Ever since the Coronavirus pandemic broke out, CSIR has mounted a strategic, well-coordinated and integrated approach towards mitigating the Coronavirus outbreak ranging from containing the spread of the virus by providing sanitisation and disinfection solutions to equipping the frontline workers and health warriors with protective gear, and from exploring repurposing of existing drugs to discovering new drugs and vaccines. Here are some major recent developments.
Digital and Molecular Surveillance
Surveillance at the level of the virus, humans, and geographical origins and distributions is a critical step in combating Covid-19. While molecular surveillance involves large-scale sequencing of viral genomes, digital surveillance utilises big data at the population level. CSIR is using digital and molecular methods to conduct surveillance using a three-pronged approach; (i) gathering information about the virus (ii) pooled testing for greater outreach (iii) patient-centric approach
• Community surveillance pilot project: In Kolar community surveillance pilot, a survey of 1100 persons including 300 doctors and hospital staff has been carried out. RT-PCR based testing and RBD Homemade ELISA testing, which have 98% sensitivity and 99% specificity, have been deployed for the surveillance.
• CSIR-ICMR MoU on clinical data collection and sharing: CSIR-IGIB and ICMR have entered into an MoU for collection and sharing of clinical data, which will accelerate the digital and molecular surveillance aspect. Eighteen hospitals are part of the network for providing patient samples and metadata.
• Genome sequencing: CSIR-IGIB has completed sequencing of 250 genomes, of which >100 have been deposited at the Global Initiative on Sharing All Influenza Data (GISAID) database. Viral samples have been received from Kerala and the institute has tied-up with government and private hospitals for sample collection. So far 166 viral genomes have been deposited by CSIR labs in the database.
• AI-based diagnosis: CSIR has initiated efforts to reduce the time taken for diagnosis using Artificial Intelligence tools. The “CovBase-AI” is an artificial intelligence algorithm that can screen a Chest X-ray and distinguish between normal and abnormal scans with a high degree of accuracy.
• Mega testing labs: CSIR proposes to create mega labs in major cities across India for keeping the economic and commercial hubs open for business during this pandemic. These labs will use ultra-high-throughput sequencing of SARS-CoV-2 using the Novaseq 6000 platforms. The advantage of this platform is that, when it is combined with automation, it can scale to 3000 to 6000 samples every 12 hours, thus increasing scope and lowering costs.
• ELISA-based kits: CSIR is developing new ELISA-based kits to improve the scope of the existing ones. The commercially available serology kits indicate the presence or absence of SARS-CoV-2-IgG. However, the ELISA being developed by CSIR is aimed to determine viral titers. Plasma from convalescent donors will be collected and used for validating the serology ELISA.
• Faecal DNA is also being collected for future research on the role of the gut microbiome in COVID-19 disease.
• CSIR-IGIB has developed a sample sequence workflow for micro labs. Employing the use of the Oxford Nanopore Technology (ONT), the sample run on this system can be studied for understanding the COVID-19 footprint in India.
Rapid and Economical Diagnosis
The key to flattening the curve of growth in Coronavirus cases is the detection of the infected at the earliest and isolating them. A combination of digital and molecular surveillance with rapid diagnosis is the need and CSIR is striving towards that using multiple strategies.
Till date, CSIR laboratories have tested about 34,500 samples for COVID-19, which includes about 8,000 tested this week. In addition to this, CSIR labs have also facilitated testing of 13500 samples in the government hospitals around them.
• CSIR-IIP as a testing lab: CSIR-Indian Institute of Petroleum, Dehradun commenced RT-PCR testing of COVID-19 patient samples. The newly developed state-of-the-art BSL-2+ facility was inaugurated by Mr. Yugal Kishore Pant, Additional Secretary, Health & Director, Medical Education, Uttarakhand. This facility is designed using a porta-cabin so that it can be replicated in remote areas. The testing facility is capable of processing about 100 patient samples per day.
• COVID-19 testing lab inaugurated in CSIR-NEIST, Jorhat: A COVID-19 testing laboratory has been established in the Jorhat campus of the North East Institute of Science and Technology (NEIST). Dr Himanta Biswa Sarma, Minister of Health and Family Welfare, Finance, Education (Higher, Secondary and Elementary), Transformation and Development, PWD, Govt. of Assam, inaugurated the laboratory. A team of 10 scientists of the institute is actively involved in isolation of RNA from the virus besides 40 other staff members are acting as support system. The institute’s Biotechnology Division is playing a pivotal role in carrying out RT-PCR-based COVID-19 testing. Besides, the Govt. of Assam and the district administration of Jorhat are actively cooperating and facilitating the efforts put in by the institute.
• CSIR-CLRI as a new testing lab: The Indian Council of Medical Research has included CSIR-Central Leather Research Institute (CSIR-CLRI) as a test lab for testing samples in the Chennai zone.
Developments/Improvements in existing technologies/methods:
• Paper-based detection: In addition to Tata Sons, CSIR-IGIB’s paper-based COVID-19 detection kit, FELUDA that is under validation by ICMR, has attracted the attention of 17 more companies who are interested to adopt the technology. An agreement with Trivitron Neuberg is the latest addition.
• Nested PCR: During the week, CSIR-CCMB reached an advanced stage of Nested polymerase chain reaction (Nested PCR) development. Nested PCR is a modification of polymerase chain reaction intended to reduce non-specific binding in products due to the amplification of unexpected primer binding sites. This enables more sensitive detection of the coronavirus. The technique also enables pooling 20 samples for testing (as compared to the current ability to pool 5 samples together) in areas where COVID-19 incidence is not too high or too low. This strategy also does not need a qPCR machine, and can be done with a regular PCR setup that many more biology and pathology labs have.
• Large scale sample testing using NGS: CSIR-CCMB has partnered with Syngene to use large scale genome testing methods using Next-Gen Sequencing which can test up to 10-20,000 samples in a day at a cost of Rs 25 per sample. This would be ideal for testing in containment and red zones.
• Pooled Sample Testing: To further increase the pace and scope of testing, CSIR has developed methodology for pooled sample testing. Diagnostic assays using quantitative Polymerase Chain Reaction most commonly process patient samples one by one. While this is usually an effective and reliable method, the current efforts against the COVID-19 pandemic demand more efficient measures. Diagnostic assays can be scaled up by the method of High-Throughput qPCR via sample pooling. Pooling, the action of combining multiple samples into one tube, is most effective when the chance of positive detection of the target, SARS-CoV-2 RNA, is low. In such cases, large groups of samples can be conclusively classified as negative with a single test, with no need to individually test every sample.
• Improved and Simplified Diagnosis of COVID-19: A new method using dry swabs and with no step of RNA isolation, which is laborious and expensive, has been developed. This is cost-effective and can be used as a quick screening procedure. In addition, sensitivity is enhanced by at least 20% by using RNA isolated from TE buffer extract compared to the traditional method.
• Feluda Test Validation: Feluda, the paper-based diagnostic kit developed by CSIR-IGIB for testing samples for COVID-19 is on a fast track development and commercialisation. The Indian Council of Medical Research (ICMR) has devised a protocol for the approval process of the diagnostic kit.
• RT-LAMP Diagnostic test: A new diagnostic technique of RT-LAMP for COVID-19 has been developed by CSIR-IIIM and Reliance Indian Limited (RIL). It is cost-effective, fast (30 min), needs simple instrumentation and has been tested on patient samples and larger validation is underway.
Repurposed Drugs/New Drugs/Vaccines/Ayush Products
To combat the virus, CSIR is exploring all avenues and supporting new ideas that have a clear deployment strategy. CSIR has further defined its strategy in this vertical by setting up focused groups to look at multiple pathways for developing drugs: i) Molecular modelling of drugs; ii) Host-target interactions; iii) Crystal engineering; iv) Batch to continuous process; v) In-silico screening of existing drugs and natural products; vi) Scouting for non-infringing routes, and vii) Host-dependent pathways for APIs.
Repurposed Drugs: CSIR is working with Cipla and other industries for leading repurposed drug candidates Remdesivir and Favipiravir by synthesizing API and Key Starting Materials and providing to the industry.
• Remdesivir has received emergency approval by FDA and Gilead has given voluntary license to several Indian companies. CSIR is working on cost-effective synthetic processes and has already demonstrated to industry.
• Cipla has received approval for clinical trials of Favipiravir which are set to begin soon. CSIR-IICT is working with Cipla. Further, CSIR-IIIM is working on cost effective synthetic process for Favipiravir with M/s Anaphar and also nicolosamide and ribavirin internally.
• CSIR-CDRI has submitted application to DCGI for Umifenovir and many CSIR labs are working on synthesis of repurposed drugs so as to build a pipeline.
• Host-dependent pathways for APIs: A combination of Bromhexine, the mucolytic drug, and Favipiravir, the antiviral targeting RdRp of COVID-19, is being evaluated for clinical trials.
• Sepsivac Clinical Trials: CSIR and Cadila Pharmaceuticals are conducting three clinical trials to evaluate the efficacy of an existing gram-negative sepsis drug called Sepisvac (Mw) for COVID-19. The three trials are on critically ill COVID-19 patients; hospitalized (but not critically ill) patients, and high-risk contacts of COVID-19.
- The clinical trial on critically ill COVID-19 patients is progressing well at AIIMS-Bhopal, AIIMS-New Delhi and PGI Chandigarh.
• Clinical trial of ACQH: CSIR and Sun Pharma have received approval for Phase 2 clinical trial of a phytopharmaceutical formulation, ACQH developed by CSIR-IIIM and DBT-ICGEB for dengue
- This is the first phytopharmaceutical to receive clinical approval and trial will start on 5 June 2020.
• Clinical trials on Ayush drugs: CSIR with ICMR and Ministry of Ayush is conducting clinical trials for Ayurveda interventions as prophylaxis and as an add-on to standard care to COVID-19. They include Ayurvedic medicines such as Ashwagandha, Yashtimadhu, Guduchi Pippali, and a polyherbal formulation (Ayush-64). Trials to start soon.
- Clinical trial protocols are being worked out with Ministry of Ayush.
• Clinical trials on convalescent plasma therapy: CSIR-IICB has received approval for a clinical trial for plasma therapy.
- The plasma therapy RCT has been initiated in Kolkata. Currently, convalescent donors are being recruited and plasma being collected. These plasma samples will be very useful for validating the serology ELISA as well.
• CSIR-CCMB collaboration to develop antibody fragment-based immunotherapy: CSIR-CCMB and University of Hyderabad (UoH) are collaborating with Vins Bioproducts Ltd, an antisera manufacturing company, to develop antibody fragment-based immunotherapy for the treatment of COVID-19. Plasma-based passive immunity against COVID-19 has several limitations. The use of antibodies has been an effective method in protecting against several human and animal diseases. Scientists are exploring alternative strategies of using horses to generate antibodies against the SARS-COV-2 viral antigens. Horse-based immunoglobulins can be produced in large quantities as a promising alternative therapy, which would be economical and can be made readily available to a larger population.
• Drug Hackathon: CSIR and All India Council for Technical Education (AICTE) have launched a hackathon for drug discovery for Covid-19 disease. The Principal Scientific Adviser of the Government of India is supporting the hackathon. The ideas holding potential that emerge from the hackathon will be developed by CSIR labs, startups and any other interested organisation. Indian students and researchers from across the world can participate in the competition.
Hospital Assistive Devices and PPEs
Ever since the pandemic reared its devastating head in the country, CSIR has been introducing low-cost and effective hospital assistive devices and PPEs and consistently improving their efficiency and design. CSIR has made considerable progress in this area and many technologies and designs have been transferred to the industry while some are at the stage of beta testing, which will be followed by certification
• CSIR-CMERI develops mechanical ventilator: CSIR-Central Mechanical Engineering Research Institute (CSIR-CMERI), Durgapur, has developed a Mechanical Ventilator. These Automated Portable Mechanical Ventilators might be deployed to help huge volumes of prospective patients if required. The prototype has been equipped with multiple life-saving control features such as Tidal Volume, Breaths per Minute and Inspiratory/Expiratory ratios.
Keeping in the mind the probable mass requirement of this Life-Saving medical equipment, portability and cost-effectiveness are two of the most primary elements of the product.
• Biopolymer Nano coated Medical Grade Mask: CSIR-National Chemical Laboratory (CSIR-NCL), Pune has developed a superior face mask which has better filtration efficiency than the available face masks in the market. CSIR-NCL’s patented bacterial nano-cellulose technology along with nano-coating was used for this purpose. The cotton cloth coated in a solution of bacterial cellulose and nano-material completely prevents the penetration of bacterial growth. The Bacterial Filtration Efficiency (BFE) of CSIR-NCL mask is 99.9% and Particulate Filter Efficiency (PFE) is 92.63% PFE. This indicates a high restriction of hazardous particulates. The masks are made for easy breathability, of medical grade and are of low flammability.
• Respiratory Assistance Intervention Device (Respi-AID): CSIR-CSIO, Chandigarh has developed the Respiration Assistance Intervention Device: A Portable Ventilator (Respi-AID) in collaboration with Govt Medical College and Hospital, Chandigarh. The technology was transferred on a digital platform to M/s Sivapriya Exim Private Limited, Chennai on 29 May 2020.
• Bi-Level Positive Airway Pressure System (Bi+APV1): Named ‘SwasthVayu’, the BiPAP Ventilator is an electronic breathing device used in the treatment of sleep apnea, lung disease, and to treat respiratory weakness and will be used for COVID-19 patients. Blower motor and controller are the critical components of the BiPAP ventilator and currently are imported from Switzerland. To lower costs, alternate sources in Taiwan and China have been identified for these critical components. The system has been certified for calibration by NABL accredited agencies as well as TUV Rheinland (meeting the minimum requirements of the German Equipment and Product Safety Act). CSIR-NAL will make 25 BiPAP devices and 100 devices will be made by licensee companies. Thus, a total of 125 devices will be made, to begin with.
• Personal Protective Coverall: The production rights for the coverall developed by CSIR-NAL have been given to MAF Clothing, Bengaluru on a non-exclusive basis. The first lot of 5000 coveralls has been supplied to HLL Life Care, Trivandrum by MAF clothing. CSIR-NAL will soon sign agreements with some manufacturers to start production.
• Mobile indoor disinfection sprayer units: CSIR-CMERI has developed mobile indoor disinfection sprayer units. These can be used for cleaning and disinfecting pathogenic microorganisms effectively, especially in hospitals. The institute has developed two variants of the indoor disinfection units. One is the Battery Powered Disinfectant Sprayer (BPDS), and the other is the Pneumatically Operated Mobile Indoor Disinfection (POMID). The two units can be used to clean and disinfect frequently touched surfaces such as tables, doorknobs, etc.
• Electrostatic Disinfection Machine: CSIR-CSIO has developed Electrostatic Disinfection Machine technology which was transferred to the industry a few weeks ago. As the country eases lockdown and more people get back to work, the machine will play a vital role in disinfecting and sanitizing public places especially hospitals, poultry, trains and buses, airports and aeroplanes, offices, classrooms and hotels. The industrial partner, Rite Water Solutions today announced that it is ready to mass-produce the machine.
• Palm Safe: CSIR-NIIST has developed a Free Hand Sanitizer (“Palm Safe”), the technology was transferred to Tachlog Industry, Trivandrum.
• Face Mask: CSIR-CECRI's tri-layered Face Mask with antimicrobial and hydrophobic coating received certification from SITRA.
• Herbal Inhaler: CSIR-National Botanical Research Institute (CSIR-NBRI) has developed a herbal inhaler technology which is ready for transfer to the industry. The inhaler based on ayurvedic formulation, when sprayed on masks makes breathing easier by decongesting the nasal passage.
• CSIR-NIIST’s technology for air sanitizer was transferred to an MSME M/s Ecocure Technologies.
• Smart hand sanitizer dispenser ("Palm Safe") technology developed by CSIR-NIIST transferred to Tachlog, a Trivandrum based industry.
• Flocculation-based Disinfection Systems: CSIR-NIIST signed a non-disclosure agreement with CML Biotech (P) Ltd. Angamaly, Kerala for the development of Flocculation-based Disinfection Systems for Pathogenic Medical Waste Disposal.
CSIR Supply Chain & Logistics Support
KisanSabha App: The KisanSabha portal and app was launched by Dr Trilochan Mahaptra, Director-General, Indian Council of Agricultural Research (ICAR) on 1 May 2020. In a short time, nearly 30,000 transporters, 3200 farmers, and over 1000 other service providers and customers have already registered. Going by the feedback received, many farmers who have used the app have received higher prices for their produce. The KisanSabha app will soon be launched in six languages – Tamil, Telugu, Kannada, Marathi, Gujarati, Bengali & Urdu.
• Rapid Health Supply Chain Information Platform: Aarogyapath (????????), the National healthcare supply chain platform that was initiated recently is now under development. The important functionalities have been identified and the various interfaces (screens) have been finalized. As of now, three stakeholders categories, viz., Manufacturers/Suppliers, Buyers, and Hospital & Labs have been identified for the primary launch.