Post-acute COVID-19 associated with evidence of bystander T-cell activation and a recurring AMR bacterial pneumonia
- University of Bristol, United Kingdom
- North Bristol NHS Trust, United Kingdom
- Bristol Veterinary School in the Faculty of Health Sciences, United Kingdom
- Imperial College London, United Kingdom
- University of Birmingham, United Kingdom
Abstract
Here we describe the case of a COVID-19 patient who developed recurring ventilator-associated pneumonia caused by Pseudomonas aeruginosa that acquired increasing levels of antimicrobial resistance (AMR) in response to treatment. Metagenomic analysis revealed the AMR genotype, while immunological analysis revealed massive and escalating levels of T-cell activation. These were both SARS-CoV-2 and P. aeruginosa specific, and bystander activated, which may have contributed to this patient's persistent symptoms and radiological changes.
Data availability
Human-filtered sequencing data for this study have been deposited in the European Nucleotide Archive (ENA) at EMBL-EBI under accession PRJEB40239.
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Metagenomic analysis of respiratory samples from a COVID-19 ICU patientEuropean Nucleotide Archive, PRJEB40239.
Article and author information
Author details
Michaela Gregorova
Mahableshwar Albur
Funding
Southmead Hospital Charity
- Fergus Hamilton
Wellcome Trust (212258/Z/18/Z)
- Ruth C Massey
Elizabeth Blackwell Institute
- Laura Rivino
UKRI (MR/S019553/1)
- Rosemary J Boyton
UKRI (MR/R02622X/1)
- Daniel M Altmann
Cystic Fibrosis Trust (CF Trust SRC 015)
- David K Butler
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Anurag Agrawal, CSIR Institute of Genomics and Integrative Biology, India
Ethics
Human subjects: The patient was enrolled onto the DISCOVER study (Diagnostic and Severity markers of COVID-19 to Enable Rapid triage study), a single centre prospective study recruiting consecutive patients admitted with COVID-19, from 30.03.2020 until present (Ethics approval via South Yorkshire REC: 20/YH/0121, CRN approval no: 45469). Blood/serum samples from pre-pandemic healthy controls and asymptomatic healthy controls were obtained under the Bristol Biobank (NHS Research Ethics Committee approval ref 14/WA/1253).
Version history
- Received: September 24, 2020
- Accepted: December 16, 2020
- Accepted Manuscript published: December 17, 2020 (version 1)
- Version of Record published: December 31, 2020 (version 2)
Copyright
© 2020, Gregorova et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Post-acute COVID-19 associated with evidence of bystander T-cell activation and a recurring AMR bacterial pneumonia
eLife 9:e63430.
https://doi.org/10.7554/eLife.63430
Further reading
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- Epidemiology and Global Health
- Microbiology and Infectious Disease
Background:
Few national-level studies have evaluated the impact of ‘hybrid’ immunity (vaccination coupled with recovery from infection) from the Omicron variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Methods:
From May 2020 to December 2022, we conducted serial assessments (each of ~4000–9000 adults) examining SARS-CoV-2 antibodies within a mostly representative Canadian cohort drawn from a national online polling platform. Adults, most of whom were vaccinated, reported viral test-confirmed infections and mailed self-collected dried blood spots (DBSs) to a central lab. Samples underwent highly sensitive and specific antibody assays to spike and nucleocapsid protein antigens, the latter triggered only by infection. We estimated cumulative SARS-CoV-2 incidence prior to the Omicron period and during the BA.1/1.1 and BA.2/5 waves. We assessed changes in antibody levels and in age-specific active immunity levels.
Results:
Spike levels were higher in infected than in uninfected adults, regardless of vaccination doses. Among adults vaccinated at least thrice and infected more than 6 months earlier, spike levels fell notably and continuously for the 9-month post-vaccination. In contrast, among adults infected within 6 months, spike levels declined gradually. Declines were similar by sex, age group, and ethnicity. Recent vaccination attenuated declines in spike levels from older infections. In a convenience sample, spike antibody and cellular responses were correlated. Near the end of 2022, about 35% of adults above age 60 had their last vaccine dose more than 6 months ago, and about 25% remained uninfected. The cumulative incidence of SARS-CoV-2 infection rose from 13% (95% confidence interval 11–14%) before omicron to 78% (76–80%) by December 2022, equating to 25 million infected adults cumulatively. However, the coronavirus disease 2019 (COVID-19) weekly death rate during the BA.2/5 waves was less than half of that during the BA.1/1.1 wave, implying a protective role for hybrid immunity.
Conclusions:
Strategies to maintain population-level hybrid immunity require up-to-date vaccination coverage, including among those recovering from infection. Population-based, self-collected DBSs are a practicable biological surveillance platform.
Funding:
Funding was provided by the COVID-19 Immunity Task Force, Canadian Institutes of Health Research, Pfizer Global Medical Grants, and St. Michael’s Hospital Foundation. PJ and ACG are funded by the Canada Research Chairs Program.
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- Microbiology and Infectious Disease
Antimicrobial resistance (AMR) poses a significant threat to human health. Although vaccines have been developed to combat AMR, it has proven challenging to associate specific vaccine antigens with AMR. Bacterial plasmids play a crucial role in the transmission of AMR. Our recent research has identified a group of bacterial plasmids (specifically, IncHI plasmids) that encode large molecular mass proteins containing bacterial immunoglobulin-like domains. These proteins are found on the external surface of the bacterial cells, such as in the flagella or conjugative pili. In this study, we show that these proteins are antigenic and can protect mice from infection caused by an AMR Salmonella strain harboring one of these plasmids. Furthermore, we successfully generated nanobodies targeting these proteins, that were shown to interfere with the conjugative transfer of IncHI plasmids. Considering that these proteins are also encoded in other groups of plasmids, such as IncA/C and IncP2, targeting them could be a valuable strategy in combating AMR infections caused by bacteria harboring different groups of AMR plasmids. Since the selected antigens are directly linked to AMR itself, the protective effect extends beyond specific microorganisms to include all those carrying the corresponding resistance plasmids.
