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COVID-19

The sudden onset of the COVID-19 pandemic in 2020 provided a serious challenge to the Foundation's work. Its identity as a biomedical and public health research organization pushed us to take up this challenge. The unique mask-based method developed at FMR for TB diagnosis was modified to capture expelled viral particles and project risk of transmission. Genome sequencing expertise was translated to analyze the characteristics of circulating variants. Simultaneously, we initiated clinical trials to evaluate usefulness of vitamin D and Zinc supplementation for reducing serious outcomes in COVID-19. In 2021, as the vaccination drive unfolded and simultaneously Delta variant ravaged the country, we turned to address important questions about breakthrough infections- what were the characteristics of these variants that caused breakthrough infections and did vaccination have the potential to reduce transmission. Now as the pandemic appears to be retreating, but with the resurgence threat still looming, we have now focused our attention to wastewater surveillance of the virus intending to predict potential oncoming waves.


Covid-19
Covid-19
Covid-19

Some key achievements in this period have been

  • Demonstrating a technology for gauging transmission of COVID-19
  • Deciphering the impact of vaccination on transmission risk and strain patterns of the virus in order to generate evidence related to breakthrough infections

PROJECTS

  • Principal Investigator

    Dr. Kayzad Nilgiriwala

  • Collaborators/Partners

    1. Dr. Mangala D. Gomare, Municipal Corporation of Greater Mumbai
    2. Dr. Daksha Shah, Municipal Corporation of Greater Mumbai

  • Project Team

    Ms. Tejal Mestry, Ms. Grishma Patel, Mr. Nilesh Shahasne, Ms Pratibha Kadam

  • Funded by

    Science and Engineering Research Board

  • Duration

    July 2022 – June 2023

  • Budget

    INR 44 lakhs

  • Status

    Ongoing

ABOUT THE PROJECT

This project aims to undertake periodic genomic surveillance for SARS-CoV-2 variants in effluents in urban localities with a vulnerable population. The emergence of any new mutations/variants in the vulnerable communities in Mumbai through comparison with the local and global database of mutations will also be conducted. The biological significance of specific trends of mutations with respect to transmission, immune evasion and viral load will be assessed. This will lead to a better understanding of the sustainability of targeted environmental surveillance for the detection of known and newly emerging variants in vulnerable populations. It will also serve as a warning system for subsequent waves of SARS-CoV-2 infection.

In this project, the effluent/wastewater samples from 8 sites located in slum areas (Dharavi, Kherwadi, Beharampada in Bandra East and Sidharth Nagar in Worli) will be collected twice weekly for 10 months from the selected slum areas. The wastewater/sewage will be processed for RNA isolation, and RT-qPCR will be conducted to determine the viral load. Sequencing will be undertaken in 10% of the positive environmental samples. Data processing and analyses will be focused on periodic surveillance / new mutations or variants / biological significance of new mutations.

  • Principal Investigators

    1. Dr. Kevin Kain, University of Toronto, Canada
    2. Dr. Wafaie Fawzi, Harvard School of Public Health, USA
    3. Dr. Yatin Dholakia

  • Co-Investigator

    Dr. Nerges Mistry

  • Collaborators

    1. Dr. Pradeep D’Costa, King Edward Memorial (KEM) Hospital and Research Center, Pune
    2. Dr. Gaurav Gupta, Saifee Hospital, Mumbai

  • Project Team

    Mr. Kamalkant Sharma, Ms. Sanaa Shaikh, Mr. Yogesh Marathe (FMR); Dr. Vrushali Patil, Dr.Rohit Kumar, Dr. Bhushan Labhane, Ms. Deepa Patil, Ms. Komal Dalvi, Ms. Priti Vidhate (KEM); Dr. Sashidhar, Dr. Atmashakti, Ms. Latika Raju Mhatre, Ms. Janhvi Jitendra Shelatkar (Saifee)

  • Funded by

    Canadian Institute of Health Research, Canada

  • Duration

    October 2020 –October 2022

  • Budget

    INR 368 lakhs

  • Status

    Completed

  • Clinical Trial Registry India Registration number

    CTRI/2021/04/032593 (www.ctri.nic.in)

ABOUT THE PROJECT

Micronutrient deficiencies, particularly vitamin D and zinc, are associated with impaired host-immune response and may play important roles in COVID-19. While supplementation is important in the context of other infections, there are no well-designed studies on the potential effects of such supplements on COVID-19. A randomized, placebo-controlled trial using a 2x2 factorial was designed to examine individual effects of vitamin D or zinc supplements as immune-based therapy among 700 COVID-19 patients in India. Eligible participants included non-pregnant women or men >18 years with PCR-confirmed infection, recruited from KEM Hospital, Pune and Saifee Hospital, Mumbai. The unpredictability of COVID-19 waves was a challenge to the study to maintain recruitment during periods where cases were declining. Early anticipation of the scenario led to a modification of enrollment criteria.

Interventions: Patients randomized to 8 weeks of (1) Vitamin D (180,000 IU bolus followed by 2000 IU daily); (2) Zinc (daily doses of 40 mg); (3) Vitamin D + Zinc; or (4) Placebo.

Primary Aims: To determine the effect of vitamin D and/or zinc supplementation versus placebo on time to recovery among patients with COVID-19.

Secondary Aims: To determine the effect of vitamin D or zinc supplementation on all-cause mortality, duration of hospital stay, the necessity for assisted ventilation, individual symptoms duration, change in inflammatory and immunologic biomarkers levels.

A total of 409 patients (average age of 47 years) were screened between April 2021 to January 2022. Of these, 181 were recruited and randomized to the 4 arms. Significantly, 48.6% of the screened patients refused to consent to participate.

INTERIM FINDINGS/ACHIEVEMENTS

At this stage of the Project, the data is still blinded and awaits decoding for analysis. However, our baseline analysis shows

  • A high degree (~ 50%) of Vit D3 insufficiency/ deficiency
  • 15.6% of patients had comorbidities
  • 75% had been vaccinated against COVID-19
  • Levels of Lactate Dehydrogenase (LDH) and Interleukin -6 (IL-6) biomarkers performed at baseline were reduced significantly in fully and partially vaccinated people compared to the unvaccinated group, whereas immunological markers (IgG and IgM) showed an increasing trend of protection with the number of vaccination doses
  • Other inflammatory markers associated with disease severity such as CRP, Serum Ferritin, D-Dimer, Angiopoietin-2 and sTREM-1 also showed decreased levels in vaccinated participants than in unvaccinated participants

PUBLICATION

  • Sharma, K.K, Partap, U., Mistry, N., Marathe, Y., Wang, M., Shaikh, S., et al. Randomized trial to determine the effect of vitamin D and zinc supplementation for improving treatment outcomes among patients with COVID-19 in India: trial protocol. BMJ Open. 2022;12(8):e061301.

Two research studies were conducted in parallel with interlinked objectives and common funding.

Study 1: Impact of COVID-19 Vaccination on Transmission Risk of Acquired Infection and Strain Characteristics

  • Principal Investigator

    Dr. Kalpana Sriraman

  • Clinical Trial Registry India Registration Number

    CTRI/2021/07/035143 (www.ctri.nic.in)

  • Co-Investigators

    1. Dr. Nerges Mistry, Dr. Ambreen Shaikh, Dr. Kayzad Nilgiriwala
    2. Dr. Vikas Oswal, Vikas Nursing Home, Mumbai
    3. Dr. Mangala D. Gomare, Municipal Corporation of Greater Mumbai
    4. Dr. Daksha Shah, Municipal Corporation of Greater Mumbai

Study 2: Genomic characterization of SARS-CoV-2 in fully vaccinated hospital patients with breakthrough infections

  • Principal Investigators

    1. Dr. Nerges Mistry
    2. Dr. Zarir Udwadia ,Breach Candy Medical Research Centre (BCMRC), Mumbai

  • Co-Investigators

    1. Dr. Kayzad Nilgiriwala, Dr Kalpana Sriraman, Dr. Ambreen Shaikh, FMR
    2. Dr. Aruna Poojary , BCMRC
    3. Dr. Bhavesh Gandhi , BCMRC

  • Project Team

    1. Ms. Smriti Vaswani, Ms. Tejal Mestry, Ms. Grishma Patel, Ms. Pratibha Kadam
    2. Ms. Niharika Shinde; Dr. Seema Kukreja, BCMRC

  • Funded by

    Members of HBS Alumni Club of India, General donation of Zoroastrian Charity Trust of Hong Kong

  • Duration

    June 2021– April 2022

  • Budget

    INR 46 lakhs

  • Status

    Completed

ABOUT THE PROJECT

Vaccines are the most potent weapon we have for controlling the COVID-19 pandemic. Although the efficacy of current vaccines was well established, there was increasing concern in India in early 2021 about COVID-19 infection despite vaccination. The incidence of infection post-vaccination raised several questions- why were some people susceptible despite vaccination, do they get infected with the mutated virus not protected by the vaccine and do vaccinated individuals transmit the virus? It was important to address these clinical research gaps more systematically to guide disease control efforts.

Study 1 aimed to a) to assess the transmission risk from vaccinated COVID-19 positive individuals using adapted N-95 mask sampling and investigate its relationship to SARS-CoV-2 specific antibody responses b) to characterize the strains in infections acquired after partial or full COVID-19 vaccination by whole genome sequencing in home isolated patients with mild disease. The study prospectively followed up vaccinated and unvaccinated 95 COVD-19 patients who were primarily home isolated with mild disease in Mumbai region between June and September 2021. Mask, swab, and blood samples were collected from these patients at two time points- within 48 hours of diagnosis and between 8-12 days of symptom onset. Mask and swab samples were analyzed by RT-PCR for viral RNA and blood was evaluated for SARS-CoV-2 anti-spike and nucleocapsid antibody responses. Whole genome sequencing of swab samples was also carried out to understand the mutations and strain characteristics of the infected strains.

Study 2 aimed to genomically characterize the strains from fully vaccinated mild to severe hospitalized patients with breakthrough infections and investigate the association between SARS-CoV-2 specific antibody responses and genome characteristics. The study recruited 74 mild to severe fully vaccinated COVID-19 patients from Breach Candy Hospital between June – Dec 2021. Nasopharyngeal swab and blood samples collected from these patients were subjected to RT-PCR, whole genome sequencing and antibody testing.

KEY FINDINGS/ACHIEVEMENTS

Transmission risk analysis (Study 1)

  • Compared to the 2020 Wuhan strain dominated wave, a significant proportion (90%) of people with COVID-19 expelled SARS-CoV2 virus in their breath and the amount virus expelled was 100-fold higher, explaining the high transmission rates of Delta strain in 2021. Results highlighted that mask-based sampling would be useful for understanding transmission risk from emerging variants
  • Vaccinated patients with poor antibody responses to SARS-CoV-2 tend to emit significantly more virus in their breath and hence carry a higher risk of causing secondary transmission than vaccinated individuals who have good immune responses to the virus
  • The adapted N-95 mask sampling tool and methods used in this study have many applications, including a) understanding the potential transmission risk of any new variants or interventions that can guide the development of patient isolation policies or disease control strategies, b) screening new vaccines or therapeutic candidates for their ability to block transmission

Genome Analysis (Study 1 & 2)

  • All sequences from both studies collected between Jun-Dec 2021 belonged to -three clades (21A, 21I and 21J), lineages -Delta (B.1.617.2) or Delta+ (B.1.617.2 + K417N) or sub-lineages of Delta variant (AY.120/AY.38/AY.99)
  • 620 mutations were identified in these sequences, of which 10 mutations showed an increase in trend with time (May-Oct 2021), highlighting the evolving pattern of the virus
  • 6 mutations- 2 in spike protein, 3 in Orf1ab protein and 1 in nucleocapsid protein of the virus were associated with milder forms of the disease. The results indicated a trend toward reduction in disease severity with the progression of the wave
  • The study results emphasized the need for continued genomic surveillance to keep track of emerging newer variants

PUBLICATION

  • Nilgiriwala, K., Kadam, P., Patel, G…Mistry, N. et al. (2022). Genomics of Post-Vaccination SARS-CoV-2 infections during the dela dominated second wave of COVID-19 pandemic, from Mumbai Metropolitan Region (MMR), India. J Med Virol 2022;94(9):4206-4215.
  • Sriraman, K., Shaikh, A., Vaswani, S....Mistry, N. et al. (2022). Impact of COVID vaccination on transmission risk of breakthrough infections: Lessons from Adapted N95 mask sampling for emerging variants and interventions. J Med Virol. 1-10.

CONFERENCE PRESENTATIONS

  • Shaikh, A. SARS-CoV-2 viral load in the respiratory particles expelled by COVID-19 patients in the wake of second-wave in Mumbai, India: What’s new? Poster Presentation. 52nd World Conference on Lung Health and TB Science, 2021”, organized by the Union, 19th to 22nd October, 2021 (Virtual).
  • Mistry, N. SARS-CoV-2 variants of concern/interest in India. Invited talk. Maharashtra COVID-19 Taskforce Meeting”, organized by Maharashtra COVID-19 Taskforce, 24th May 2021 (Virtual).
  • Principal Investigator

    Dr. Nerges Mistry

  • Co-Investigators

    Dr. Kalpana Sriraman, Dr. Kayzad Nilgiriwala, Dr. Ambreen Shaikh

  • Collaborator

    Dr. Jayanthi Shastri, Kasturba Hospital for Infectious Diseases, Mumbai

  • Project Team

    Ms. Smriti Vaswani, Ms. Tejal Mestry, Mr. Nilesh Shahasne (FMR)
    Dr. Swapneil Parikh, Dr. Shreevatsa Udupa, Dr. Nirjhar Chatterjee, Dr. Meet Visaria and Dr. Aishvarya Singh, (Kasturba Hospital)

  • Funded by

    Grants and donations from Godrej Agrovet Limited-Mumbai, Zoroastrian Charity Funds of Hong Kong, Canton and Macao, and The Vasketu Foundation, Mumbai

  • Duration

    June 2020 – November 2020

  • Budget

    INR 18.2 lakhs

  • Status

    Completed

ABOUT THE PROJECT

The project investigated the potential of aerosols expelled/exhaled by COVID-19 patients and captured on a modified mask as a diagnostic tool and for studying viral genomics. This was a pilot study wherein mask based detection of COVID-19 was evaluated against concomitantly collected nasopharyngeal swabs in 31 patients who were confirmed to have COVID-19 and an equal number of healthy volunteers.

KEY FINDINGS/ACHIEVEMENTS

  • Only 42% of COVID-19 patients expelled the virus in their breath during the 2020 wave and among the people who expelled the virus, there were distinct groups of high viral emitters and low viral emitters
  • Though the method did not appear to be useful for diagnostics, the emission pattern observed reflected secondary transmission rates of the strain in the communities suggesting its usefulness as an indicator of infectiousness of the patients
  • Essentially, the study had shown the feasibility of detecting the SARS-CoV-2 virus in respiratory particles expelled by patients using a simple collection method that may be used for assessing transmission risks of hosts at different time points and during different activities

PUBLICATION

  • Sriraman, K., Shaikh, A., Parikh, S., Udupa, S., Chatterjee, N., Shastri, J., Mistry, N. (2021). Non-invasive adapted N-95 mask sampling captures variation in viral particles expelled by COVID-19 patients: Implications in understanding SARS-CoV2 transmission. PLOS One, 16: e0249525.