CoronaVac and ChAdOx1 Vaccination and Gamma Infection Elicited Neutralizing Antibodies against the SARS-CoV-2 Delta Variant

The emergence of new SARS-CoV-2 variants represents a constant threat to world public health. The SARS-CoV-2 Delta variant was identified in late 2020 in India; since then, it has spread to many other countries, replacing other predominant lineages and raising concerns about vaccination efficiency. We evaluated the sensitivity of the Delta variant to antibodies elicited by COVID-19 vaccinated (CoronaVac and ChAdOx1) and convalescent individuals previously infected by earlier lineages and by the Gamma variant. No reduction in the neutralizing efficacy of the Delta variant was observed when compared to B lineage and a reduced neutralization was observed for the Gamma variant. Our results indicate that neutralization of the Delta variant is not compromised in individuals vaccinated by CoronaVac or ChAdOx1; however, a reduction in neutralization efficacy is expected for individuals infected by the Gamma variant, highlighting the importance of continuous vaccination even for previously infected individuals.     

First confirmation of importation and transmission in Spain of the newly identified SARS-CoV-2 B.1.1.7 variant

IntroductionA newly identified SARS-CoV-2 variant, VOC202012/01 originating lineage B.1.1.7, recently emerged in the United Kingdom. The rapid spread in the UK of this new variant has caused other countries to be vigilant.Material and methodsWe based our initial screening of B.1.1.7 on the dropout of the S gene signal in the TaqPath assay, caused by the 69/70 deletion. Subsequently, we confirmed the B.1.1.7 candidates by whole genome sequencing.ResultsWe describe the first three imported cases of this variant from London to Madrid, subsequent post-arrival household transmission to three relatives, and the two first cases without epidemiological links to UK. One case required hospitalization. In all cases, drop-out of gene S was correctly associated to the B.1.1.7 variant, as all the corresponding sequences carried the 17 lineage-marker mutations.ConclusionThe first identifications of the SARS-CoV-2 B.1.1.7 variant in Spain indicate the role of independent introductions from the UK coexisting with post-arrival transmission in the community, since the early steps of this new variant in our country.     

First Detection of SARS-CoV-2 B.1.1.7 Variant of Concern in an Asymptomatic Dog in Spain

Natural SARS-CoV-2 infection in pets has been widely documented during the last year. Although the majority of reports suggested that dogs’ susceptibility to the infection is low, little is known about viral pathogenicity and transmissibility in the case of variants of concern, such as B.1.1.7 in this species. Here, as part of a large-scale study on SARS-CoV-2 prevalence in pets in Spain, we have detected the B.1.1.7 variant of concern (VOC) in a dog whose owners were infected with SARS-CoV-2. The animal did not present any symptoms, but viral loads were high in the nasal and rectal swabs. In addition, viral isolation was possible from both swabs, demonstrating that the dog was shedding infectious virus. Seroconversion occurred 23 days after the first sampling. This study documents the first detection of B.1.1.7 VOC in a dog in Spain and emphasizes the importance of performing active surveillance and genomic investigation on infected animals.     

Vaccination with BNT162b2 and ChAdOx1 nCoV-19 Induces Cross-Reactive Anti-RBD IgG against SARS-CoV-2 Variants including Omicron

SARS-CoV-2 variants of concern (VOCs) have caused a significant increase in infections worldwide. Despite high vaccination rates in industrialized countries, the fourth VOC, Omicron, has outpaced the Delta variant and is causing breakthrough infections in individuals with two booster vaccinations. While the magnitude of morbidity and lethality is lower in Omicron, the infection rate and global spread are rapid. Using a specific IgG multipanel-ELISA with the spike protein’s receptor-binding domain (RBD) from recombinant Alpha, Gamma, Delta, and Omicron variants, sera from health-care workers from the Medical University of Vienna were tested pre-pandemic and post-vaccination (BNT162b2; ChAdOx1 nCoV-19). The cohort was continuously monitored by SARS-CoV-2 testing and commercial nucleocapsid IgG ELISA. RBD IgG ELISA showed significantly lower reactivity against the Omicron-RBD compared to the Alpha variant in all individuals (p < 0.001). IgG levels were independent of sex, but were significantly higher in BNT162b2 recipients <45 years of age for Alpha, Gamma, and Delta (p < 0.001; p = 0.040; p = 0.004, respectively). Pre-pandemic cross-reactive anti-Omicron IgG was detected in 31 individuals and was increased 8.78-fold after vaccination, regardless of vaccine type. The low anti-RBD Omicron IgG level could explain the breakthrough infections and their presence could also contribute to a milder COVID-19 course by cross-reactivity and broadening the adaptive immunity.     

Previous SARS-CoV-2 Infection Increases B.1.1.7 Cross-Neutralization by Vaccinated Individuals

With the spread of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is a need to assess the protection conferred by both previous infections and current vaccination. Here we tested the neutralizing activity of infected and/or vaccinated individuals against pseudoviruses expressing the spike of the original SARS-CoV-2 isolate Wuhan-Hu-1 (WH1), the D614G mutant and the B.1.1.7 variant. Our data show that parameters of natural infection (time from infection and nature of the infecting variant) determined cross-neutralization. Uninfected vaccinees showed a small reduction in neutralization against the B.1.1.7 variant compared to both the WH1 strain and the D614G mutant. Interestingly, upon vaccination, previously infected individuals developed more robust neutralizing responses against B.1.1.7, suggesting that vaccines can boost the neutralization breadth conferred by natural infection.     

An outbreak caused by the SARS-CoV-2 Delta (B.1.617.2) variant in a care home after partial vaccination with a single dose of the COVID-19 vaccine Vaxzevria,London, England,April 2021

We investigated a COVID-19 outbreak of the SARS-CoV-2 Delta variant of concern in a London care home, where 8/21 residents and 14/21 staff had received a single dose of Vaxzevria (ChAdOx1-S; AstraZeneca) vaccine. We identified 24 SARS-CoV-2 infections (16 residents, 8 staff) among 40 individuals (19 residents, 21 staff); four (3 residents, 1 staff) were hospitalised, and none died. The attack rate after one vaccine dose was 35.7% (5/14) for staff and 81.3% (13/16) for residents.     

SARS-CoV-2 Genomic Surveillance in Brazil: A Systematic Review with Scientometric Analysis

Several studies have monitored the SARS-CoV-2 variants in Brazil throughout the pandemic. Here, we systematically reviewed and conducted a scientometric analysis of the SARS-CoV-2 genomic surveillance studies using Brazilian samples. A Pubmed database search on October 2022 returned 492 articles, of which 106 were included. Ninety-six different strains were reported, with variant of concern (VOC) gamma (n = 35,398), VOC delta (n = 15,780), and the variant of interest zeta (n = 1983) being the most common. The top three states with the most samples in the published articles were São Paulo, Rio de Janeiro, and Minas Gerais. Whereas the first year of the pandemic presented primary circulation of B.1.1.28 and B.1.1.33 variants, consecutive replacements were observed between them and VOI zeta, VOC gamma, VOC delta, and VOC omicron. VOI mu, VOI lambda, VOC alpha, and VOC beta were also detected but failed to reach significant circulation. Co-infection, re-infection, and vaccine breakthrough reports were found. Article co-citation differed from the co-authorship structure. Despite the limitations, we expect to give an overview of Brazil’s genomic surveillance studies and contribute to future research execution.     

SARS-CoV-2 RBD-Specific Antibodies Induced Early in the Pandemic by Natural Infection and Vaccination Display Cross-Variant Binding and Inhibition

The development of vaccine candidates for COVID-19 has been rapid, and those that are currently approved display high efficacy against the original circulating strains. However, recently, new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged with increased transmission rates and less susceptibility to vaccine induced immunity. A greater understanding of protection mechanisms, including antibody longevity and cross-reactivity towards the variants of concern (VoCs), is needed. In this study, samples collected in Denmark early in the pandemic from paucisymptomatic subjects (n = 165) and symptomatic subjects (n = 57) infected with SARS-CoV-2 were used to assess IgG binding and inhibition in the form of angiotensin-converting enzyme 2 receptor (ACE2) competition against the wild-type and four SARS-CoV-2 VoCs (Alpha, Beta, Gamma, and Omicron). Antibodies induced early in the pandemic via natural infection were cross-reactive and inhibited ACE2 binding of the VoC, with reduced inhibition observed for the Omicron variant. When examined longitudinally, sustained cross-reactive inhibitory responses were found to exist in naturally infected paucisymptomatic subjects. After vaccination, receptor binding domain (RBD)-specific IgG binding increased by at least 3.5-fold and inhibition of ACE2 increased by at least 2-fold. When vaccination regimens were compared (two doses of Pfizer-BioNTech BNT162b2 (n = 50), or one dose of Oxford-AstraZeneca ChAdOx1 nCoV-19 followed by Pfizer-BioNTech BNT162b2 (ChAd/BNT) (n = 15)), higher levels of IgG binding and inhibition were associated with mix and match (ChAd/BNT) prime-boosting and time since vaccination. These results are particularly relevant for countries where vaccination levels are low.     

Steep Decline in Binding Capability of SARS-CoV-2 Omicron Variant (B.1.1.529) RBD to the Antibodies in Early COVID-19 Convalescent Sera and Inactivated Vaccine Sera

A new SARS-CoV-2 variant B.1.1.529 was named by the WHO as Omicron and classified as a Variant of Concern (VOC) on 26 November 2021. Because this variant has more than 50 mutations, including 30 mutations on the spike, it has generated a lot of concerns on the potential impacts of the VOC on COVID-19. Here through ELISA assays using the recombinant RBD proteins with sequences the same to that of SARS-CoV-2 WIV04 (lineage B.1), the Delta variant and the Omicron variant as the coating antigens, the binding capabilities between the RBDs and the antibodies in COVID-19 convalescent sera and vaccine sera after two doses of the inactivated vaccine produced by Sinopharm WIBP are compared with each other. The results showed that the Omicron variant may evade antibodies induced by the ancestral strain and by the inactivated vaccine, with significant reduction in the binding capability of its RBD much greater than that of the Delta variant.     

Comparison of the Antibody Responses Following Vaccination with AstraZeneca and Sinopharm

Background: Vaccines are the most effective way to prevent Coronavirus 2 severe acute respiratory syndrome (SARS-CoV-2).Objectives: To compare the antibody response of healthy individuals vaccinated with either the AstraZeneca (ChAdOx1 nCoV-19) or the Sinopharm (BBIBP-CorV) vaccine, in those who had no prior infection with SARS-CoV-2.Methods: Thirty seven participants were included, of which 17 were administered the AstraZeneca (ChAdOx1 nCoV-19) vaccine, while 20 were given the Sinopharm (BBIBP-CorV) vaccine. SARS-CoV-2 neutralizing antibody and anti-receptor-binding domain (RBD) IgG levels were checked 4 weeks after giving the first and the second dose of either vaccine using the enzyme-linked immunosorbent assay (ELISA) technique.Results: The AstraZeneca (ChAdOx1 nCoV-19) vaccine exhibited a higher levels of anti-(RBD) IgG compared with the Sinopharm (BBIBP-CorV) in both the first (14.51 μg/ml vs. 1.160 μg/ml) and the second (46.68 μg/ml vs. 11.43 μg/ml) doses. About neutralizing Abs, the titer of the antibody was higher in the AstraZeneca (ChAdOx1 nCoV-19) recipients than in the Sinopharm (BBIBP-CorV) subjects after the first (7.77 μg/ml vs. 1.79 μg/ml, p < 0.0001) and the second dose (10. 36 μg/ml vs. 4.88 μg/ml, p < 0.0001).Conclusions: Recipients vaccinated with two doses of the AstraZeneca (ChAdOx1 nCoV-19) had superior quantitative antibody levels than Sinopharm (BBIBP-CorV)-vaccinated subjects. These data suggest that a booster dose may be needed for the Sinopharm (BBIBP-CorV) recipients, to control the COVID-19 pandemic.     

Case fatality risk of the SARS-CoV-2 variant of concern B.1.1.7 in England, 16 November to 5 February

The SARS-CoV-2 B.1.1.7 variant of concern (VOC) is increasing in prevalence across Europe. Accurate estimation of disease severity associated with this VOC is critical for pandemic planning. We found increased risk of death for VOC compared with non-VOC cases in England (hazard ratio: 1.67; 95% confidence interval: 1.34–2.09; p < 0.0001). Absolute risk of death by 28 days increased with age and comorbidities. This VOC has potential to spread faster with higher mortality than the pandemic to date.     

Replication Kinetics of B.1.351 and B.1.1.7 SARS-CoV-2 Variants of Concern Including Assessment of a B.1.1.7 Mutant Carrying a Defective ORF7a Gene

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, is a readily transmissible and potentially deadly pathogen which is currently re-defining human susceptibility to pandemic viruses in the modern world. The recent emergence of several genetically distinct descendants known as variants of concern (VOCs) is further challenging public health disease management, due to increased rates of virus transmission and potential constraints on vaccine effectiveness. We report the isolation of SARS-CoV-2 VOCs imported into Australia belonging to the B.1.351 lineage, first described in the Republic of South Africa (RSA), and the B.1.1.7 lineage originally reported in the United Kingdom, and directly compare the replication kinetics of these two VOCs in Vero E6 cells. In this analysis, we also investigated a B.1.1.7 VOC (QLD1516/2021) carrying a 7-nucleotide deletion in the open reading frame 7a (ORF7a) gene, likely truncating and rendering the ORF7a protein of this virus defective. We demonstrate that the replication of the B.1.351 VOC (QLD1520/2020) in Vero E6 cells can be detected earlier than the B.1.1.7 VOCs (QLD1516/2021 and QLD1517/2021), before peaking at 48 h post infection (p.i.), with significantly higher levels of virus progeny. Whilst replication of the ORF7a defective isolate QLD1516/2021 was delayed longer than the other viruses, slightly more viral progeny was produced by the mutant compared to the unmutated isolate QLD1517/2021 at 72 h p.i. Collectively, these findings contribute to our understanding of SARS-CoV-2 replication and evolutionary dynamics, which have important implications in the development of future vaccination, antiviral therapies, and epidemiological control strategies for COVID-19.     

Previous Infection with SARS-CoV-2 Correlates with Increased Protective Humoral Responses after a Single Dose of an Inactivated COVID-19 Vaccine

Previous studies have indicated that antibody responses can be robustly induced after the vaccination in individuals previously infected by SARS-CoV-2. To evaluate anti-SARS-CoV-2 humoral responses in vaccinated individuals with or without a previous history of COVID-19, we compared levels of anti-SARS-CoV-2 antibodies in the sera from 21 vaccinees, including COVID-19-recovered or -naïve individuals in different times, before and after immunization with an inactivated COVID-19 vaccine. Anti-SARS-CoV-2-specific antibodies elicited after COVID-19 and/or immunization with an inactivated vaccine were measured by ELISA and Plaque Reduction Neutralizing assays. Antibody kinetics were consistently different between the two vaccine doses for naïve individuals, contrasting with the SARS-CoV-2-recovered subjects in which we observed no additional increase in antibody levels following the second dose. Sera from SARS-CoV2-naïve individuals had no detectable neutralizing activity against lineage B.1 SARS-CoV-2 or Gamma variant five months after the second vaccine dose. Contrarily, SARS-CoV-2-recovered subjects retained considerable neutralizing activity against both viruses. We conclude that a single inactivated SARS-CoV-2 vaccine dose may be sufficient to induce protective antibody responses in individuals with previous history of SARS-CoV-2 infection.     

Detection of the new SARS-CoV-2 variants of concern B.1.1.7 and B.1.351 in five SARS-CoV-2 rapid antigen tests (RATs), Germany,March 2021

SARS-CoV-2 variants of concern (VOC) should not escape molecular surveillance. We investigated if SARS-CoV-2 rapid antigen tests (RATs) could detect B.1.1.7 and B.1.351 VOCs in certain laboratory conditions. Infectious cell culture supernatants containing B.1.1.7, B.1.351 or non-VOC SARS-CoV-2 were respectively diluted both in DMEM and saliva. Dilutions were analysed with Roche, Siemens, Abbott, nal von minden and RapiGEN RATs. While further studies with appropriate real-life clinical samples are warranted, all RATs detected B.1.1.7 and B.1.351, generally comparable to non-VOC strain.     

The effectiveness of primary series CoronaVac vaccine in preventing COVID-19 illness: A prospective cohort study among healthcare workers in Azerbaijan,May–November 2021

Background

Healthcare workers (HCWs) have suffered considerable morbidity and mortality during the COVID-19 pandemic. Few studies have evaluated the CoronaVac vaccine effectiveness (VE), particularly in Eastern Europe, where the vaccine has been widely used.

Methods

We conducted a prospective cohort study among HCWs in seven hospitals in Baku, Azerbaijan between May 17 and November 30, 2021, to evaluate primary series (two-dose) CoronaVac VE against symptomatic SARS-CoV-2 infection. Participants completed weekly symptom questionnaires, provided nasopharyngeal swabs for SARS-CoV-2 RT-PCR testing when symptomatic, and provided serology samples at enrollment that were tested for anti-spike and anti-nucleocapsid antibodies. We estimated VE as (1 – hazard ratio)*100 using a Cox proportional hazards model with vaccination status as a time-varying exposure, adjusting for hospital and previous SARS-CoV-2 infection status.

Results

We enrolled 1582 HCWs. At enrollment, 1040 (66%) had received two doses of CoronaVac; 421 (27%) were unvaccinated. During the study period, 72 PCR-positive SARS-CoV-2 infections occurred; 36/39 (92%) sequenced samples were classified as Delta variants. Primary series VE against COVID-19 illness was 29% (95% CI: −51%; 67%) for the entire analysis period. For the Delta-only period (July 1–November 30, 2021), primary series VE was 19% (95% CI: −81%; 64%). For the entire analysis period, primary series VE was 39% (95% CI: −40%; 73%) for HCWs vaccinated within 14–149 days and 19% (95% CI: −81%; 63%) for those vaccinated ≥150 days.

Conclusions

During a period in Azerbaijan characterized by mostly Delta circulation, VE point estimates suggested that primary series CoronaVac protected nearly 1 in 3 HCWs against COVID-19, but 95% confidence intervals were wide, with lower bounds that crossed zero, reflecting the limited precision of our VE estimates. Our findings underscore the need to consider booster doses for individuals who have received the primary series of CoronaVac.     

Long-COVID Symptoms in Individuals Infected with Different SARS-CoV-2 Variants of Concern: A Systematic Review of the Literature

The association of SARS-CoV-2 variants with long-COVID symptoms is still scarce, but new data are appearing at a fast pace. This systematic review compares the prevalence of long-COVID symptoms according to relevant SARS-CoV-2 variants in COVID-19 survivors. The MEDLINE, CINAHL, PubMed, EMBASE and Web of Science databases, as well as the medRxiv and bioRxiv preprint servers, were searched up to 25 October 2022. Case-control and cohort studies analyzing the presence of post-COVID symptoms appearing after an acute SARS-CoV-2 infection by the Alpha (B.1.1.7), Delta (B.1.617.2) or Omicron (B.1.1.529/BA.1) variants were included. Methodological quality was assessed using the Newcastle–Ottawa Scale. From 430 studies identified, 5 peer-reviewed studies and 1 preprint met the inclusion criteria. The sample included 355 patients infected with the historical variant, 512 infected with the Alpha variant, 41,563 infected with the Delta variant, and 57,616 infected with the Omicron variant. The methodological quality of all studies was high. The prevalence of long-COVID was higher in individuals infected with the historical variant (50%) compared to those infected with the Alpha, Delta or Omicron variants. It seems that the prevalence of long-COVID in individuals infected with the Omicron variant is the smallest, but current data are heterogeneous, and long-term data have, at this stage, an obviously shorter follow-up compared with the earlier variants. Fatigue is the most prevalent long-COVID symptom in all SARS-CoV-2 variants, but pain is likewise prevalent. The available data suggest that the infection with the Omicron variant results in fewer long-COVID symptoms compared to previous variants; however, the small number of studies and the lack of the control of cofounders, e.g., reinfections or vaccine status, in some studies limit the generality of the results. It appears that individuals infected with the historical variant are more likely to develop long-COVID symptomatology.     

Protective Immunity against Gamma and Zeta Variants after Inactivated SARS-CoV-2 Virus Immunization

The persistent circulation of SARS-CoV-2 represents an ongoing global threat due to the emergence of new viral variants that can sometimes evade the immune system of previously exposed or vaccinated individuals. We conducted a follow-up study of adult individuals that had received an inactivated SARS-CoV-2 vaccine, evaluating antibody production and neutralizing activity over a period of 6 months. In addition, we performed mice immunization with inactivated SARS-CoV-2, and evaluated the immune response and pathological outcomes against Gamma and Zeta variant infection. Vaccinated individuals produced high levels of antibodies with robust neutralizing activity, which was significantly reduced against Gamma and Zeta variants. Production of IgG anti-S antibodies and neutralizing activity robustly reduced after 6 months of vaccination. Immunized mice demonstrated cellular response against Gamma and Zeta variants, and after viral infection, reduced viral loads, IL-6 expression, and histopathological outcome in the lungs. TNF levels were unchanged in immunized or not immunized mice after infection with the Gamma variant. Furthermore, serum neutralization activity rapidly increases after infection with the Gamma and Zeta variants. Our data suggest that immunization with inactivated WT SARS-CoV-2 induces a promptly responsive cross-reactive immunity response against the Gamma and Zeta variants, reducing COVID-19 pathological outcomes.     

Kinetics of Neutralizing Antibodies of COVID-19 Patients Tested Using Clinical D614G,B.1.1.7, and B 1.351 Isolates in Microneutralization Assays

Increasing evidence suggests that some newly emerged SARS-CoV-2 variants of concern (VoCs) resist neutralization by antibodies elicited by the early-pandemic wild-type virus. We applied neutralization tests to paired recoveree sera (n = 38) using clinical isolates representing the first wave (D614G), VoC1, and VoC2 lineages (B.1.1.7 and B 1.351). Neutralizing antibodies inhibited contemporary and VoC1 lineages, whereas inhibition of VoC2 was reduced 8-fold, with 50% of sera failing to show neutralization. These results provide evidence for the increased potential of VoC2 to reinfect previously SARS-CoV-infected individuals. The kinetics of NAbs in different patients showed similar decline against all variants, with generally low initial anti-B.1.351 responses becoming undetectable, but with anti-B.1.1.7 NAbs remaining detectable (>20) for months after acute infection.     

Antiviral Effect of Budesonide against SARS-CoV-2

Treatment options for COVID-19, a disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, are currently severely limited. Therefore, antiviral drugs that efficiently reduce SARS-CoV-2 replication or alleviate COVID-19 symptoms are urgently needed. Inhaled glucocorticoids are currently being discussed in the context of treatment for COVID-19, partly based on a previous study that reported reduced recovery times in cases of mild COVID-19 after inhalative administration of the glucocorticoid budesonide. Given various reports that describe the potential antiviral activity of glucocorticoids against respiratory viruses, we aimed to analyze a potential antiviral activity of budesonide against SARS-CoV-2 and circulating variants of concern (VOC) B.1.1.7 (alpha) and B.1.351 (beta). We demonstrate a dose-dependent inhibition of SARS-CoV-2 that was comparable between all viral variants tested while cell viability remains unaffected. Our results are encouraging as they could indicate a multimodal mode of action of budesonide against SARS-CoV-2 and COVID-19, which could contribute to an improved clinical performance.     

Case Study of Two Post Vaccination SARS-CoV-2 Infections with P1 Variants in CoronaVac Vaccinees in Brazil

The rapid development of efficacious and safe vaccines against coronavirus disease 2019 (COVID-19) has been instrumental in mitigating the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Moreover, the emergence of SARS-CoV-2 variants raised concerns on the efficacy of these vaccines. Herein, we report two cases of breakthrough infections with the P1 variant in patients vaccinated with CoronaVac, which is one of the two vaccines authorized for emergency use in the Brazilian immunization program. Our observations suggest that the vaccine reduced the severity of the disease and highlight the potential risk of illness following vaccination and subsequent infection with the P1 variant as well as for continued efforts to prevent and diagnose infection in vaccinated persons.