SARS-CoV-2 infection dynamics and genomic surveillance to detect variants in wastewater - a longitudinal study in Bengaluru, India.

Background: Environmental surveillance (ES) of a pathogen is crucial for understanding the community load of disease. As an early warning system, ES for SARS-CoV-2 has complemented routine diagnostic surveillance by capturing near real-time virus circulation at a population level. Methods: In this longitudinal study conducted between January 2022 and June 2022 in 28 sewershed sites in Bengaluru city (∼11 million inhabitants), we quantified weekly SARS-CoV-2 RNA concentrations to track infection dynamics and provide evidence of change in the relative abundance of emerging variants. Findings: We describe an early warning system using the exponentially weighted moving average control chart and demonstrate how SARS-CoV-2 RNA concentrations in wastewater correlated with clinically diagnosed new COVID-19 cases, with the trends appearing 8-14 days earlier in wastewater than in clinical data. This was further corroborated by showing that the estimated number of infections is strongly correlated with SARS-CoV-2 RNA copies detected in the wastewater. Using a deconvolution matrix, we detected emerging variants of concern up to two months earlier in wastewater samples. In addition, we found a huge diversity in variants detected in wastewater compared to clinical samples. The findings from this study have been discussed regularly with local authorities to inform policy-making decisions. Interpretation: Our study highlights that quantifying viral titre, correlating it with a known number of cases in the area, and combined with genomic surveillance helps in tracking variants of concern (VOC) over time and space, enabling timely and making informed policy decisions. Funding: This work has been supported by funding from the Rockefeller Foundation grant to National Centre for Biological Sciences, TIFR) and the Indian Council of Medical Research grant to (FI) Tata Institute for Genetics and Society and Tata Trusts.

Identification and Genomic Characterization of Parvovirus B19V Genotype 3 Viruses from Cases of Meningoencephalitis in West Bengal, India.

Brain infections are a major public health problem in India and other parts of the world, causing both mortality and lifelong disability. Even after a thorough investigation, many cases remain without an etiological diagnosis. Primate erythroparvovirus 1 (B19V) has been identified as a pathogen associated with undiagnosed meningoencephalitis in other settings, including the United Kingdom, France, and Latvia. Here, we reported 13/403 (3.2%) B19V PCR positive cases of meningoencephalitis in West Bengal, India. The positive samples were mostly from children (10/13, 76.92%) and presented as a spectrum consisting of acute encephalitis (7/13), acute meningoencephalitis (3/13), and meningitis (3/13). Of the 13 cases, 8/13 (61.5%) had no known etiology and 5/13 (38.5%) had a previous etiological diagnosis. The cases did not cluster in time or by location, suggesting sporadic occurrence rather than outbreaks. We were able to retrieve the complete B19V genomes from cerebrospinal fluid (CSF) in 12/13 cases. The sequences clustered into genotype 3b with complete genomes from Brazil, Ghana, and France, and partial genomes from India and Kyrgyzstan. This is the first report of B19V in cases of neurological infections from India. It highlights the need to evaluate the causal relationship between B19V with meningoencephalitis in the country. These were also the first complete genomes of genotype 3b from CSF and will be critical in the evaluation of the relationship between genotypes and disease. IMPORTANCE Cases of meningoencephalitis with no known etiology remain a major challenge to clinical management of brain infections across the world. In this study, we detected and characterized the whole-genome of primate erythroparvovirus 1 (B19V) in cases of meningoencephalitis in India. Our work highlighted the association between B19V and brain infections which has been reported in other countries. Our work also emphasized the need to examine the role of B19V in meningoencephalitis, specifically whether it caused or contributed to the disease together with other pathogens in India. Our study provided the first 12 genomes of B19V from cerebrospinal fluid. These genomes will contribute to an understanding of how the virus is changing across different locations and over time.

Importation, circulation, and emergence of variants of SARS-CoV-2 in the South Indian state of Karnataka.

Background: As the coronavirus disease 2019 (COVID-19) pandemic continues, the selection of genomic variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associated with higher transmission, more severe disease, re-infection, and immune escape are a cause for concern. Such variants have been reported from the UK (B.1.1.7), South Africa (B.1.351) and, Brazil (P.1/B.1.1.28). We performed this study to track the importation, spread, and emergence of variants locally. Methods: We sequenced whole genomes of SARS-CoV-2 from international travellers (n=75) entering Karnataka, South India, between Dec 22, 2020 and Jan 31, 2021, and from positive cases in the city of Bengaluru (n=108), between Nov 22, 2020- Jan 22, 2021, as well as a local outbreak. We present the lineage distribution and analysis of these sequences. Results: Genomes from the study group into 34 lineages. Variant B.1.1.7 was introduced by international travel (24/73, 32.9%). Lineage B.1.36 and B.1 formed a major fraction of both imported (B.1.36: 20/73, 27.4%; B.1: 14/73, 19.2%), and circulating viruses (B.1.36: 45/103; 43.7%,. B.1: 26/103; 25.2%). The lineage B.1.36 was also associated with a local outbreak. We detected nine amino acid changes, previously associated with immune escape, spread across multiple lineages. The N440K change was detected in 45/162 (27.7%) of the sequences, 37 of these were in the B.1.36 lineage (37/65, 56.92%) Conclusions: Our data support the idea that variants of concern spread by travel. Viruses with amino acid replacements associated with immune escape are already circulating. It is critical to check transmission and monitor changes in SARS-CoV-2 locally.