Vibrant research needs transparent government backing in India’s coronavirus fight

A new research ecosystem, an exclusive laboratory to take on the novel coronavirus and fast-track funding for COVID-19-related projects – these are some of the things India’s scientists and science administrators are working overtime on.

From low cost masks and ventilators to new and repurposed drugs, a whole host of disease mapping tools to large scale genomic sequencing efforts and even the talk of a vaccine – the research landscape in India is on an overdrive to find solutions to the novel coronavirus crisis.

Start-ups have mushroomed and researchers, like in many other countries of the world, have repositioned their laboratories to conduct experiments related to the virus.

Though questions have been raised on on the transparency of methods adopted by the Indian Council of Medical Research (ICMR), the nodal medical research body maintains that its efforts have borne fruit in checking the pandemic. “We are participating in global trials and are making all efforts towards the development of a vaccine. But we should understand that vaccine development takes time,” ICMR director general Balram Bhargava told Nature India when asked about the council’s strategy to deal with the pandemic.

Experts feel that social distancing due to the lockdowns has helped bring down the number of infected to some extent but soaring unemployment has had a detrimental effect on the socio-economy. The need of the hour, they feel, is large scale testing even for those who are asymptomatic, developing low cost ventilators, adopting robust quarantine management and fostering a vibrant public -private partnership to prepare for a large scale public health eventuality.

Trouncing the virus

India’s Department of Science and Technology maintains that the country’s scientists have mounted a never-before effort to address the public health emergency. Department secretary Ashutosh Sharma says the rapid response involved identifying and supporting COVID-19 solution technologies and products from across academia, start-ups, R&D labs, and medium and small industries.

For instance, the department supported a Pune start-up Seagull Biosolutions, which developed the versatile Active Virosome technology (AVT) platform that could be used to produce safe vaccines for a wide range of viral diseases. “This will be useful in producing an AV-vaccine for COVID-19 in a very short time,” sharma told Nature India . The AV-expressing S protein of the novel coronavirus will be used for developing immunodiagnostics ELISA kits.

DST also supported development of a diagnostic test kit that confirms COVID-19 in 10 minutes. The confirmatory diagnostic test developed by Thiruvananthapuram-based Sree Chitra Tirunal Institute for Medical Sciences and Technology (SCTIMST) detects the N Gene of SARS- CoV-2 using a reverse transcriptase loop-mediated amplification of viral nucleic acid (RT-LAMP) – one of the world’s first few. The instituted has also designed a disinfection gateway that sanitizes everyone fully when they pass through a hydrogen peroxide mist.

DST is scaling up its membrane oxygenator equipment (MOE) developed to treat COVID-19 patients. Based on innovative, indigenous hollow-fibre membrane technology, the MOE enriches oxygen in the air up to 35% under pressure.

India’s Council of Scientific and Industrial Research (CSIR), with 38 labs across the country, has also mounted its coronavirus research efforts through five technology verticals. CSIR director general Shekhar Chintamani Mande says the council is also working on promoting rural employment and providing ready to eat food to jobless migrant workers across the country.

Anurag Agrawal, director of Delhi-based CSIR-Institute of Genomics and Integrative Biology says the key to flattening the virus’ curve lies in identifying infected people as early as possible, so that they may be quarantined. “To do this, testing must go closer to the people.” Agrawal is hopeful that IGIB’s cheap paper-based rapid test using CRISPR technology, knowhow for which has been non-exclusively licensed by TATA Sons, can be used in community surveillance efforts within this month. The commercial diagnostic kits are expected by late June.

The National Centre of Disease Control, in association with IGIB, is also involved in the surveillance of viral strains in India. “This is critical for molecular epidemiology, by which we can better define case-clusters and also understand the spread of infection between regions,” says Agrawal. So far, about 200 samples have been taken up for sequencing between NCDC and IGIB, with another 100 samples at CCMB. “Based on initial data, we can see clear molecularly defined case-clusters, helpful in understanding the spread.”

The collaborative team has sequenced 100 viral genomes from across the country, 53 of which it has deposited in the global repository GISAID. The nation-wide genome surveillance has also thrown up interesting mutations in regions important for diagnostics as well as in viral proteins, which are vaccine targets. “While we see unique combinations of mutations in some Indian strains, there is no really uniquely mutated Indian strain of proven clinical significance, so far,” Agarwal says.

India’s department of biotechnology (DBT) has undertaken a massive project to sequence 1,000 SARS-CoV-2 genomes from samples across the country to understand the evolving behaviour of the virus.

Tech schools join the fight

India’s leading technology schools, the Indian Institutes of Technology (IITs) have redeployed many scientists into COVID-19 research.

At IIT Delhi, researchers have developed a detection assay for COVID-19, validated by ICMR as being 100% sensitive and specific. IIT Delhi start-up ETEX has made smart textile solutions for healthcare professionals and launched an affordable face mask called KAWACH (meaning shied in Hindi) comparable with N95 masks in terms of fitting, and filtration efficiency. IITD’s web-based dashboard gives detailed state-wise and district-wise predictions of COVID-19 cases in India. The institute's Department of Textile and Fibre Engineering has developed breathable and light-weight Personal Protective Equipment (PPE) for healthcare workers

Santanu Dhara and Sangeeta Das Bhattacharya, researchers at the School of Medical Science and Technology at IIT Kharagpur, have also made face shield prototypes for health care workers. IIT Hyderabad’s aerospace engineers have created small ‘bag valve masks’ that can be used to deliver breathing support in emergency situations. The engineers have supplied first batches of these small, inexpensive devices to frontline healthcare workers and are scaling up mass production. IIT Madras-supported start-up Fabheads Automation has 3-D printed Personal Protective Equipment (PPE) such as face shields and intubation boxes.

At IIT Roorkee, scientist Kamal Jain and his team have developed an X-Ray scanner that can detect COVID-19 in patients within seconds by identifying opacities in the pattern of fluid build-up in lungs, the nature of such clumps and their overall arrangement. ”With our AI-based app, we can classify such patterns in no time,” Jain says.

Researchers at IIT Bombay have developed a smart pool testing technique that is currently undergoing clinical trials. “Results are obtained in a single round of PCR testing as opposed to two or more rounds for other pooling schemes,” says Manoj Gopalkrishnan, associate professor in the electrical engineering department.

Drugs, repurposes and vaccines

Nearly 30 groups in India, including big industries and academics, are trying to develop vaccines against the novel coronavirus, says the country’s Principal Science Adviser Krishnaswamy VijayRaghavan. Repurposing of extant drugs, phyto-pharmaceuticals and extracts from medicinal plants and computational drug discovery were high on the government’s agenda, he says.

The CSIR lab Indian Institute of Integrative Medicine (IIIM) in Jammu has begun phase 2 clinical trials of an anti-leprosy immunomodulatory drug derived from Mycobacterium w. The repurposed drug could be a game changer in the treatment of COVID-19, Mande says. “The clinical trials results will be out very soon. If this is successful, we can provide a viable solution to the whole world,” he says.

In collaboration with India’s alternate medicine ministry AYUSH, CSIR has started four randomised clinical trials to study the role of drugs derived from medicinal plants in the viral replication and host-directed responses of SARS-CoV-2. “These clinical trials will set the stage for the integration of Indian Ayurveda with modern medicine,” IIIM director Ram Vishwakarma says.

CSIR has also identified 25 existing drugs and drug candidates that can be potentially repurposed to treat COVID-19. DBT is working with at least 10 institutions for developing a vaccine.

Virologist and Chief Executive Officer of the DBT Wellcome Trust India Alliance Shahid Jameel feels that Indian scientists and science agencies have come together to fight COVID-19 through a slew of new, quick funding schemes to promote an innovation network. While DBT has funded academia-industry partnerships for vaccine development, and fast track funding of innovative ideas, CSIR has quickly mobilised its network of institutions to not just do research but also provide control solutions such as PPEs, masks and retrofitting of ventilators.

The DBT has entered public-private partnership ventures to help develop reagents, diagnostics, vaccines and therapeutics for COVID-19. The consortium will be based out of the Centre for Cellular and Molecular Platform in Bengaluru. Kiran Mazumdar-Shaw, Chairperson of the consortium says it will optimise capabilities in academic research labs, start-ups and enterprises.

Self-reliance in manufacturing, components, reagents and resources across the product development chain is the need of the hour, says DBT secretary Renu Swarup. “The mission is to bring solutions through affordable and acceptable mechanisms,” she says. DBT is supporting vaccines, diagnostics, therapeutics, repurposing of drugs and other interventions like ventilators, PPE’s masks and other medical devices for COVID-19 under its consortia call. Funding has already been recommended to 70 proposals.

Need for transparency

Irrespective of the large scale research efforts, several loopholes need to be plugged in the government’s efforts to arrest the disease and communicate risk to the public, experts feel.

For one, the government agencies should be more transparent in their working, says Gautam Menon, a disease modeller at the Ashoka University in Sonepat, Haryana. “At present, we know very little about the models that are informing the government’s response to COVID-19. This lack of transparency is alarming.” Menon says the fact that the National Center for Diesase Control has not put out data for patients reporting with influenza-like illness for a long time also hampers independent evaluation of the epidemic's trajectory.

Menon also raises concerns about the quality of data for case counts and deaths. “There have been reports of an increased numbers of deaths that are not mirrored in official numbers, especially from Delhi.” He says India should urgently roll out large scale serological testing. “The ICMR has announced more broad-based random testing (24,000 adults in 69 districts of 21 states and Union Territories) and this is a good move. It should give us a far better idea of the spread of the disease than we have currently.”

The government’s Aarogya Setu COVID-19 tracker app, despite its apparent advantages, has also come in for criticism, especially owing to privacy and security concerns. “There is a need for the government to speak with doctors and epidemiological professionals rather than lean on disaster management authorities,” says Sidharth Deb of the digital liberties organisation Internet Freedom Foundation.

The app fails to replicate legitimate on-ground contact tracing even though testing is a key component of the exercise. “Unfortunately, the app is becoming mandatory just like the Aadhar tool which could be used to coerce people’s movements. Its design is less about detecting and treating people infected with SARS-CoV 2,” he points out. Citizens must be assured that the app will not become a conduit to a permanent system of mass surveillance. “We need the government to consider systems which are less intrusive where there is no need for the creation of an external centralised server,” Deb says.

Fast and cheap testing, independent experts say, is the most required now as the country comes out of a two-month lockdown with more than 0.2 million cases and over six thousand deaths (as on 4 June 2020). “India's science community has responded quickly and purposefully backed by new funding schemes,” says Jameel. The disappointment, he says, lies in ICMR’s opaque handling of the crisis in the beginning, which was a setback for the country. “For example, there are scores of compounds to test based on in silico work, but very few labs are culturing the virus due to a closed system for over two months into the outbreak.”

Overall though, the atmosphere has been collaborative. “My wish is that once this is over, science should remain the centrepiece for our future preparedness,” Jameel says.

Nature India's latest coverage on the novel coronavirus and COVID-19 pandemic here . More updates on the global crisis here .