Sero-survey on Long-term Care Facility Residents Reveals Increased Risk of Sub-optimal Antibody Response to BNT162B2: Implications for Breakthrough Prevention (preprint)

Background: The impact of coronavirus disease 2019 caused by Severe Acute Respiratory Syndrome Coronavirus 2 on hosts of Long Term Care Facilities (LTCFs) has been dramatic at global scale as aging and comorbitities pose individuals at increased risk of severe disease and death. Methods: Aim of this study was to evaluate SARS-CoV-2 S-IgG antibodies titers in 478 residents and 649 health care workers of the largest Italian nurse facility two months after the complete vaccination with BNT162B2. Associations among host-related factors and predictors of humoral response were investigated. Results: By stratifying levels of humoral responses, we found that 62.1%, 21.6%, 12.1% and 4.2% of hosts has high (>1,000 BAU/ml), medium (101-1,000), low (1-100) and null (<1 BAU/mL) S-IgG titers, respectively. Hosts with previous COVID-19 and those with SARS-CoV-2 N-IgG positive serology showed higher level of serological response (p<0.001 and p<0.001, respectively), while the administration of corticosteroid or cancer diminished all levels of specific antibodies (p=0.019 and p=0.004). Significant associations were observed for these parameters in those with suboptimal response (p<0.001, p<0.001, p=0.028 and p=0.005) and with a null one (p=0.005, p<0.001 and p=0.039). Predictors of an increased risk of null response were advanced age, corticosteroid therapy and diabetes mellitus (p=0.025, p=0.017 and p=0.037). In contrast, previous diagnosis of COVID-19 resulted strongly associated with a reduced risk of null response to vaccination (p<0.001). Conclusions: SARS-CoV-2 specific antibodies in elderly individuals need to be measured to consider a third dose of vaccine after mass vaccination for prevention of reinfections in LTCFs despite the maintenance of barrier measures.

Molecular Tracing of SARS-CoV-2 in Italy in the First Three Months of the Epidemic (preprint)

The aim of this study is the characterization and genomic tracing by phylogenetic analyses of 59 new SARS-CoV-2 Italian isolates obtained from patients attending clinical centres in North and Central Italy until the end of April 2020. All but one of the newly characterized genomes belonged to the lineage B.1, the most frequently identified in European countries, including Italy. Only a single sequence was found to belong to lineage B. A mean of 6 nucleotide substitutions per viral genome was observed, without significant differences between synonymous and non-synonymous mutations, indicating genetic drift as a major source for virus evolution. tMRCA estimation confirmed the probable origin of the epidemic between the end of January and the beginning of February with a rapid increase in the number of infections between the end of February and mid-March. Since early February, an effective reproduction number (Re) greater than 1 was estimated, which then increased reaching the peak of 2.3 in early March, confirming the circulation of the virus before the first COVID-19 cases were documented. Continuous use of state-of-the-art methods for molecular surveillance is warranted to trace virus circulation and evolution and inform effective prevention and containment of future SARS-CoV-2 outbreaks.

Molecular tracing of SARS-CoV-2 in Italy in the first three months of the epidemic (preprint)

The aim of this study is the characterization and genomic tracing by phylogenetic analyses of 59 new SARS-CoV-2 Italian isolates obtained from patients attending clinical centres in North and Central Italy until the end of April 2020. All but one of the newly characterized genomes belonged to the lineage B.1, the most frequently identified in European countries, including Italy. Only a single sequence was found to belong to lineage B. A mean of 6 nucleotide substitutions per viral genome was observed, without significant differences between synonymous and non-synonymous mutations, indicating genetic drift as a major source for virus evolution. tMRCA estimation confirmed the probable origin of the epidemic between the end of January and the beginning of February with a rapid increase in the number of infections between the end of February and mid-March. Since early February, an effective reproduction number (Re) greater than 1 was estimated, which then increased reaching the peak of 2.3 in early March, confirming the circulation of the virus before the first COVID-19 cases were documented. Continuous use of state-of-the-art methods for molecular surveillance is warranted to trace virus circulation and evolution and inform effective prevention and containment of future SARS-CoV-2 outbreaks.

GENOMIC CHARACTERISATION AND PHYLOGENETIC ANALYSIS OF SARS-COV-2 IN ITALY (preprint)

This report describes the isolation, the molecular characterization and the phylogenetic analysis of the first three complete genomes of SARS-CoV-2 isolated from three patients involved in the first outbreak of COVID-19 in Lombardy, Italy. Early molecular epidemiological tracing suggests that SARS-CoV-2 was present in Italy weeks before the first reported cases of infection.