Special Issue "SARS-CoV-2 Variants Research and Ending the COVID-19 Pandemic"

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "COVID-19 Vaccines and Vaccination".

Deadline for manuscript submissions: 31 December 2022 | Viewed by 12363

Special Issue Editors

Dr. Claudia Maria Trombetta
E-Mail Website
Guest Editor
Department of Molecular and Developmental Medicine, University of Siena, Banchi di Sotto, 55, 53100 Siena, SI, Italy
Interests: influenza vaccines; correlates of protection; vaccine-preventable diseases; seroepidemiology; SARS-CoV-2
Special Issues, Collections and Topics in MDPI journals
Prof. Emanuele Montomoli
E-Mail Website
Guest Editor
Department of Molecular and Developmental Medicine, Universita degli Studi di Siena, Siena, Italy
Interests: clinical trials of influenza vaccines
Special Issues, Collections and Topics in MDPI journals
Dr. Serena Marchi
E-Mail Website
Guest Editor
Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy
Interests: emerging viruses; vaccine-preventable diseases; seroepidemiology; SARS-CoV-2

Special Issue Information

Dear Colleagues,

Since the end of January 2020, the world has been experiencing a disastrous pandemic caused by a novel coronavirus, named SARS-CoV-2, first identified in Wuhan, China, and which rapidly spread worldwide. The pandemic has devastated healthcare systems, imposed strict national lockdown, and is responsible for over a million deaths across the world.

The emergence of new and more infectious SARS-CoV-2 variants is raising concern, and vaccination may represent a primary tool to counteract the pandemic, virus spread, and mortality.

In this Special Issue, we aim to cover all aspects related to SARS-CoV-2 variants, vaccines, and immune response. The goal is to provide an overview of the most relevant investigations related to SARS-CoV-2 and the COVID-19 pandemic.

Dr. Claudia Maria Trombetta
Prof. Emanuele Montomoli
Dr. Serena Marchi
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • SARS-CoV-2
  • SARS-CoV-2 variants
  • COVID-19 pandemic
  • vaccines
  • antibodies
  • immune response

Published Papers (10 papers)

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Research

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Article
Development of a T Cell-Based COVID-19 Vaccine Using a Live Attenuated Influenza Vaccine Viral Vector
Vaccines 2022, 10(7), 1142; https://doi.org/10.3390/vaccines10071142 - 18 Jul 2022
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Abstract
The COVID-19 pandemic emerged in 2020 and has caused an unprecedented burden to all countries in the world. SARS-CoV-2 continues to circulate and antigenically evolve, enabling multiple reinfections. To address the issue of the virus antigenic variability, T cell-based vaccines are being developed, [...] Read more.
The COVID-19 pandemic emerged in 2020 and has caused an unprecedented burden to all countries in the world. SARS-CoV-2 continues to circulate and antigenically evolve, enabling multiple reinfections. To address the issue of the virus antigenic variability, T cell-based vaccines are being developed, which are directed to more conserved viral epitopes. We used live attenuated influenza vaccine (LAIV) virus vector to generate recombinant influenza viruses expressing various T-cell epitopes of SARS-CoV-2 from either neuraminidase (NA) or non-structural (NS1) genes, via the P2A self-cleavage site. Intranasal immunization of human leukocyte antigen-A*0201 (HLA-A2.1) transgenic mice with these recombinant viruses did not result in significant SARS-CoV-2-specific T-cell responses, due to the immunodominance of NP366 influenza T-cell epitope. However, side-by-side stimulation of peripheral blood mononuclear cells (PBMCs) of COVID-19 convalescents with recombinant viruses and LAIV vector demonstrated activation of memory T cells in samples stimulated with LAIV/SARS-CoV-2, but not LAIV alone. Hamsters immunized with a selected LAIV/SARS-CoV-2 prototype were protected against challenge with influenza virus and a high dose of SARS-CoV-2 of Wuhan and Delta lineages, which was confirmed by reduced weight loss, milder clinical symptoms and less pronounced histopathological signs of SARS-CoV-2 infection in the lungs, compared to LAIV- and mock-immunized animals. Overall, LAIV is a promising platform for the development of a bivalent vaccine against influenza and SARS-CoV-2. Full article
(This article belongs to the Special Issue SARS-CoV-2 Variants Research and Ending the COVID-19 Pandemic)
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Article
COVID-19 Outbreak and BNT162b2 mRNA Vaccination Coverage in a Correctional Facility during Circulation of the SARS-CoV-2 Omicron BA.1 Variant in Italy
Vaccines 2022, 10(7), 1137; https://doi.org/10.3390/vaccines10071137 - 17 Jul 2022
Viewed by 421
Abstract
Background. The recent spread of the highly mutated SARS-CoV-2 Omicron variant (B.1.1.529) has raised concerns about protection against COVID-19 in congregate settings such as prisons, characterized by a high risk of transmission and possible difficulties in obtaining adequate vaccination coverage. The present [...] Read more.
Background. The recent spread of the highly mutated SARS-CoV-2 Omicron variant (B.1.1.529) has raised concerns about protection against COVID-19 in congregate settings such as prisons, characterized by a high risk of transmission and possible difficulties in obtaining adequate vaccination coverage. The present study aims to investigate the spread of an outbreak of COVID-19 in an Italian correctional facility during the dominant circulation of the Omicron BA.1 variant, and also considers BNT162b2 mRNA vaccination coverage among inmates. A COVID-19 screening campaign by RT-PCR was performed on 515 detainees from 4–30 January 2022, in response to an outbreak that began in the correctional facility. Furthermore, 101 serum samples collected from healthy inmates 21 days after having received the second dose of the BNT162b2 vaccine were tested for neutralizing antibodies against both the wild-type SARS-CoV-2 strain and the Omicron BA.1 variant. The global attack rate during the study period was 43.6% (RR 0.8), progressively reducing from unvaccinated inmates (62.7%, RR 1.8) to those who had one dose (52.3%, RR 1.5), two doses (full cycle) (45.0%, RR 1.3), and the third dose (booster) vaccinated group (31.4%, RR 0.7). The percentage of SARS-CoV-2 positive subjects among unvaccinated inmates was significantly higher than in the other groups (p < 0.001), while no significant difference was observed between inmates with one or two vaccine doses. Only two of the positive inmates were hospitalized for COVID-19. The geometric mean titer of neutralizing antibodies in the tested sub-group after two doses of vaccine was lower than in previous studies against the wild-type virus, and showed a complete lack of neutralization against the Omicron variant in 92.1% of individuals. The findings support the need to prioritize vaccination in correctional facilities, as a public health measure to increase the protection of inmates and consequently of prison workers and the community against COVID-19, in coordination with the other prevention strategies. Full article
(This article belongs to the Special Issue SARS-CoV-2 Variants Research and Ending the COVID-19 Pandemic)
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Article
mRNA Booster Vaccination Enhances Antibody Responses against SARS-CoV2 Omicron Variant in Individuals Primed with mRNA or Inactivated Virus Vaccines
Vaccines 2022, 10(7), 1057; https://doi.org/10.3390/vaccines10071057 - 30 Jun 2022
Viewed by 570
Abstract
The advent of the Omicron variant globally has hastened the requirement for a booster vaccination dose to confer continuous protection against symptomatic SARS-CoV2 infection. However, different vaccines are available in different countries, and individuals who had adverse reactions to certain vaccine types require [...] Read more.
The advent of the Omicron variant globally has hastened the requirement for a booster vaccination dose to confer continuous protection against symptomatic SARS-CoV2 infection. However, different vaccines are available in different countries, and individuals who had adverse reactions to certain vaccine types require heterologous vaccine boosters. To understand the efficacy of different vaccination regimens in inducing humoral responses to SARS-CoV2, we examined plasma antibodies and frequencies of Omicron RBD-specific B cells in individuals who had different priming-booster vaccination regimens. We found that individuals with three homologous doses of mRNA vaccines had higher levels of IgG of all subclasses against RBD of Omicron than individuals with three homologous doses of inactivated virus vaccine. A booster with mRNA vaccine resulted in significant increases in median levels of RBD-reactive IgG1 (17–19 fold) and IgG3 (2.3–3.3 fold) as compared to individuals receiving inactivated virus booster shots regardless of priming vaccine types. More importantly, individuals who received a booster dose of mRNA vaccine, irrespective of the priming vaccine, had antibodies with higher neutralizing capability against the Omicron variant than those who received a booster dose of inactivated virus vaccine. Corroborating the antibody results, boosting with the mRNA vaccine increased the frequencies of Omicron RBD-binding B cells by (1.5–3.3 fold) regardless of priming vaccine types. Together, our data demonstrate that an mRNA vaccine (BNT162b2 or mRNA-1273) booster enhances humoral responses against the Omicron variant in individuals vaccinated with either two prior doses of mRNA or inactivated virus vaccine (CoronaVac or BBIBP-CorV), potentially providing more effective protection against SARS-CoV-2 infection, particularly by the Omicron variant. Full article
(This article belongs to the Special Issue SARS-CoV-2 Variants Research and Ending the COVID-19 Pandemic)
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Article
Increased Receptor Affinity and Reduced Recognition by Specific Antibodies Contribute to Immune Escape of SARS-CoV-2 Variant Omicron
Vaccines 2022, 10(5), 743; https://doi.org/10.3390/vaccines10050743 - 09 May 2022
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Abstract
In this report, we mechanistically reveal how the Variant of Concern (VOC) SARS-CoV-2 Omicron (B.1.1.529) escapes neutralizing antibody responses, by physio-chemical characterization of this variant in comparison to the wild-type Wuhan and the Delta variant (B.1.617.2). Convalescent sera, as well as sera obtained [...] Read more.
In this report, we mechanistically reveal how the Variant of Concern (VOC) SARS-CoV-2 Omicron (B.1.1.529) escapes neutralizing antibody responses, by physio-chemical characterization of this variant in comparison to the wild-type Wuhan and the Delta variant (B.1.617.2). Convalescent sera, as well as sera obtained from participants who received two or three doses of mRNA vaccines (Moderna-mRNA-1273® or Pfizer-BNT162b2®), were used for comparison in this study. Our data demonstrate that both Delta, as well as Omicron variants, exhibit a higher affinity for the receptor ACE2, facilitating infection and causing antibody escape by receptor affinity (affinity escape), due to the reduced ability of antibodies to compete with RBD-receptor interaction and virus neutralization. In contrast, only Omicron but not the Delta variant escaped antibody recognition, most likely because only Omicron exhibits the mutation at E484A, a position associated with reduced recognition, resulting in further reduced neutralization (specificity escape). Nevertheless, the immunizations with RNA-based vaccines resulted in marked viral neutralization in vitro for all strains, compatible with the fact that Omicron is still largely susceptible to vaccination-induced antibodies, despite affinity- and specificity escape. Full article
(This article belongs to the Special Issue SARS-CoV-2 Variants Research and Ending the COVID-19 Pandemic)
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Communication
A Third Dose of the COVID-19 Vaccine, CVnCoV, Increased the Neutralizing Activity against the SARS-CoV-2 Wild-Type and Delta Variant
Vaccines 2022, 10(4), 508; https://doi.org/10.3390/vaccines10040508 - 25 Mar 2022
Cited by 1 | Viewed by 747
Abstract
A third dose of CVnCoV, a former candidate mRNA vaccine against SARS-CoV-2, was previously shown to boost neutralizing antibody responses against SARS-CoV-2 wild-type in adults aged 18–60 and >60 years in a phase 2a clinical study. In the present study, we report the [...] Read more.
A third dose of CVnCoV, a former candidate mRNA vaccine against SARS-CoV-2, was previously shown to boost neutralizing antibody responses against SARS-CoV-2 wild-type in adults aged 18–60 and >60 years in a phase 2a clinical study. In the present study, we report the neutralizing antibody responses to a wild-type and a variant of concern, Delta, after a third dose of the vaccine on day (D)57 and D180. Neutralization activity was assessed using a microneutralization assay. Comparable levels of neutralizing antibodies against the wild-type and Delta were induced. These were higher than those observed after the first two doses, irrespective of age or pre-SARS-CoV-2-exposure status, indicating that the first two doses induced immune memory. Four weeks after the third dose on D180, the neutralizing titers for wild-type and Delta were two-fold higher in younger participants than in older participants; seroconversion rates were 100% for wild-type and Delta in the younger group and for Delta in the older group. A third CVnCoV dose induced similar levels of neutralizing responses against wild-type virus and the Delta variant in both naïve and pre-exposed participants, aligning with current knowledge from licensed COVID-19 vaccines that a third dose is beneficial against SARS-CoV-2 variants. Full article
(This article belongs to the Special Issue SARS-CoV-2 Variants Research and Ending the COVID-19 Pandemic)
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Article
Autochthonous Outbreak of SARS-CoV-2 Omicron Variant in Booster-Vaccinated (3 Doses) Healthcare Workers in Southern Italy: Just the Tip of the Iceberg?
Vaccines 2022, 10(2), 283; https://doi.org/10.3390/vaccines10020283 - 13 Feb 2022
Cited by 6 | Viewed by 1016
Abstract
The Omicron variant of concern (VOC), first detected in Italy at the end of November 2021, has since spread rapidly, despite high vaccine coverage in the Italian population, especially in healthcare workers (HCWs). This study describes an outbreak of SARS-CoV-2 Omicron infection in [...] Read more.
The Omicron variant of concern (VOC), first detected in Italy at the end of November 2021, has since spread rapidly, despite high vaccine coverage in the Italian population, especially in healthcare workers (HCWs). This study describes an outbreak of SARS-CoV-2 Omicron infection in 15 booster-vaccinated HCWs. On 16 December 2021, two HCWs working in the same ward were infected with SARS-CoV-2. The Omicron VOC was suspected due to S gene target failure on molecular testing. Further investigation revealed that 15 (65%) of 23 HCWs attending a social gathering on 13 December were infected with Omicron, as shown by whole-genome sequencing, with a phylogenetic tree suggesting a common source of exposure. Five of these HCWs experienced mild symptoms. A patient with multiple chronic conditions hospitalized in the same ward was also infected by one of the HCWs involved in the outbreak. Despite being booster vaccinated, this patient required ICU treatment. Ten subjects achieved negativity in 10–19 days. The outbreak in booster-vaccinated subjects confirms the high transmissibility and immune evasion of the Omicron VOC. More stringent non-pharmaceutical interventions, administration of booster doses, and genomic surveillance are crucial long-term strategies to mitigate the consequences of the spread of the Omicron VOC. Full article
(This article belongs to the Special Issue SARS-CoV-2 Variants Research and Ending the COVID-19 Pandemic)
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Article
COVID-19 Vaccine Booster Hesitancy (VBH) of Healthcare Workers in Czechia: National Cross-Sectional Study
Vaccines 2021, 9(12), 1437; https://doi.org/10.3390/vaccines9121437 - 06 Dec 2021
Cited by 25 | Viewed by 2414
Abstract
The emerging SARS-CoV-2 variants and waning vaccine-elicited immunity are two public health challenges that occurred simultaneously and synergistically during the summer of 2021 and led to a surging demand for COVID-19 vaccine booster dose (BD) rollout. This study aimed to evaluate the COVID-19 [...] Read more.
The emerging SARS-CoV-2 variants and waning vaccine-elicited immunity are two public health challenges that occurred simultaneously and synergistically during the summer of 2021 and led to a surging demand for COVID-19 vaccine booster dose (BD) rollout. This study aimed to evaluate the COVID-19 vaccine booster hesitancy (VBH) among Czech healthcare workers to explore the potential determinants of VBH. A national cross-sectional survey-based study was carried out between 3 and 11 November 2021, using an online self-administered questionnaire (SAQ) that explored the participants’ demographic characteristics, COVID-19 infection and vaccine anamneses, willingness to receive COVID-19 vaccine BD, and the psychosocial drivers of VBH. A total of 3454 HCW properly responded to the online SAQ, of which 80.9% were females, 30.3% were medical professionals, and 50.5% were ≤47 years old. Most of the participants were already inoculated against SARS-CoV-2 (95.2%), and BTN162b2 was the most commonly administered vaccine (90.7%). As the study sample was planned to represent the target population, it revealed a high level of BD acceptance (71.3%) among Czech HCW, while 12.2% were still hesitant and 16.6% were against the currently available BD. These results are consistent with other recent results from central Europe. Medical professional, male, and older participants were more likely to accept BD rather than allied health professional, female, and younger participants. The BDs’ perceived effectiveness against severe illness, symptomatic infection, and community transmission was a significant and strong predictor for BD acceptance, while the effectiveness against the circulating variants was not that important for our target population. The BDs’ perceived safety and ethical dilemmas of vaccine justice should be addressed sufficiently while communicating with HCW and other population groups. The altruistic reasons for BD acceptance, i.e., family protection, patient protection, and community health protection, underpin the recommendation of postponing the COVID-19 vaccine mandating in favour of stressing these altruistic concerns amid public health messaging. Full article
(This article belongs to the Special Issue SARS-CoV-2 Variants Research and Ending the COVID-19 Pandemic)
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Article
Robust SARS-CoV-2 Antibody Responses in Asian COVID-Naïve Subjects 180 Days after Two Doses of BNT162b2 mRNA COVID-19 Vaccine
Vaccines 2021, 9(11), 1241; https://doi.org/10.3390/vaccines9111241 - 25 Oct 2021
Cited by 6 | Viewed by 868
Abstract
Background: Subjects with previous COVID-19 have augmented post-vaccination responses. However, the antibody response in COVID-naïve subjects from Southeast Asia is not well known. Methods: 77 COVID-naïve vaccinees were tested with a full antibody panel [spike antibodies (total (T-Ab), IgG, IgM) and neutralizing antibodies [...] Read more.
Background: Subjects with previous COVID-19 have augmented post-vaccination responses. However, the antibody response in COVID-naïve subjects from Southeast Asia is not well known. Methods: 77 COVID-naïve vaccinees were tested with a full antibody panel [spike antibodies (total (T-Ab), IgG, IgM) and neutralizing antibodies (N-Ab)] pre-vaccination, 10 days after dose 1, and 20/40/60/90/120/150/180 days after dose 2. Results: 10 days after dose 1, 67.6% (48/71)/69.0% (49/71) were T-Ab/IgG positive; only 15.5% (11/71)/14.1% (10/71) were N-Ab/IgM positive. While all (100%) subjects had brisk T-Ab, IgG and N-Ab antibody responses 20 days after complete vaccination, only 79.1% (53/67) were IgM positive. At 180 days (n = 8), T-Ab/IgG/N-Ab were still reactive (lowest T-Ab 186 U/mL, IgG 617 AU/mL, N-Ab 0.39 µg/mL), but IgM was negative in all samples. Spike antibody thresholds of T-Ab 74.1 U/mL (r = 0.95) and IgG 916 AU/mL (r = 0.95) corresponded to N-Ab reactivity (>0.3 µg/mL). Non-linear regression analysis showed that N-Ab would decrease to 0.3 µg/mL by 241 days, whereas T-Ab/IgG would need 470/163 days to reach titers of T-Ab/IgG associated with a N-Ab 0.3 µg/mL (76.4 U/mL and 916 AU/mL respectively). Conclusions: The antibody responses of T-Ab, IgG and N-Ab remain high and durable even at 180 days. N-Ab titers are expected to remain reactive up to 241 days post-vaccination. Full article
(This article belongs to the Special Issue SARS-CoV-2 Variants Research and Ending the COVID-19 Pandemic)
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Article
COVID-19 Vaccine Hesitancy among Parents of Children and Adolescents Living in Brazil
Vaccines 2021, 9(10), 1115; https://doi.org/10.3390/vaccines9101115 - 30 Sep 2021
Cited by 27 | Viewed by 3021
Abstract
Background: The immunization of large portions of populations in low/middle-income countries is considered one of the key measures to limit the development of new SARS-CoV-2 variants. However, parental vaccine hesitancy might be an important obstacle to pediatric vaccination. The aim of this survey [...] Read more.
Background: The immunization of large portions of populations in low/middle-income countries is considered one of the key measures to limit the development of new SARS-CoV-2 variants. However, parental vaccine hesitancy might be an important obstacle to pediatric vaccination. The aim of this survey was to study the prevalence and extent of COVID-19 vaccine hesitancy among parents of children and adolescents living in Brazil. Methods: Caregivers of children and adolescents referred to the emergency department of Hospital Estadual de Bauru, São Paulo (Brazil) were invited to fill in a validated questionnaire on vaccine hesitancy and to report their willingness for themselves and their offspring to receive a COVID-19 vaccine. Results: A total of 501 consecutive caregivers filled in the survey. Response rate was 100%. A minority (N = 14, 2.8%) of caregivers were hesitant about vaccines. Despite this, half of them declared they were willing to vaccinate their offspring against COVID-19. Conclusions: This survey identifies that vaccine hesitancy is very low among caregivers living in Brazil and that even many of the hesitant caregivers are willing to vaccinate their offspring against COVID-19. This study highlights the importance of offering the COVID-19 vaccination to the whole population, including subjects that present uncertainty about other vaccines. Full article
(This article belongs to the Special Issue SARS-CoV-2 Variants Research and Ending the COVID-19 Pandemic)

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Brief Report
Characteristics of the First 284 Patients Infected with the SARS-CoV-2 Omicron BA.2 Subvariant at a Single Center in the Apulia Region of Italy, January–March 2022
Vaccines 2022, 10(5), 674; https://doi.org/10.3390/vaccines10050674 - 24 Apr 2022
Cited by 1 | Viewed by 722
Abstract
Since its initial detection, the SARS-CoV-2 Omicron sublineage BA.2 has been spreading rapidly worldwide. The aims of this study were to describe the first 284 patients infected with the Omicron BA.2 variant of concern (VOC) in the Apulia region of southern Italy and [...] Read more.
Since its initial detection, the SARS-CoV-2 Omicron sublineage BA.2 has been spreading rapidly worldwide. The aims of this study were to describe the first 284 patients infected with the Omicron BA.2 variant of concern (VOC) in the Apulia region of southern Italy and to assess the differences in the demographic and clinical characteristics of patients infected with the SARS-CoV-2 BA.1 and BA.2 variants. The demographic characteristics of patients, as well as information about symptoms, vaccinations and hospitalizations for COVID-19, were collected. A subset of samples from patients infected with the BA.2 variant was subjected to whole-genome sequencing. The characteristics of the first 284 patients infected with Omicron BA.2 and the first 175 patients infected with Omicron BA.1 were compared. The proportion of patients infected with the BA.2 variant rapidly increased, from 0.5% during the third week of 2022 to 29.6% during the tenth week of 2022. Ten isolates (out of 34 BA.2 isolates) contain the substitutional mutation, H78K in ORF3a, and four isolates include two mutations, A2909V in ORF1a and L140F in ORDF3a. Compared with patients infected with BA.1, those infected with BA.2 were more likely to be symptomatic and booster-vaccinated, and showed a shorter time from the last dose of vaccine to infection. The high transmissibility and immune-evasive properties of Omicron BA.2, which will become the leading SARS-CoV-2 VOC, suggest that short-term public health measures should not be discontinued in Italy. Full article
(This article belongs to the Special Issue SARS-CoV-2 Variants Research and Ending the COVID-19 Pandemic)
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