BACKGROUND: Key knowledge gaps remain in the understanding of viral dynamics and immune response of SARS-CoV-2 infection. METHODS: We evaluated these characteristics and established their association with clinical severity in a prospective observational cohort study of 100 patients with PCR-confirmed SARS-CoV-2 infection (mean age 46 years, 56% male, 38% with comorbidities). Respiratory samples (n=74) were collected for viral culture, serum samples for measurement of IgM/IgG levels (n=30), and plasma samples for levels of inflammatory cytokines and chemokines (n=81). Disease severity was correlated with results from viral culture, serologic testing, and immune markers. RESULTS: 57 (57%) patients developed viral pneumonia, of whom 20 (20%) required supplemental oxygen including 12 (12%) invasive mechanical ventilation. Viral culture from respiratory samples was positive for 19 of 74 patients (26%). No virus was isolated when the PCR cycle threshold (Ct) value was >30 or >14 days after symptom onset. Seroconversion occurred at a median of 12.5 days (IQR 9-18) for IgM and 15.0 days (IQR 12-20) for IgG; 54/62 patients (87.1%) sampled at day 14 or later seroconverted. Severe infections were associated with earlier seroconversion and higher peak IgM and IgG levels. Levels of IP-10, HGF, IL-6, MCP-1, MIP-1α, IL-12p70, IL-18, VEGF-A, PDGF-BB and IL-1RA significantly correlated with disease severity. CONCLUSION: We found virus viability was associated with lower PCR Ct value in early illness. A stronger antibody response was associated with disease severity. The overactive proinflammatory immune signatures offers targets for host-directed immunotherapy which should be evaluated in randomised controlled trials.
BACKGROUND: Key knowledge gaps remain in the understanding of viral dynamics and immune response of SARS-CoV-2 infection. METHODS: We evaluated these characteristics and established their association with clinical severity in a prospective observational cohort study of 100 patients with PCR-confirmed SARS-CoV-2 infection (mean age 46 years, 56% male, 38% with comorbidities). Respiratory samples (n=74) were collected for viral culture, serum samples for measurement of IgM/IgG levels (n=30), and plasma samples for levels of inflammatory cytokines and chemokines (n=81). Disease severity was correlated with results from viral culture, serologic testing, and immune markers. RESULTS: 57 (57%) patients developed viral pneumonia, of whom 20 (20%) required supplemental oxygen including 12 (12%) invasive mechanical ventilation. Viral culture from respiratory samples was positive for 19 of 74 patients (26%). No virus was isolated when the PCR cycle threshold (Ct) value was >30 or >14 days after symptom onset. Seroconversion occurred at a median of 12.5 days (IQR 9-18) for IgM and 15.0 days (IQR 12-20) for IgG; 54/62 patients (87.1%) sampled at day 14 or later seroconverted. Severe infections were associated with earlier seroconversion and higher peak IgM and IgG levels. Levels of IP-10, HGF, IL-6, MCP-1, MIP-1α, IL-12p70, IL-18, VEGF-A, PDGF-BB and IL-1RA significantly correlated with disease severity. CONCLUSION: We found virus viability was associated with lower PCR Ct value in early illness. A stronger antibody response was associated with disease severity. The overactive proinflammatory immune signatures offers targets for host-directed immunotherapy which should be evaluated in randomised controlled trials.
Authors: Jose L Garrido; Matías A Medina; Felipe Bravo; Sarah McGee; Francisco Fuentes-Villalobos; Mario Calvo; Yazmin Pinos; James W Bowman; Christopher D Bahl; Maria Ines Barria; Rebecca A Brachman; Raymond A Alvarez Journal: Cell Rep Date: 2022-05-16 Impact factor: 9.995
Authors: Dorothy Hui Lin Ng; Mei Yi Sim; Hong Hong Huang; Jean Xiang Ying Sim; Jenny Guek Hong Low; Jay Kheng Sit Lim Journal: Eur J Clin Microbiol Infect Dis Date: 2021-07-05 Impact factor: 3.267
Authors: Agnieszka Smolinska; David S Jessop; Kirk L Pappan; Alexandra De Saedeleer; Amerjit Kang; Alexandra L Martin; Max Allsworth; Charlotte Tyson; Martine P Bos; Matt Clancy; Mike Morel; Tony Cooke; Tom Dymond; Claire Harris; Jacqui Galloway; Paul Bresser; Nynke Dijkstra; Viresh Jagesar; Paul H M Savelkoul; Erik V H Beuken; Wesley H V Nix; Renaud Louis; Muriel Delvaux; Doriane Calmes; Benoit Ernst; Simona Pollini; Anna Peired; Julien Guiot; Sara Tomassetti; Andries E Budding; Frank McCaughan; Stefan J Marciniak; Marc P van der Schee Journal: Sci Rep Date: 2021-06-29 Impact factor: 4.379
Authors: David M Smadja; Steven J Mentzer; Michaela Fontenay; Mike A Laffan; Maximilian Ackermann; Julie Helms; Danny Jonigk; Richard Chocron; Gerald B Pier; Nicolas Gendron; Stephanie Pons; Jean-Luc Diehl; Coert Margadant; Coralie Guerin; Elisabeth J M Huijbers; Aurélien Philippe; Nicolas Chapuis; Patrycja Nowak-Sliwinska; Christian Karagiannidis; Olivier Sanchez; Philipp Kümpers; David Skurnik; Anna M Randi; Arjan W Griffioen Journal: Angiogenesis Date: 2021-06-28 Impact factor: 9.596