Neutralizing antibodies against Omicron BA.4/5 after COVID-19 vaccination in SARS-CoV-2 experienced versus naïve individuals in the general population

This work was supported in part by the European Commission NextGenerationEU fund, awarded to RG through CSIC's Global Health Platform (PTI Salud Global).Peer reviewe

SARS-CoV-2 adaptive immunity in nursing home residents following a third dose of the Comirnaty® COVID-19 vaccine

A third Comirnaty® vaccine dose increased SARS-CoV-2-receptor binding domain antibody levels (median of 93-fold) and neutralizing antibody titers against Wuhan-Hu-1 (median, 57-fold), Beta (median, 22-fold), Delta, (median, 43-fold) and Omicron (median, 8-fold) variants, particularly in SARS-CoV-2-naïve individuals, but had a negligible impact on S-reactive T-cell immunity in nursing home residents.Peer reviewe

Cumulative incidence of SARS-CoV-2 infection in the general population of the Valencian Community (Spain) after the surge of the Omicron BA.1 variant

Background Studies investigating the cumulative incidence of and immune status against SARS-CoV-2 infection provide valuable information for shaping public health decision-making. Methods The current cross-sectional, population-based study, conducted in April 2022 in the Valencian Community (VC), recruited 935 participants of all ages. Anti-SARS-CoV-2-Receptor Binding Domain-RBD-total antibodies and anti-Nucleocapsid (N)- IgGs were measured by electrochemiluminescence assays. To account for past SARS-CoV-2 infection the VC microbiology registry (RedMiVa) was interrogated. |Quantitation of neutralizing antibodies (NtAb) against the ancestral and Omicron BA.1 and BA.2 (sub)variants by an S-pseudotyped neutralization assay and for enumeration of SARS-CoV-2-S specific-IFNγ-producing CD4+ and CD8+ T cells by Intracellular Cytokine Staining assay was performed in a subset of participants (n=100 and 137, respectively). Findings The weighted cumulative incidence was 51□9% (95% CI, 48□7–55□1), and was inversely related to age. Anti-RBD total antibodies were detected in 906/931 (97□3%) participants, those vaccinated and SARS-CoV-2-experienced (VAC-ex;=442) displaying higher levels (P<0.001) than vaccinated/naïve (VAC-n;(n=472) and non-vaccinated/experienced (UNVAC-ex; n(n=63). Antibody levels correlated inversely with the time elapsed since receipt of last vaccine dose in VAC-n (Rho, -0□52; 95% CI, -0□59 to -0□45; P<0.001) but not in VAC-ex. NtAbs against Omicron BA.1 were detected in 94%, 75% and 50% of VAC-ex, VAC-n and UNVAC-ex groups, respectively, while in 97%, 84% and 40%, against Omicron BA.2. SARS-CoV-2-S-reactive IFN-γ T cells were detected in 73%, 75%, and 64% for VAC-ex, VAC-n, UNVAC-ex, respectively. Interpretation By April 2022 around half of the VC population had been infected with SARS-CoV-2 and due to extensive vaccination display hybrid immunity. The large percentage of participants with detectable functional antibody and T-cell responses against SARS-CoV-2, which may be cross-reactive to some extent, points towards lower expected severity than in previous waves.We also thank Ana Berenguer, General Director of Analysis and Public Policies of the Presidency of the Generalitat. Eliseo Albert (Juan Rodés Contract; JR20/00011) Estela Giménez (Juan Rodés Contract, JR18/00053) and Ignacio Torres (Río Hortega Contract; CM20/00090) hold contracts funded by the Carlos III Health Institute (co-financed by the European Regional Development Fund, ERDF/FEDER). Ron Geller holds a Ramon y Cajal fellowship from the Spanish Ministry of Economics and Competitiveness (RYC-2015-17517).N

SARS-CoV-2-spike antibody and T-cell responses elicited by a homologous third mRNA COVID-19 dose in hemodialysis and kidney transplant recipients

This article belongs to the Section Medical Microbiology.The effect of a third vaccine dose (3D) of homologous mRNA vaccine on blood levels of SARS-CoV-2-receptor binding domain (RBD)-total antibodies was assessed in 40 hemodialysis patients (HD) and 21 kidney transplant recipients (KTR) at a median of 46 days after 3D. Anti-RBD antibodies were detected in 39/40 HD and 19/21 KTR. Overall, 3D boosted anti-RBD antibody levels (median: 58-fold increase). Neutralizing antibodies (NtAb) against the Wuhan-Hu-1, Delta, and Omicron variants were detected in 14, 13, and 11 out of 14 HD patients, and in 5, 5, and 4 out of 8 KTR patients, respectively. The median fold increase in NtAb titers in HD patients was 77, 28, and 5 and 56, 37, and 9 in KTR patients for each respective variant. SARS-CoV-2-S S-IFN-γ-producing CD8+ and CD4+ T-cell responses were detected in the majority of HD (35 and 36/37, respectively) and all KTR (16/16) patients at 3D. Overall, the administration of 3D boosted T-cell levels in both population groups. In conclusion, a homologous mRNA COVID-19 vaccine 3D exerts a booster effect on anti-RBD antibodies, NtAb binding to Wuhan-Hu-1, Delta, and Omicron variants, and SARS-CoV-2-S-IFN-γ-producing T cells in both HD and KTR patients. The magnitude of the effect was more marked in HD than KTR patients.This research work was supported by funding from the Instituto de Salud Carlos III, Madrid, Spain (FIS, PI21/00563) to DN and by funding from the European Commission NextGenerationEU fund (EU 2020/2094), through CSIC’s Global Health Platform (PTI Salud Global), to RG, and funding from the Valencian Society of Neprology. The project received the Isabel Burches grant from the Valencian Society of Nephrology (2/2/21).Peer reviewe

Breastfeeding during the COVID-19 pandemic: analysis of the breastmilk antibodies, neutralization capacity and microbiota profile from infected and vaccinated wome

Resumen del póster presentado a las III Jornadas Científicas PTI+ Salud Global, celebradas en el Centro de Ciencias Humanas y Sociales (CCHS), CSIC (Madrid) del 20 al 22 de noviembre de 2023.[Background] Breastmilk is considered the gold standard in infant nutrition and provides bioactive compounds to the neonate, among them antibodies and microbiota. In the context of the COVID- 19 pandemics, there were great concerns about a possible mother-to-infant transfer of SARS-CoV-2, since limited knowledge about the safety of breastfeeding after natural infection or vaccination, as well as the transfer of protective antibodies and their neutralization capacity, was available. Additionally, there are concerns about potential short- and long-term adverse effects of SARS-CoV-2 infection and vaccine-induced changes to the breastmilk microbiome composition, which contributes in shaping the early-life microbiome.[Methods] This study included 60 mothers which had a confirmed SARS-CoV-2 infection and also, 86 mothers vaccinated with mRNA-based (Comirnaty, mRNA-1273) and adenoviral-vectored vaccines (ChAdOx1 nCoV-19) were recruited and breastmilk samples were collected longitudinally from baseline up to 30 days after the second dose at seven or eight time points (depending on vaccine type). In COVID-19 lactating mothers, the presence of SARS-CoV-2 was assessed by RT-qPCR targeting the N1 region of the nucleocapsid gene and the envelope (E) gene. In both studies, the levels of SARS-CoV-2 RBD-specific IgA, IgM and IgG were determined by ELISA. The neutralization capacity was tested using pseudotyped vesicular stomatitis virus carrying either the Wuhan-Hu-1, Delta, or BA.1 Omicron spike proteins. To assess the microbiome composition, DNA from breastmilk samples was extracted and the V3-V4 region of the 16S rRNA gene was sequenced using the MiSeq system of Illumina.[Results] After SARS-CoV-2 infection, no virus-specific RNA was detected in breastmilk samples. Determination of antibody levels in mothers with confirmed SARS-CoV-2 infection showed that 82.9% (58 of 70) of milk samples were positive for at least one of the three tested antibody isotypes. Vaccination elicited also a strong induction of SARS-CoV-2-specific antibodies, which was higher in IgG when compared to COVID-19 convalescent women and was strongly increased after the 2nd dose. mRNA-based vaccines induced higher IgG and IgA levels when compared to the adenovirus- vectored vaccine, and women with previous virus exposure increased their IgG antibodies levels after the first dose to a similar level observed in vaccinated women after the second dose. When assessing the neutralization capacity, natural infection resulted in higher neutralizing titers that correlated positively with levels of SARS-CoV-2-specific immunoglobulin A in breastmilk. Breastmilk samples from COVID-19 convalescent mothers infected during the first wave (Wuhan-Hu-1 strain) neutralized less effectively Omicron BA.1 than the Wuhan-Hu-1 variant. In addition, significant differences in the capacity to produce neutralizing antibodies were observed between both mRNA- based vaccines and the adenovirus-vectored ChAdOx1 COVID-19 vaccine. First results of the analysis of the breastmilk microbiome found no significant differences in the mean diversity of species (alpha-diversity) after natural SARS-CoV-2 infection, whereas some specific bacterial groups were increased (e.g. Enterobacteriaceae).[Conclusions] Overall, our results indicate that breastmilk from naturally infected women or those vaccinated with mRNA-based vaccines contain SARS-CoV-2 neutralizing antibodies that could potentially provide protection to breastfed infants from infection.Peer reviewe

Analysis of Some Essential Aspects Related to the Navigation Conditions on the Danube River

The European Union has emphasized the creation of an appropriate framework to optimize the internal market and inland transport waterways, and remove barriers to their wider use. Administrative barriers in the logistics of goods on the Danube waterway and its navigable tributaries constitute a significant obstacle to the efficient and sustainable use of the Danube as the region&rsquo;s central transport hub. The approach proposed in this paper was designed to identify and analyze the relationship between the main variables leading to problematic inland waterway traffic, in this case, on the Danube, and the measures taken by the European Commission to improve it. In terms of the applied research method, &ldquo;Quality Function Deployment&rdquo; (QFD), we assign global (overall) and local priority degrees. The proposed framework for adapting QFD as a tool for improving quality and, therefore, performance, aims to identify and prioritize directions for this improvement. The House of Quality (HOQ) is the tool that links areas for improvement to technical requirements. The disclosure of these connections helps identify and prioritize the technical features that will generate the most significant improvements

Antiviral activity of synthetic heparan sulfate mimics

Resumen del póster presentado a las III Jornadas Científicas PTI+ Salud Global, celebradas en el Centro de Ciencias Humanas y Sociales (CCHS), CSIC (Madrid) del 20 al 22 de noviembre de 2023.Cell surface proteoglycans are found on virtually all animal cells, including epithelial cells of the respiratory and gastrointestinal tracts. Many viruses have evolved to use heparan sulfate proteoglycans (HSPG), which are found on the surface of host cells, as an attachment site before entering the cell. Due to the heavily sulfated HS chains, they present a global negative charge that can interact electrostatically with the basic residues of viral surface glycoproteins or viral capsid proteins of non-enveloped viruses. Viruses exploit these weak interactions to increase their concentration at the cell surface and augment their chances of binding a more specific entry receptor. In 2018, we reported that chitosan sulfate (ChS), easily obtained from readily available chitosan polysaccharide, can mimic some biological functions of HS. In the context of the COVID-19 pandemic, we decided to test the activity of synthetic ChS as antivirals under the hypothesis that soluble ChS could act as decoy traps by interacting with viral coat proteins, thereby blocking the binding of the virus to target cells. Since then a large number of ChS derivatives have been synthesized and tested in vitro against different virus families: RSV, SARS-CoV-1, SARS-CoV-2, Ebola and Nipah. Some of the compounds were able to drastically inhibit the infection of the cells compared to controls. Among the most active compounds, ET36 was selected for further studies in animals. The toxicity of ET36 was assayed in mice after nasal administration at the doses from 1 to 100 mg/kg. No adverse effect was observed, even at the highest dose tested. The antiviral effect in animals was studied in mice also by intranasal delivery of ET36, prior and after infection with SARS-CoV-2. In all cases, viral loads in lungs harvested three days after infection were significantly reduced in mice treated with ET36 as compared to the control group. Likewise, the expression levels of key proinflammatory cytokines in the lung of infected mice were significantly reduced in animals treated with ET-36 compared with control mice.Peer reviewe

Cetylpyridinium chloride and chlorhexidine show antiviral activity against Influenza A virus and Respiratory Syncytial virus in vitro.

BackgroundThe oral cavity is the site of entry and replication for many respiratory viruses. Furthermore, it is the source of droplets and aerosols that facilitate viral transmission. It is thought that appropriate oral hygiene that alters viral infectivity might reduce the spread of respiratory viruses and contribute to infection control.Materials and methodsHere, we analyzed the antiviral activity of cetylpyridinium chloride (CPC), chlorhexidine (CHX), and three commercial CPC and CHX-containing mouthwash preparations against the Influenza A virus and the Respiratory syncytial virus. To do so the aforementioned compounds and preparations were incubated with the Influenza A virus or with the Respiratory syncytial virus. Next, we analyzed the viability of the treated viral particles.ResultsOur results indicate that CPC and CHX decrease the infectivity of both the Influenza A virus and the Respiratory Syncytial virus in vitro between 90 and 99.9% depending on the concentration. Likewise, CPC and CHX-containing mouthwash preparations were up to 99.99% effective in decreasing the viral viability of both the Influenza A virus and the Respiratory syncytial virus in vitro.ConclusionThe use of a mouthwash containing CPC or CHX alone or in combination might represent a cost-effective measure to limit infection and spread of enveloped respiratory viruses infecting the oral cavity, aiding in reducing viral transmission. Our findings may stimulate future clinical studies to evaluate the effects of CPC and CHX in reducing viral respiratory transmissions

A performance comparison of two (electro) chemiluminescence immunoassays for detection and quantitation of serum anti-spike antibodies according to SARS-CoV-2 vaccination and infections status

The information provided by SARS-CoV-2 spike (S)-targeting immunoassays can be instrumental in clinical-decision making. We compared the performance of the Elecsys® Anti-SARS-CoV-2 S assay (Roche Diagnostics) and the LIAISON® SARS-CoV-2 TrimericS IgG assay (DiaSorin) using a total of 1176 sera from 797 individuals, of which 286 were from vaccinated-SARS-CoV-2/experienced (Vac-Ex), 581 from vaccinated/naïve (Vac-N), 147 from unvaccinated/experienced (Unvac-Ex), and 162 from unvaccinated/naïve (Unvac-N) individuals. The Roche assay returned a higher number of positive results (907 vs. 790; p = 0.45; overall sensitivity: 89.3% vs. 77.6%). The concordance between results provided by the two immunoassays was higher for sera from Vac-N (ϰ: 0.58; interquartile ranges [IQR]: 0.50-0.65) than for sera from Vac-Ex (ϰ: 0.19; IQR: -0.14 to 0.52) or Unvac-Ex (ϰ: 0.18; IQR: 0.06-0.30). Discordant results occurred more frequently among sera from Unvac-Ex (34.7%) followed by Vac-N (14.6%) and Vac-Ex (2.7%). Antibody levels quantified by both immunoassays were not significantly different when <250 (p = 0.87) or <1000 BAU/ml (p = 0.13); in contrast, for sera ≥1000 BAU/ml, the Roche assay returned significantly higher values than the DiaSorin assay (p < 0.008). Neutralizing antibody titers (NtAb) were measured in 127 sera from Vac-Ex or Vac-N using a S-pseudotyped virus neutralization assay of Wuhan-Hu-1, Omicron BA.1, and Omicron BA.2. The correlation between antibody levels and NtAb titers was higher for sera from Vac-N than those from Vac-Ex, irrespective of the (sub)variant considered. In conclusion, neither qualitative nor quantitative results returned by both immunoassays are interchangeable. The performance of both assays was found to be greatly influenced by the vaccination and SARS-CoV-2 infection status of individuals.Estela Giménez (Juan Rodés Contract, JR18/00053) and Eliseo Albert (Juan Rodés Contract; JR20/00011) hold contracts funded by the Carlos III Health Institute (co-financed by the European Regional Development Fund, ERDF/FEDER). Beatriz Álvarez-Rodríguez holds the GVA postdoctoral fellowship (APOSTD/2021/017). This study work was supported by Instituto de Salud Carlos III, Madrid, Spain (FIS, PI21/00563) to David Navarro, and by the European Commission NextGenerationEU fund (EU 2020/2094), through CSIC's Global Health Platform (PTI Salud Global) to Ron Geller. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.Peer reviewe