India needs all hands on deck

On February 6, the World Health Organization (WHO) recognised the Pune-based National Institute of Virology (NIV) as one of the 15 laboratories that would provide reference testing support for the novel coronavirus.

The number of COVID-19 cases remained constant at three for nearly a month in India, but now it is going up steadily. Anticipating such a scenario, more labs are screening COVID-19 samples now. Besides the 52 labs belonging to the Viral Research and Diagnostic Laboratories network of the Indian Council of Medical Research (ICMR), 10 labs under the National Centre for Disease Control (NCDC) have been included for testing COVID-19 samples.

Till recently, all the 52 labs were allowed to only screen samples; only NIV was authorised to confirm positive cases. With more suspected cases piling up, a long delay in confirming positive test results would have become inevitable for NIV. So, in a welcome move, ICMR has pre-empted such a scenario. “Four-five days ago, 13 labs were authorised to confirm positive cases without sending them to NIV. Another 17 labs will be authorised to do so on March 11 and the remaining labs on March 13,” says Nivedita Gupta of ICMR. With the 10 labs under the NCDC regularly confirming positive H1N1 cases, we can expect these labs to be authorised to also confirm positive COVID-19 cases.

Unfortunately, several national labs have not been brought up to speed to perform other vital functions during an outbreak.

Sequencing the genome

NIV is the only lab in India which has a bio-safety level-4 (BSL-4) facility to culture pathogenic, novel viruses, study the origin of such viruses and provide a comprehensive characterisation of them by sequencing the entire viral genome. NIV has sequenced the SARS-CoV-2 genome collected from two patients in Kerala.

When the entire genome is sequenced it helps researchers understand the arrangement of the four chemical entities or bases that make up the DNA or RNA. The differences in the arrangement of the bases make organisms different from one another. Sequencing the genome of SARS-CoV-2 will help us understand where the virus came from and how it spread.

In the last decade or so, many national laboratories have developed the expertise to sequence the entire genome of viruses and bacteria using the latest equipment (next-generation sequencing, or NGS). About a dozen labs have a BSL-3 facility to inactivate the virus and sequence the genome using advanced equipment. They also have the expertise to undertake such work.

It is therefore puzzling why India relies solely on NIV for undertaking genome sequencing. If there’s a compelling need to have all hands on deck to sequence the genome, it is now.

While NIV sequenced two of the three COVID-19 samples collected from Kerala in late January-early February, it is not clear if more samples have been sequenced. Contrast this with how other countries have responded. Many of the 263 sequences shared with the Global Initiative on Sharing All Influenza Data (GISAID), a public platform started by the WHO in 2008 for countries to share genome sequences, are by universities and hospitals. In mainland China, many of the sequences are shared by the Chinese Center for Disease Control and Prevention, which is present in all the 31 provinces. At 90, China has posted the most sequence data on GISAID. This is followed by the U.S. (37).

Unutilised expertise in India

“We tested around 75,000 samples of H1N1 during the 2009-2010 outbreak. We have a BSL-3 facility and the latest sequencing equipment. We are ready to help out if ICMR reaches out to us,” says Professor V. Ravi, Head of the Department of Virology at the National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, about sequencing.

“It is time for team building, not the time to work in silos,” says Dr. Chitra Pattabiraman from NIMHANS. “If we are not given an opportunity to develop these skill sets and not encouraged to participate, then how are we ever going to get good at it?”

During the 2018 Nipah virus outbreak in Kerala, a lab outside NIV, the Manipal Centre for Virus Research, successfully proved that given an opportunity it could not only diagnose the novel virus but also partially sequence it. The Manipal Centre confirmed the Nipah virus in 17 of the 24 samples it received from Kerala. Unfortunately, since April 2019, the Manipal Centre has been directed to restrict itself to processing the samples of pathogens specific to the BSL-2 facility. It is not even one of the designated labs to test for the novel coronavirus.

Virologist Professor Gagandeep Kang, executive director of the Translational Health Science and Technology Institute, however feels that given that the number of COVID-19 cases in India is still under 60, NIV does not feel overwhelmed.

While agreeing that many labs/ institutions in India have the ability to sequence the viral genome, Professor Kang emphasises that sequencing is useful to know where the virus strain came from and to check if the strain is evolving, but does not inform us of the immediate strategy to control the outbreak or its spread.

With the latest sequencing equipment widely available in many research labs and the cost of sequencing falling, researchers are using genome sequences for genomic epidemiology. This becomes possible as scientists already know the number of mutations that arise on an average in a month in the case of COVID-19, its incubation period, and the average time between cases in a chain transmission (serial interval). Using this data, it has become possible to identify the index case even when the source of infection is not known, and find the link between two seemingly unconnected outbreaks.

How China built capacity

China was completely unprepared when the Severe Acute Respiratory Syndrome (SARS) struck in 2002-2003. The outbreak infected over 8,000 people globally and killed nearly 800. The bird flu (H5N1) outbreak that followed in 2003 underscored the need for influenza detection and response in China. This led to a collaboration between the Chinese National Influenza Center and the Atlanta-based Centers for Disease Control and Prevention in 2004 to build capacity in influenza surveillance in China.

For the next 10 years the collaboration worked in many ways: it led to developed human technical expertise in virology and epidemiology, a comprehensive influenza surveillance system, strengthened analysis, the dissemination of surveillance data, and improved early response to influenza viruses with pandemic potential. By 2014, the national influenza surveillance and response system included 408 labs and 554 sentinel hospitals.

Today, there is a Centre for Disease Control and Prevention in each of the 31 provinces in mainland China. The infrastructure and capacity-building that was put in place by China for influenza surveillance stood in good stead when the H1N1 pandemic struck in 2009.