Alpha to Omicron 'Patient 1' All Confirmed Here... Visiting the KDCA Laboratory
Frontline of COVID-19 Diagnosis and Analysis
All Variants First Identified Here
[Asia Economy Reporter Kim Young-won] "When the first COVID-19 patient entered the country on January 19, 2020, this laboratory analyzed the nucleotide sequence overnight and released the analysis results the next morning. The Alpha, Beta, and Omicron lineages that first entered Korea all originated here."
Now in the third year of COVID-19, confirming 'variants' has become as important as diagnosis. Unlike the past when the initial Wuhan strain accounted for all infections, from late last year during the Delta dominance period until recently, various sub-lineage variants have emerged, causing detection rates to fluctuate. On the 18th, we visited the front line of Korean virus diagnosis and analysis that confirms and analyzes COVID-19 variants, the Disease Control and Prevention Agency's nucleotide sequencing laboratory.
All Past Variant Determinations Were Made Here
Upon entering the laboratory, what was visible were more 'machines' than people. Dozens of devices were busily operating, including equipment for each step of whole genome sequencing, variant PCR for rapid variant confirmation, and targeted genome analysis equipment.
Genomic surveillance to identify COVID-19 variant viruses is conducted through nucleotide sequencing, which involves three methods. The simplest method, variant PCR testing, amplifies characteristic single nucleotide sequences to estimate the variant type. This method was developed for rapid epidemiological response by local governments and can provide results within 1 to 2 days.
More detailed analyses such as targeted genome analysis and whole genome sequencing take longer. Whole genome sequencing analyzes all 30,000 viral sequences to distinguish all COVID-19 sub-lineages. It takes about 6 to 7 days to confirm results. Targeted genome analysis amplifies and sequences only 4,000 to 5,000 spike protein sequences out of the 30,000, allowing differentiation of variant viruses and some sub-lineages.
All methods involve RNA extraction after sample collection, but whole genome sequencing requires an additional 'library preparation' process due to the large volume handled. Researcher Kim Il-hwan of the Disease Control Agency explained, "It's like attaching a catalog card to a book in a library," adding, "Because there are so many genes, it's difficult to read them one by one, so they are divided into groups of 300, and each sample is labeled." On that day, library preparation was underway using two pieces of equipment inside the laboratory, each processing 96 samples in about 5 hours.
After completing quality control (QC) to verify that the library was properly prepared, the samples enter the whole genome sequencing equipment. There are five types of sequencing machines. Depending on the equipment, the number of samples analyzed and the time required vary, so they are used according to purpose. For routine mass testing, the 'NextSeq 2000' machine, capable of analyzing up to 400 samples, is used, while in urgent cases, the 'iSeq 100' machine, which can quickly analyze 4 to 6 samples, is employed. Researcher Kim said, "When Omicron was first detected in Korea, Delta was 100% dominant, and it was not identified by variant PCR, so the samples were urgently sent to us," adding, "We analyzed those samples with this equipment and were able to announce the detection of Omicron the next day."
Kim Eun-jin, head of the Emerging Pathogen Analysis Division at the Disease Control Agency, explained, "Especially for newly emerging variants, local public health and environment research institutes cannot make determinations," adding, "Therefore, data is sent to the headquarters, and the first determination is made here."
From Diagnosis to Analysis... How Was Capacity Built?
The Disease Control Agency's Infectious Disease Diagnosis and Analysis Bureau, which oversees diagnosis and analysis of pathogens including COVID-19, was established after experiencing MERS in 2015. Director Yoo Cheon-gwon of the bureau explained, "In 2016, during the Korea Centers for Disease Control and Prevention era, a policy headquarters called the Diagnostic Management Division was created, and the following year, to enable more proactive response, it was reorganized into the Infectious Disease Diagnosis and Analysis Center, combining laboratory departments."
The lessons from MERS also influenced the preemptive response to COVID-19. The bureau's task force (TF) began tabletop exercises (TTX) for laboratory response to unknown infectious diseases on December 17, 2019, before COVID-19, then called 'pneumonia of unknown cause,' was first identified in China. The exercises involved scenarios of unknown infectious diseases entering Korea and addressed how to conduct diagnosis and epidemiology step by step. The TF created a scenario responding to 'a person returning from China carrying a novel coronavirus.' Kim said, "Through the exercises, we concluded that a pan-coronavirus testing method was necessary," adding, "Before that, we had not considered a pan-coronavirus test method, so this was a significant event."
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After the exercises, the Infectious Disease Diagnosis and Analysis Bureau expanded diagnostic and analysis institutions and diversified techniques. Researchers who started developing the pan-coronavirus test method established the test on January 9, 2020, before COVID-19 entered Korea. The first confirmed domestic case was diagnosed using this test. Subsequently, the pan-coronavirus test method was expanded nationwide to 17 local governments, and after PCR testing methods were established, these were also expanded to local governments nationwide. Whole genome sequencing was only possible at the Disease Control Agency and one private institution until January last year, but now it is also available at regional response centers, city and provincial public health and environment research institutes, and the Defense Science Research Institute within the Ministry of National Defense.
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