest that SARS-CoV-2 induces a dysbalanced polyfunctional inflammatory response that is different from the immune response against pandemic influenza A(H1N1). Furthermore, we demonstrated the diagnostic potential of some clinical and immune factors to differentiate both diseases. These findings might be relevant for the ongoing and future influenza seasons in the Northern Hemisphere, which are historically unique due to their convergence with the COVID-19 pandemic.

Infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or seasonal influenza may lead to respiratory failure requiring intubation and mechanical ventilation. The pathophysiology of this respiratory failure is attributed to local immune dysregulation, but how the immune response to viral infection in the lower airways of the human lung differs between individuals with respiratory failure and those without is not well understood. We used quantitative multiparameter flow cytometry and multiplex cytokine assays to evaluate matched blood and bronchoalveolar lavage (BAL) samples from control human subjects, subjects with symptomatic seasonal influenza who did not have respiratory failure, and subjects with severe seasonal influenza or SARS-CoV-2 infection with respiratory failure. We find that severe cases are associated with an influx of nonclassical monocytes, activated T cells, and plasmablast B cells into the lower airways. Cytokine concentrations were not elevated in the lower airways of moderate influenza patients compared with controls; however, 28 of 35 measured cytokines were significantly elevated in severe influenza, severe SARS-CoV-2 infection, or both. We noted the largest elevations in IL-6, IP-10, MCP-1, and IL-8. IL-1 family cytokines and RANTES were higher in severe influenza infection than severe SARS-CoV-2 infection. Interestingly, only the concentration of IP-10correlated between blood and BAL during severe infection. Our results demonstrate inflammatory immune dysregulation in the lower airways during severe viral pneumonia that is distinct from lower airway responses seen in human patients with symptomatic, but not severe, illness and suggest that measurement of blood IP-10 concentration may predict this unique dysregulation.

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Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

Specific spatial organization of granulomas within the lungs is crucial for protective anti-tuberculosis (TB) immune responses. However, only large animal models such as macaques are thought to reproduce the morphological hallmarks of human TB granulomas. In this study, we show that infection of mice with clinical “hypervirulent” Mycobacterium tuberculosis (Mtb) HN878 induces human-like granulomas composed of bacilli-loaded macrophages surrounded by lymphocytes and organized localization of germinal centers and B-cell follicles. Infection with laboratory-adapted Mtb H37Rv resulted in granulomas that are characterized by unorganized clusters of macrophages scattered between lymphocytes. An in-depth exploration of the functions of B cells within these follicles suggested diverse roles and the activation of signaling pathways associated with antigen presentation and immune cell recruitment. These findings support the use of clinical Mtb HN878 strain for infection in mice as an appropriate model to study immune parameters associated with human TB granulomas.