10 research outputs found
Copper/Zinc Superoxide Dismutase from the Crocodile Icefish Chionodraco hamatus: Antioxidant Defense at Constant Sub-Zero Temperature
No full textIn the present study, we describe the purification and molecular characterization of Cu,Zn superoxide dismutase (SOD) from Chionodraco hamatus, an Antarctic teleost widely distributed in many areas of the Ross Sea that plays a pivotal role in the Antarctic food chain. The primary sequence was obtained using biochemical and molecular biology approaches and compared with Cu,Zn SODs from other organisms. Multiple sequence alignment using the amino acid sequence revealed that Cu,Zn SOD showed considerable sequence similarity with its orthologues from various vertebrate species, but also some specific substitutions directly linked to cold adaptation. Phylogenetic analyses presented the monophyletic status of Antartic Teleostei among the Perciformes, confirming the erratic differentiation of these proteins and concurring with the theory of the “unclock-like” behavior of Cu,Zn SOD evolution. Expression of C. hamatus Cu,Zn SOD at both the mRNA and protein levels were analyzed in various tissues, highlighting the regulation of gene expression related to environmental stress conditions and also animal physiology. The data presented are the first on the antioxidant enzymes of a fish belonging to the Channichthyidae family and represent an important starting point in understanding the antioxidant systems of these organisms that are subject to constant risk of oxidative stress
Impact of antigen test target failure and testing strategies on the transmission of SARS-CoV-2 variants
No full textPopulation testing remains central to COVID-19 control and surveillance, with countries increasingly using antigen tests rather than molecular tests. Here we describe a SARS-CoV-2 variant that escapes N antigen tests due to multiple disruptive amino-acid substitutions in the N protein. By fitting a multistrain compartmental model to genomic and epidemiological data, we show that widespread antigen testing in the Italian region of Veneto favored the undetected spread of the antigen-escape variant compared to the rest of Italy. We highlight novel limitations of widespread antigen testing in the absence of molecular testing for diagnostic or confirmatory purposes. Notably, we find that genomic surveillance systems which rely on antigen population testing to identify samples for sequencing will bias detection of escape antigen test variants. Together, these findings highlight the importance of retaining molecular testing for surveillance purposes, including in contexts where the use of antigen tests is widespread
Author Correction: SARS-CoV-2 antibody dynamics and transmission from community-wide serological testing in the Italian municipality of Vo’ (Nature Communications, (2021), 12, 1, (4383), 10.1038/s41467-021-24622-7)
No full textThe original version of this Article contained an error in the author affiliations. Affiliation 1 incorrectly read ‘MRC Centre for Global Infectious Disease Analysis and the Abdul Latif Jameel Institute for Disease and Emergency Analytics (J-IDEA), School of Public Health, Imperial College London, London, UK’ instead of the correct ‘MRC Centre for Global Infectious Disease Analysis and the Abdul Latif Jameel Institute for Disease and Emergency Analytics, School of Public Health, Imperial College London, London, UK’. The original version of this Article also contained an error in the Acknowledgements: ‘We acknowledge the Abdul Latif Jameel Institute for Disease and Emergency Analytics, funded by the Abdul Latif Jameel Foundation’ should have read ‘We acknowledge the Abdul Latif Jameel Institute for Disease and Emergency Analytics, funded by Community Jameel’. These errors have been corrected in both the PDF and HTML versions of the Article
Rapid SARS-CoV-2 Intra-Host and Within-Household Emergence of Novel Haplotypes
No full textIn February 2020, the municipality of Vo’, a small town near Padua (Italy) was quarantined due to the first coronavirus disease 19 (COVID-19)-related death detected in Italy. To investigate the viral prevalence and clinical features, the entire population was swab tested in two sequential surveys. Here we report the analysis of 87 viral genomes, which revealed that the unique ancestor haplotype introduced in Vo’ belongs to lineage B, carrying the mutations G11083T and G26144T. The viral sequences allowed us to investigate the viral evolution while being transmitted within and across households and the effectiveness of the non-pharmaceutical interventions implemented in Vo’. We report, for the first time, evidence that novel viral haplotypes can naturally arise intra-host within an interval as short as two weeks, in approximately 30% of the infected individuals, regardless of symptom severity or immune system deficiencies. Moreover, both phylogenetic and minimum spanning network analyses converge on the hypothesis that the viral sequences evolved from a unique common ancestor haplotype that was carried by an index case. The lockdown extinguished both the viral spread and the emergence of new variants
Neutralising reactivity against SARS-CoV-2 delta and omicron variants by vaccination and infection history.
No full textBACKGROUND: The continuous emergence of SARS-CoV-2 variants of concern (VOC) with immune escape properties, such as Delta (B.1.617.2) and Omicron (B.1.1.529), questions the extent of the antibody-mediated protection against the virus. Here we investigated the long-term antibody persistence in previously infected subjects and the extent of the antibody-mediated protection against B.1, B.1.617.2 and BA.1 variants in unvaccinated subjects previously infected, vaccinated naïve and vaccinated previously infected subjects. METHODS: Blood samples collected 15 months post-infection from unvaccinated (n=35) and vaccinated (n=41) previously infected subjects (Vo' cohort) were tested for the presence of antibodies against the SARS-CoV-2 spike (S) and nucleocapsid (N) antigens using the Abbott, DiaSorin, and Roche immunoassays. The serum neutralising reactivity was assessed against B.1, B.1.617.2 (Delta), and BA.1 (Omicron) SARS-CoV-2 strains through micro-neutralisation. The antibody titres were compared to those from previous timepoints, performed at 2- and 9-months post-infection on the same individuals. Two groups of naïve subjects were used as controls, one from the same cohort (unvaccinated n=29 and vaccinated n=20) and a group of vaccinated naïve healthcare workers (n=61). RESULTS: We report on the results of the third serosurvey run in the Vo' cohort. With respect to the 9-month time point, antibodies against the S antigen significantly decreased (P=0.0063) among unvaccinated subjects and increased (P<0.0001) in vaccinated individuals, whereas those against the N antigen decreased in the whole cohort. When compared with control groups (naïve Vo' inhabitants and naïve healthcare workers), vaccinated subjects that were previously infected had higher antibody levels (P<0.0001) than vaccinated naïve subjects. Two doses of vaccine elicited stronger anti-S antibody response than natural infection (P<0.0001). Finally, the neutralising reactivity of sera against B.1.617.2 and BA.1 was 4-fold and 16-fold lower than the reactivity observed against the original B.1 strain. CONCLUSIONS: These results confirm that vaccination induces strong antibody response in most individuals, and even stronger in previously infected subjects. Neutralising reactivity elicited by natural infection followed by vaccination is increasingly weakened by the recent emergence of VOCs. While immunity is not completely compromised, a change in vaccine development may be required going forward, to generate cross-protective pan-coronavirus immunity in the global population
Immune System Deficiencies Do Not Alter SARS-CoV-2 Evolutionary Rate but Favour the Emergence of Mutations by Extending Viral Persistence
No full textDuring the COVID-19 pandemic, immunosuppressed patients showed prolonged SARS-CoV-2 infections, with several studies reporting the accumulation of mutations in the viral genome. The weakened immune system present in these individuals, along with the effect of antiviral therapies, are thought to create a favourable environment for intra-host viral evolution and have been linked to the emergence of new viral variants which strongly challenged containment measures and some therapeutic treatments. To assess whether impaired immunity could lead to the increased instability of viral genomes, longitudinal nasopharyngeal swabs were collected from eight immunocompromised patients and fourteen non-immunocompromised subjects, all undergoing SARS-CoV-2 infection. Intra-host viral evolution was compared between the two groups through deep sequencing, exploiting a probe-based enrichment method to minimise the possibility of artefactual mutations commonly generated in amplicon-based methods, which heavily rely on PCR amplification. Although, as expected, immunocompromised patients experienced significantly longer infections, the acquisition of novel intra-host viral mutations was similar between the two groups. Moreover, a thorough analysis of viral quasispecies showed that the variability of viral populations in the two groups is comparable not only at the consensus level, but also when considering low-frequency mutations. This study suggests that a compromised immune system alone does not affect SARS-CoV-2 within-host genomic variability
SARS-CoV-2 antibody dynamics, within-household transmission and the impact of contact tracing from community-wide serological testing in the Italian Municipality of Vo’
No full textBackground: In February and Mach 2020, two mass swab testing campaigns conducted in Vo’, Italy demonstrated the extent of asymptomatic SARS-CoV-2 infection and the feasibility of epidemic suppression.
Methods: We tested 86% of the Vo’ population (2,602 subjects) in May with three immuno-assays detecting antibodies against the spike (S) and nucleocapsid (N) antigens, a neutralisation assay and Polymerase Chain Reaction (PCR). Subjects testing positive to PCR in February/March or a serological assay in May were tested again in November.
Findings: Combining the results obtained with the three assays, we estimate a seroprevalence of 3.5% (95% Credible Interval (CrI) 2.8%-4.3%) in May. In November, all assays showed a reduction in antibody titres, though 98.8% (95% Confidence Interval (CI) 93.7%-100.0%) of sera still reacted against at least one antigen. Conversely, 18.6% (95% CI 11.0%-28.5%) showed a marked increase of antibody or viral neutralisation reactivity between May and November, linked to documented or likely re-exposures. We found significant differences in the magnitude and persistence of the antibody response by age group but not by symptom occurrence, hospitalisation, or sex. Analysis of the serostatus of 1,118 households indicated a 27.3% (95% CrI 19.2%-34.6%) probability of SARS-CoV-2 transmission among household members and that 81.8% (95% CrI 55.9%-95.2%) of transmission could be attributed to 20% of infections. Contact tracing correctly identified 44% of the infected subjects and had limited impact on the epidemic.
Interpretation: We find evidence of antibody persistence up to nine months post infection. Different assays provided significantly different seroprevalence estimates, making it challenging to compare seroprevalence estimates globally. Due to the high population susceptibility and the limited impact of contact tracing, rigorous testing and improvements in contact tracing are essential to control SARS-CoV-2.
Funding: Veneto Region, Medical Research Council, Wellcome Trust, Royal Society, University of Padua, UK National Institute for Health Research.
Declaration of Interests: The authors declare no competing interests.
Ethics Approval Statement: The first and second serosurveys of the Vo' population were approved by the Ethics Committee for Clinical Research of the province of Padova
Author Correction: SARS-CoV-2 antibody dynamics and transmission from community-wide serological testing in the Italian municipality of Vo’
No full textPhylogeography and genomic epidemiology of SARS-CoV-2 in Italy and Europe with newly characterized Italian genomes between February-June 2020
No full textThe aims of this study were to characterize new SARS-CoV-2 genomes sampled all over Italy and to reconstruct the origin and the evolutionary dynamics in Italy and Europe between February and June 2020. The cluster analysis showed only small clusters including < 80 Italian isolates, while most of the Italian strains were intermixed in the whole tree. Pure Italian clusters were observed mainly after the lockdown and distancing measures were adopted. Lineage B and B.1 spread between late January and early February 2020, from China to Veneto and Lombardy, respectively. Lineage B.1.1 (20B) most probably evolved within Italy and spread from central to south Italian regions, and to European countries. The lineage B.1.1.1 (20D) developed most probably in other European countries entering Italy only in the second half of March and remained localized in Piedmont until June 2020. In conclusion, within the limitations of phylogeographical reconstruction, the estimated ancestral scenario suggests an important role of China and Italy in the widespread diffusion of the D614G variant in Europe in the early phase of the pandemic and more dispersed exchanges involving several European countries from the second half of March 202
Additional file 1 of Neutralising reactivity against SARS-CoV-2 Delta and Omicron variants by vaccination and infection history
No full textAdditional file 1: Figure S1. Anti-N antibody titres and dynamics in vaccinated and unvaccinated subjects; Figure S2. Anti-N antibody titres of vaccinated and unvaccinated individuals previously exposed to SARS-CoV-2 infection differ according to age; Figure S3. Correlation among DiaSorin S1/S2, DiaSorin trimeric tests and neutralisation assay; Figure S4. Features of the cohorts analysed in this study. Table S1. Concordance between S1/S2 and trimericS DiaSorin assays
