COVID-19: role of co-infections, and drug repurposing for treament

Lead Research Organisation: Queen's University of Belfast
Department Name: Centre for Experimental Medicine

Abstract

Clinical studies have reported co-infections in at least 20% of Covid-19 patients. This figure is likely underestimated because ICU mechanical ventilation results in up to 75% of patients developing nosocomial pneumonia. Moreover, pathological analysis of post-mortem biopsies of lung from patients who died of severe COVID-19 revealed histopathologic findings consistent with superimposed bacterial pneumonia in some patients. Alarmingly, this occurs in a scenario of a limited arsenal of antibiotics to target these infections.Nothing is known on the effect of co-infections in SARS-CoV-2-induced pathophysiology. It is also unknown whether SARS-CoV-2 infection may affect the pathophysiology of nosocomial infections. Addressing this knowledge gap is critical if we are to develop therapeutics; otherwise, treatments may tip the balance from one infection to the other. This happens in a scenario of a limited arsenal of antibiotics to target nosocomial infections. We will investigate the interface between SARS-CoV-2 and bacterial infections (Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii and Staphylococcus aureus) by exploiting relevant translational research models: well-differentiated primary human airway epithelial cell cultures (WD-PAECs), excellent surrogates of human airway epithelium in vivo, and PBMCs, reflecting the complexity of the human immune system. Single-cell RNA seq and multiplexed single-cell mass cytometry (CyTOF) will reveal cell-type specific immune pathways associated with the infections. These responses might be suitable for therapeutic manipulation. Cytopathogenesis, viral and bacterial replication in co-infection, and cytokines/chemokines will be additional read-outs. The effect of SARS-CoV-2 and bacteria on each other's virulence will be analysed by determining the transcriptome of exposed bacteria, and investigating viral and bacterial infection parameters upon infection of WD-PAECs and PMBCs. We will screen a panel of FDA-approved drugs affecting host-pathogen interactions to identify drugs against SARS-CoV-2 in the co-infection interface. These drugs shall be considered as new therapeutics entering clinical trials.

Publications

10 25 50
 
Description We have already demonstrated that infectionm of PB
Exploitation Route Our findings should result in considering bacterial co-infections in Covid19 patients hospitalized, but also in those with mild disease as they may become more susceptible to other bacterial infections. Therapeutics against Covid19 should considered the impact on bacterial infections. Our work should lead to identify drugs useful against SARS-CoV-2 in the context of bacterial co-infections.
Sectors Pharmaceuticals and Medical Biotechnology

 
Title Method to assess SARS-CoV-2 and bacterial co-infections 
Description We have developed a method to assess virus and bacteria co-infections challenging a translational relevant human model , PBMCs. The method allows to ass viral and bacterial outcomes, cell activation by mass optometry, and cell transcriptomics (single cell RNA seq, and bulk RNA seq). 
Type Of Material Technology assay or reagent 
Year Produced 2020 
Provided To Others? Yes  
Impact This method has allowed us to decipher for the first time the effect of SARS-CoV-2 and immune cells resulting in an impairment to clear bacterila infections. This method can be applied to other viral infections. 
 
Title Methos to assess the interaction between pathogens and immune cells in vivo using mass cytometry 
Description We have developed a novel method to detect the interaction between Klebsiella pneumoniaer and immune cells in vivo and ex vivo by exploiting mass cytometry. This method allows the simultaneous detection of bacteria, and immune cells characterized with more than 30 markers. 
Type Of Material Technology assay or reagent 
Year Produced 2021 
Provided To Others? Yes  
Impact This method has allowed to detect interactions between K. pneumoniae and cells never reported before. These findings will allow to investigate how Klebsiella manipulate immune cells, and to better understand how the immune system senses this infection. 
 
Description Collaboration National Biotechnology Centre (Spain) 
Organisation Spanish National Centre for Biotechnology
Country Spain 
Sector Public 
PI Contribution Researchers led by Prof Isable Sola to develop a SARS-CoV-2 vaccine will leverage the infection human models developed by the Bengoechea laboratory.
Collaborator Contribution The Bengoechea laboratory will have access to attenuated strains of SARS-CoV-2, and to tools to manipulate the virus.
Impact No outputs yet as this is still an ongoing collaboration.
Start Year 2020
 
Description Northern Ireland Science Festival COVID19 research 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact More than 4000 viewers watched the videos on Covid19 research posted in YouTube by the Northern Ireland Science Festival. The videos sparked questions and comments, and resulted in additional interactions.
Year(s) Of Engagement Activity 2021
URL https://nisciencefestival.com/e21486-spotlight-on-covid-19-research-at-the-wellcome-wolfson-institut...