Post-Vaccination Coronavirus Disease 2019: A Case-Control Study and Genomic Analysis of 119 Breakthrough Infections in Partially Vaccinated Individuals.

BACKGROUND: Post-vaccination infections challenge the control of the coronavirus disease 2019 (COVID-19) pandemic. METHODS: We matched 119 cases of post-vaccination severe acute respiratory syndrome coronavirus 2 infection with BNT162b2 mRNA or ChAdOx1 nCOV-19 to 476 unvaccinated patients with COVID-19 (September 2020-March 2021) according to age and sex. Differences in 60-day all-cause mortality, hospital admission, and hospital length of stay were evaluated. Phylogenetic, single-nucleotide polymorphism (SNP), and minority variant allele (MVA) full-genome sequencing analysis was performed. RESULTS: Overall, 116 of 119 cases developed COVID-19 post-first vaccination dose (median, 14 days). Thirteen of 119 (10.9%) cases and 158 of 476 (33.2%) controls died (P < .001), corresponding to the 4.5 number needed to treat (NNT). Multivariably, vaccination was associated with a 69.3% (95% confidence interval [CI]: 45.8 to 82.6) relative risk (RR) reduction in mortality. Similar results were seen in subgroup analysis for patients with infection onset ≥14 days after first vaccination and across vaccine subgroups. Hospital admissions (odds ratio, 0.80; 95% CI: .51 to 1.28) and length of stay (-1.89 days; 95% CI: -4.57 to 0.78) were lower for cases, while cycle threshold values were higher (30.8 vs 28.8, P = .053). B.1.1.7 was the predominant lineage in cases (100 of 108, 92.6%) and controls (341 of 446, 76.5%). Genomic analysis identified 1 post-vaccination case that harbored the E484K vaccine-escape mutation (B.1.525 lineage). CONCLUSIONS: Previous vaccination reduces mortality when B.1.1.7 is the predominant lineage. No significant lineage-specific genomic changes during phylogenetic, SNP, and MVA analysis were detected.

Molecular Epidemiology Analysis of SARS-CoV-2 Strains Circulating in Romania during the First Months of the Pandemic.

BACKGROUND: The spread of SARS-CoV-2 generated an unprecedented global public health crisis. Soon after Asia, Europe was seriously affected. Many countries, including Romania, adopted lockdown measures to limit the outbreak. AIM: We performed a molecular epidemiology analysis of SARS-CoV-2 viral strains circulating in Romania during the first two months of the epidemic in order to detect mutation profiles and phylogenetic relatedness. METHODS: Respiratory samples were directly used for shotgun sequencing. RESULTS: All Romanian sequences belonged to lineage B, with a different subtype distribution between northern and southern regions (subtype B.1.5 and B.1.1). Phylogenetic analysis suggested that the Romanian epidemic started with multiple introduction events from other European countries followed by local transmission. Phylogenetic links between northern Romania and Spain, Austria, Scotland and Russia were observed, as well as between southern Romania and Switzerland, Italy, France and Turkey. One viral strain presented a previously unreported mutation in the Nsp2 gene, namely K489E. Epidemiologically-defined clusters displayed specific mutations, suggesting molecular signatures for strains coming from areas that were isolated during the lockdown. CONCLUSIONS: Romanian epidemic was initiated by multiple introductions from European countries followed by local transmissions. Different subtype distribution between northern and southern Romania was observed after two months of the pandemic.