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

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

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).