Correlation of severity & clinical outcomes of COVID-19 with virus variants: A prospective, multicentre hospital network study
Authors: Wadhwa Komal , Malik Shilpa , Balaji Srinigila , Thiruvengadam Ramachandran , Bashyam Murali Dharan , Bhattacharya Prasanta Kumar , Behera Bijayini , Bhardwaj Pankaj , Biswas Nidhan K. , Das Asim , Dey Anindya , Dhotre Dhiraj , Dias Mary , Dubey Pankaj , Dutta Shreelekha , Gadepalli Ravisekhar , Gosain Mudita , Goud Kalal Iravaty , Gupta Neeraj Kumar , Gupta Nitesh , Jana Pradipta , Jena Deepak , John Elizabeth , Karunanidhi Arunkumar , Khan S. Muhammad Salim , Khattar Sahil , Paul Abhilash Prabhakar Kundavaram , Kumar Shakti , Maitra Arindam , Modi Nikhil , Moorthy Mahesh , Nagaraj Savitha , Palakodeti Dasaradhi , Pandey Anil Kumar , Pandey Aparna , Raghav Sunil Kumar , Ramasubban Suresh , Raghavan Sreevatsan , Harikrishnan S. , Krishnamoorthy S. , Selvamurugan Selvaraj , Sardana Raman , Shouche Yogesh , Singh Akanksha , Singh Arvind Kumar , Ramasubramaniyan V. , Yadav Monika , Zahoor Danish , Narreddy Suneetha , Bhatnagar Shinjini , Wadhwa Nitya , Das Bhabatosh , Garg Pramod Kumar 
Published: April 2024

Background & objectives:
The clinical course of COVID-19 and its prognosis are influenced by both viral and host factors. The objectives of this study were to develop a nationwide platform to investigate the molecular epidemiology of SARS-CoV-2 (Severe acute respiratory syndrome Corona virus 2) and correlate the severity and clinical outcomes of COVID-19 with virus variants.

Methods:
A nationwide, longitudinal, prospective cohort study was conducted from September 2021 to December 2022 at 14 hospitals across the country that were linked to a viral sequencing laboratory under the Indian SARS-CoV-2 Genomics Consortium. All participants (18 yr and above) who attended the hospital with a suspicion of SARS-CoV-2 infection and tested positive by the reverse transcription–PCR method were included. The participant population consisted of both hospitalized as well as outpatients. Their clinical course and outcomes were studied prospectively. Nasopharyngeal samples collected were subjected to whole genome sequencing to detect SARS-CoV-2 variants.

Results:
Of the 4972 participants enrolled, 3397 provided samples for viral sequencing and 2723 samples were successfully sequenced. From this, the evolution of virus variants of concern including Omicron subvariants which emerged over time was observed and the same reported here. The mean age of the study participants was 41 yr and overall 49.3 per cent were female. The common symptoms were fever and cough and 32.5 per cent had comorbidities. Infection with the Delta variant evidently increased the risk of severe COVID-19 (adjusted odds ratio: 2.53, 95% confidence interval: 1.52, 4.2), while Omicron was milder independent of vaccination status. The independent risk factors for mortality were age >65 yr, presence of comorbidities and no vaccination.

Interpretation & conclusions:
The authors believe that this is a first-of-its-kind study in the country that provides real-time data of virus evolution from a pan-India network of hospitals closely linked to the genome sequencing laboratories. The severity of COVID-19 could be correlated with virus variants with Omicron being the milder variant.