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PubMed; 2020.
Preprint in English | PubMed | ID: ppcovidwho-333583


While SARS-CoV-2 infection has pleiotropic and systemic effects in some patients, many others experience milder symptoms. We sought a holistic understanding of the severe/mild distinction in COVID-19 pathology, and its origins. We performed a whole-blood preserving single-cell analysis protocol to integrate contributions from all major cell types including neutrophils, monocytes, platelets, lymphocytes and the contents of serum. Patients with mild COVID-19 disease display a coordinated pattern of interferon-stimulated gene (ISG) expression across every cell population and these cells are systemically absent in patients with severe disease. Severe COVID-19 patients also paradoxically produce very high anti-SARS-CoV-2 antibody titers and have lower viral load as compared to mild disease. Examination of the serum from severe patients demonstrates that they uniquely produce antibodies with multiple patterns of specificity against interferon-stimulated cells and that those antibodies functionally block the production of the mild disease-associated ISG-expressing cells. Overzealous and auto-directed antibody responses pit the immune system against itself in many COVID-19 patients and this defines targets for immunotherapies to allow immune systems to provide viral defense. ONE SENTENCE SUMMARY: In severe COVID-19 patients, the immune system fails to generate cells that define mild disease;antibodies in their serum actively prevents the successful production of those cells.

PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-329535


Hong Kong utilized an elimination strategy with intermittent use of public health and social measures and increasingly stringent travel regulations to control SARS-CoV-2 transmission. By analyzing >1700 genome sequences representing 17% of confirmed cases from 23-January-2020 to 26-January-2021, we reveal the effects of fluctuating control measures on the evolution and epidemiology of SARS-CoV-2 lineages in Hong Kong. Despite numerous importations, only three introductions were responsible for 90% of locally-acquired cases, two of which circulated cryptically for weeks while less stringent measures were in place. We found that SARS-CoV-2 within-host diversity was most similar among transmission pairs and epidemiological clusters due to a strong transmission bottleneck through which similar genetic background generates similar within-host diversity. One sentence summary: Out of the 170 detected introductions of SARS-CoV-2 in Hong Kong during 2020, three introductions caused 90% of community cases.

Preprint in English | EMBASE | ID: ppcovidwho-326897


The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in southern Africa has been characterised by three distinct waves. The first was associated with a mix of SARS-CoV-2 lineages, whilst the second and third waves were driven by the Beta and Delta variants respectively1–3. In November 2021, genomic surveillance teams in South Africa and Botswana detected a new SARS-CoV-2 variant associated with a rapid resurgence of infections in Gauteng Province, South Africa. Within three days of the first genome being uploaded, it was designated a variant of concern (Omicron) by the World Health Organization and, within three weeks, had been identified in 87 countries. The Omicron variant is exceptional for carrying over 30 mutations in the spike glycoprotein, predicted to influence antibody neutralization and spike function4. Here, we describe the genomic profile and early transmission dynamics of Omicron, highlighting the rapid spread in regions with high levels of population immunity.

British Journal of Surgery ; 108(SUPPL 5):V15, 2021.
Article in English | EMBASE | ID: covidwho-1408559


Introduction: During the corona virus disease (COVID-19) pandemic frontline units worldwide faced the challenging task of providing highrisk services (like surgical tracheostomy) while safe-guarding the very people performing the high risk procedures. The aim of our study was to assess the incidence of COVID-19 infection among staff involved in surgical tracheostomy on COVID-19 patients Method: A surgical tracheostomy protocol and operation theatre modifications were put in place at our centre, dictated by local resources staff availability and previous tracheostomy experience. Between 26/ 03/2020 and 27/05/2020, staff participating in 71 tracheostomy procedures were sent a questionnaire. The presence of COVID-19 symptoms (new onset continuous cough, fever, loss of taste and/or loss of smell) in tracheostomy staff and patient related data were analysed Result: Among the responders (72/122), compliance with personal prophylaxis equipment use was 100%. Eleven (15%,11/72) reported key COVID-19 symptoms and self-isolated. 10 had a COVID-19 swab test and three tested positive. One staff attended (1/72) hospital for symptomatic treatment, none required hospitalisation. 43/72 staff (60%) underwent a COVID-19 antibody test, 18.6% (8/43) were positive Among the tracheostomised patients, the mean age was 58 years(29- 78) and 65.5% were males. The median time from intubation to ST was 15 days (range 5-33, IQR=9). There were no tracheostomy related deaths and overall mortality was 11%(6/55) Conclusion: Safe delivery of tracheostomy during a pandemic like COVID-19 is possible with strict adherence to personnel protective equipment, surgical protocols and regulation of traffic flow in theatres to mitigate the potential transmission of COVID-19 among surgical staff Take-home Message: Compliance with PPE, adherence to tracheostomy protocol and local modifications can mitigate potential COVID-19 transmission among health care personnel .