Impact of COVID-19 vaccination on transmission risk of breakthrough infections: Lessons from adapted N95 mask sampling for emerging variants and interventions.

This study used an adapted N95 mask sampling to understand the effect of COVID-19 vaccination in the context of circulating variants on infected individuals to emit the virus into the air, a key risk factor of transmission. Mask, swab, and blood samples were collected from 92 COVID-19 patients vaccinated (Covishield/COVAXIN-partial/fully) or unvaccinated between July and September 2021 during the Delta-dominated period in Mumbai. Mask/swab samples were analyzed by reverse transcription polymerase chain reaction for viral RNA. Blood was evaluated for SARS-CoV-2 anti-spike and nucleocapsid antibody responses. At <48 h of diagnosis, 93% of the patients emitted detectable viral RNA, with 40% emitting >1000 copies in 30 min (high emitters). About 8% continued to be high emitters even after 8 days of symptom onset. No significant difference was observed in emission patterns between partial, full, and unvaccinated patients. However, when vaccinated patients were stratified based on spike protein neutralization and nucleocapsid immunoglobulin G (IgG), the group with moderate/high neutralization showed a significantly lower proportion of high emitters and viral RNA copies than the group with no/low neutralization, which further reduced in the group having antinucleocapsid IgG. In conclusion, mask sampling showed that Delta infections were associated with greater virus emission in patients, which was significantly reduced only in vaccinated patients with moderate/high SARS-CoV-2 neutralization, especially with evidence of past infection. The study demonstrated that mask sampling could be useful for understanding the transmission risk of emerging variants, screening vaccine/booster candidates, and guiding control interventions.

Randomised trial to determine the effect of vitamin D and zinc supplementation for improving treatment outcomes among patients with COVID-19 in India: trial protocol.

INTRODUCTION: Presently, there are few population-level strategies to address SARS-CoV-2 infection except preventive measures such as vaccination. Micronutrient deficiency, particularly vitamin D and zinc deficiency, has been associated with dysregulated host responses, and may play an important role in COVID-19. METHODS AND ANALYSIS: We have designed a 2×2 factorial, randomised, double-blind, multi-centre placebo-controlled trial to evaluate the effect of vitamin D and zinc on COVID-19 outcomes in Maharashtra, India. COVID-19 positive individuals are recruited from hospitals in Mumbai and Pune. Participants are provided (1) vitamin D3 bolus (180 000 IU) maintained by daily dose of 2000 IU and/or (2) zinc gluconate (40 mg daily), versus placebo for 8 weeks. Participants undergo a detailed assessment at baseline and at 8 weeks, and are monitored daily in hospital or every 3 days after leaving the hospital to assess symptoms and other clinical measures. A final follow-up telephone call occurs 12 weeks post-enrolment to assess long-term outcomes. The primary outcome of the study is to time to recovery, defined as time to resolution of all of fever, cough and shortness of breath. Secondary outcomes include: duration of hospital stay, all-cause mortality, necessity of assisted ventilation, change in blood biomarker levels and individual symptoms duration. Participant recruitment commenced on April 2021. ETHICS AND DISSEMINATION: Ethical approval was obtained from institutional ethical committees of all participating institutions. The study findings will be presented in peer-reviewed medical journals. TRIAL REGISTRATION NUMBERS: NCT04641195, CTRI/2021/04/032593, HMSC (GOI)-2021-0060.

Genomics of postvaccination SARS-CoV-2 infections during the Delta dominated second wave of COVID-19 pandemic, from Mumbai Metropolitan Region (MMR), India.

The present study was initiated to understand the proportion of predominant variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in postvaccination infections during the Delta dominated second wave of coronavirus disease 2019 (COVID-19) in the Mumbai Metropolitan Region (MMR) in India and to understand any mutations selected in the postvaccination infections or showing association with any patient demographics. Samples were collected (n = 166) from severe/moderate/mild COVID-19 patients who were either vaccinated (COVISHIELD/COVAXIN-partial/fully vaccinated) or unvaccinated, from a city hospital and from home isolation patients in MMR. A total of 150 viral genomes were sequenced by Oxford Nanopore sequencing and the data of 136 viral genomes were analyzed for clade/lineage and for identifying mutations. The sequences belonged to three clades (21A, 21I, and 21J) and their lineage was identified as either Delta (B.1.617.2) or Delta+ (B.1.617.2 + K417N) or sub-lineages of Delta variant (AY.120/AY.38/AY.99). A total of 620 mutations were identified of which 10 mutations showed an increase in trend with time (May-October 2021). Associations of six mutations (two in spike, three in orf1a, and one in nucleocapsid) were shown with milder forms of the disease and one mutation (in orf1a) with partial vaccination status. The results indicate a trend toward reduction in disease severity as the wave progressed.

Genome Sequences of Five SARS-CoV-2 Variants from Mumbai, India, Obtained by Nanopore Sequencing.

We report here the genome sequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants from five coronavirus disease 2019 (COVID-19) patients in Mumbai, India. Viral genomic RNA was isolated from nasopharyngeal swabs and/or respiratory particles from the masks of the patients. Genomic variant analysis determined 8 to 22 mutations, and the variants belong to lineages previously associated with Indian variants.

Non-invasive adapted N-95 mask sampling captures variation in viral particles expelled by COVID-19 patients: Implications in understanding SARS-CoV2 transmission.

Infectious respiratory particles expelled by SARS-CoV-2 positive patients are attributed to be the key driver of COVID-19 transmission. Understanding how and by whom the virus is transmitted can help implement better disease control strategies. Here we have described the use of a noninvasive mask sampling method to detect and quantify SARS-CoV-2 RNA in respiratory particles expelled by COVID-19 patients and discussed its relationship to transmission risk. Respiratory particles of 31 symptomatic SARS-CoV-2 positive patients and 31 asymptomatic healthy volunteers were captured on N-95 masks layered with a gelatin membrane in a 30-minute process that involved talking/reading, coughing, and tidal breathing. SARS-CoV-2 viral RNA was detected and quantified using rRT-PCR in the mask and in concomitantly collected nasopharyngeal swab (NPS) samples. The data were analyzed with respect to patient demographics and clinical presentation. Thirteen of 31(41.9%) patients showed SARS-COV-2 positivity in both the mask and NPS samples, while 16 patients were mask negative but NPS positive. Two patients were both mask and NPS negative. All healthy volunteers except one were mask and NPS negative. The mask positive patients had significantly lower NPS Ct value (26) compared to mask negative patients (30.5) and were more likely to be rapid antigen test positive. The mask positive patients could be further grouped into low emitters (expelling <100 viral copies) and high emitters (expelling >1000 viral copies). The study presents evidence for variation in emission of SARS-CoV-2 virus particles by COVID-19 patients reflecting differences in infectivity and transmission risk among individuals. The results conform to reported secondary infection rates and transmission and also suggest that mask sampling could be explored as an effective tool to assess individual transmission risks, at different time points and during different activities.