ABSTRACT
Pronounced immune escape by the SARS-CoV-2 Omicron variant has resulted in large numbers of individuals with hybrid immunity, generated through a combination of vaccination and infection. Based primarily on circulating neutralizing antibody (NAb) data, concerns have been raised that omicron breakthrough infections in triple-vaccinated individuals result in poor induction of omicron-specific immunity, and that a history of prior SARS-CoV-2 in particular is associated with profound immune dampening. Taking a broader and comprehensive approach, we characterized mucosal and blood immunity to both spike and non-spike antigens following BA.1/BA.2 infections in triple mRNA-vaccinated individuals, with and without a history of previous SARS-CoV-2 infection. We find that the majority of individuals increase BA.1/BA.2/BA.5-specific NAb following infection, but confirm that the magnitude of increase and post-omicron titres are indeed higher in those who were infection-naive. In contrast, significant increases in nasal antibody responses are seen regardless of prior infection history, including neutralizing activity against BA.5 spike. Spike-specific T cells increase only in infection-naive vaccinees; however, post-omicron T cell responses are still significantly higher in previously-infected individuals, who appear to have maximally induced responses with a CD8+ phenotype of high cytotoxic potential after their 3rd mRNA vaccine dose. Antibody and T cell responses to non-spike antigens also increase significantly regardless of prior infection status, with a boost seen in previously-infected individuals to immunity primed by their first infection. These findings suggest that hybrid immunity induced by omicron breakthrough infections is highly dynamic, complex, and compartmentalised, with significant immune enhancement that can help protect against COVID-19 caused by future omicron variants.
Subject(s)
Breakthrough Pain , COVID-19 , Status EpilepticusABSTRACT
Objectives - To characterise within-hospital SARS-CoV-2 transmission across two waves of the COVID-19 pandemic. Design - A retrospective Bayesian modelling study to reconstruct transmission chains amongst 2181 patients and healthcare workers using combined viral genomic and epidemiological data. Setting - A large UK NHS Trust with over 1400 beds and employing approximately 17,000 staff. Participants - 780 patients and 522 staff testing SARS-CoV-2 positive between 1st March 2020 and 25th July 2020 (Wave 1); and 580 patients and 299 staff testing SARS-CoV-2 positive between 30th November 2020 and 24th January 2021 (Wave 2). Main outcome measures - Transmission pairs including who-infected-whom; location of transmission events in hospital; number of secondary cases from each individual, including differences in onward transmission from community and hospital onset patient cases. Results - Staff-to-staff transmission was estimated to be the most frequent transmission type during Wave 1 (31.6% of observed hospital-acquired infections; 95% CI 26.9 to 35.8%), decreasing to 12.9% (95% CI 9.5 to 15.9%) in Wave 2. Patient-to-patient transmissions increased from 27.1% in Wave 1 (95% CI 23.3 to 31.4%) to 52.1% (95% CI 48.0 to 57.1%) in Wave 2, to become the predominant transmission type. Over 50% of hospital-acquired infections were concentrated in 8/120 locations in Wave 1 and 10/93 locations in Wave 2. Approximately 40% to 50% of hospital-onset patient cases resulted in onward transmission compared to less than 4% of definite community-acquired cases. Conclusions - Prevention and control measures that evolved during the COVID-19 pandemic may have had a significant impact on reducing infections between healthcare workers, but were insufficient during the second wave to prevent a high number of patient-to-patient transmissions. As hospital-acquired cases appeared to drive most onward transmissions, more frequent and rapid identification and isolation of these cases will be required to break hospital transmission chains in subsequent pandemic waves
Subject(s)
COVID-19ABSTRACT
SARS-CoV-2 lineage B.1.1.7 viruses are more transmissible, may lead to greater clinical severity, and result in modest reductions in antibody neutralization. subgenomic RNA (sgRNA) is produced by discontinuous transcription of the SARS-CoV-2 genome and is a crucial step in the SARS-CoV-2 life cycle. Applying our tool (periscope) to ARTIC Network Oxford Nanopore genomic sequencing data from 4400 SARS-CoV-2 positive clinical samples, we show that normalised sgRNA expression profiles are significantly increased in B.1.1.7 infections (n=879). This increase is seen over the previous dominant circulating lineage in the UK, B.1.177 (n=943), which is independent of genomic reads, E gene cycle threshold and day of illness when sampling occurred. A noncanonical subgenomic RNA which could represent ORF9b is significantly enriched in B.1.1.7 SARS-CoV-2 infections, potentially as a result of a triple nucleotide mutation leading to amino acid substitution D3L in nucleocapsid in this lineage which increases complementarity with the genomic leader sequence. These findings provide a unique insight into the biology of B.1.1.7 and support monitoring of sgRNA profiles in sequence data to evaluate emerging potential variants of concern.