One year of CSIR's initiatives against SARS-CoV-2

For more than a year now, the COVID-19 wave has swept through the globe. It has peaked and plummeted but has not shown any sign of plateauing yet. Presently, with variant strains appearing and people not following the COVID appropriate behaviour strictly, there is a resurgence in the number of COVID-19 cases.

A positive development has been that vaccination drives have become more intense. However, there is a large population yet to be vaccinated globally.

Scientific organisations have been at the forefront of the fight against COVID-19. Diagnostics, drugs, devices, vaccines, PPEs and ventilators have been developed in a short period. Among the many organisations in India, CSIR, with its chain of 37 laboratories, rose to the nation's call in the most trying of times.

CSIR is not new to dealing with challenges and crises. In the face of technology denials and handling natural disasters like earthquakes and floods, CSIR has quickly and effortlessly developed technology solutions.

In its fight against COVID-19, even before the end of the first lockdown in March 2020, CSIR had a blueprint ready on the role that it will play in the nation's fight against coronavirus. A 5-pronged strategy was adopted. The CSIR's 5 COVID-19 Verticals as they came to be known were: Digital and Molecular Surveillance, Rapid and Economic Diagnosis, Development of New/Repurposed Drugs, PPEs and Hospital Assistive Devices, and Supply Chain & Logistics.

All the CSIR laboratories, irrespective of their specialisation, rallied around to fight the virus. The interdisciplinary character of CSIR, its nationwide network, need-based and industry-focused research and development, technology transfer expertise, strength in basic research, and world-class R&D infrastructure were put to use by its vibrant pool of students, scientists, researcher scholars and other staff. Under the most challenging of circumstances, CSIR, as one entity, fought back. The result is that in about 100 days, CSIR developed an assortment of several COVID-19 technologies.

On the testing front, 13 CSIR labs have carried out over 12,00,000 tests to date. The significant aspect is that many of these testing facilities are at locations distant from towns and metros like the hilly regions of Uttarakhand, Himachal Pradesh and the North East. In March 2020, when there were very few testing facilities in the country, CSIR-CCMB set up one of India's earliest RT-PCR testing facilities. However, India would require to carry out testing in massive numbers in the ensuing months. There was a need for a low-cost, quick and accurate testing kit.

The CSIR-IGIB was up to the challenge, and in a few months, the premier Institute introduced the CRISPR-Cas-9-based kit called FELUDA. DCGI has approved it, and it is cheap, fast and accurate. CSIR transferred the technology to Tata Sons, which now is marketing the kit in India and is being used at many places. CSIR-CCMB has come up with an improved method of RT-PCR testing called the Dry Swab-based direct RT-PCR method. This involves dry swab based safe collection, storage and transportation of viral samples. It also effectively reduces the time taken for RT-PCR testing as it omits the step of the laborious RNA isolation. This method not only cuts downtime and cost but is relatively safer and is an ICMR approved method. CSIR-NEERI has successfully utilised this method and tested more than 50,000 samples. Many industries have licensed this method and have developed kits that will enable large scale testing, which is the need of the day.

By the middle of last year, hospital beds across the country were filling up with COVID-19 infected patients. Not every patient who has a breathing problem needs invasive ventilation, which is used in ICUs. There is a need for non-invasive ventilators, which can be used in makeshift hospitals or at home with medical supervision. With the ventilators being in short supply, CSIR-NAL, in a record time of 36 days, developed a non-invasive Bilevel Positive Airway Pressure (BiPAP) ventilator. Here again, the low cost, high effectiveness and indigenous development were its key attributes. The ventilator underwent rigorous clinical trials and was certified by accreditation agencies and approved by DGHS before being transferred to the industry. Today, a few thousand CSIR-NAL's Swasthvayu, BiPAP ventilators are used in many hospitals in Delhi and other places to treat mild to moderate COVID-19 patients.

The recent wave of the pandemic has brought to attention the need for oxygen for many of those afflicted by COVID-19. CSIR labs such as CSIR-IIP, Dehradun, CSIR-CEMRI Durgapur and CSIR-NCL have developed oxygen concentrators and oxygen enrichment units. CSIR-IIP developed static oxygen concentrators are being deployed across India through industry partners, and 120 units are expected to be installed by July 2021.

CSIR has also embarked on the design and setting up of makeshift hospitals, which can quickly provide the much-needed beds during the pandemic. Leading this effort has been CSIR-CBRI in Roorkee. CSIR-SERC has also set up a makeshift hospital in Tamil Nadu. CSIR-CBRI efforts have led to 11 makeshift hospitals with about 350 beds in Himachal Pradesh, Jammu and other states. Currently, they are working on building makeshift hospitals in Delhi, Punjab and Himachal Pradesh.

Even after more than a year into the global pandemic, there is no new drug yet to cure COVID-19. It is known that drug development is a complex and lengthy process, sometimes taking decades to discover the right drug molecule for a disease. The immediate approach is to look at existing drugs that can alleviate COVID-19 caused distress. Globally, a few medications such as Remdesivir, Favipiravir and Umifenovir have been identified as being helpful to treat COVID-19 patients.

CSIR-IICT, the premier chemical technology laboratory, is well known for developing innovative and low-cost industrial processes for drugs and chemicals. Favipiravir is structurally less complex than the other two molecules. The institute, in record time, came with an efficient method for synthesising Favipiravir. As is characteristic of CSIR technologies, the Hyderabad based institute's process made it possible to produce Favipiravir at much lower costs. The industrial process was transferred to pharma major Cipla, and today the drug named Ciplenza is being used to treat mildly infected COVID-19 patients.

CSIR is also involved in the clinical trials of many repurposed drugs. The clinical trials are being carried out in partnership with several medical and research institutions and industry partners, including Cipla, Cadilla, Sun Pharma, LAXAI etc. In addition to synthetic drugs, the well-known naturally occurring plant-based prophylactics and therapeutics are also undergoing clinical trials. Presently, safety and efficacy trials of AYUSH prophylactics and therapeutics based on Withania somnifera, Glycyrrhiza glabra, Tinospora cordifolia & Adhatoda vasica (individually and in combination), Tinospora cordifolia & Piper longum (in combination) are being carried out jointly by CSIR and Ministry of AYUSH. The Ministry of AYUSH-CSIR collaboration has recently completed a multi-centre clinical trial to evaluate the safety and efficacy of AYUSH 64 in the management of mild to moderate COVID-19 patients.

Ever since the pandemic hit the country, CSIR has been very carefully studying the SARS-CoV-2 genome. It is known that viral genomes undergo mutations, and new strains of the virus come into being. It is essential to look at the viral variations as some mutant strains can become more virulent than the existing strain. Labs such as CSIR-IGIB, CSIR-CCMB, CSIR-IMTech and many more have been involved in sequencing the viral genomes. Sequencing identifies the mutations in viral strains and examines and monitor the prevalence of viral strains in different parts of the country.

Further, with new strains appearing elsewhere in the world, such as the UK strain, it is essential to know about the appearance of the new strains in India. CSIR-IGIB and CSIR-CCMB are two among the ten members of the Indian SARS-CoV-2 Genomics Consortium (INSACOG). The consortium monitors the genomic variations in the SARS-CoV-2 on a regular basis through a multi-laboratory network. INSACOG has carried out genomic sequencing and analysis of circulating COVID-19 viruses and correlating epidemiological trends with genomic variants. A few CSIR labs have also been culturing coronavirus to provide for vaccine and antisera development.

CSIR labs such as CSIR-CCMB, CSIR-IMTech, CSIR-NEERI and others have also been involved in community-level surveillance via sewage samples. This surveillance can provide public health management strategies for controlling the spread. An interesting study undertaken by CSIR-IMTech and CSIR-CCMB has found coronavirus in the air of closed rooms. Much before the recent emphasis for airborne transmission of the SARS-CoV-2, CSIR had demonstrated that virus in the air can be detected and is dependent on several factors such as the number of infected people, the usage of masks etc. Guidelines have been designed for ventilation in residential and office buildings by CSIR-CBRI and other CSIR labs.

Another initiative has been the design and development of UV-C based virus inactivation by CSIR-CSIO. The UV installation in the air ducts will help have safe indoor spaces such as auditoriums, buses, metro and rail coaches. Currently, the auditorium in CSIR HQ has such an installation.

Many CSIR laboratories also produced personal protection kits such as coveralls, face shields, and face masks in large numbers to ensure no shortage of these essential supplies. Notably, the protective coveralls turned out to be a must-have item for hospital, healthcare and other public personnel like police, sanitation workers and so on. As demand soared, by mid-April 2020, CSIR-NAL, in association with MAF clothing, developed polypropylene spun laminated multi-layered non-woven fabric based coverall. The coveralls underwent stringent testing and certification at SITRA, Coimbatore. Following this, lakhs of pieces of the low cost and safe protective coverall were manufactured.

The disease surveillance, drugs, and diagnostics discussed thus far involve high science. In the face of the pandemic, several thousand people lost their livelihoods and faced many hardships. So that people at the bottom of the pyramid do not go hungry and can prevail during pandemic times, CSIR-IHBT and CSIR-CFTRI provided tonnes of nutritive and immune-boosting food. A large number of CSIR labs also distributed several thousand gallons of sanitisers and thousands of face masks. The CSIR-IICT, through the Corporate Social Responsibility of Cipla Foundation, designed and distributed lakhs of masks in rural Telangana.

In addition to CSIR's outreach activities through the distribution of food, masks and sanitisers, CSIR also put in place a communication strategy. The objective was to regularly communicate COVID-19 related developments to the masses and combat the rapidly spreading malaise of misinformation and disinformation. Posters in different Indian languages, both printed and digital, on the COVID appropriate behaviours were disseminated widely. Regular webinars, again in an array of Indian languages, are being organised. The webinars have been popular among the lay audience for whom it is an opportunity to interact, clarify their doubts and find answers to their questions from the experts.

Today, CSIR has emerged as a key player in India's COVID-19 mitigation programmes. At CSIR, there have been many learnings. We have built new capabilities and developed new capacities. We have once again effectively capitalised on the power of collaborations and networking with multiple stakeholders, be it across CSIR and other laboratories, industries of all sizes, ministries and state governments, non-governmental organisations, self-help groups and so on. We also realised that while science and technology can provide solutions, for the uptake of technological solutions, effective communication, connectedness, and engagement with multiple stakeholders are also important. In a pandemic of this kind, communication to influence or effect pandemic appropriate behaviour holds the key.

The learnings will enable CSIR to efficiently and effectively handle such crises in the future. Lastly, all this has been possible due to the tireless efforts and unstinting cooperation of the CSIR family comprising the leadership, scientists, technical, administration and support staff, students and countless others who have worked throughout the pandemic.

Dr G. Mahesh and Dr Geetha Vani Rayasam