Editorial

9 pages, 228 KiB

Open AccessEditorial

COVID-19 Pandemic: Therapeutic Strategies and Vaccines

by Mariarosaria Boccellino

Int. J. Mol. Sci. 2024, 25(1), 556; https://doi.org/10.3390/ijms25010556 - 31 Dec 2023

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Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), a highly pathogenic and transmissible virus, has spurred an impressive accumulation of knowledge [...] Full article

(This article belongs to the Special Issue COVID-19 Pandemic: Therapeutic Strategies and Vaccines)

Research

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19 pages, 3252 KiB

Open AccessArticle

Following Natural Autoantibodies: Further Immunoserological Evidence Regarding Their Silent Plasticity and Engagement in Immune Activation

by David Szinger, Timea Berki, Péter Németh, Szabina Erdo-Bonyar, Diana Simon, Ines Drenjančević, Senka Samardzic, Marija Zelić, Magdalena Sikora, Arlen Požgain and Katalin Böröcz

Int. J. Mol. Sci. 2023, 24(19), 14961; https://doi.org/10.3390/ijms241914961 - 06 Oct 2023

Cited by 3 | Viewed by 921

Abstract

Contradictory reports are available on vaccine-associated hyperstimulation of the immune system, provoking the formation of pathological autoantibodies. Despite being interconnected within the same network, the role of the quieter, yet important non-pathological and natural autoantibodies (nAAbs) is less defined. We hypothesize that upon [...] Read more.

Contradictory reports are available on vaccine-associated hyperstimulation of the immune system, provoking the formation of pathological autoantibodies. Despite being interconnected within the same network, the role of the quieter, yet important non-pathological and natural autoantibodies (nAAbs) is less defined. We hypothesize that upon a prompt immunological trigger, physiological nAAbs also exhibit a moderate plasticity. We investigated their inducibility through aged and recent antigenic triggers. Anti-viral antibodies (anti-MMR n = 1739 and anti-SARS-CoV-2 IgG n = 330) and nAAbs (anti-citrate synthase IgG, IgM n = 1739) were measured by in-house and commercial ELISAs using Croatian (Osijek) anonymous samples with documented vaccination backgrounds. The results were subsequently compared for statistical evaluation. Interestingly, the IgM isotype nAAb showed a statistically significant connection with anti-MMR IgG seropositivity (p < 0.001 in all cases), while IgG isotype nAAb levels were elevated in association with anti-SARS CoV-2 specific seropositivity (p = 0.019) and in heterogeneous vaccine regimen recipients (unvaccinated controls vector/mRNA vaccines p = 0.002). Increasing evidence supports the interplay between immune activation and the dynamic expansion of nAAbs. Consequently, further questions may emerge regarding the ability of nAAbs silently shaping the effectiveness of immunization. We suggest re-evaluating the impact of nAAbs on the complex functioning of the immunological network. Full article

(This article belongs to the Special Issue COVID-19 Pandemic: Therapeutic Strategies and Vaccines)

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21 pages, 3533 KiB

Open AccessArticle

The Local Anaesthetic Procaine Prodrugs ProcCluster^® and Procaine Hydrochloride Impair SARS-CoV-2 Replication and Egress In Vitro

by Clio Häring, Johannes Jungwirth, Josefine Schroeder, Bettina Löffler, Beatrice Engert and Christina Ehrhardt

Int. J. Mol. Sci. 2023, 24(19), 14584; https://doi.org/10.3390/ijms241914584 - 26 Sep 2023

Cited by 1 | Viewed by 951

Abstract

As vaccination efforts against SARS-CoV-2 progress in many countries, there is still an urgent need for efficient antiviral treatment strategies for those with severer disease courses, and lately, considerable efforts have been undertaken to repurpose existing drugs as antivirals. The local anaesthetic procaine [...] Read more.

As vaccination efforts against SARS-CoV-2 progress in many countries, there is still an urgent need for efficient antiviral treatment strategies for those with severer disease courses, and lately, considerable efforts have been undertaken to repurpose existing drugs as antivirals. The local anaesthetic procaine has been investigated for antiviral properties against several viruses over the past decades. Here, we present data on the inhibitory effect of the procaine prodrugs ProcCluster^® and procaine hydrochloride on SARS-CoV-2 infection in vitro. Both procaine prodrugs limit SARS-CoV-2 progeny virus titres as well as reduce interferon and cytokine responses in a proportional manner to the virus load. The addition of procaine during the early stages of the SARS-CoV-2 replication cycle in a cell culture first limits the production of subgenomic RNA transcripts, and later affects the replication of the viral genomic RNA. Interestingly, procaine additionally exerts a prominent effect on SARS-CoV-2 progeny virus release when added late during the replication cycle, when viral RNA production and protein production are already largely completed. Full article

(This article belongs to the Special Issue COVID-19 Pandemic: Therapeutic Strategies and Vaccines)

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14 pages, 2711 KiB

Open AccessArticle

A Novel Probiotic-Based Oral Vaccine against SARS-CoV-2 Omicron Variant B.1.1.529

by Eddie Chung Ting Chau, Tsz Ching Kwong, Chun Keung Pang, Lee Tung Chan, Andrew Man Lok Chan, Xiaoqiang Yao, John Siu Lun Tam, Shun Wan Chan, George Pak Heng Leung, William Chi Shing Tai and Yiu Wa Kwan

Int. J. Mol. Sci. 2023, 24(18), 13931; https://doi.org/10.3390/ijms241813931 - 11 Sep 2023

Cited by 3 | Viewed by 1417

Abstract

COVID-19 pandemic, caused by the SARS-CoV-2 virus, is still affecting the entire world via the rapid emergence of new contagious variants. Vaccination remains the most effective prevention strategy for viral infection, yet not all countries have sufficient access to vaccines due to limitations [...] Read more.

COVID-19 pandemic, caused by the SARS-CoV-2 virus, is still affecting the entire world via the rapid emergence of new contagious variants. Vaccination remains the most effective prevention strategy for viral infection, yet not all countries have sufficient access to vaccines due to limitations in manufacturing and transportation. Thus, there is an urgent need to develop an easy-to-use, safe, and low-cost vaccination approach. Genetically modified microorganisms, especially probiotics, are now commonly recognized as attractive vehicles for delivering bioactive molecules via oral and mucosal routes. In this study, Lactobacillus casei has been selected as the oral vaccine candidate based on its’ natural immunoadjuvant properties and the ability to resist acidic gastric environment, to express antigens of SARS-CoV-2 Omicron variant B.1.1.529 with B-cell and T-cell epitopes. This newly developed vaccine, OMGVac, was shown to elicit a robust IgG systemic immune response against the spike protein of Omicron variant B.1.1.529 in Golden Syrian hamsters. No adverse effects were found throughout this study, and the overall safety was evaluated in terms of physiological and histopathological examinations of different organs harvested. In addition, this study illustrated the use of the recombinant probiotic as a live delivery vector in the initiation of systemic immunity, which shed light on the future development of next-generation vaccines to combat emerging infectious diseases. Full article

(This article belongs to the Special Issue COVID-19 Pandemic: Therapeutic Strategies and Vaccines)

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11 pages, 1474 KiB

Open AccessArticle

Development of a Cell-Based SARS-CoV-2 Pseudovirus Neutralization Assay Using Imaging and Flow Cytometry Analysis

by Jerilyn R. Izac, Edward J. Kwee, Linhua Tian, Elzafir Elsheikh, Adolfas K. Gaigalas, John T. Elliott and Lili Wang

Int. J. Mol. Sci. 2023, 24(15), 12332; https://doi.org/10.3390/ijms241512332 - 02 Aug 2023

Cited by 6 | Viewed by 1145

Abstract

COVID-19 is an ongoing, global pandemic caused by the novel, highly infectious SARS-CoV-2 virus. Efforts to mitigate the effects of SARS-CoV-2, such as mass vaccination and development of monoclonal therapeutics, require precise measurements of correlative, functional neutralizing antibodies that block virus infection. The [...] Read more.

COVID-19 is an ongoing, global pandemic caused by the novel, highly infectious SARS-CoV-2 virus. Efforts to mitigate the effects of SARS-CoV-2, such as mass vaccination and development of monoclonal therapeutics, require precise measurements of correlative, functional neutralizing antibodies that block virus infection. The development of rapid, safe, and easy-to-use neutralization assays is essential for faster diagnosis and treatment. Here, we developed a vesicular stomatitis virus (VSV)-based neutralization assay with two readout methods, imaging and flow cytometry, that were capable of quantifying varying degrees of neutralization in patient serum samples. We tested two different spike-pseudoviruses and conducted a time-course assay at multiple multiplicities of infection (MOIs) to optimize the assay workflow. The results of this assay correlate with the results of previously developed serology and surrogate neutralization assays. The two pseudovirus readout methods produced similar values of 50% neutralization titer values. Harvest-free in situ readouts for live-cell imaging and high-throughput analysis results for flow cytometry can provide unique capabilities for fast evaluation of neutralization, which is critical for the mitigation of future pandemics. Full article

(This article belongs to the Special Issue COVID-19 Pandemic: Therapeutic Strategies and Vaccines)

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12 pages, 912 KiB

Open AccessCommunication

miRNAs in Neurological Manifestation in Patients Co-Infected with SARS-CoV-2 and Herpesvírus 6 (HHV-6)

by Vanessa Cristine de Souza Carneiro, Otacilio da Cruz Moreira, Wagner Luis da Costa Nunes Pimentel Coelho, Beatriz Chan Rio, Dmitry José de Santana Sarmento, Andreza Lemos Salvio, Soniza Vieira Alves-Leon, Vanessa Salete de Paula and Luciane Almeida Amado Leon

Int. J. Mol. Sci. 2023, 24(13), 11201; https://doi.org/10.3390/ijms241311201 - 07 Jul 2023

Cited by 3 | Viewed by 999

Abstract

Human herpesviruses (HHVs) can establish latency and be reactivated, also are neurotropic viruses that can trigger neurological disorders. HHV-6 is a herpesvirus that is associated with neurological disorders. Studies have reported the detection of HHV-6 in patients with COVID-19 and neurological manifestations. However, [...] Read more.

Human herpesviruses (HHVs) can establish latency and be reactivated, also are neurotropic viruses that can trigger neurological disorders. HHV-6 is a herpesvirus that is associated with neurological disorders. Studies have reported the detection of HHV-6 in patients with COVID-19 and neurological manifestations. However, specific diagnoses of the neurological disorders caused by these viruses tend to be invasive or difficult to interpret. This study aimed to establish a relationship between miRNA and neurological manifestations in patients co-infected with COVID-19 and HHV-6 and evaluate miRNAs as potential biomarkers. Serum samples from COVID-19 patients in the three cohorts were analyzed. miRNA analysis by real-time polymerase chain reaction (qPCR) revealed miRNAs associated with neuroinflammation were highly expressed in patients with neurological disorders and HHV-6 detection. When compared with the group of patients without detection of HHVs DNA and without neurological alterations, the group with detection of HHV-6 DNA and neurological alteration, displayed significant differences in the expression of mir-21, mir-146a, miR-155 and miR-let-7b (p < 0.01). Our results reinforce the involvement of miRNAs in neurological disorders and provide insights into their use as biomarkers for neurological disorders triggered by HHV-6. Furthermore, understanding the expression of miRNAs may contribute to therapeutic strategies. Full article

(This article belongs to the Special Issue COVID-19 Pandemic: Therapeutic Strategies and Vaccines)

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11 pages, 1730 KiB

Open AccessArticle

Antisera Produced Using an E. coli-Expressed SARS-CoV-2 RBD and Complemented with a Minimal Dose of Mammalian-Cell-Expressed S1 Subunit of the Spike Protein Exhibits Improved Neutralization

by Takahiro Yoshizue, Subbaian Brindha, Rawiwan Wongnak, Hitoshi Takemae, Mami Oba, Tetsuya Mizutani and Yutaka Kuroda

Int. J. Mol. Sci. 2023, 24(13), 10583; https://doi.org/10.3390/ijms241310583 - 24 Jun 2023

Cited by 1 | Viewed by 1175

Abstract

E. coli-expressed proteins could provide a rapid, cost-effective, and safe antigen for subunit vaccines, provided we can produce them in a properly folded form inducing neutralizing antibodies. Here, we use an E. coli-expressed SARS-CoV-2 receptor-binding domain (RBD) of the spike protein [...] Read more.

E. coli-expressed proteins could provide a rapid, cost-effective, and safe antigen for subunit vaccines, provided we can produce them in a properly folded form inducing neutralizing antibodies. Here, we use an E. coli-expressed SARS-CoV-2 receptor-binding domain (RBD) of the spike protein as a model to examine whether it yields neutralizing antisera with effects comparable to those generated by the S1 subunit of the spike protein (S1 or S1 subunit, thereafter) expressed in mammalian cells. We immunized 5-week-old Jcl-ICR female mice by injecting RBD (30 µg) and S1 subunit (5 µg) according to four schemes: two injections 8 weeks apart with RBD (RBD/RBD), two injections with S1 (S1/S1), one injection with RBD, and the second one with S1 (RBD/S1), and vice versa (S1/RBD). Ten weeks after the first injection (two weeks after the second injection), all combinations induced a strong immune response with IgG titer > 10⁵ (S1/RBD < S1/S1 < RBD/S1 < RBD/RBD). In addition, the neutralization effect of the antisera ranked as S1/RBD~RBD/S1 (80%) > S1/S1 (56%) > RBD/RBD (42%). These results indicate that two injections with E. coli-expressed RBD, or mammalian-cell-produced spike S1 subunit alone, can provide some protection against SARS-CoV-2, but a mixed injection scheme yields significantly higher protection. Full article

(This article belongs to the Special Issue COVID-19 Pandemic: Therapeutic Strategies and Vaccines)

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13 pages, 2570 KiB

Open AccessCommunication

Antigenic Cartography Indicates That the Omicron BA.1 and BA.4/BA.5 Variants Remain Antigenically Distant to Ancestral SARS-CoV-2 after Sputnik V Vaccination Followed by Homologous (Sputnik V) or Heterologous (Comirnaty) Revaccination

by Ekaterina A. Astakhova, Alexey A. Morozov, Maria G. Byazrova, Maria M. Sukhova, Artem A. Mikhailov, Aygul R. Minnegalieva, Andrey A. Gorchakov and Alexander V. Filatov

Int. J. Mol. Sci. 2023, 24(13), 10493; https://doi.org/10.3390/ijms241310493 - 22 Jun 2023

Cited by 1 | Viewed by 1171

Abstract

The rapid emergence of evasive SARS-CoV-2 variants is an ongoing challenge for COVID-19 vaccinology. Traditional virus neutralization tests provide detailed datasets of neutralization titers against the viral variants. Such datasets are difficult to interpret and do not immediately inform of the sufficiency of [...] Read more.

The rapid emergence of evasive SARS-CoV-2 variants is an ongoing challenge for COVID-19 vaccinology. Traditional virus neutralization tests provide detailed datasets of neutralization titers against the viral variants. Such datasets are difficult to interpret and do not immediately inform of the sufficiency of the breadth of the antibody response. Some of these issues could be tackled using the antigenic cartography approach. In this study, we created antigenic maps using neutralization titers of sera from donors who received the Sputnik V booster vaccine after primary Sputnik V vaccination and compared them with the antigenic maps based on serum neutralization titers of Comirnaty-boosted donors. A traditional analysis of neutralization titers against the WT (wild-type), Alpha, Beta, Delta, Omicron BA.1, and BA.4/BA.5 variants showed a significant booster humoral response after both homologous (Sputnik V) and heterologous (Comirnaty) revaccinations against all of the studied viral variants. However, despite this, a more in-depth analysis using antigenic cartography revealed that Omicron variants remain antigenically distant from the WT, which is indicative of the formation of insufficient levels of cross-neutralizing antibodies. The implications of these findings may be significant when developing a new vaccine regimen. Full article

(This article belongs to the Special Issue COVID-19 Pandemic: Therapeutic Strategies and Vaccines)

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15 pages, 2367 KiB

Open AccessArticle

Inflammatory Response in COVID-19 Depending on the Severity of the Disease and the Vaccination Status

by Felicia Trofin, Eduard Vasile Nastase, Manuel Florin Roșu, Aida Corina Bădescu, Elena Roxana Buzilă, Egidia Gabriela Miftode, Doina Carmen Manciuc and Olivia Simona Dorneanu

Int. J. Mol. Sci. 2023, 24(10), 8550; https://doi.org/10.3390/ijms24108550 - 10 May 2023

Cited by 7 | Viewed by 1576

Abstract

The aim of this study was to analyze the serum concentration of interleukin-6 (IL-6), C-reactive protein (CRP), D-dimer, lactate dehydrogenase (LDH), ferritin, and procalcitonin in COVID-19 patients with different forms of the disease. We performed a prospective cohort study on 137 COVID-19 consecutive [...] Read more.

The aim of this study was to analyze the serum concentration of interleukin-6 (IL-6), C-reactive protein (CRP), D-dimer, lactate dehydrogenase (LDH), ferritin, and procalcitonin in COVID-19 patients with different forms of the disease. We performed a prospective cohort study on 137 COVID-19 consecutive patients, divided into four groups according to the severity of the disease as follows: 30 patients in the mild form group, 49 in the moderate form group, 28 in the severe form group, and 30 in the critical form group. The tested parameters were correlated with COVID-19 severity. Significant differences were registered between the form of COVID-19 depending on the vaccination status, between LDH concentrations depending on the virus variant, and in IL-6, CRP, and ferritin concentrations and vaccination status depending on the gender. ROC analysis revealed that D-dimer best predicted COVID-19 severe forms and LDH predicted the virus variant. Our findings confirmed the interdependence relationships observed between inflammation markers in relation to the clinical severity of COVID-19, with all the tested biomarkers increasing in severe and critical COVID-19. IL-6, CRP, ferritin, LDH, and D-dimer were increased in all COVID-19 forms. These inflammatory markers were lower in Omicron-infected patients. The unvaccinated patients developed more severe forms compared to the vaccinated ones, and a higher proportion of them needed hospitalization. D-dimer could predict a severe form of COVID-19, while LDH could predict the virus variant. Full article

(This article belongs to the Special Issue COVID-19 Pandemic: Therapeutic Strategies and Vaccines)

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19 pages, 2052 KiB

Open AccessArticle

Dynamic Evolution of Humoral and T-Cell Specific Immune Response to COVID-19 mRNA Vaccine in Patients with Multiple Sclerosis Followed until the Booster Dose

by Serena Ruggieri, Alessandra Aiello, Carla Tortorella, Assunta Navarra, Valentina Vanini, Silvia Meschi, Daniele Lapa, Shalom Haggiag, Luca Prosperini, Gilda Cuzzi, Andrea Salmi, Maria Esmeralda Quartuccio, Anna Maria Gerarda Altera, Anna Rosa Garbuglia, Tommaso Ascoli Bartoli, Simonetta Galgani, Stefania Notari, Chiara Agrati, Vincenzo Puro, Emanuele Nicastri, Claudio Gasperini and Delia Goletti Show full author list Hide full author list

Int. J. Mol. Sci. 2023, 24(10), 8525; https://doi.org/10.3390/ijms24108525 - 10 May 2023

Cited by 3 | Viewed by 1781

Abstract

This study characterizes antibody and T-cell immune responses over time until the booster dose of COronaVIrus Disease 2019 (COVID-19) vaccines in patients with multiple sclerosis (PwMS) undergoing different disease-modifying treatments (DMTs). We prospectively enrolled 134 PwMS and 99 health care workers (HCWs) having [...] Read more.

This study characterizes antibody and T-cell immune responses over time until the booster dose of COronaVIrus Disease 2019 (COVID-19) vaccines in patients with multiple sclerosis (PwMS) undergoing different disease-modifying treatments (DMTs). We prospectively enrolled 134 PwMS and 99 health care workers (HCWs) having completed the two-dose schedule of a COVID-19 mRNA vaccine within the last 2–4 weeks (T0) and followed them 24 weeks after the first dose (T1) and 4–6 weeks after the booster (T2). PwMS presented a significant reduction in the seroconversion rate and anti-receptor-binding domain (RBD)-Immunoglobulin (IgG) titers from T0 to T1 (p < 0.0001) and a significant increase from T1 to T2 (p < 0.0001). The booster dose in PwMS showed a good improvement in the serologic response, even greater than HCWs, as it promoted a significant five-fold increase of anti-RBD-IgG titers compared with T0 (p < 0.0001). Similarly, the T-cell response showed a significant 1.5- and 3.8-fold increase in PwMS at T2 compared with T0 (p = 0.013) and T1 (p < 0.0001), respectively, without significant modulation in the number of responders. Regardless of the time elapsed since vaccination, most ocrelizumab- (77.3%) and fingolimod-treated patients (93.3%) showed only a T-cell-specific or humoral-specific response, respectively. The booster dose reinforces humoral- and cell-mediated-specific immune responses and highlights specific DMT-induced immune frailties, suggesting the need for specifically tailored strategies for immune-compromised patients to provide primary prophylaxis, early SARS-CoV-2 detection and the timely management of COVID-19 antiviral treatments. Full article

(This article belongs to the Special Issue COVID-19 Pandemic: Therapeutic Strategies and Vaccines)

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18 pages, 4637 KiB

Open AccessArticle

Multiplex Lithographic SERS Aptasensor for Detection of Several Respiratory Viruses in One Pot

by Vladimir Kukushkin, Oganes Ambartsumyan, Alexei Subekin, Anna Astrakhantseva, Vladimir Gushchin, Alexandra Nikonova, Anastasia Dorofeeva, Vitaly Zverev, Anna Keshek, Nadezda Meshcheryakova, Olga Zaborova, Alexandra Gambaryan and Elena Zavyalova

Int. J. Mol. Sci. 2023, 24(9), 8081; https://doi.org/10.3390/ijms24098081 - 29 Apr 2023

Cited by 4 | Viewed by 1823

Abstract

Rapid and reliable techniques for virus identification are required in light of recurring epidemics and pandemics throughout the world. Several techniques have been distributed for testing the flow of patients. Polymerase chain reaction with reverse transcription is a reliable and sensitive, though not [...] Read more.

Rapid and reliable techniques for virus identification are required in light of recurring epidemics and pandemics throughout the world. Several techniques have been distributed for testing the flow of patients. Polymerase chain reaction with reverse transcription is a reliable and sensitive, though not rapid, tool. The antibody-based strip is a rapid, though not reliable, and sensitive tool. A set of alternative tools is being developed to meet all the needs of the customer. Surface-enhanced Raman spectroscopy (SERS) provides the possibility of single molecule detection taking several minutes. Here, a multiplex lithographic SERS aptasensor was developed aiming at the detection of several respiratory viruses in one pot within 17 min. The four labeled aptamers were anchored onto the metal surface of four SERS zones; the caught viruses affect the SERS signals of the labels, providing changes in the analytical signals. The sensor was able to decode mixes of SARS-CoV-2 (severe acute respiratory syndrome coronavirus two), influenza A virus, respiratory syncytial virus, and adenovirus within a single experiment through a one-stage recognition process. Full article

(This article belongs to the Special Issue COVID-19 Pandemic: Therapeutic Strategies and Vaccines)

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Graphical abstract

10 pages, 811 KiB

Open AccessArticle

Persistence of Immune Response Elicited by Three Doses of mRNA Vaccine against SARS-CoV-2 in a Cohort of Patients with Solid Tumors: A One-Year Follow-Up

by Angioletta Lasagna, Irene Cassaniti, Francesca Arena, Federica Bergami, Elena Percivalle, Giuditta Comolli, Antonella Sarasini, Alessandro Ferrari, Daniela Cicognini, Roberta Schiavo, Giuliana Lo Cascio, Paolo Pedrazzoli and Fausto Baldanti

Int. J. Mol. Sci. 2023, 24(7), 6731; https://doi.org/10.3390/ijms24076731 - 04 Apr 2023

Cited by 3 | Viewed by 1590

Abstract

The role and durability of the immunogenicity of the BNT162b2 mRNA vaccine against severe acute respiratory virus 2 (SARS-CoV-2), in cancer patients one year after receiving the third dose have to be elucidated. We have prospectively evaluated the long-term immunogenicity of the third [...] Read more.

The role and durability of the immunogenicity of the BNT162b2 mRNA vaccine against severe acute respiratory virus 2 (SARS-CoV-2), in cancer patients one year after receiving the third dose have to be elucidated. We have prospectively evaluated the long-term immunogenicity of the third dose of the SARS-CoV-2 BNT162b2 mRNA vaccine in 55 patients undergoing active treatment. Neutralizing antibody (NT Ab) titers against Omicron variants and total anti-trimeric S IgG levels were measured one year after the third dose. Heparinized whole-blood samples were used for the assessment of the SARS-CoV-2 interferon-γ release assay (IGRA). Thirty-seven patients (67.3%) showed positive total anti-trimeric S IgG one year after the third dose. Looking at the T-cell response against the spike protein, the frequency of responder patients did not decrease significantly between six and twelve months after the third dose. Finally, less than 20% of cancer patients showed an undetectable NT Ab titer against BA.1 and BA.5 variants of concern (VOCs). Underlying therapies seem to not affect the magnitude or frequency of the immune response. Our work underlines the persistence of humoral and cellular immune responses against BNT162b2 in a cohort of cancer patients one year after receiving the third dose, regardless of the type of underlying therapy. Full article

(This article belongs to the Special Issue COVID-19 Pandemic: Therapeutic Strategies and Vaccines)

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11 pages, 2382 KiB

Open AccessCommunication

Immunogenicity and Safety of the BNT162b2 COVID-19 Vaccine in Patients with Cystic Fibrosis with or without Lung Transplantation

by Francesca Lucca, Valentino Bezzerri, Elisa Danese, Debora Olioso, Denise Peserico, Christian Boni, Giulia Cucchetto, Martina Montagnana, Gloria Tridello, Ilaria Meneghelli, Mirco Ros, Giuseppe Lippi and Marco Cipolli

Int. J. Mol. Sci. 2023, 24(2), 908; https://doi.org/10.3390/ijms24020908 - 04 Jan 2023

Cited by 5 | Viewed by 1722

Abstract

Cystic fibrosis (CF) is characterized by a progressive decline in lung function, which may be further impaired by viral infections. CF is therefore considered a comorbidity of coronavirus disease 2019 (COVID-19), and SARS-CoV-2 vaccine prioritization has been proposed for patients with (pw)CF. Poor [...] Read more.

Cystic fibrosis (CF) is characterized by a progressive decline in lung function, which may be further impaired by viral infections. CF is therefore considered a comorbidity of coronavirus disease 2019 (COVID-19), and SARS-CoV-2 vaccine prioritization has been proposed for patients with (pw)CF. Poor outcomes have been reported in lung transplant recipients (LTR) after SARS-CoV-2 infections. LTR have also displayed poor immunization against SARS-CoV-2 after mRNA-based BNT162b2 vaccination, especially in those undergoing immunosuppressive treatment, mostly those receiving mycophenolate mofetil (MMF) therapy. We aimed to determine here the immunogenicity and safety of the BNT162b2 vaccine in our cohort of 260 pwCF, including 18 LTR. Serum levels of neutralizing anti-SARS-CoV-2 IgG and IgA antibodies were quantified after the administration of two doses. PwCF displayed a vaccine-induced IgG and IgA antiviral response comparable with that seen in the general population. We also observed that the immunogenicity of the BNT162b2 vaccine was significantly impaired in the LTR subcohort, especially in patients undergoing MMF therapy. The BNT162b2 vaccine also caused minor adverse events as in the general population, mostly after administration of the second dose. Overall, our results justify the use of the BNT162b2 vaccine in pwCF and highlight the importance of a longitudinal assessment of the anti-SARS-CoV-2 IgG and IgA neutralizing antibody response to COVID-19 vaccination. Full article

(This article belongs to the Special Issue COVID-19 Pandemic: Therapeutic Strategies and Vaccines)

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Review

Jump to: Editorial, Research, Other

24 pages, 422 KiB

Open AccessReview

Mesenchymal Stem Cells in the Treatment of COVID-19

by Bei-Cyuan Guo, Kang-Hsi Wu, Chun-Yu Chen, Wen-Ya Lin, Yu-Jun Chang, Tai-An Lee, Mao-Jen Lin and Han-Ping Wu

Int. J. Mol. Sci. 2023, 24(19), 14800; https://doi.org/10.3390/ijms241914800 - 30 Sep 2023

Cited by 2 | Viewed by 1328

Abstract

Since the emergence of the coronavirus disease 2019 (COVID-19) pandemic, many lives have been tragically lost to severe infections. The COVID-19 impact extends beyond the respiratory system, affecting various organs and functions. In severe cases, it can progress to acute respiratory distress syndrome [...] Read more.

Since the emergence of the coronavirus disease 2019 (COVID-19) pandemic, many lives have been tragically lost to severe infections. The COVID-19 impact extends beyond the respiratory system, affecting various organs and functions. In severe cases, it can progress to acute respiratory distress syndrome (ARDS) and multi-organ failure, often fueled by an excessive immune response known as a cytokine storm. Mesenchymal stem cells (MSCs) have considerable potential because they can mitigate inflammation, modulate immune responses, and promote tissue regeneration. Accumulating evidence underscores the efficacy and safety of MSCs in treating severe COVID-19 and ARDS. Nonetheless, critical aspects, such as optimal routes of MSC administration, appropriate dosage, treatment intervals, management of extrapulmonary complications, and potential pediatric applications, warrant further exploration. These research avenues hold promise for enriching our understanding and refining the application of MSCs in confronting the multifaceted challenges posed by COVID-19. Full article

(This article belongs to the Special Issue COVID-19 Pandemic: Therapeutic Strategies and Vaccines)

12 pages, 572 KiB

Open AccessReview

Arrhythmias after COVID-19 Vaccination: Have We Left All Stones Unturned?

by Nino Cocco, Gregor Leibundgut, Francesco Pelliccia, Valeria Cammalleri, Annunziata Nusca, Fabio Mangiacapra, Giulio Cocco, Valerio Fanale, Gian Paolo Ussia and Francesco Grigioni

Int. J. Mol. Sci. 2023, 24(12), 10405; https://doi.org/10.3390/ijms241210405 - 20 Jun 2023

Cited by 5 | Viewed by 13520

Abstract

SARS-CoV-2 vaccination offered the opportunity to emerge from the pandemic and, thereby, worldwide health, social, and economic disasters. However, in addition to efficacy, safety is an important issue for any vaccine. The mRNA-based vaccine platform is considered to be safe, but side effects [...] Read more.

SARS-CoV-2 vaccination offered the opportunity to emerge from the pandemic and, thereby, worldwide health, social, and economic disasters. However, in addition to efficacy, safety is an important issue for any vaccine. The mRNA-based vaccine platform is considered to be safe, but side effects are being reported more frequently as more and more people around the world become treated. Myopericarditis is the major, but not the only cardiovascular complication of this vaccine; hence it is important not to underestimate other side effects. We report a case series of patients affected by cardiac arrhythmias post-mRNA vaccine from our clinical practice and the literature. Reviewing the official vigilance database, we found that heart rhythm disorders after COVID vaccination are not uncommon and deserve more clinical and scientific attention. Since the COVID vaccine is the only vaccination related to this side effect, questions arose about whether these vaccines could affect heart conduction. Although the risk–benefit ratio is clearly in favor of vaccination, heart rhythm disorders are not a negligible issue, and there are red flags in the literature about the risk of post-vaccination malignant arrhythmias in some predisposed patients. In light of these findings, we reviewed the potential molecular pathways for the COVID vaccine to impact cardiac electrophysiology and cause heart rhythm disorders. Full article

(This article belongs to the Special Issue COVID-19 Pandemic: Therapeutic Strategies and Vaccines)

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17 pages, 497 KiB

Open AccessReview

Detection of SARS-CoV-2–Specific Antibodies in Human Breast Milk and Their Neutralizing Capacity after COVID-19 Vaccination: A Systematic Review

by Vicky Nicolaidou, Rafaela Georgiou, Maria Christofidou, Kyriacos Felekkis, Myrtani Pieri and Christos Papaneophytou

Int. J. Mol. Sci. 2023, 24(3), 2957; https://doi.org/10.3390/ijms24032957 - 03 Feb 2023

Cited by 5 | Viewed by 2800

Abstract

SARS-CoV-2 is the virus that causes the infectious disease known as Corona Virus Disease 2019 (COVID-19). The severe impact of the virus on humans is undeniable, which is why effective vaccines were highly anticipated. As of 12 January 2022, nine vaccines have obtained [...] Read more.

SARS-CoV-2 is the virus that causes the infectious disease known as Corona Virus Disease 2019 (COVID-19). The severe impact of the virus on humans is undeniable, which is why effective vaccines were highly anticipated. As of 12 January 2022, nine vaccines have obtained Emergency Use Listing by the World Health Organization (WHO), and four of these are approved or authorized by the Centers for Disease Control and Prevention (CDC) in the United States. The initial clinical trials studying COVID-19 vaccine efficacy excluded pregnant and lactating individuals, meaning that data on the effects of the vaccine on breast milk were lacking. Until today, none of the authorized vaccines have been approved for use in individuals under six months. During the first months of life, babies do not produce their own antibodies; therefore, antibodies contained in their mothers’ breastmilk are a critical protective mechanism. Several studies have shown the presence of SARS-CoV-2 antibodies in the breast milk of women who have been vaccinated or had been naturally infected. However, whether these are protective is still unclear. Additionally, research on the BNT162b2 mRNA vaccine developed by Pfizer-BioNTech and the mRNA-1273 vaccine developed by Moderna suggests that these vaccines do not release significant amounts, if any, of mRNA into breast milk. Hence, there is no evidence that vaccination of the mother poses any risk to the breastfed infant, while the antibodies present in breast milk may offer protection against the virus. The primary objective of this systematic review is to summarize the current understanding of the presence of immunoglobulins in human milk that are elicited by SARS-CoV-2 vaccines and to evaluate their ability to neutralize the virus. Additionally, we aim to quantify the side effects experienced by lactating mothers who have been vaccinated, as well as the potential for adverse effects in their infants. This study is critical because it can help inform decision-making by examining the current understanding of antibody secretion in breastmilk. This is particularly important because, although the virus tends to be less severe in younger individuals, infants who contract the disease are at a higher risk of requiring hospitalization compared to older children. Full article

(This article belongs to the Special Issue COVID-19 Pandemic: Therapeutic Strategies and Vaccines)

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Persistence of Anti-S1 IgG against SARS-CoV-2 Eight Months after the Booster Dose of Vaccine in Naive and Previously Infected Healthcare Workers

by Sonia Algarate, Laura Serrano, Jessica Bueno, Beatriz Herrero-Cortina, Elena Alvarado, María T. González-Barriga, María Ducons, Jesica Montero-Marco, Sara Arnal, Beatriz Acha, María Riesgo, Ana Taboada, Pilar Sanz-Burillo, Cristina Yuste, Rafael Benito and on behalf of the RIPOVAC Study Group

Int. J. Mol. Sci. 2023, 24(13), 10713; https://doi.org/10.3390/ijms241310713 - 27 Jun 2023

Cited by 2 | Viewed by 936

Abstract

Our aim was to evaluate the immune response of healthcare workers included in the RIPOVAC study, after receiving a booster dose (third dose), in terms of intensity and persistence of induced antibodies. In the second phase of the RIPOVAC study, between December 2021 [...] Read more.

Our aim was to evaluate the immune response of healthcare workers included in the RIPOVAC study, after receiving a booster dose (third dose), in terms of intensity and persistence of induced antibodies. In the second phase of the RIPOVAC study, between December 2021 and January 2022, eight months after the second dose, 389 voluntary, immunocompetent, non-pregnant healthcare workers received a booster dose of SARS-CoV-2 vaccine, and a serum sample was obtained. Two groups of patients were established: with and without previous SARS-CoV-2 infection. In order to quantify anti-S1 IgG (AU/mL) we used CMIA (Abbott). All of the health workers were anti-S IgG positive 8 months after receiving the booster dose of the vaccine, with a mean of 17,040 AU/mL. In 53 patients without previous infection, antibody levels increased by a mean of 10,762 AU/mL. This figure is seven times higher than the one produced after the second dose (1506 AU/mL). The booster dose produces a robust elevation of the antibody level, which persists at 8 months, with levels significantly higher than those reached after the second dose, which allow one to predict a persistence of more than one year. The study demonstrates the efficacy of the booster dose of anti-SARS-CoV-2 vaccines. Full article

(This article belongs to the Special Issue COVID-19 Pandemic: Therapeutic Strategies and Vaccines)

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