Unraveling the Effects of the COVID-19 Pandemic on the Burden of Respiratory Syncytial Virus in a Tertiary Hospital in Catalonia, Spain: Season 2022-2023 Analysis (preprint)

Purpose: Respiratory Syncytial Virus (RSV) associated infections have historically been the cause of seasonal paediatric hospital departments’ saturation. During the COVID-19 pandemic, the community incidence of RSV was reduced, thus the hospital burden. The last RSV season broke out in early October 2022, 4-6 weeks earlier than in pre-pandemic years, and was thought to be the most demanding to date. Our aim was to assess the burden of RSV-related hospitalizations on a referral hospital (Catalonia, Spain) during the pre-pandemic years and the most recent 2022-2023 season. Methods: We analysed the paediatric hospital and intensive care (PICU) admissions data (January 2016 – January 2023) of a tertiary referral hospital in Catalonia, Spain. All-cause pediatric admissions, admissions related to confirmed RSV infections, and occupancy-related variables were collected. Results and conclusion: RSV-related hospitalizations incidence was lower during the pandemic years, particularly in 2020. The majority of RSV cases within an epidemic peak primarily affected children ≤3 months. Although the number of daily admissions during the last RSV 2022-2023 season was not higher than in the pre-pandemic years, the mean occupancy of the hospital was significantly higher (p= 0.04) due to a longer period of days with more than 20 RSV infected children inpatients per day.

The frequency of defective genomes in Omicron differs from that of the Alpha, Beta and Delta variants (preprint)

The SARS-CoV-2 Omicron variant emerged showing higher transmissibility and possibly higher resistance to current COVID-19 vaccines than other variants dominating the global pandemic. In a March 2020 study performed in clinical samples, we found that a portion of genomes in the SARS-CoV-2 viral population accumulated deletions at the S1/S2 cleavage site (PRRAR/S) of the spike gene, generating a frameshift and appearance of a premature stop codon. The main aim of this study was to determine the frequency of defective deletions in prevalent variants from the first to sixth pandemic waves in our setting and discuss whether the differences observed might support epidemiological proposals.The complete SARS-CoV-2 spike gene was deeply studied by next-generation sequencing using the MiSeq platform. More than 90 million reads were obtained from respiratory swab specimens of 78 COVID-19 patients with mild infection caused by the predominant variants circulating in the Barcelona city area during the six pandemic waves: B.1.5, B.1.1, B.1.177, Alpha, Beta, Delta, and Omicron.The frequency of defective genomes found in variants dominating the first and second waves was similar to that seen in Omicron, but differed from the frequencies seen in the Alpha, Beta and Delta variants.Our results support the notion cited in epidemiological reports that Omicron did not emerge from continuous evolution of the Alpha, Beta or Delta variant.

Naturally occurring SARS-CoV-2 gene deletions close to the spike S1/S2 cleavage site in the viral quasispecies of COVID19 patients (preprint)

The SARS-CoV-2 spike (S) protein, the viral mediator for binding and entry into the host cell, has sparked great interest as a target for vaccine development and treatments with neutralizing antibodies. Initial data suggest that the virus has low mutation rates, but its large genome could facilitate recombination, insertions, and deletions, as has been described in other coronaviruses. Here, we deep-sequenced the complete SARS-CoV-2 S gene from 18 patients (10 with mild and 8 with severe COVID-19), and found that the virus accumulates deletions upstream and very close to the S1/S2 cleavage site, generating a frameshift with appearance of a stop codon. These deletions were found in a small percentage of the viral quasispecies (2.2%) in samples from all the mild and only half the severe COVID-19 patients. Our results suggest that the virus may generate free S1 protein released to the circulation. We propose that natural selection has favored a "Dont burn down the house" strategy, in which free S1 protein may compete with viral particles for the ACE2 receptor, thus reducing the severity of the infection and tissue damage without losing transmission capability.