Immune responses in COVID-19 respiratory tract and blood reveal mechanisms of disease severity

Although the respiratory tract is the primary site of SARS-CoV-2 infection and the ensuing immunopathology, respiratory immune responses are understudied and urgently needed to understand mechanisms underlying COVID-19 disease pathogenesis. We collected paired longitudinal blood and respiratory tract samples (endotracheal aspirate, sputum or pleural fluid) from hospitalized COVID-19 patients and non-COVID-19 controls. Cellular, humoral and cytokine responses were analysed and correlated with clinical data. SARS-CoV-2-specific IgM, IgG and IgA antibodies were detected using ELISA and multiplex assay in both the respiratory tract and blood of COVID-19 patients, although a higher receptor binding domain (RBD)-specific IgM and IgG seroconversion level was found in respiratory specimens. SARS-CoV-2 neutralization activity in respiratory samples was detected only when high levels of RBD-specific antibodies were present. Strikingly, cytokine/chemokine levels and profiles greatly differed between respiratory samples and plasma, indicating that inflammation needs to be assessed in respiratory specimens for the accurate assessment of SARS-CoV-2 immunopathology. Diverse immune cell subsets were detected in respiratory samples, albeit dominated by neutrophils. Importantly, we also showed that dexamethasone and/or remdesivir treatment did not affect humoral responses in blood of COVID-19 patients. Overall, our study unveils stark differences in innate and adaptive immune responses between respiratory samples and blood and provides important insights into effect of drug therapy on immune responses in COVID-19 patients.

Coleridge's choleras: cholera morbus, Asiatic cholera, and dysentery in early nineteenth-century England.

Samuel Taylor Coleridge suffered from a variety of bowel disorders throughout his life; though a large part of his ailment was caused by his famous opium habit, he continuously sought an organic origin, and on at least two separate occasions, in 1804 and 1831-32, he ascribed his disorders to attacks of "cholera." With Asiatic cholera apparently first reaching England in late 1831, there was considerable argument among both physicians and the general public as to whether it was a distinctly new disease, or merely a severer variation of traditional English cholera, known as "cholera morbus." Coleridge took a particular interest in these discussions. In this paper, we attempt to establish the exact nature of his attacks of illness, and point to the complexities of describing and framing new diseases and bowel disorders in the early nineteenth century.