Exploring the therapeutic potential of defective interfering particles in reducing the replication of SARS-CoV-2 (preprint)

SARS-CoV-2 still presents a global threat to human health due to the continued emergence of new strains and waning immunity amongst vaccinated populations. Therefore, it is still relevant to investigate potential therapeutics, such as therapeutic interfering particles (TIPs). Mathematical and computational modelling are valuable tools to study viral infection dynamics for predictive analysis. Here, we expand on the previous work by Grebennikov et al. (2021) on SARS-CoV-2 intra-cellular replication dynamics to include defective interfering particles (DIPs) as potential therapeutic agents. We formulate a deterministic model that describes the replication of wild-type (WT) SARS-CoV-2 virus in the presence of DIPs. Sensitivity analysis of parameters to several model outputs is employed to inform us on those parameters to be carefully calibrated from experimental data. We then study the effects of co-infection on WT replication and how DIP dose perturbs the release of WT viral particles. Furthermore, we provide a stochastic formulation of the model that is compared to the deterministic one. These models could be further developed into population-level models or used to guide the development and dose of TIPs.

A 17-month longitudinal environmental sampling study carried out on public transport vehicles operating in England during the COVID-19 pandemic identified low levels of SARS-CoV-2 RNA contamination (preprint)

AimsTo monitor severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA contamination in vehicles operating in England during the pandemic, to better understand transmission risk of SARS-CoV-2 on public transport. Methods and ResultsWe collected 1,314 surface samples between December 2020 and April 2022 on trains and buses managed by five different transport operators. The presence of SARS-CoV-2 RNA was investigated through reverse transcription polymerase chain reaction (RT-PCR). SARS-CoV-2 RNA was found on 197 (15%) of the 1,314 surfaces sampled, including seat head rests, handholds, and air extract grilles, but the levels of RNA recovered on those samples (median value of 23.4, inter-quartile range: 14.3-35.4, N gene copies per extraction) made the presence of infectious virus at the time of sampling extremely unlikely. However, detection rates varied over time with peaks broadly coinciding with times of high community transmission, suggesting that people infected with SARS-CoV-2 when travelling on public transport could create opportunities for transmission. ConclusionDuring the pandemic, and as in other public spaces, low levels of SARS-CoV-2 RNA were found on surfaces associated with public transport. Impact statementThe results of this study will inform modelling approaches and the implementation of mitigation strategies to minimise the risk of transmission of respiratory viruses in public transport.

Modelling the risk of SARS-CoV-2 infection through PPE doffing in a hospital environment (preprint)

Self-contamination during doffing of personal protective equipment (PPE) is a concern for healthcare workers (HCW) following SARS-CoV-2 positive patient care. Staff may subconsciously become contaminated through improper glove removal, so quantifying this risk is critical for safe working procedures. HCW surface contact sequences on a respiratory ward were modelled using a discrete-time Markov chin for: IV-drip care, blood pressure monitoring and doctors' rounds. Accretion of viral RNA on gloves during care was modelled using a stochastic recurrence relation. The HCW then doffed PPE and contaminated themselves in a fraction of cases based on increasing case load. The risk of infection from this exposure was quantified using a dose-response methodology. A parametric study was conducted to analyse the effect of: 1a) increasing patient numbers on the ward, 1b) the proportion of COVID-19 cases, 2) the length of a shift and 3) the probability of touching contaminated PPE. The driving factors for infection risk were surface contamination and number of surface contacts. HCWs on a 100% COVID-19 ward were less than 2-fold more at risk than on a 50% COVID ward (1.6% vs 1%), whilst on a 5% COVID-19 ward, the risk dropped to 0.1% per shift (sd=0.6%). IV-drip care resulted in higher risk than blood pressure monitoring (1.1% vs 1% p<0.0001), whilst doctors' rounds produced a 0.6% risk (sd=0.8%). Recommendations include supervised PPE doffing procedures such as the "doffing buddy" scheme, maximising hand hygiene compliance post-doffing and targeted surface cleaning for surfaces away from the patient vicinity.