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1.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-338443

ABSTRACT

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.

2.
O'Toole, A.; Hill, V.; Pybus, O. G.; Watts, A.; Bogoch, II, Khan, K.; Messina, J. P.; consortium, Covid- Genomics UK, Network for Genomic Surveillance in South, Africa, Brazil, U. K. Cadde Genomic Network, Tegally, H.; Lessells, R. R.; Giandhari, J.; Pillay, S.; Tumedi, K. A.; Nyepetsi, G.; Kebabonye, M.; Matsheka, M.; Mine, M.; Tokajian, S.; Hassan, H.; Salloum, T.; Merhi, G.; Koweyes, J.; Geoghegan, J. L.; de Ligt, J.; Ren, X.; Storey, M.; Freed, N. E.; Pattabiraman, C.; Prasad, P.; Desai, A. S.; Vasanthapuram, R.; Schulz, T. F.; Steinbruck, L.; Stadler, T.; Swiss Viollier Sequencing, Consortium, Parisi, A.; Bianco, A.; Garcia de Viedma, D.; Buenestado-Serrano, S.; Borges, V.; Isidro, J.; Duarte, S.; Gomes, J. P.; Zuckerman, N. S.; Mandelboim, M.; Mor, O.; Seemann, T.; Arnott, A.; Draper, J.; Gall, M.; Rawlinson, W.; Deveson, I.; Schlebusch, S.; McMahon, J.; Leong, L.; Lim, C. K.; Chironna, M.; Loconsole, D.; Bal, A.; Josset, L.; Holmes, E.; St George, K.; Lasek-Nesselquist, E.; Sikkema, R. S.; Oude Munnink, B.; Koopmans, M.; Brytting, M.; Sudha Rani, V.; Pavani, S.; Smura, T.; Heim, A.; Kurkela, S.; Umair, M.; Salman, M.; Bartolini, B.; Rueca, M.; Drosten, C.; Wolff, T.; Silander, O.; Eggink, D.; Reusken, C.; Vennema, H.; Park, A.; Carrington, C.; Sahadeo, N.; Carr, M.; Gonzalez, G.; Diego, Search Alliance San, National Virus Reference, Laboratory, Seq, Covid Spain, Danish Covid-19 Genome, Consortium, Communicable Diseases Genomic, Network, Dutch National, Sars-CoV-surveillance program, Division of Emerging Infectious, Diseases, de Oliveira, T.; Faria, N.; Rambaut, A.; Kraemer, M. U. G..
Wellcome Open Research ; 6:121, 2021.
Article in English | MEDLINE | ID: covidwho-1450989

ABSTRACT

Late in 2020, two genetically-distinct clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with mutations of biological concern were reported, one in the United Kingdom and one in South Africa. Using a combination of data from routine surveillance, genomic sequencing and international travel we track the international dispersal of lineages B.1.1.7 and B.1.351 (variant 501Y-V2). We account for potential biases in genomic surveillance efforts by including passenger volumes from location of where the lineage was first reported, London and South Africa respectively. Using the software tool grinch (global report investigating novel coronavirus haplotypes), we track the international spread of lineages of concern with automated daily reports, Further, we have built a custom tracking website (cov-lineages.org/global_report.html) which hosts this daily report and will continue to include novel SARS-CoV-2 lineages of concern as they are detected.

3.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-290674

ABSTRACT

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.

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