Phages to treat secondary bacterial infections in COVID-19 patients?

Issue 69 | March 27, 2020
11 min read
Capsid and Tail

Wash your hands. Don’t touch your face. Photo by Clay Banks on Unsplash

Can phages help COVID patients? We’ve been hearing chatter about this subject from the phage community over the last few days, so we’ve decided to start the conversation here and keep it going. What, if anything, can the phage community do to help with the COVID-19 crisis?

Also in this issue: a phage biotech company helps with COVID-19 vaccine, new phage therapy history uncovered, phages delaying wound healing and manipulating host CRISPR via new pathways, and more!

What’s New

Adaptive Phage Therapeutics (APT), having recently doubled its biologics manufacturing capability (intended for its upcoming phage clinical trials), is currently in talks with a partner to help with rapid production of a COVID-19 vaccine candidate for a clinical study. APT does not anticipate delays with its phage trials, and plans to soon expand its workforce (doubling or tripling its 30-person size).

BiotechNewsCOVID

Ella Balasa, one of our guest writers and volunteers, and former phage therapy recipient, has written about what it’s like being at high risk for COVID-19; a very sobering read (though it ends on a positive note!).

BlogCystic FibrosisCOVID

Gabriel Magno de Freitas Almeida and Lotta-Riina Sundberg (University of Jyvaskyla, Finland) have published a historical review in The Lancet Infectious Diseases that dives into the forgotten history of phage therapy in Brazil. They show that Brazil was an important (yet little-known) player in phage therapy, and uncover interesting priority claims and missing pieces of phage therapy’s history.

ReviewHistoryPhage Therapy

Michelle Bach (Stanford University) and colleagues published a new preprint on how the filamentous phage Pf (present in 69% of Pseudomonas aeruginosa wounds) delays healing of P. aeruginosa-infected wounds by provoking an anti-phage immune response that leads to impaired keratinocyte migration and delayed wound re-epithelialization.

ResearchFilamentous phage

Przemysław Decewicz (University of Warsaw, Poland) and colleagues have isolated two virulent phages infecting Ochrobactrum spp. for the first time. The host, due to its extensive repertoire of enzymatic properties, is a key player in the biotech industry, and virulent phages could be explored as a means of biocontrol and bioaugmentation of related industrial practices.

ResearchBiotechBiocontrol

Adair Borges and colleagues from the Bondy-Denomy lab at UCSF have published a paper discussing how Pseudomonas aeruginosa host factors, previously characterized for their role in alginate biosynthesis, affect its Type I-F CRISPR–Cas system. The presence of homologs of alginate regulators in Pseudomonas phages suggests they can adapt this regulation mechanism to repress CRISPR-Cas immunity.

Research

Cédric Lood (KU Leuven) and colleagues published a new paper on jumbo phage-host interactions: they used an integrative omics approach (hybrid sequencing, RNAseq, and mass spectrometry) to look at Pseudomonas aeruginosa phage PA5oct and its host. They were able to annotate it accurately, look at gene expression patterns during infection, and place the phage among other phages using a gene-sharing network.

ResearchPhage-host interactions

Latest Jobs

A PhD position investigating phage immunogenicity is available at the Institute of Virology, University of Bonn Medical School, Germany. The PhD studentship, under the supervision of Prof. Dr. med. Hendrik Streeck, will explore the potential effects of phages on the human immune system.
Lawrence Berkeley National Lab’s Environmental Genomics & Systems Biology Division has an opening for a postdoc position that will develop and apply mass spectrometry-based metabolomic analysis methods to understand viral reprogramming of microbial cells, including the metabolic effects phages have on their hosts.
A postdoc position focusing on studying the role of phages in the gut microbiota and engineering them for therapeutic function is available in the lab of Dr. Bryan Hsu at Virginia Tech (Blacksburg, VA).
A 3-year position as an Assistant Professor working on the characterization of phages and determining the mechanisms of host recognition and resistance development is open at the University of Copenhagen, Denmark.
A Senior Associate Scientist position is open with Pfizer working on the isolation and optimization of antibodies using phage display.

Community Board

Anyone can post a message to the phage community — and it could be anything from collaboration requests, post-doc searches, sequencing help — just ask!

A warm welcome to our new volunteers!

Phage Directory has three new volunteers! Please welcome Lauren Dunlop, Dr. Rohit Kongari and Lizzie Richardson! Lauren helps us behind the scenes with things like finding out about grants we can apply for. Rohit and Lizzie are currently helping us with Capsid & Tail: finding cool phage articles, jobs and anything else the phage community should know about. Thanks so much to each of you, we are incredibly grateful for your hard work and enthusiasm!

Also, we’d also like to acknowledge all of our Capsid & Tail guest writers and social media assistants we’ve had to date; these are all volunteers too!

Thank you to all of you for helping us keep our community informed and inspired!!

New VolunteersPhage Directory

Viruses of Microbes 2020 Conference Update

On account of the current situation of worldwide spreading coronavirus SARS-CoV2, the organising committee might have to consider post-postponing Viruses of Microbes 2020, initially planned to take place on the 13-17 July. However, due to the uncertainty related to the effect of this worldwide spreading, it would be too premature to set now a new date. As a result we have decided to:
i) Extend the abstract submission period until the end of April;
ii) Suspend, for now, registration.

We will of course continue monitoring the situation concerning COVID-19 and as soon as we have a clearer picture of the situation we will update this information.

On behalf of the Organizing Committee,
Joana Azeredo and Madalena Pimentel

ConferenceCOVIDUpdate

Twitter Q&A: SARS-CoV2-like phages?

From Karen Maxwell, via Twitter: #phage community - which phage is most SARS-CoV2 like? Seems like many assays for inactivation, etc could be widely performed and then translated. Who has stocks???

Q&A

Free Bioinformatics Resources

From Elizabeth McDaniel, via Twitter: There’s a lot of interest right now for learning bioinformatics skills while lab research is suspended and everybody is working from home. I wanted to share free resources for learning coding basics and field-specific materials. (See thread for tons of resources!)

BioinformaticsResources

Phages to treat secondary bacterial infections in COVID-19 patients?

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Phage microbiologist and co-founder of Phage Directory
Co-founder
Phage Directory, Atlanta, GA, United States

Jessica Sacher is a co-founder of Phage Directory and has a Ph.D in Microbiology and Biotechnology from the University of Alberta.

For Phage Directory, she takes care of the science, writing, communications, and business aspects.

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Assistant Professor
University at Buffalo

Can phages help COVID patients? We’ve been hearing chatter about this subject from the phage community over the last few days, so we’ve decided to start the conversation here and keep it going. What, if anything, can the phage community do to help with the COVID-19 crisis?

Bacterial infections associated with many flu patient deaths; this may also be true for COVID-19 patients

This week, Dr. Julie Gerberding, MD, the former CDC director and current Chief Patient Officer and executive vice president for strategic communications, global public policy, and population health at Merck, wrote an article for STAT News about the problem of secondary antimicrobial resistant (AMR) bacterial infections (also known as co-infections) in the context of COVID-19. She talks about how AMR bacterial co-infections will likely complicate treatment of COVID-19 patients, and how patients at high risk for AMR infections are the same ones at high risk of COVID-19.

She highlights a review on influenza research that showed that secondary bacterial pneumonia was detected in 29-55% of mortalities associated with the 2009 flu pandemic. This review also refers to a study that showed that the majority of deaths from the 1918 flu pandemic likely resulted from secondary bacterial pneumonia (though of course, the latter occurred before antibiotics were discovered).

Then she discusses a recent report from this month in the Lancet, which looked at COVID-19 patients in two hospitals in China, and found that 1/7 patients hospitalized with COVID-19 had secondary infections (including 50% of those that died). This study also found that 100% of patients who died of COVID-19 had sepsis, though it was not determined whether this sepsis was viral or bacterial.

Open Questions

  • To what extent are patients around the world with COVID-19 dealing with secondary bacterial infections?
  • To what extent is the sepsis being seen in COVID-19 patients caused by bacterial infections?
  • Are bacterial strains infecting COVID-19 patients antibiotic-resistant?
  • Which bacterial species are the biggest problem for COVID-19 patients with bacterial secondary infections? (Note that Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus are reported as the most common bacterial culprits in influenza co-infections)
  • Can phages help these patients?
  • Even if phages could help, are healthcare professionals too busy stemming the flow of COVID-19 cases to have time for experimental compassionate use therapies?
  • Would regulatory agencies be open to considering compassionate phage therapy treatments for COVID-19 patients? (Would they have the bandwidth to do so?)
  • Are phage labs open, or would they be willing to open, to help source and/or screen phages for COVID-19 patients? Would phage companies be willing to do the same? Of note, TAILΦR, the phage therapy service center at Baylor College of Medicine, is still open and working to provide safe, characterized phage cocktails to physicians for treatment of patients. They have not yet been approached on behalf of any COVID-19 patients, but would be open to this possibility if asked (personal communication with Dr. Austen Terwilliger, Director of Operations at BCM Tailor Labs).

Let us know your thoughts

  • Do you know clinicians who are thinking about how to treat these secondary infections? (Feel free to connect them with us, if so)
  • Is your lab open right now? Would you be willing/able to help source and/or screen phages if we ended up determining there was a need? (This goes for now and in the future, given the likelihood that COVID-19 is not going to disappear, even if we do get a handle on it in the short term)

Looking ahead, making plans

Even if not now, while things are out of control, perhaps in the future, when COVID-19 is still present but clinicians have more time per patient, phage therapy may be a viable option for some of these patients. So even if this doesn’t become a rapid, emergency-level phage community effort right now, we think it’s worthwhile to start talking about how we as a community of phage professionals could set ourselves up to accept COVID-19 patient bacterial isolates, develop phage libraries against these pathogens, and possibly help coordinate compassionate phage therapy treatments for eligible patients.

Join the conversation: phage.directory/slack

If you’d like to help, or you have thoughts, please join our Slack workspace, phage.directory/slack; we have a channel called #covid-amr dedicated to this topic and would love to hear from you.

More resources

Check out our Wiki, “COVID AMR & Secondary Infections” (https://phage.directory/covid-amr), where we’re tracking articles, posts, threads and other resources around this topic.

*If you’d like to add links to the collection, that would be great! Use this link to download Notion (https://phage.directory/notion) (we get credits when you use our link!), then email [email protected], and we’ll give you edit access.

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