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1.
Nat Commun ; 13(1): 5870, 2022 Oct 05.
Article in English | MEDLINE | ID: covidwho-2050380

ABSTRACT

Population 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.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , COVID-19/epidemiology , Humans , Italy/epidemiology , SARS-CoV-2/genetics
2.
Genome Med ; 14(1): 61, 2022 06 10.
Article in English | MEDLINE | ID: covidwho-1951320

ABSTRACT

BACKGROUND: 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.


Subject(s)
COVID-19 , Viral Vaccines , Antibodies, Viral , COVID-19/prevention & control , Humans , SARS-CoV-2 , Vaccination
3.
JCI Insight ; 7(10)2022 05 23.
Article in English | MEDLINE | ID: covidwho-1794307

ABSTRACT

T cells play a prominent role in orchestrating the immune response to viral diseases, but their role in the clinical presentation and subsequent immunity to SARS-CoV-2 infection remains poorly understood. As part of a population-based survey of the municipality of Vo', Italy, conducted after the initial SARS-CoV-2 outbreak, we sampled the T cell receptor (TCR) repertoires of the population 2 months after the initial PCR survey and followed up positive cases 9 and 15 months later. At 2 months, we found that 97.0% (98 of 101) of cases had elevated levels of TCRs associated with SARS-CoV-2. T cell frequency (depth) was increased in individuals with more severe disease. Both depth and diversity (breadth) of the TCR repertoire were positively associated with neutralizing antibody titers, driven mostly by CD4+ T cells directed against spike protein. At the later time points, detection of these TCRs remained high, with 90.7% (78 of 96) and 86.2% (25 of 29) of individuals having detectable signal at 9 and 15 months, respectively. Forty-three individuals were vaccinated by month 15 and showed a significant increase in TCRs directed against spike protein. Taken together, these results demonstrate the central role of T cells in mounting an immune defense against SARS-CoV-2 that persists out to 15 months.


Subject(s)
COVID-19 , CD4-Positive T-Lymphocytes , Humans , Receptors, Antigen, T-Cell/metabolism , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
4.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-331841

ABSTRACT

Population 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. Critically, in the presence of a variant that escapes antigen testing, following up a proportion of negative antigen tests with a molecular test is the optimal testing strategy. Together, these findings highlight the importance of retaining molecular testing for surveillance purposes, also in contexts where the use of antigen tests is widespread.

5.
Viruses ; 14(2)2022 02 15.
Article in English | MEDLINE | ID: covidwho-1687058

ABSTRACT

In 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.


Subject(s)
Family Characteristics , Genome, Viral , Haplotypes , Host Microbial Interactions/genetics , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , COVID-19/epidemiology , COVID-19/transmission , COVID-19/virology , Communicable Disease Control/methods , Evolution, Molecular , Humans , Italy/epidemiology , Mutation , Phylogeny , SARS-CoV-2/classification
6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296781

ABSTRACT

In February and March 2020, one of the first Italian clusters of SARS-CoV-2 infection was detected in the municipality of Vo’. Positive subjects were followed up at 2 and 9 months post-infection with different immuno-assays and a micro-neutralisation test. Here we report on the results of the third serosurvey conducted in the same population in June 2021, 15 months post-infection, when we tested 61% of the infected individuals (n=76). Antibodies against the spike (S) antigen significantly decreased (P<0.006, Kruskal-Wallis test) among unvaccinated subjects (n=35) and increased (P<0.0001) in vaccinated individuals (n=41), whereas those against the nucleocapsid (N) decreased in the whole cohort. From the comparison with two control groups (naïve Vo’ inhabitants (n=20) and healthcare workers (HCW, n=61)), subjects vaccinated post exposure (hybrid immunity) had higher antibody levels (P<0.0001) than subjects vaccinated when naïve. Two doses of vaccine elicited stronger anti-S antibody response than natural infection (P<0.0001). Finally, the neutralising reactivity of sera against the B.1.617.2 (Delta) was lower than compared to the B.1 strain (median 1:320 versus 1:1280 1/dil, P<0.0001, and 1:640 versus 1:2560 1/dil, P=0.0014, after one or two vaccine doses, respectively), although subjects with hybrid immunity maintained neutralising titres above 1:40 1/dil.

8.
Nat Commun ; 12(1): 4383, 2021 07 19.
Article in English | MEDLINE | ID: covidwho-1317806

ABSTRACT

In February and March 2020, two mass swab testing campaigns were conducted in Vo', Italy. In May 2020, we tested 86% of the Vo' population with three immuno-assays detecting antibodies against the spike and nucleocapsid 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. Here we report on the results of the analysis of the May and November surveys. We estimate a seroprevalence of 3.5% (95% Credible Interval (CrI): 2.8-4.3%) in May. In November, 98.8% (95% Confidence Interval (CI): 93.7-100.0%) of sera which tested positive in May still reacted against at least one antigen; 18.6% (95% CI: 11.0-28.5%) showed an increase of antibody or neutralisation reactivity from May. Analysis of the serostatus of the members of 1,118 households indicates a 26.0% (95% CrI: 17.2-36.9%) Susceptible-Infectious Transmission Probability. Contact tracing had limited impact on epidemic suppression.


Subject(s)
Antibodies, Viral/immunology , COVID-19 Testing/methods , COVID-19/immunology , COVID-19/transmission , SARS-CoV-2/immunology , Serologic Tests/methods , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19 Nucleic Acid Testing , Contact Tracing , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Italy/epidemiology , Male , Nucleocapsid , Seroepidemiologic Studies , Spike Glycoprotein, Coronavirus/immunology
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