A junior researcher’s publication experience on and during the COVID-19 pandemic

The story behind my most recent manuscript on SARS-CoV-2 sample pooling strategies is a long one. What started as a small side project aimed at facilitating the COVID-19 pandemic response became a publication effort with an extraordinarily enduring submission endeavor.

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In March 2020, SARS-CoV-2 also hit Belgium. A novel, highly contagious virus entering a population with hardly any specific immunity was doomed to cause widespread disease and panic. As massive testing was a crucial part of the initial response, the first clear hurdle was the testing capacity. We transformed our lab from an RNA-cancer-focused group to the upstream sample processing part of a high-throughput testing facility as part of a nation-wide public-private collaboration. The work demanded flexibility, perseverance, and caution: an exhausting combination. It was clear that this approach was unsustainable, especially as cases, and therefore workload, increased. The necessity for alternative approaches was obvious.

Researchers presented sample pooling as a viable option to combat rising cases, especially in resource limiting environments. The most straightforward strategy consists of combining multiple samples and testing them as a group. When the pooled test is negative, all samples are regarded as negative; in contrast, all individual samples in the group are tested again if the pool is positive. Although this strategy requires two rounds of qPCR, it significantly lowers the number of reagents used. In certain countries, such as Israel, pooling samples became crucial for their COVID-19 response strategies. At that time, many labs were researching the applicability of various pooling strategies and how the pool sizes impacted outcomes, such as testing efficiency. However, at that time, the literature largely disregarded the influence of sample pooling on the analytical sensitivity (apart from some sporadic mentions and small experiments). Indeed, as samples are pooled, positive samples get diluted by negative samples. As a result, the viral RNA can become so diluted that it becomes undetectable with qPCR. Therefore, grouping samples in large pools may result in false negatives.

In our study, we showed that the optimal pool size depends on a sensitivity-efficiency trade-off and we discussed the influence of a number of factors, including the epidemiological situation and viral load. To help other labs, we developed an interactive online tool to determine the optimal pooling size based on those labs’ own data and preferred efficiency-sensitivity trade-off. We submitted the initial version of our manuscript for the first time in September 2020.

Little did I know this was the beginning of a cumbersome submission process with many delays and disappointments. The journal sent us the first reviewers’ comments halfway through January 2021: almost four months later. By that time, the second wave had died down in many countries, and our manuscript missed its chance to be available when it was needed the most. Finally, after tackling all concerns raised by the reviewers, the revised manuscript was resubmitted, just to be rejected in early May 2021, seven months after initial submission. The argumentation for rejection from the Editor-in-Chief was astounding: ‘Even if you addressed the reviewers’ comments, we do not believe it would achieve sufficient priority score to merit publication in Journal X, given that we have already published manuscripts on sample pooling in SARS-CoV-2’. The rejection was not only a hard hit to take, especially for an early-career researcher as myself, but also surfaces a more general problem with this reasoning. If the importance of a topic is (speculatively) linked to its investigative interest, then rejection based on prior publication is not only inexplicable but also harmful. 

In dire situations like the COVID-19 pandemic, preprint archives such as bioRxiv and medRxiv (when cautiously approached) prove their use as catalysts for scientific advancements. While our manuscript was under review, such preprint servers allowed the scientific community and health agencies (such as Sciensano in Belgium) to critically inspect our results and reap the benefits of our hard work when it was most vital. The number of citations the preprint received evidenced the relevance and urgency of our message.

After additional submission attempts to four other journals and two pre-submission inquiries to two more journals, I finally submitted our manuscript to Scientific Reports in September 2021 and (after one round of revisions) accepted for publication in March 2022. In the end, eight individual researchers peer-reviewed our paper. It is a relief that the manuscript can now finally serve its purpose during the current COVID-19 pandemic response and future global public health threats.

You can find the manuscript at https://www.nature.com/articles/s41598-022-10581-6.

Jasper Verwilt

PhD student, Ghent University