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22 pages, 7213 KiB

Open AccessArticle

SARS-CoV-2 mRNA Vaccine-Induced Cellular and Humoral Immunity in Hemodialysis Patients

by Ewa Kwiatkowska, Krzysztof Safranow, Iwona Wojciechowska-Koszko, Paulina Roszkowska, Violetta Dziedziejko, Marek Myślak, Jacek Różański, Kazimierz Ciechanowski, Tomasz Stompór, Jarosław Przybyciński, Piotr Wiśniewski, Norbert Kwella, Sebastian Kwiatkowski, Tomasz Prystacki, Wojciech Marcinkowski and Leszek Domański

Biomedicines 2022, 10(3), 636; https://doi.org/10.3390/biomedicines10030636 - 09 Mar 2022

Cited by 7 | Viewed by 2392

Abstract

Background/Aims: Chronic kidney disease CKD patients on intermittent hemodialysis IHD are exposed to SARS-CoV-2 infection and carry a risk of developing severe symptoms. The aim of this study was to evaluate the humoral and cellular immunity induced by two doses of mRNA vaccines, [...] Read more.

Background/Aims: Chronic kidney disease CKD patients on intermittent hemodialysis IHD are exposed to SARS-CoV-2 infection and carry a risk of developing severe symptoms. The aim of this study was to evaluate the humoral and cellular immunity induced by two doses of mRNA vaccines, the Pfizer-BioNTech (Comirnaty) COVID-19 Vaccine and the Moderna (mRNA-1273) COVID-19 vaccine. Patients and methods: The study included 281 patients from five dialysis centers in northern Poland. Within 2 weeks prior to the first dose of the vaccine, a blood sample was collected for an evaluation of SARS-CoV-2 antibodies. Thirty to forty-five days after the second dose of the vaccine, a blood sample was taken to evaluate humoral and cellular response. Results: Patients with stage 5 CKD on IHD were characterized by a considerable SARS-CoV-2 vaccine-induced seroconversion rate. The strongest factors influencing the antibodies AB level after vaccination were a pre-vaccination history of SARS-CoV-2 infection, age, the neutrophil-to-lymphocyte ratio NLR, neutrophil absolute count, and the hemoglobin level. Cellular immunity was higher in patients with a pre-vaccination history of SARS-CoV-2 infection. Cellular immunity depended on the albumin level. Positive cellular response to vaccination was a positive factor reducing all-cause mortality, except for COVID-19 mortality (no such deaths were reported during our follow-up). Cellular immunity and humoral immunity were positively mutually dependent. High levels of albumin and hemoglobin, low neutrophil count, and a reduced NLR, translated into better response to vaccination. Conclusions: Patients with stage 5 CKD on IHD were characterized by a considerable SARS-CoV-2 vaccine-induced seroconversion rate and a good rate of cellular immunity. The factors that change with exacerbating inflammation and malnutrition (albumin, hemoglobin, neutrophil count, the NLR) affected the efficacy of the vaccination. Full article

(This article belongs to the Special Issue Immunology in COVID-19 Disease: From Pathophysiology to Novel Therapeutic Approaches)

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12 pages, 1593 KiB

Open AccessCommunication

Comparison of Neutralizing Antibody Responses at 6 Months Post Vaccination with BNT162b2 and AZD1222

by Evangelos Terpos, Vangelis Karalis, Ioannis Ntanasis-Stathopoulos, Zoi Evangelakou, Maria Gavriatopoulou, Maria S. Manola, Panagiotis Malandrakis, Despoina D. Gianniou, Efstathios Kastritis, Ioannis P. Trougakos and Meletios A. Dimopoulos

Biomedicines 2022, 10(2), 338; https://doi.org/10.3390/biomedicines10020338 - 01 Feb 2022

Cited by 19 | Viewed by 3921

Abstract

Along with their level of protection against COVID-19, SARS-CoV-2-specific antibodies decline over time following vaccination with BNT162b2. However, relevant data on AZD1222 are scarce. In this context, the aim of this study was to compare SARS-CoV-2 neutralizing antibody (NAb) levels at one, three [...] Read more.

Along with their level of protection against COVID-19, SARS-CoV-2-specific antibodies decline over time following vaccination with BNT162b2. However, relevant data on AZD1222 are scarce. In this context, the aim of this study was to compare SARS-CoV-2 neutralizing antibody (NAb) levels at one, three and six months after second vaccination with the BNT162b2 mRNA vaccine and the ChAdOx1 (AZD1222) viral vector vaccine (NCT04743388). The measurements were performed with the GenScript’s cPassTM SARS-CoV-2 NAbs Detection Kit (GenScript, Inc.; Piscataway, NJ, USA). Overall, data from 282 individuals were included (BNT162b2 n = 83, AZD1222 n = 199). Both vaccines induced strong NAbs responses at 1 month following vaccination. Interestingly, NAb activity seemed superior with BNT162b2 compared with AZD1222. A gradual decline in NAbs titers was evident at 3 and 6 months post vaccination with both vaccines. However, the superiority of NAb response with BNT162b2 over AZD1222 remained consistent at all time points examined. Furthermore, the elimination rate of the NAb titer was higher throughout during the study period for those vaccinated with AZD1222 compared with BNT162b2. Age, gender, body mass index or comorbidities did not have a significant impact on NAbs levels over time. Our results may inform public health policies regarding the timing of booster COVID-19 vaccine shots. Full article

(This article belongs to the Special Issue Immunology in COVID-19 Disease: From Pathophysiology to Novel Therapeutic Approaches)

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22 pages, 3081 KiB

Open AccessEditor’s ChoiceArticle

An Early Th1 Response Is a Key Factor for a Favorable COVID-19 Evolution

by Francisco Javier Gil-Etayo, Sara Garcinuño, Alberto Utrero-Rico, Oscar Cabrera-Marante, Daniel Arroyo-Sanchez, Esther Mancebo, Daniel Enrique Pleguezuelo, Edgard Rodríguez-Frías, Luis M. Allende, Pablo Morales-Pérez, María José Castro-Panete, Antonio Lalueza, Carlos Lumbreras, Estela Paz-Artal and Antonio Serrano

Biomedicines 2022, 10(2), 296; https://doi.org/10.3390/biomedicines10020296 - 27 Jan 2022

Cited by 19 | Viewed by 3686

Abstract

The Th1/Th2 balance plays a crucial role in the progression of different pathologies and is a determining factor in the evolution of infectious diseases. This work has aimed to evaluate the early, or on diagnosis, T-cell compartment response, T-helper subsets and anti-SARS-CoV-2 antibody [...] Read more.

The Th1/Th2 balance plays a crucial role in the progression of different pathologies and is a determining factor in the evolution of infectious diseases. This work has aimed to evaluate the early, or on diagnosis, T-cell compartment response, T-helper subsets and anti-SARS-CoV-2 antibody specificity in COVID-19 patients and to classify them according to evolution based on infection severity. A unicenter, randomized group of 146 COVID-19 patients was divided into four groups in accordance with the most critical events during the course of disease. The immunophenotype and T-helper subsets were analyzed by flow cytometry. Asymptomatic SARS-CoV-2 infected individuals showed a potent and robust Th1 immunity, with a lower Th17 and less activated T-cells at the time of sample acquisition compared not only with symptomatic patients, but also with healthy controls. Conversely, severe COVID-19 patients presented with Th17-skewed immunity, fewer Th1 responses and more activated T-cells. The multivariate analysis of the immunological and inflammatory parameters, together with the comorbidities, showed that the Th1 response was an independent protective factor for the prevention of hospitalization (OR 0.17, 95% CI 0.03–0.81), with an AUC of 0.844. Likewise, the Th1 response was found to be an independent protective factor for severe forms of the disease (OR 0.09, 95% CI: 0.01–0.63, p = 0.015, AUC: 0.873). In conclusion, a predominant Th1 immune response in the acute phase of the SARS-CoV-2 infection could be used as a tool to identify patients who might have a good disease evolution. Full article

(This article belongs to the Special Issue Immunology in COVID-19 Disease: From Pathophysiology to Novel Therapeutic Approaches)

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17 pages, 2973 KiB

Open AccessArticle

COVID-19 Specific Immune Markers Revealed by Single Cell Phenotypic Profiling

by Francesca Sansico, Mattia Miroballo, Daniele Salvatore Bianco, Francesco Tamiro, Mattia Colucci, Elisabetta De Santis, Giovanni Rossi, Jessica Rosati, Lazzaro Di Mauro, Giuseppe Miscio, Tommaso Mazza, Angelo Luigi Vescovi, Gianluigi Mazzoccoli, Vincenzo Giambra and on behalf of CSS-COVID 19 Group

Biomedicines 2021, 9(12), 1794; https://doi.org/10.3390/biomedicines9121794 - 29 Nov 2021

Cited by 5 | Viewed by 3010

Abstract

COVID-19 is a viral infection, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and characterized by a complex inflammatory process and clinical immunophenotypes. Nowadays, several alterations of immune response within the respiratory tracts as well as at the level of the [...] Read more.

COVID-19 is a viral infection, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and characterized by a complex inflammatory process and clinical immunophenotypes. Nowadays, several alterations of immune response within the respiratory tracts as well as at the level of the peripheral blood have been well documented. Nonetheless, their effects on COVID-19-related cell heterogeneity and disease progression are less defined. Here, we performed a single-cell RNA sequencing of about 400 transcripts relevant to immune cell function including surface markers, in mononuclear cells (PBMCs) from the peripheral blood of 50 subjects, infected with SARS-CoV-2 at the diagnosis and 27 healthy blood donors as control. We found that patients with COVID-19 exhibited an increase in COVID-specific surface markers in different subsets of immune cell composition. Interestingly, the expression of cell receptors, such as IFNGR1 and CXCR4, was reduced in response to the viral infection and associated with the inhibition of the related signaling pathways and immune functions. These results highlight novel immunoreceptors, selectively expressed in COVID-19 patients, which affect the immune functionality and are correlated with clinical outcomes. Full article

(This article belongs to the Special Issue Immunology in COVID-19 Disease: From Pathophysiology to Novel Therapeutic Approaches)

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18 pages, 3973 KiB

Open AccessEditor’s ChoiceArticle

Relationship between Vitamin D Status and Antibody Response to COVID-19 mRNA Vaccination in Healthy Adults

by Thilo Samson Chillon, Kamil Demircan, Raban Arved Heller, Ines Maria Hirschbil-Bremer, Joachim Diegmann, Manuel Bachmann, Arash Moghaddam and Lutz Schomburg

Biomedicines 2021, 9(11), 1714; https://doi.org/10.3390/biomedicines9111714 - 18 Nov 2021

Cited by 33 | Viewed by 6255

Abstract

The immune response to vaccination with SARS-CoV-2 vaccines varies greatly from person to person. In addition to age, there is evidence that certain micronutrients influence the immune system, particularly vitamin D. Here, we analysed SARS-CoV-2 IgG and neutralisation potency along with 25-hydroxy-cholecalciferol [25(OH)D] [...] Read more.

The immune response to vaccination with SARS-CoV-2 vaccines varies greatly from person to person. In addition to age, there is evidence that certain micronutrients influence the immune system, particularly vitamin D. Here, we analysed SARS-CoV-2 IgG and neutralisation potency along with 25-hydroxy-cholecalciferol [25(OH)D] concentrations in a cohort of healthy German adults from the time of vaccination over 24 weeks. Contrary to our expectations, no significant differences were found in the dynamic increase or decrease of SARS-CoV-2 IgG as a function of the 25(OH)D status. Furthermore, the response to the first or second vaccination, the maximum SARS-CoV-2 IgG concentrations achieved, and the decline in SARS-CoV-2 IgG concentrations over time were not related to 25(OH)D status. We conclude that the vaccination response, measured as SARS-CoV-2 IgG concentration, does not depend on 25(OH)D status in healthy adults with moderate vitamin D status. Full article

(This article belongs to the Special Issue Immunology in COVID-19 Disease: From Pathophysiology to Novel Therapeutic Approaches)

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11 pages, 1476 KiB

Open AccessFeature PaperArticle

A Short Corticosteroid Course Reduces Symptoms and Immunological Alterations Underlying Long-COVID

by Alberto Utrero-Rico, María Ruiz-Ruigómez, Rocío Laguna-Goya, Estíbaliz Arrieta-Ortubay, Marta Chivite-Lacaba, Cecilia González-Cuadrado, Antonio Lalueza, Patricia Almendro-Vazquez, Antonio Serrano, José María Aguado, Carlos Lumbreras and Estela Paz-Artal

Biomedicines 2021, 9(11), 1540; https://doi.org/10.3390/biomedicines9111540 - 26 Oct 2021

Cited by 22 | Viewed by 6086

Abstract

Despite the growing number of patients with persistent symptoms after acute SARS-CoV-2 infection, the pathophysiology underlying long-COVID is not yet well characterized, and there is no established therapy. We performed a deep immune profiling in nine patients with persistent symptoms (PSP), before and [...] Read more.

Despite the growing number of patients with persistent symptoms after acute SARS-CoV-2 infection, the pathophysiology underlying long-COVID is not yet well characterized, and there is no established therapy. We performed a deep immune profiling in nine patients with persistent symptoms (PSP), before and after a 4-day prednisone course, and five post-COVID-19 patients without persistent symptoms (NSP). PSP showed a perturbed distribution of circulating mononuclear cell populations. Symptoms in PSP were accompanied by a pro-inflammatory phenotype characterized by increased conventional dendritic cells and augmented expression of antigen presentation, co-stimulation, migration, and activation markers in monocytes. The adaptive immunity compartment in PSP showed a Th1-predominance, decreased naïve and regulatory T cells, and augmentation of the PD-1 exhaustion marker. These immune alterations reverted after the corticosteroid treatment and were maintained during the 4-month follow-up, and their normalization correlated with clinical amelioration. The current work highlights an immunopathogenic basis together with a possible role for steroids in the treatment for long-COVID. Full article

(This article belongs to the Special Issue Immunology in COVID-19 Disease: From Pathophysiology to Novel Therapeutic Approaches)

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8 pages, 780 KiB

Open AccessCommunication

The Slower Antibody Response in Myelofibrosis Patients after Two Doses of mRNA SARS-CoV-2 Vaccine Calls for a Third Dose

by Fabio Fiorino, Anna Sicuranza, Annalisa Ciabattini, Adele Santoni, Gabiria Pastore, Martina Simoncelli, Jacopo Polvere, Sara Galimberti, Stefano Auddino, Claudia Baratè, Francesca Montagnani, Vincenzo Sammartano, Monica Bocchia and Donata Medaglini

Biomedicines 2021, 9(10), 1480; https://doi.org/10.3390/biomedicines9101480 - 15 Oct 2021

Cited by 18 | Viewed by 2080

Abstract

Immunization with mRNA SARS-CoV-2 vaccines has been highly recommended and prioritized in fragile subjects, including patients with myelofibrosis (MF). Available data on the vaccine immune response developed by MF patients and the impact of ruxolitinib treatment are still too fragmented to support an [...] Read more.

Immunization with mRNA SARS-CoV-2 vaccines has been highly recommended and prioritized in fragile subjects, including patients with myelofibrosis (MF). Available data on the vaccine immune response developed by MF patients and the impact of ruxolitinib treatment are still too fragmented to support an informed decision on a third dose for this category of subjects. Here, we show that 76% of MF patients develop spike-specific IgG after the second mRNA SARS-CoV-2 vaccine dose, but the response has a slower kinetics compared to healthy subjects, suggesting a reduced capability of their immune system to promptly react to vaccination. A reduced ACE2/RBD binding inhibition activity of spike-specific antibodies was also observed, especially in ruxolitinib-treated patients. Our results, showing slow kinetics of antibody responses in MF patients following vaccination with mRNA SARS-CoV-2 vaccines, support the need for a third vaccine dose. Full article

(This article belongs to the Special Issue Immunology in COVID-19 Disease: From Pathophysiology to Novel Therapeutic Approaches)

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16 pages, 1710 KiB

Open AccessArticle

Children’s Privilege in COVID-19: The Protective Role of the Juvenile Lung Morphometry and Ventilatory Pattern on Airborne SARS-CoV-2 Transmission to Respiratory Epithelial Barriers and Disease Severity

by Norbert Hofstätter, Sabine Hofer, Albert Duschl and Martin Himly

Biomedicines 2021, 9(10), 1414; https://doi.org/10.3390/biomedicines9101414 - 08 Oct 2021

Cited by 1 | Viewed by 11760

Abstract

The incidence of severe COVID-19 in children is low, and underlying mechanisms for lower SARS-CoV-2 susceptibility and self-limiting disease severity are poorly understood. Severe clinical manifestations in adults require SARS-CoV-2 inoculation in the lower respiratory tract, establishing a pulmonary disease phase. This may [...] Read more.

The incidence of severe COVID-19 in children is low, and underlying mechanisms for lower SARS-CoV-2 susceptibility and self-limiting disease severity are poorly understood. Severe clinical manifestations in adults require SARS-CoV-2 inoculation in the lower respiratory tract, establishing a pulmonary disease phase. This may be either accomplished by direct inoculation of the thoracic region upon exposure to virion-laden aerosols, or by infection of the upper respiratory system and aspiration of virion-laden aerosols originating right there into the lower respiratory tract. The particularities of epithelial barriers as the anatomical site of first viral deposition specifically determine the initial characteristics of an innate immune response, emerging respiratory tissue damage and dysfunctionality, and hence, severity of clinical symptoms. We, thus, investigated by in silico modeling whether the combined effect of juvenile lung morphometry, children’s ventilatory pattern and the peculiarities of the virion-laden aerosols’ properties, render children more resilient to aerosol deposition in the lower respiratory tract. Our study presents evidence for major age-dependent differences of the regional virion-laden aerosol deposition. We identified deposition hotspots in the alveolar–interstitial region of the young adult. Our data reveal that children are void of corresponding hotspots. The inoculum quantum in the alveolar–interstitial region hotspots is found to be considerably related to age. Our results suggest that children are intrinsically protected against SARS-CoV-2 inoculation in the lower respiratory tract, which may help to explain the lower risk of severe clinical manifestations associated with a pulmonary phase. Full article

(This article belongs to the Special Issue Immunology in COVID-19 Disease: From Pathophysiology to Novel Therapeutic Approaches)

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19 pages, 3314 KiB

Open AccessArticle

Alterations in Circulating Monocytes Predict COVID-19 Severity and Include Chromatin Modifications Still Detectable Six Months after Recovery

by Alberto Utrero-Rico, Cecilia González-Cuadrado, Marta Chivite-Lacaba, Oscar Cabrera-Marante, Rocío Laguna-Goya, Patricia Almendro-Vazquez, Carmen Díaz-Pedroche, María Ruiz-Ruigómez, Antonio Lalueza, María Dolores Folgueira, Enrique Vázquez, Ana Quintas, Marcos J. Berges-Buxeda, Moisés Martín-Rodriguez, Ana Dopazo, Antonio Serrano-Hernández, José María Aguado and Estela Paz-Artal

Biomedicines 2021, 9(9), 1253; https://doi.org/10.3390/biomedicines9091253 - 17 Sep 2021

Cited by 29 | Viewed by 3302

Abstract

An early analysis of circulating monocytes may be critical for predicting COVID-19 course and its sequelae. In 131 untreated, acute COVID-19 patients at emergency room arrival, monocytes showed decreased surface molecule expression, including low HLA-DR, in association with an inflammatory cytokine status and [...] Read more.

An early analysis of circulating monocytes may be critical for predicting COVID-19 course and its sequelae. In 131 untreated, acute COVID-19 patients at emergency room arrival, monocytes showed decreased surface molecule expression, including low HLA-DR, in association with an inflammatory cytokine status and limited anti-SARS-CoV-2-specific T cell response. Most of these alterations had normalized in post-COVID-19 patients 6 months after discharge. Acute COVID-19 monocytes transcriptome showed upregulation of anti-inflammatory tissue repair genes such as BCL6, AREG and IL-10 and increased accessibility of chromatin. Some of these transcriptomic and epigenetic features still remained in post-COVID-19 monocytes. Importantly, a poorer expression of surface molecules and low IRF1 gene transcription in circulating monocytes at admission defined a COVID-19 patient group with impaired SARS-CoV-2-specific T cell response and increased risk of requiring intensive care or dying. An early analysis of monocytes may be useful for COVID-19 patient stratification and for designing innate immunity-focused therapies. Full article

(This article belongs to the Special Issue Immunology in COVID-19 Disease: From Pathophysiology to Novel Therapeutic Approaches)

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10 pages, 1667 KiB

Open AccessArticle

Picture of the Favourable Immune Profile Induced by Anti-SARS-CoV-2 Vaccination

by Paola Lanuti, Claudia Rossi, Ilaria Cicalini, Laura Pierdomenico, Verena Damiani, Daniela Semeraro, Sara Verrocchio, Piero Del Boccio, Adelia Evangelista, Annalina Sarra, Mirco Zucchelli, Giuseppina Bologna, Pasquale Simeone, Giulia Catitti, Federica Di Marco, Simone Stefanetti, Simone Vespa, Bruna Sinjari, Ines Bucci, Vincenzo De Laurenzi, Tonio Di Battista, Liborio Stuppia and Damiana Pieragostino Show full author list Hide full author list

Biomedicines 2021, 9(8), 1035; https://doi.org/10.3390/biomedicines9081035 - 18 Aug 2021

Cited by 7 | Viewed by 2309

Abstract

COVID-19 pandemic has hit people’s health, economy, and society worldwide. Great confidence in returning to normality has been placed in the vaccination campaign. The knowledge of individual immune profiles and the time required to achieve immunological protection is crucial to choose the best [...] Read more.

COVID-19 pandemic has hit people’s health, economy, and society worldwide. Great confidence in returning to normality has been placed in the vaccination campaign. The knowledge of individual immune profiles and the time required to achieve immunological protection is crucial to choose the best vaccination strategy. We compared anti-S1 antibody levels produced over time by BNT162b2 and AZD1222 vaccines and evaluated the induction of antigen-specific T-cells. A total of 2569 anti-SARS-CoV-2 IgG determination on dried blood spot samples were carried out, firstly in a cohort of 1181 individuals at random time-points, and subsequently, in an independent cohort of 88 vaccinated subjects, up to the seventeenth week from the first dose administration. Spike-specific T-cells were analysed in seronegative subjects between the two doses. AZD1222 induced lower anti-S1 IgG levels as compared to BNT162b2. Moreover, 40% of AZD1222 vaccinated subjects and 3% of BNT162b2 individuals resulted in seronegative during all the time-points, between the two doses. All these subjects developed antigen-specific T cells, already after the first dose. These results suggest that this test represents an excellent tool for a wide sero-surveillance. Both vaccines induce a favourable immune profile guaranteeing efficacy against severe adverse effects of SARS-CoV-2 infection, already after the first dose administration. Full article

(This article belongs to the Special Issue Immunology in COVID-19 Disease: From Pathophysiology to Novel Therapeutic Approaches)

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13 pages, 1674 KiB

Open AccessArticle

Innate and Adaptive Immune Assessment at Admission to Predict Clinical Outcome in COVID-19 Patients

by David San Segundo, Francisco Arnáiz de las Revillas, Patricia Lamadrid-Perojo, Alejandra Comins-Boo, Claudia González-Rico, Marta Alonso-Peña, Juan Irure-Ventura, José Manuel Olmos, María Carmen Fariñas and Marcos López-Hoyos

Biomedicines 2021, 9(8), 917; https://doi.org/10.3390/biomedicines9080917 - 29 Jul 2021

Cited by 10 | Viewed by 2824

Abstract

During the COVID-19 pandemic, many studies have been carried out to evaluate different immune system components to search for prognostic biomarkers of the disease. A broad multiparametric antibody panel of cellular and humoral components of the innate and the adaptative immune response in [...] Read more.

During the COVID-19 pandemic, many studies have been carried out to evaluate different immune system components to search for prognostic biomarkers of the disease. A broad multiparametric antibody panel of cellular and humoral components of the innate and the adaptative immune response in patients with active SARS-CoV-2 infection has been evaluated in this study. A total of 155 patients were studied at admission into our center and were categorized according to the requirement of oxygen therapy as mild or severe (the latter being those with the requirement). The patients with severe disease were older and had high ferritin, D-dimer, C-reactive protein, troponin, interleukin-6 (IL-6) levels, and neutrophilia with lymphopenia at admission. Moreover, the patients with mild symptoms had significantly increased circulating non-classical monocytes, innate lymphoid cells, and regulatory NK cells. In contrast, severe patients had a low frequency of Th1 and regulatory T cells with increased activated and exhausted CD8 phenotype (CD8⁺CD38⁺HLADR⁺ and CD8⁺CD27⁻CD28⁻, respectively). The predictive model included age, ferritin, D-dimer, lymph counts, C4, CD8⁺CD27⁻CD28⁻, and non-classical monocytes in the logistic regression analysis. The model predicted severity with an area under the curve of 78%. Both innate and adaptive immune parameters could be considered potential predictive biomarkers of the prognosis of COVID-19 disease. Full article

(This article belongs to the Special Issue Immunology in COVID-19 Disease: From Pathophysiology to Novel Therapeutic Approaches)

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10 pages, 2275 KiB

Open AccessArticle

Immune Assessment of BNT162b2 m-RNA-Spike Based Vaccine Response in Adults

by David San Segundo, Alejandra Comins-Boo, Juan Irure-Ventura, Mónica Renuncio-García, Adriel Roa-Bautista, Elena González-López, David Merino-Fernández, Patricia Lamadrid-Perojo, Marta Alonso-Peña, Javier Gonzalo Ocejo-Vinyals, Maria Gutiérrez-Larrañaga, Sandra Guiral-Foz and Marcos López-Hoyos

Biomedicines 2021, 9(8), 868; https://doi.org/10.3390/biomedicines9080868 - 22 Jul 2021

Cited by 6 | Viewed by 2948

Abstract

Vaccine efficacy is based on clinical data. Currently, the assessment of immune response after SARS-CoV-2 vaccination is scarce. A total of 52 healthcare workers were immunized with the same lot of BNT162b2 vaccine. The immunological response against the vaccine was tested using a [...] Read more.

Vaccine efficacy is based on clinical data. Currently, the assessment of immune response after SARS-CoV-2 vaccination is scarce. A total of 52 healthcare workers were immunized with the same lot of BNT162b2 vaccine. The immunological response against the vaccine was tested using a T-specific assay based on the expression of CD25 and CD134 after stimulation with anti-N, -S, and -M specific peptides of SARS-CoV-2. Moreover, IgG anti-S2 and -RBD antibodies were detected using ELISA. Furthermore, the cell subsets involved in the response to the vaccine were measured in peripheral blood by flow cytometry. Humoral-specific responses against the vaccine were detected in 94% and 100% after the first and second doses, respectively. Therefore, anti-S T-specific responses were observed in 57% and 90% of the subjects after the first and second doses of the vaccine, respectively. Thirty days after the second dose, significant increases in T helper 1 memory cells (p < 0.001), peripheral memory T follicular helper (pT_FH) cells (p < 0.032), and switched memory (p = 0.005) were observed. This study describes the specific humoral and cellular immune responses after vaccination with the new mRNA-based BNT162b2 vaccine. A mobilization of T_FH into the circulation occurs, reflecting a specific activation of the immune system. Full article

(This article belongs to the Special Issue Immunology in COVID-19 Disease: From Pathophysiology to Novel Therapeutic Approaches)

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12 pages, 604 KiB

Open AccessEditor’s ChoiceArticle

Different Within-Host Viral Evolution Dynamics in Severely Immunosuppressed Cases with Persistent SARS-CoV-2

by Laura Pérez-Lago, Teresa Aldámiz-Echevarría, Rita García-Martínez, Leire Pérez-Latorre, Marta Herranz, Pedro J. Sola-Campoy, Julia Suárez-González, Carolina Martínez-Laperche, Iñaki Comas, Fernando González-Candelas, Pilar Catalán, Patricia Muñoz, Darío García de Viedma and on behalf of Gregorio Marañón Microbiology-ID COVID 19 Study Group

Biomedicines 2021, 9(7), 808; https://doi.org/10.3390/biomedicines9070808 - 13 Jul 2021

Cited by 25 | Viewed by 3312

Abstract

A successful Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variant, B.1.1.7, has recently been reported in the UK, causing global alarm. Most likely, the new variant emerged in a persistently infected patient, justifying a special focus on these cases. Our aim in this [...] Read more.

A successful Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variant, B.1.1.7, has recently been reported in the UK, causing global alarm. Most likely, the new variant emerged in a persistently infected patient, justifying a special focus on these cases. Our aim in this study was to explore certain clinical profiles involving severe immunosuppression that may help explain the prolonged persistence of viable viruses. We present three severely immunosuppressed cases (A, B, and C) with a history of lymphoma and prolonged SARS-CoV-2 shedding (2, 4, and 6 months), two of whom finally died. Whole-genome sequencing of 9 and 10 specimens from Cases A and B revealed extensive within-patient acquisition of diversity, 12 and 28 new single nucleotide polymorphisms, respectively, which suggests ongoing SARS-CoV-2 replication. This diversity was not observed for Case C after analysing 5 sequential nasopharyngeal specimens and one plasma specimen, and was only observed in one bronchoaspirate specimen, although viral viability was still considered based on constant low Ct values throughout the disease and recovery of the virus in cell cultures. The acquired viral diversity in Cases A and B followed different dynamics. For Case A, new single nucleotide polymorphisms were quickly fixed (13–15 days) after emerging as minority variants, while for Case B, higher diversity was observed at a slower emergence: fixation pace (1–2 months). Slower SARS-CoV-2 evolutionary pace was observed for Case A following the administration of hyperimmune plasma. This work adds knowledge on SARS-CoV-2 prolonged shedding in severely immunocompromised patients and demonstrates viral viability, noteworthy acquired intra-patient diversity, and different SARS-CoV-2 evolutionary dynamics in persistent cases. Full article

(This article belongs to the Special Issue Immunology in COVID-19 Disease: From Pathophysiology to Novel Therapeutic Approaches)

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12 pages, 1495 KiB

Open AccessArticle

Beneficial Effects of Mineralocorticoid Receptor Pathway Blockade against Endothelial Inflammation Induced by SARS-CoV-2 Spike Protein

by Eva Jover, Lara Matilla, Mattie Garaikoetxea, Amaya Fernández-Celis, Pieter Muntendam, Frédéric Jaisser, Patrick Rossignol and Natalia López-Andrés

Biomedicines 2021, 9(6), 639; https://doi.org/10.3390/biomedicines9060639 - 03 Jun 2021

Cited by 20 | Viewed by 3927

Abstract

Background: Vascular endothelial cells activation and dysfunction mediate inflammation and abnormal coagulation in COVID-19 patients. Mineralocorticoid receptor (MR) signaling and its downstream target Galectin-3 (Gal-3) are known to mediate cardiovascular inflammation and might be involved in the pathogenesis of COVID-19 complications. Accordingly, we [...] Read more.

Background: Vascular endothelial cells activation and dysfunction mediate inflammation and abnormal coagulation in COVID-19 patients. Mineralocorticoid receptor (MR) signaling and its downstream target Galectin-3 (Gal-3) are known to mediate cardiovascular inflammation and might be involved in the pathogenesis of COVID-19 complications. Accordingly, we aimed to investigate the potential beneficial effects of MR antagonism and Gal-3 inhibition on the inflammatory response induced by SARS-CoV-2 Spike protein in human aortic endothelial cells (HAECs). Methods: HAECs were treated with recombinant SARS-COV2 Spike (S) protein. MR antagonists (namely spironolactone and eplerenone) or the Gal-3 inhibitor G3P-01 were supplemented before and after S protein challenge. HAECs supernatants were assessed by ELISA or Western blotting. Results: HAECs treated with recombinant S protein resulted in enhanced secretion of inflammatory molecules (interleukin-6, monocyte chemoattractant protein-1, interleukin-18, interleukin-27, and interferon-γ) as well as in the thrombosis marker plasminogen activator inhibitor (PAI)-1. This was prevented and reversed by both MR antagonists and G3P-01. Conclusions: These findings indicate that MR/Gal-3 pathway blockade could be a promising option to reduce endothelial inflammation in SARS-CoV-2 infection. Full article

(This article belongs to the Special Issue Immunology in COVID-19 Disease: From Pathophysiology to Novel Therapeutic Approaches)

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Review

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20 pages, 1502 KiB

Open AccessReview

Antiviral Cell Products against COVID-19: Learning Lessons from Previous Research in Anti-Infective Cell-Based Agents

by Irina Chikileva, Irina Shubina, Anzhelika-Mariia Burtseva, Kirill Kirgizov, Nara Stepanyan, Svetlana Varfolomeeva and Mikhail Kiselevskiy

Biomedicines 2022, 10(4), 868; https://doi.org/10.3390/biomedicines10040868 - 07 Apr 2022

Viewed by 2274

Abstract

COVID-19 is a real challenge for the protective immunity. Some people do not respond to vaccination by acquiring an appropriate immunological memory. The risk groups for this particular infection such as the elderly and people with compromised immunity (cancer patients, pregnant women, etc.) [...] Read more.

COVID-19 is a real challenge for the protective immunity. Some people do not respond to vaccination by acquiring an appropriate immunological memory. The risk groups for this particular infection such as the elderly and people with compromised immunity (cancer patients, pregnant women, etc.) have the most serious problems in developing an adequate immune response. Therefore, dendritic cell (DC) vaccines that are loaded ex vivo with SARS-CoV-2 antigens in the optimal conditions are promising for immunization. Lymphocyte effector cells with chimeric antigen receptor (CAR lymphocytes) are currently used mainly as anti-tumor treatment. Before 2020, few studies on the antiviral CAR lymphocytes were reported, but since the outbreak of SARS-CoV-2 the number of such studies has increased. The basis for CARs against SARS-CoV-2 were several virus-specific neutralizing monoclonal antibodies. We propose a similar, but basically novel and more universal approach. The extracellular domain of the immunoglobulin G receptors will be used as the CAR receptor domain. The specificity of the CAR will be determined by the antibodies, which it has bound. Therefore, such CAR lymphocytes are highly universal and have functional activity against any infectious agents that have protective antibodies binding to a foreign surface antigen on the infected cells. Full article

(This article belongs to the Special Issue Immunology in COVID-19 Disease: From Pathophysiology to Novel Therapeutic Approaches)

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28 pages, 2291 KiB

Open AccessReview

Targeting Inflammasome Activation in COVID-19: Delivery of RNA Interference-Based Therapeutic Molecules

by Lealem Gedefaw, Sami Ullah, Thomas M. H. Lee, Shea Ping Yip and Chien-Ling Huang

Biomedicines 2021, 9(12), 1823; https://doi.org/10.3390/biomedicines9121823 - 03 Dec 2021

Cited by 7 | Viewed by 3311

Abstract

Mortality and morbidity associated with COVID-19 continue to be significantly high worldwide, owing to the absence of effective treatment strategies. The emergence of different variants of SARS-CoV-2 is also a considerable source of concern and has led to challenges in the development of [...] Read more.

Mortality and morbidity associated with COVID-19 continue to be significantly high worldwide, owing to the absence of effective treatment strategies. The emergence of different variants of SARS-CoV-2 is also a considerable source of concern and has led to challenges in the development of better prevention and treatment strategies, including vaccines. Immune dysregulation due to pro-inflammatory mediators has worsened the situation in COVID-19 patients. Inflammasomes play a critical role in modulating pro-inflammatory cytokines in the pathogenesis of COVID-19 and their activation is associated with poor clinical outcomes. Numerous preclinical and clinical trials for COVID-19 treatment using different approaches are currently underway. Targeting different inflammasomes to reduce the cytokine storm, and its associated complications, in COVID-19 patients is a new area of research. Non-coding RNAs, targeting inflammasome activation, may serve as an effective treatment strategy. However, the efficacy of these therapeutic agents is highly dependent on the delivery system. MicroRNAs and long non-coding RNAs, in conjunction with an efficient delivery vehicle, present a potential strategy for regulating NLRP3 activity through various RNA interference (RNAi) mechanisms. In this regard, the use of nanomaterials and other vehicle types for the delivery of RNAi-based therapeutic molecules for COVID-19 may serve as a novel approach for enhancing drug efficacy. The present review briefly summarizes immune dysregulation and its consequences, the roles of different non-coding RNAs in regulating the NLRP3 inflammasome, distinct types of vectors for their delivery, and potential therapeutic targets of microRNA for treatment of COVID-19. Full article

(This article belongs to the Special Issue Immunology in COVID-19 Disease: From Pathophysiology to Novel Therapeutic Approaches)

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19 pages, 2610 KiB

Open AccessReview

Acute Respiratory Distress Syndrome: Focus on Viral Origin and Role of Pulmonary Lymphatics

by Eleonore Fröhlich

Biomedicines 2021, 9(11), 1732; https://doi.org/10.3390/biomedicines9111732 - 20 Nov 2021

Cited by 3 | Viewed by 4517

Abstract

Acute respiratory distress syndrome (ARDS) is a serious affection of the lung caused by a variety of pathologies. Great interest is currently focused on ARDS induced by viruses (pandemic influenza and corona viruses). The review describes pulmonary changes in ARDS and specific effects [...] Read more.

Acute respiratory distress syndrome (ARDS) is a serious affection of the lung caused by a variety of pathologies. Great interest is currently focused on ARDS induced by viruses (pandemic influenza and corona viruses). The review describes pulmonary changes in ARDS and specific effects of the pandemic viruses in ARDS, and summarizes treatment options. Because the known pathogenic mechanisms cannot explain all aspects of the syndrome, the contribution of pulmonary lymphatics to the pathology is discussed. Organization and function of lymphatics in a healthy lung and in resorption of pulmonary edema are described. A future clinical trial may provide more insight into the role of hyaluronan in ARDS but the development of promising pharmacological treatments is unlikely because drugs play no important role in lymphedema therapy. Full article

(This article belongs to the Special Issue Immunology in COVID-19 Disease: From Pathophysiology to Novel Therapeutic Approaches)

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14 pages, 1186 KiB

Open AccessReview

The Potential Role of Cytokine Storm Pathway in the Clinical Course of Viral Respiratory Pandemic

by Giuseppe Murdaca, Francesca Paladin, Alessandro Tonacci, Stefania Isola, Alessandro Allegra and Sebastiano Gangemi

Biomedicines 2021, 9(11), 1688; https://doi.org/10.3390/biomedicines9111688 - 15 Nov 2021

Cited by 12 | Viewed by 3574

Abstract

The “cytokine storm” (CS) consists of a spectrum of different immune dysregulation disorders characterized by constitutional symptoms, systemic inflammation and multiorgan dysfunction triggered by an uncontrolled immune response. Particularly in respiratory virus infections, the cytokine storm plays a primary role in the pathogenesis [...] Read more.

The “cytokine storm” (CS) consists of a spectrum of different immune dysregulation disorders characterized by constitutional symptoms, systemic inflammation and multiorgan dysfunction triggered by an uncontrolled immune response. Particularly in respiratory virus infections, the cytokine storm plays a primary role in the pathogenesis of respiratory disease and the clinical outcome of respiratory diseases, leading to complications such as alveolar edema and hypoxia. In this review, we wanted to analyze the different pathogenetic mechanisms involved in the various respiratory viral pandemics (COVID-19; SARS; MERS; H1N1 influenza A and Spanish flu) which have affected humans in this and last century, with particular attention to the phenomenon of the “cytokine storm” which determines the clinical severity of the respiratory disease and consequently its lethality. Full article

(This article belongs to the Special Issue Immunology in COVID-19 Disease: From Pathophysiology to Novel Therapeutic Approaches)

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25 pages, 1110 KiB

Open AccessReview

Immune Responses against SARS-CoV-2—Questions and Experiences

by Harald Mangge, Markus Kneihsl, Wolfgang Schnedl, Gerald Sendlhofer, Francesco Curcio and Rossana Domenis

Biomedicines 2021, 9(10), 1342; https://doi.org/10.3390/biomedicines9101342 - 28 Sep 2021

Cited by 10 | Viewed by 5141

Abstract

Understanding immune reactivity against SARS-CoV-2 is essential for coping with the COVID-19 pandemic. Herein, we discuss experiences and open questions about the complex immune responses to SARS-CoV-2. Some people react excellently without experiencing any clinical symptoms, they do not get sick, and they [...] Read more.

Understanding immune reactivity against SARS-CoV-2 is essential for coping with the COVID-19 pandemic. Herein, we discuss experiences and open questions about the complex immune responses to SARS-CoV-2. Some people react excellently without experiencing any clinical symptoms, they do not get sick, and they do not pass the virus on to anyone else (“sterilizing” immunity). Others produce antibodies and do not get COVID-19 but transmit the virus to others (“protective” immunity). Some people get sick but recover. A varying percentage develops respiratory failure, systemic symptoms, clotting disorders, cytokine storms, or multi-organ failure; they subsequently decease. Some develop long COVID, a new pathologic entity similar to fatigue syndrome or autoimmunity. In reality, COVID-19 is considered more of a systemic immune–vascular disease than a pulmonic disease, involving many tissues and the central nervous system. To fully comprehend the complex clinical manifestations, a profound understanding of the immune responses to SARS-CoV-2 is a good way to improve clinical management of COVID-19. Although neutralizing antibodies are an established approach to recognize an immune status, cellular immunity plays at least an equivalent or an even more important role. However, reliable methods to estimate the SARS-CoV-2-specific T cell capacity are not available for clinical routines. This deficit is important because an unknown percentage of people may exist with good memory T cell responsibility but a low number of or completely lacking peripheral antibodies against SARS-CoV-2. Apart from natural immune responses, vaccination against SARS-CoV-2 turned out to be very effective and much safer than naturally acquired immunity. Nevertheless, besides unwanted side effects of the currently available vector and mRNA preparations, concerns remain whether these vaccines will be strong enough to defeat the pandemic. Altogether, herein we discuss important questions, and try to give answers based on the current knowledge and preliminary data from our laboratories. Full article

(This article belongs to the Special Issue Immunology in COVID-19 Disease: From Pathophysiology to Novel Therapeutic Approaches)

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25 pages, 1198 KiB

Open AccessReview

Emerging SARS-CoV-2 Variants of Concern (VOCs): An Impending Global Crisis

by Angel Yun-Kuan Thye, Jodi Woan-Fei Law, Priyia Pusparajah, Vengadesh Letchumanan, Kok-Gan Chan and Learn-Han Lee

Biomedicines 2021, 9(10), 1303; https://doi.org/10.3390/biomedicines9101303 - 23 Sep 2021

Cited by 88 | Viewed by 9885

Abstract

The worldwide battle against the SARS-CoV-2 virus rages on, with millions infected and many innocent lives lost. The causative organism, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a beta coronavirus that belongs to the Coronaviridae family. Many clinically significant variants have emerged, [...] Read more.

The worldwide battle against the SARS-CoV-2 virus rages on, with millions infected and many innocent lives lost. The causative organism, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a beta coronavirus that belongs to the Coronaviridae family. Many clinically significant variants have emerged, as the virus’s genome is prone to various mutations, leading to antigenic drift and resulting in evasion of host immune recognition. The current variants of concern (VOCs) include B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617/B.1.617.2 (Delta), and P.1 (Gamma). The emerging variants contain various important mutations on the spike protein, leading to deleterious consequences, such as immune invasion and vaccine escape. These adverse effects result in increased transmissibility, morbidity, and mortality and the evasion of detection by existing or currently available diagnostic tests, potentially delaying diagnosis and treatment. This review discusses the key mutations present in the VOC strains and provides insights into how these mutations allow for greater transmissibility and immune evasion than the progenitor strain. Continuous monitoring and surveillance of VOC strains play a vital role in preventing and controlling the virus’s spread. Full article

(This article belongs to the Special Issue Immunology in COVID-19 Disease: From Pathophysiology to Novel Therapeutic Approaches)

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20 pages, 795 KiB

Open AccessReview

The Fight against COVID-19 on the Multi-Protease Front and Surroundings: Could an Early Therapeutic Approach with Repositioning Drugs Prevent the Disease Severity?

by Annamaria Vianello, Serena Del Turco, Serena Babboni, Beatrice Silvestrini, Rosetta Ragusa, Chiara Caselli, Luca Melani, Luca Fanucci and Giuseppina Basta

Biomedicines 2021, 9(7), 710; https://doi.org/10.3390/biomedicines9070710 - 23 Jun 2021

Cited by 6 | Viewed by 4119

Abstract

The interaction between the membrane spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the transmembrane angiotensin-converting enzyme 2 (ACE2) receptor of the human epithelial host cell is the first step of infection, which has a critical role for viral [...] Read more.

The interaction between the membrane spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the transmembrane angiotensin-converting enzyme 2 (ACE2) receptor of the human epithelial host cell is the first step of infection, which has a critical role for viral pathogenesis of the current coronavirus disease-2019 (COVID-19) pandemic. Following the binding between S1 subunit and ACE2 receptor, different serine proteases, including TMPRSS2 and furin, trigger and participate in the fusion of the viral envelope with the host cell membrane. On the basis of the high virulence and pathogenicity of SARS-CoV-2, other receptors have been found involved for viral binding and invasiveness of host cells. This review comprehensively discusses the mechanisms underlying the binding of SARS-CoV2 to ACE2 and putative alternative receptors, and the role of potential co-receptors and proteases in the early stages of SARS-CoV-2 infection. Given the short therapeutic time window within which to act to avoid the devastating evolution of the disease, we focused on potential therapeutic treatments—selected mainly among repurposing drugs—able to counteract the invasive front of proteases and mild inflammatory conditions, in order to prevent severe infection. Using existing approved drugs has the advantage of rapidly proceeding to clinical trials, low cost and, consequently, immediate and worldwide availability. Full article

(This article belongs to the Special Issue Immunology in COVID-19 Disease: From Pathophysiology to Novel Therapeutic Approaches)

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