Know Your Enemy: Finding Certainty in Uncertain Times

An enemy shrouded by darkness

Nyctophobia (nyc·to·pho·bia | \nik-tə-ˈfō-bē-ə\) is defined as an “irrational fear of darkness”; however, I would argue (and I’m sure many would agree) that a fear of the dark is anything but irrational. What is it about the dark that is so scary? It's not the darkness itself that's frightening. It's the fear of what the darkness masks. It is this exact feeling of uncertainty—the feeling of suddenly being pulled out of our safe and comfortable daily routines, the feeling of not knowing what’s to come or when this will end—that we all face in the midst of the COVID-19 pandemic. As cases continue to rise worldwide, the public is left anxious and unsure about the future, but the heroic efforts of health officials, healthcare workers, and scientists provide hope that there is a way out of the darkness.

"A pneumonia of an unknown cause"

In the nearly six months since the WHO was officially notified of a “pneumonia of an unknown cause” sweeping over Wuhan, researchers, virologists, and epidemiologists have all banded together to learn all that they can about the novel coronavirus we now call SARS-CoV-2. Here, we highlight a study seminal in identifying and characterizing the virus, and one of the first studies contributing to the viral genome sequence being shared with the world (Wu et al. 2020).

The study focused on a 41-year-old patient admitted to the Central Hospital of Wuhan on December 26, 2019, with symptoms including fever, chest tightness, cough, pain, and weakness, along with lung abnormalities—all indicative of pneumonia, cause unknown. On January 5, 2020, next-generation meta-transcriptomic sequencing analysis performed on the patient’s bronchoalveolar lavage fluid (BALF) enabled the researchers to obtain a complete viral genome of the unknown pathogen. Subsequent analysis identified the virus as belonging to a family of SARS-like viruses, Coronaviridae. These analyses were made possible in part by kits and reagents produced by Takara Bio: an RNA library was constructed from the total RNA collected from the patient’s BALF sample using the SMARTer Stranded Total RNA-Seq Kit v2 - Pico Input Mammalian, the viral genome sequence was determined and confirmed by real-time quantitative PCR (RT-qPCR) via the One Step PrimeScript RT-PCR Kit (Perfect Real Time), and genome termini were studied by 5′/3′ rapid amplification of cDNA ends (RACE) using the SMARTer RACE 5′/3′ kit. This result was immediately reported to the relevant authorities, and an annotated version of the genome sequence (strain Wuhan-Hu-1) was submitted to NCBI/GenBank on the same day.

Since this study, laboratories around the world have been generating viral genome sequence data with unprecedented speed. At the time of writing this, there are nearly 60,000 SARS-CoV-2 genomes publicly available. Research efforts that help to update public viral genome sequence databases—such as the study conducted by Wu et al.—are important as they are used to inform international preparedness and response to the novel coronavirus pandemic. Takara Bio’s kits, reagents, instruments, and services help to identify and characterize previously unknown pathogens by allowing researchers to explore important questions about viral gene discovery, regulation, and function. Our broad NGS portfolio provides unmatched sensitivity and reproducibility for demanding sequencing applications—regardless of sample type or input amount—therefore facilitating the rapid development of diagnostic tests and identifying potential medical intervention options including treatments and vaccines.

Seeing the light

Finding light at the end of this tunnel of darkness called COVID-19 is especially hard not knowing how long the tunnel is or in which direction it will branch out. One thing is for certain: in order to fight your enemy, you must know your enemy. Without the viral genome sequencing efforts of research groups such as Wu et al., the mystery pathogen spreading across Wuhan and later throughout the world would have remained unknown. As public genome databases continue to be updated daily, more is known about the structure, function, and evolutionary trajectory of SARS-CoV-2. Takara Bio’s advances in next-generation sequencing technology and commitment to providing best-in-class products empower researchers to know the enemy from every angle in order to better predict the evolutionary dynamics of novel viruses as well as gauge differences in inter-patient response to antiviral therapies and vaccines.