Case Study: A Journey in Preprinting

(Guest post by Phillip Bogdan from Research Square)

Juliane S. Walz, a researcher at the Tübingen University Hospital in Tübingen, Germany, along with nearly 40 other colleagues from her hospital and the nearby University of Tübingen, were one of many groups of researchers around the world racing to develop a COVID-19 vaccine. 

Before Walz and colleagues could develop an effective vaccine, they first had to identify which areas of the SARS-CoV-2 virus, or epitopes, could activate the human body’s immune cells, also called T-cells. She and colleagues used computer algorithms to predict which epitopes of SARS-CoV-2 could activate these cells. Then, to confirm their predictions, they measured T-cell responses using more than 360 blood samples, half from patients infected with SARS-CoV-2 and half who were not exposed to the virus. 

The team discovered that 81% of unexposed individuals had some T-cell response to SARS-CoV-2 epitopes, showing that there is at least some level of natural human immunity to SARS-CoV-2. The study also suggested that promoting T-cell responses to SARS-CoV-2 may be an important factor in the design of an effective vaccine.

From manuscript to preprint

In order to get their findings out quickly—and to stake a claim on their research, Walz and her colleagues decided to publish their manuscript, titled “SARS-CoV-2 T-cell epitopes define heterologous and COVID-19-induced T-cell recognition,” as a preprint on Research Square. They did this before submitting to Nature Immunology. 

A preprint of their manuscript was posted on Research Square June 17, 2020. Like all preprints published on Research Square, the manuscript was screened for adherence to the platform’s publication standards.  Also like all other preprints, the manuscript was assigned a digital object identifier (DOI) instantly upon publication. This allowed their preprint to be instantly discoverable and citable by researchers and other interested parties. 

Various researchers cited the preprint in the second half of 2020. It was cited 17 times across immunology and medical/health science journals during this time, according to Dimensions.

Individuals could also make comments on their preprint using Research Square’s commenting feature. The preprint received its first comment from a member of the scientific community less than two weeks after publishing their preprint. Ten other comments soon came from researchers located in the United States, United Kingdom, Venezuela, and Germany. The commenters came from various backgrounds. They included several clinicians, a chemist and a plant scientist. They provided constructive comments, which gave Walz and her colleagues the opportunity to improve their manuscript.

This is another potential option Walz and her colleagues could have used for submission. There are nearly 500 partner journals tied to Research Square’s In Review service, which publicly tracks a manuscript’s progression during the peer-review process—and features revised versions of the manuscripts as they are improved. 

How does In Review help authors exactly? It allows them to post their manuscripts to Research Square, while also submitting to participating journals. In Review tracks the status of manuscripts during peer review, shows real-time updates on manuscripts, including the latest revisions. Authors can opt to use In Review directly from the submission systems of participating journals. Aside from the convenience of posting a preprint while submitting to a journal, why should authors opt into In Review? They allow authors and the scientific community to track the status of their manuscripts through a peer review timeline and real-time updates. Authors can also maintain their manuscripts as preprints if they are rejected by the journal, allowing them to keep their research (and corresponding DOI) as the publication of record.

Around the world in seven days

According to Altmetric, the study by Walz, et al. was first referenced in social media on June 24th through a single Twitter post. One day later, it began circulating on Reddit. Three days later, it was circulating on Facebook. Less than a week after it was first posted, their study went viral on Twitter, referenced in more than 5,000 tweets, and was soon featured in 23 news outlets worldwide, including El Pais, The Telegraph, De Volkskrant, and Scientific American. 

Some members of the general public misinterpreted the study, circulating the preprint and their misinterpretations on social media. In response, an immunologist on Research Square’s staff  developed a simplified summary of their study to clarify their research for the general public.

Results 

The preprint submitted by Walz and colleagues was published in Nature Immunology on September 30, 2020, roughly 14 weeks after submission. While the manuscript went through peer review and the publication process, the preprint on Research Square logged 20 citations, 5,500 pdf downloads, 168,083 HTML page views, and an Altmetric score over 3,700. After publication in Nature Immunology, the article‘s Version of Record logged an additional 15 citations, more than 59,000 accesses, and an Altmetric score of 2,376 (to date).  

Epilogue

Walz discussed her experiences with this first preprint submission on the January 30, 2021 episode of a nationally syndicated American news radio show called Reveal. The episode, titled “How the Pandemic Changed Us” highlighted, in part, how the pandemic has made preprints a fixture in many research disciplines—and a driver of collaboration.

“This really led to interesting collaborations with researchers worldwide. We now have collaborations with people from Ireland and with guys from Thailand and Indonesia. So yes, I think this was a really huge benefit.”

Learn more about the benefits of using In Review.