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16 pages, 1050 KiB

Open AccessArticle

The Predictive Performance of Risk Scores for the Outcome of COVID-19 in a 2-Year Swiss Cohort

by Maria Boesing, Giorgia Lüthi-Corridori, David Büttiker, Mireille Hunziker, Fabienne Jaun, Ugne Vaskyte, Michael Brändle and Jörg D. Leuppi

Biomedicines 2024, 12(8), 1702; https://doi.org/10.3390/biomedicines12081702 - 31 Jul 2024

Cited by 1 | Viewed by 732

Abstract

Various scoring systems are available for COVID-19 risk stratification. This study aimed to validate their performance in predicting severe COVID-19 course in a large, heterogeneous Swiss cohort. Scores like the National Early Warning Score (NEWS), CURB-65, 4C mortality score (4C), Spanish Society of [...] Read more.

Various scoring systems are available for COVID-19 risk stratification. This study aimed to validate their performance in predicting severe COVID-19 course in a large, heterogeneous Swiss cohort. Scores like the National Early Warning Score (NEWS), CURB-65, 4C mortality score (4C), Spanish Society of Infectious Diseases and Clinical Microbiology score (COVID-SEIMC), and COVID Intubation Risk Score (COVID-IRS) were assessed in patients hospitalized for COVID-19 in 2020 and 2021. Predictive accuracy for severe course (defined as all-cause in-hospital death or invasive mechanical ventilation (IMV)) was evaluated using receiver operating characteristic curves and the area under the curve (AUC). The new ‘COVID-COMBI’ score, combining parameters from the top two scores, was also validated. This study included 1,051 patients (mean age 65 years, 60% male), with 162 (15%) experiencing severe course. Among the established scores, 4C had the best accuracy for predicting severe course (AUC 0.76), followed by COVID-IRS (AUC 0.72). COVID-COMBI showed significantly higher accuracy than all established scores (AUC 0.79, p = 0.001). For predicting in-hospital death, 4C performed best (AUC 0.83), and, for IMV, COVID-IRS performed best (AUC 0.78). The 4C and COVID-IRS scores were robust predictors of severe COVID-19 course, while the new COVID-COMBI showed significantly improved accuracy but requires further validation. Full article

(This article belongs to the Special Issue The End of the COVID-19 Pandemic—What Is Currently Known and What Could Have Been Useful Four Years Ago?)

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11 pages, 1060 KiB

Open AccessArticle

Analysis of Ferritin, Hepcidin, Zinc, C-Reactive Protein and IL-6 Levels in COVID-19 in Patients Living at Different Altitudes in Peru

by Wilmer Silva-Caso, Sungmin Kym, Alfredo Merino-Luna, Miguel Angel Aguilar-Luis, Yordi Tarazona-Castro, Hugo Carrillo-Ng, Eliezer Bonifacio-Velez de Villa, Ronald Aquino-Ortega and Juana del Valle-Mendoza

Biomedicines 2024, 12(7), 1609; https://doi.org/10.3390/biomedicines12071609 - 19 Jul 2024

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Abstract

Background: Despite great scientific efforts, understanding the role of COVID-19 clinical biomarkers remains a challenge. Methods: A cross-sectional descriptive study in two Peruvian cities at different altitudes for comparison: Lima and Huaraz. In each place, three groups were formed, made up of 25 [...] Read more.

Background: Despite great scientific efforts, understanding the role of COVID-19 clinical biomarkers remains a challenge. Methods: A cross-sectional descriptive study in two Peruvian cities at different altitudes for comparison: Lima and Huaraz. In each place, three groups were formed, made up of 25 patients with COVID-19 in the ICU, 25 hospitalized patients with COVID-19 who did not require the ICU, and 25 healthy subjects as a control group. Five biomarkers were measured: IL-6, hepcidin, ferritin, C-reactive protein, and zinc using ELISA assays. Results: Ferritin, C-reactive protein, and IL-6 levels were significantly higher in the ICU and non-ICU groups at both study sites. In the case of hepcidin, the levels were significantly higher in the ICU group at both study sites compared to the non-ICU group. Among the groups within each study site, the highest altitude area presented statistically significant differences between its groups in all the markers evaluated. In the lower altitude area, differences were only observed between the groups for the zinc biomarker. Conclusion: COVID-19 patients residing at high altitudes tend to have higher levels of zinc and IL-6 in all groups studied compared to their lower altitude counterparts. Full article

(This article belongs to the Special Issue The End of the COVID-19 Pandemic—What Is Currently Known and What Could Have Been Useful Four Years Ago?)

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11 pages, 930 KiB

Open AccessArticle

Predictive Value and Diagnostic Potential of IL-10, IL-17A, IL1-β, IL-6, CXCL, and MCP for Severe COVID-19 and COVID-19 Mortality

by Roxana-Elena Cîrjaliu, Ioan-Tiberiu Tofolean, Doina-Ecaterina Tofolean, Anca Chisoi, Cristian Oancea, Emanuela Vastag, Monica Marc, Felix Bratosin, Ovidiu Rosca and Ariadna-Petronela Fildan

Biomedicines 2024, 12(7), 1532; https://doi.org/10.3390/biomedicines12071532 - 10 Jul 2024

Cited by 1 | Viewed by 1093

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates advanced prognostic tools to anticipate disease progression and optimize patient outcomes. This study evaluates the predictive value and diagnostic potential of interleukins interleukin (IL) IL-10, IL-17A, IL1-β, IL-6, chemokine ligand (CXCL), and Monocyte Chemotactic [...] Read more.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates advanced prognostic tools to anticipate disease progression and optimize patient outcomes. This study evaluates the predictive value and diagnostic potential of interleukins interleukin (IL) IL-10, IL-17A, IL1-β, IL-6, chemokine ligand (CXCL), and Monocyte Chemotactic Protein (MCP) for severe coronavirus disease 2019 (COVID-19) and COVID-19 mortality, aiming to correlate cytokine levels with disease severity. Conducted from January 2023 to January 2024, this prospective cohort study involved patients hospitalized with moderate and severe COVID-19 from Romania. This study analyzed statistically significant predictors of severe COVID-19 outcomes. IL-6 and MCP emerged as significant, with hazard ratios (HRs) of 2.35 (95% confidence interval (CI): 1.54–3.59, p = 0.014) and 2.05 (95% CI: 1.22–3.45, p = 0.007), respectively. Compound scores integrating multiple inflammatory markers also demonstrated predictive value; Compound Score 2 had an HR of 2.23 (95% CI: 1.35–3.68, p = 0.002), surpassing most single markers in association with severe disease. Notably, interleukins IL-10 and IL-1β did not show significant associations with disease severity. This study underscores the importance of IL-6 and MCP as robust predictors of severe COVID-19, substantiating their role in clinical assessments to foresee patient deterioration. The utility of compound scores in enhancing predictive accuracy suggests a composite approach may be more effective in clinical settings. Full article

(This article belongs to the Special Issue The End of the COVID-19 Pandemic—What Is Currently Known and What Could Have Been Useful Four Years Ago?)

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11 pages, 1413 KiB

Open AccessArticle

Colostrum Lactoferrin Following Active and Recovered SARS-CoV-2 Infections during Pregnancy

by Paulina Gaweł, Błażej Łukianowski, Katarzyna Kościelska-Kasprzak, Dorota Bartoszek, Magdalena Krajewska and Barbara Królak-Olejnik

Biomedicines 2024, 12(5), 1120; https://doi.org/10.3390/biomedicines12051120 - 17 May 2024

Cited by 1 | Viewed by 1516

Abstract

Lactoferrin (Lf), which is particularly abundant in human breast milk during the early stages of lactation, provides protection against a variety of infections, including viral infections, and has demonstrated activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The objective of this study [...] Read more.

Lactoferrin (Lf), which is particularly abundant in human breast milk during the early stages of lactation, provides protection against a variety of infections, including viral infections, and has demonstrated activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The objective of this study was to measure the concentrations of Lf in the colostrum of mothers with active coronavirus disease 2019 (COVID-19) infections during delivery, in mothers with a history of COVID-19 during pregnancy, and in non-infected controls. In this cross-sectional study, colostrum samples from 41 lactating mothers with a confirmed history of SARS-CoV-2 infection (asymptomatic or symptomatic) (both active and past infections) were collected. Twenty-eight colostrum samples collected during the pre-pandemic period served as a control group. An enzyme-linked immunosorbent assay was performed to analyze the Lf concentrations. Concentrations of Lf in the colostrum samples were closely related to virus infection. Colostrum samples from mothers with confirmed SARS-CoV-2 infections contained higher concentrations of lactoferrin compared with samples from mothers from the control group. The highest concentrations of Lf were found in the colostrum samples of mothers with active SARS-CoV-2 infection during delivery when compared with the post-infection and control samples. This observed increase in lactoferrin suggests that it may be an important protective factor for breastfed infants, a finding which was particularly relevant during the pandemic period and remains relevant whenever a breastfeeding mother is infected. Full article

(This article belongs to the Special Issue The End of the COVID-19 Pandemic—What Is Currently Known and What Could Have Been Useful Four Years Ago?)

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13 pages, 2067 KiB

Open AccessArticle

Natural Antibodies Produced in Vaccinated Patients and COVID-19 Convalescents Hydrolyze Recombinant RBD and Nucleocapsid (N) Proteins

by Anna M. Timofeeva, Liliya Sh. Shayakhmetova, Artem O. Nikitin, Tatyana A. Sedykh, Andrey L. Matveev, Daniil V. Shanshin, Ekaterina A. Volosnikova, Iuliia A. Merkuleva, Dmitriy N. Shcherbakov, Nina V. Tikunova, Sergey E. Sedykh and Georgy A. Nevinsky

Biomedicines 2024, 12(5), 1007; https://doi.org/10.3390/biomedicines12051007 - 2 May 2024

Cited by 2 | Viewed by 1598

Abstract

Antibodies are protein molecules whose primary function is to recognize antigens. However, recent studies have demonstrated their ability to hydrolyze specific substrates, such as proteins, oligopeptides, and nucleic acids. In 2023, two separate teams of researchers demonstrated the proteolytic activity of natural plasma [...] Read more.

Antibodies are protein molecules whose primary function is to recognize antigens. However, recent studies have demonstrated their ability to hydrolyze specific substrates, such as proteins, oligopeptides, and nucleic acids. In 2023, two separate teams of researchers demonstrated the proteolytic activity of natural plasma antibodies from COVID-19 convalescents. These antibodies were found to hydrolyze the S-protein and corresponding oligopeptides. Our study shows that for antibodies with affinity to recombinant structural proteins of the SARS-CoV-2: S-protein, its fragment RBD and N-protein can only hydrolyze the corresponding protein substrates and are not cross-reactive. By using strict criteria, we have confirmed that this proteolytic activity is an intrinsic property of antibodies and is not caused by impurities co-eluting with them. This discovery suggests that natural proteolytic antibodies that hydrolyze proteins of the SARS-CoV-2 virus may have a positive impact on disease pathogenesis. It is also possible for these antibodies to work in combination with other antibodies that bind specific epitopes to enhance the process of virus neutralization. Full article

(This article belongs to the Special Issue The End of the COVID-19 Pandemic—What Is Currently Known and What Could Have Been Useful Four Years Ago?)

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13 pages, 1289 KiB

Open AccessArticle

by Marco Dell’Aquila, Concetta Cafiero, Alessandra Micera, Egidio Stigliano, Maria Pia Ottaiano, Giulio Benincasa, Beniamino Schiavone, Leo Guidobaldi, Luigi Santacroce, Salvatore Pisconti, Vincenzo Arena and Raffaele Palmirotta

Biomedicines 2024, 12(4), 830; https://doi.org/10.3390/biomedicines12040830 - 9 Apr 2024

Cited by 1 | Viewed by 1272

Abstract

Background: The COVID-19 pandemic has been a health emergency with a significant impact on the world due to its high infectiousness. The disease, primarily identified in the lower respiratory tract, develops with numerous clinical symptoms affecting multiple organs and displays a clinical finding [...] Read more.

Background: The COVID-19 pandemic has been a health emergency with a significant impact on the world due to its high infectiousness. The disease, primarily identified in the lower respiratory tract, develops with numerous clinical symptoms affecting multiple organs and displays a clinical finding of anosmia. Several authors have investigated the pathogenetic mechanisms of the olfactory disturbances caused by SARS-CoV-2 infection, proposing different hypotheses and showing contradictory results. Since uncertainties remain about possible virus neurotropism and direct damage to the olfactory bulb, we investigated the expression of SARS-CoV-2 as well as ACE2 receptor transcripts in autoptic lung and olfactory bulb tissues, with respect to the histopathological features. Methods: Twenty-five COVID-19 olfactory bulbs and lung tissues were randomly collected from 200 initial autopsies performed during the COVID-19 pandemic. Routine diagnosis was based on clinical and radiological findings and were confirmed with post-mortem swabs. Real-time RT-PCR for SARS-CoV-2 and ACE2 receptor RNA was carried out on autoptic FFPE lung and olfactory bulb tissues. Histological staining was performed on tissue specimens and compared with the molecular data. Results: While real-time RT-PCR for SARS-CoV-2 was positive in 23 out of 25 lung samples, the viral RNA expression was absent in olfactory bulbs. ACE2-receptor RNA was present in all tissues examined, being highly expressed in lung samples than olfactory bulbs. Conclusions: Our finding suggests that COVID-19 anosmia is not only due to neurotropism and the direct action of SARS-CoV-2 entering the olfactory bulb. The mechanism of SARS-CoV-2 neuropathogenesis in the olfactory bulb requires a better elucidation and further research studies to mitigate the olfactory bulb damage associated with virus action. Full article

(This article belongs to the Special Issue The End of the COVID-19 Pandemic—What Is Currently Known and What Could Have Been Useful Four Years Ago?)

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17 pages, 1762 KiB

Open AccessArticle

GDF-15 Levels and Other Laboratory Findings as Predictors of COVID-19 Severity and Mortality: A Pilot Study

by Luka Švitek, Dubravka Lišnjić, Barbara Grubišić, Mihaela Zlosa, Ema Schönberger, Nika Vlahović Vlašić, Petra Smajić, Dario Sabadi, Tara Rolić, Kristina Kralik and Sanja Mandić

Biomedicines 2024, 12(4), 757; https://doi.org/10.3390/biomedicines12040757 - 29 Mar 2024

Viewed by 1278

Abstract

Growth differentiation factor 15 (GDF-15) is a stress-induced cytokine associated with acute and chronic inflammatory states. This prospective observational study aimed to investigate the prognostic roles of GDF-15 and routine clinical laboratory parameters in COVID-19 patients. Upon the admission of 95 adult hospitalized [...] Read more.

Growth differentiation factor 15 (GDF-15) is a stress-induced cytokine associated with acute and chronic inflammatory states. This prospective observational study aimed to investigate the prognostic roles of GDF-15 and routine clinical laboratory parameters in COVID-19 patients. Upon the admission of 95 adult hospitalized COVID-19 patients in Croatia, blood analysis was performed, and medical data were collected. The patients were categorized based on survival, ICU admission, and hospitalization duration. Logistic regression and ROC curve methods were employed for the statistical analysis. Logistic regression revealed two independent predictors of negative outcomes: CURB-65 score (OR = 2.55) and LDH (OR = 1.005); one predictor of ICU admission: LDH (OR = 1.004); and one predictor of prolonged hospitalization: the need for a high-flow nasal cannula (HFNC) upon admission (OR = 4.75). The ROC curve showed diagnostic indicators of negative outcomes: age, CURB-65 score, LDH, and GDF-15. The largest area under the curve (AUC = 0.767, specificity = 65.6, sensitivity = 83.9) was represented by GDF-15, with a cutoff value of 3528 pg/mL. For ICU admission, significant diagnostic indicators were LDH, CRP, and IL-6. Significant diagnostic indicators of prolonged hospitalization were CK, GGT, and oxygenation with an HFNC upon admission. This study reaffirms the significance of the commonly used laboratory parameters and clinical scores in evaluating COVID-19. Additionally, it introduces the potential for a new diagnostic approach and research concerning GDF-15 levels in this widespread disease. Full article

(This article belongs to the Special Issue The End of the COVID-19 Pandemic—What Is Currently Known and What Could Have Been Useful Four Years Ago?)

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12 pages, 1309 KiB

Open AccessArticle

Prospective Observational Study of COVID-19 Vaccination in Patients with Thoracic Malignancies: Adverse Events, Breakthrough Infections and Survival Outcomes

by Urska Janzic, Andrej Janzic, Abed Agbarya, Urska Bidovec-Stojkovic, Katja Mohorcic, Marina Caks, Peter Korosec, Matija Rijavec and Erik Skof

Biomedicines 2024, 12(3), 535; https://doi.org/10.3390/biomedicines12030535 - 27 Feb 2024

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Abstract

Due to the devastating COVID-19 pandemic, a preventive tool in the form of vaccination was introduced. Thoracic cancer patients had one of the highest rates of morbidity and mortality due to COVID-19 disease, but the lack of data about the safety and effectiveness [...] Read more.

Due to the devastating COVID-19 pandemic, a preventive tool in the form of vaccination was introduced. Thoracic cancer patients had one of the highest rates of morbidity and mortality due to COVID-19 disease, but the lack of data about the safety and effectiveness of vaccines in this population triggered studies like ours to explore these parameters in a cancer population. Out of 98 patients with thoracic malignancies vaccinated per protocol, 60–75% experienced some adverse events (AE) after their first or second vaccination, most of them were mild and did not interfere with their daily activities. Out of 17 severe AEs reported, all but one were resolved shortly after vaccination. No significant differences were noted considering AE occurrence between different cancer therapies received after the first or second vaccination dose, p = 0.767 and p = 0.441, respectively. There were 37 breakthrough infections either after the first (1), second (13) or third (23) vaccine dose. One patient died as a direct consequence of COVID-19 infection and respiratory failure, and another after disease progression with simultaneous severe infection. Eight patients had moderate disease courses, received antiviral therapies and survived without consequences. Vaccination did not affect the time to disease progression or death from underlying cancer. Full article

(This article belongs to the Special Issue The End of the COVID-19 Pandemic—What Is Currently Known and What Could Have Been Useful Four Years Ago?)

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13 pages, 728 KiB

Open AccessArticle

Long-Term Outcomes of COVID-19 in Hospitalized Type 2 Diabetes Mellitus Patients

by Zemfira Khamidullina, Diana Avzaletdinova, Diana Gareeva, Tatyana Morugova, Irina Lakman, Kristen Kopp, Lukas Fiedler, Lukas J. Motloch and Naufal Zagidullin

Biomedicines 2024, 12(2), 467; https://doi.org/10.3390/biomedicines12020467 - 19 Feb 2024

Cited by 4 | Viewed by 1706

Abstract

With the onset of the coronavirus pandemic, it has become clear that patients with diabetes are at risk for more severe and fatal COVID-19. Type 2 diabetes mellitus (T2D) is a major risk factor for adverse COVID-19 outcomes. The goal of study was [...] Read more.

With the onset of the coronavirus pandemic, it has become clear that patients with diabetes are at risk for more severe and fatal COVID-19. Type 2 diabetes mellitus (T2D) is a major risk factor for adverse COVID-19 outcomes. The goal of study was to assess the characteristics and outcomes of hospitalized patients with COVID-19 with or without T2D in the hospital and at 10-month follow-up (FU). Methods: A total of 2486 hospitalized patients in the first wave of COVID-19 were analyzed according to the absence/presence of T2D, with 2082 (84.1%) patients in the control COVID-19 group and 381 (15.5%) in the T2D group. Twenty-three patients had other types of diabetes and were therefore excluded from the study. In-hospital mortality and cardiovascular endpoints (myocardial infarction, stroke, cardiovascular deaths and hospitalizations and composite endpoints) at the 10-month follow-up were analyzed. To remove bias in patients’ characteristics disproportion, Propensity Score Matching (PSM) was used for hospital and follow-up endpoints. Results. Hospital mortality was considerably greater in T2D than in the control COVID-19 group (13.89% vs. 4.89%, p < 0.0001), and the difference remained after PSM (p < 0.0001). Higher glucose-level T2D patients had a higher mortality rate (p = 0.018). The most significant predictors of hospital death in T2D patients were a high CRP, glucose, neutrophils count, and Charlson Comorbidity Index. The follow-up of patients over 10 months showed a non-significant increase for all endpoints in the T2D group (p > 0.05), and significant increase in stroke (p < 0.042). After the PSM, the difference decreased in stroke (p = 0.090), but became significant in cardiovascular hospitalizations (p = 0.023). Conclusion. In T2D patients with COVID-19, an increase in hospital mortality, stroke and cardiovascular hospitalizations rates in the follow-up was observed. Full article

(This article belongs to the Special Issue The End of the COVID-19 Pandemic—What Is Currently Known and What Could Have Been Useful Four Years Ago?)

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15 pages, 1118 KiB

Open AccessArticle

Approaching Personalized Medicine: The Use of Machine Learning to Determine Predictors of Mortality in a Population with SARS-CoV-2 Infection

by Mónica Queipo, Julia Barbado, Ana María Torres and Jorge Mateo

Biomedicines 2024, 12(2), 409; https://doi.org/10.3390/biomedicines12020409 - 9 Feb 2024

Cited by 1 | Viewed by 1384

Abstract

The COVID-19 pandemic demonstrated the need to develop strategies to control a new viral infection. However, the different characteristics of the health system and population of each country and hospital would require the implementation of self-systems adapted to their characteristics. The objective of [...] Read more.

The COVID-19 pandemic demonstrated the need to develop strategies to control a new viral infection. However, the different characteristics of the health system and population of each country and hospital would require the implementation of self-systems adapted to their characteristics. The objective of this work was to determine predictors that should identify the most severe patients with COVID-19 infection. Given the poor situation of the hospitals in the first wave, the analysis of the data from that period with an accurate and fast technique can be an important contribution. In this regard, machine learning is able to objectively analyze data in hourly sets and is used in many fields. This study included 291 patients admitted to a hospital in Spain during the first three months of the pandemic. After screening seventy-one features with machine learning methods, the variables with the greatest influence on predicting mortality in this population were lymphocyte count, urea, FiO2, potassium, and serum pH. The XGB method achieved the highest accuracy, with a precision of >95%. Our study shows that the machine learning-based system can identify patterns and, thus, create a tool to help hospitals classify patients according to their severity of illness in order to optimize admission. Full article

(This article belongs to the Special Issue The End of the COVID-19 Pandemic—What Is Currently Known and What Could Have Been Useful Four Years Ago?)

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14 pages, 2847 KiB

Open AccessArticle

HB-EGF Plasmatic Level Contributes to the Development of Early Risk Prediction Nomogram for Severe COVID-19 Cases

by Alexandra Ioana Moatar, Aimee Rodica Chis, Diana Nitusca, Cristian Oancea, Catalin Marian and Ioan-Ovidiu Sirbu

Biomedicines 2024, 12(2), 373; https://doi.org/10.3390/biomedicines12020373 - 5 Feb 2024

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Abstract

(1) Background: Heparin-Binding Epidermal Growth Factor-like Growth Factor (HB-EGF) is involved in wound healing, cardiac hypertrophy, and heart development processes. Recently, circulant HB-EGF was reported upregulated in severely hospitalized COVID-19 patients. However, the clinical correlations of HB-EGF plasma levels with COVID-19 patients’ characteristics [...] Read more.

(1) Background: Heparin-Binding Epidermal Growth Factor-like Growth Factor (HB-EGF) is involved in wound healing, cardiac hypertrophy, and heart development processes. Recently, circulant HB-EGF was reported upregulated in severely hospitalized COVID-19 patients. However, the clinical correlations of HB-EGF plasma levels with COVID-19 patients’ characteristics have not been defined yet. In this study, we assessed the plasma HB-EGF correlations with the clinical and paraclinical patients’ data, evaluated its predictive clinical value, and built a risk prediction model for severe COVID-19 cases based on the resulting significant prognostic markers. (2) Methods: Our retrospective study enrolled 75 COVID-19 patients and 17 control cases from May 2020 to September 2020. We quantified plasma HB-EGF levels using the sandwich ELISA technique. Correlations between HB-EGF plasma levels with clinical and paraclinical patients’ data were calculated using two-tailed Spearman and Point-Biserial tests. Significantly upregulated parameters for severe COVID-19 cases were identified and selected to build a multivariate logistic regression prediction model. The clinical significance of the prediction model was assessed by risk prediction nomogram and decision curve analyses. (3) Results: HB-EGF plasma levels were significantly higher in the severe COVID-19 subgroup compared to the controls (p = 0.004) and moderate cases (p = 0.037). In the severe COVID-19 group, HB-EGF correlated with age (p = 0.028), pulse (p = 0.016), dyspnea (p = 0.014) and prothrombin time (PT) (p = 0.04). The multivariate risk prediction model built on seven identified risk parameters (age p = 0.043, HB-EGF p = 0.0374, Fibrinogen p = 0.009, PT p = 0.008, Creatinine p = 0.026, D-Dimers p = 0.024 and delta miR-195 p < 0.0001) identifies severe COVID-19 with AUC = 0.9556 (p < 0.0001). The decision curve analysis revealed that the nomogram model is clinically relevant throughout a wide threshold probability range. (4) Conclusions: Upregulated HB-EGF plasma levels might serve as a prognostic factor for severe COVID-19 and help build a reliable risk prediction nomogram that improves the identification of high-risk patients at an early stage of COVID-19. Full article

(This article belongs to the Special Issue The End of the COVID-19 Pandemic—What Is Currently Known and What Could Have Been Useful Four Years Ago?)

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12 pages, 1603 KiB

Open AccessArticle

Could Children’s Myopization Have Been Avoided during the Pandemic Confinement? The Conjunctival Ultraviolet Autofluorescence (CUVAF) Biomarker as an Answer

by Miriam de la Puente, Cristina Irigoyen-Bañegil, Aura Ortega Claici, Jorge González-Zamora, Valentina Bilbao-Malavé, Patricia Fernandez-Robredo, María Hernández, Jesús Barrio, Alfredo García-Layana and Sergio Recalde

Biomedicines 2024, 12(2), 347; https://doi.org/10.3390/biomedicines12020347 - 1 Feb 2024

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Abstract

Background: The objective of this study was to evaluate the association of the presence of conjunctival ultraviolet autofluorescence (CUVAF) with the level and progression of myopia and the impact of reduced sunlight exposure during the COVID-19 pandemic confinement (PC). Methods: A retrospective observational [...] Read more.

Background: The objective of this study was to evaluate the association of the presence of conjunctival ultraviolet autofluorescence (CUVAF) with the level and progression of myopia and the impact of reduced sunlight exposure during the COVID-19 pandemic confinement (PC). Methods: A retrospective observational study was carried out using three cohorts, children (9–17 years old), young adults (18–25 years old), and adults (>40 years old) with myopia (≤0.75D) and at least three annual eye examinations (before and after PC). All participants underwent an automatic objective refraction and CUVAF area analysis. All the participants filled out a questionnaire regarding lifestyle and myopia history. Results: The 298 recruited participants showed that during the PC, children’s and young adults' myopia progression rate increased on average by −0.50 and −0.30 D/year, respectively, compared with the pre-pandemic level (p < 0.0001 and p < 0.01). A significantly greater progression was observed in those with low baseline myopia compared to those with moderate or high myopia (p < 0.01). CUVAF shows its protective effect associated with outdoor activity (OA) with regard to the age of onset of myopia and mean diopters (p < 0.01). In fact, although there were no differences in the increase in diopters between children with and without CUVAF during the PC, those who had CUVAF started with lower gains (−0.3 D/year) compared to those who did not (−0.5 D/year; p < 0.05). The myopia treatments (atropine drops, Ortho-K, and MiSight^® contact lenses) showed a reduction effect in myopic progression rate post-PC in comparison with non-treated children (p < 0.0001, p < 0.0001 and p < 0.01, respectively). Conclusions: The strict restriction of OA during PC led to the rate of myopia progression doubling among children and young adults. This progression occurred mainly in children with previously low myopia, and CUVAF, as a biomarker of OA, reflects its potential to provide benefits in the form of recommended behavioral changes to protect against the development of myopia. Full article

(This article belongs to the Special Issue The End of the COVID-19 Pandemic—What Is Currently Known and What Could Have Been Useful Four Years Ago?)

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12 pages, 1653 KiB

Open AccessArticle

by Igor Aurer, Ozren Jakšić, Sandra Bašić-Kinda, Stefan Mrđenović, Slobodanka Ostojić-Kolonić, Dominik Lozić, Hrvoje Holik, Sabina Novaković-Coha, Petra Berneš, Ivan Krečak, Martina Morić-Perić, Marino Narančić, Zdravko Mitrović and Toni Valković

Biomedicines 2024, 12(2), 331; https://doi.org/10.3390/biomedicines12020331 - 31 Jan 2024

Cited by 1 | Viewed by 1278

Abstract

Patients with lymphoid malignancies are at increased risk of death or prolonged infection due to COVID-19. Data on the influence of different antineoplastic treatment modalities on outcomes are conflicting. Anti-CD20 monoclonal antibodies increase the risk of prolonged infection. It is unclear whether this [...] Read more.

Patients with lymphoid malignancies are at increased risk of death or prolonged infection due to COVID-19. Data on the influence of different antineoplastic treatment modalities on outcomes are conflicting. Anti-CD20 monoclonal antibodies increase the risk of prolonged infection. It is unclear whether this risk is affected by the choice of the antibody (rituximab vs. obinutuzumab). To elucidate the role of antineoplastic therapy on COVID-19 outcomes, KroHem collected data on patients with lymphoid malignancies diagnosed with COVID-19 between October 2020 and April 2021. A total of 314 patients were identified, 75 untreated, 61 off treatment and 178 on treatment. The mortality rate in untreated and off-treatment patients was 15% and 16%; 9% and 10% had prolonged infection. In the on-treatment group, 3% were still prolonged positive at time of data collection, 62% recovered and 35% died; 42% had prolonged infection. Disease type, use of anti-CD20 monoclonal antibodies, prior autologous stem-cell transplantation (ASCT) and line of treatment did not significantly affect mortality. Mortality was higher in older patients (p = 0.0078) and those treated with purine analogues (p = 0.012). Prolonged COVID-19 was significantly more frequent in patients treated with anti-CD20 monoclonal antibodies (p = 0.012), especially obinutuzumab, and purine analogues (p = 0.012). Age, prior ASCT and treatment line did not significantly affect risk of prolonged infection. These data suggest that increased age and use of purine analogues are main risk factors for increased mortality of COVID-19 in patients with lymphoid malignancies. Obinutuzumab further increases the risk of prolonged disease, but not of death, in comparison to rituximab. Epidemiological considerations should be taken into account when choosing the appropriate antineoplastic therapy for patients with lymphoid malignancies. Full article

(This article belongs to the Special Issue The End of the COVID-19 Pandemic—What Is Currently Known and What Could Have Been Useful Four Years Ago?)

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14 pages, 1620 KiB

Open AccessArticle

Procoagulant Status and Fibrinolytic Activity in COVID-19 Patients during Illness and Convalescence

by Olga S. Beznoshchenco, Andrey Yu. Romanov, Nataliya V. Dolgushina, Elena A. Gorodnova, Tatiana Yu. Ivanets, Ekaterina L. Yarotskaya, Aleksey V. Pyregov, Sergej V. Grachev and Gennady T. Sukhikh

Biomedicines 2024, 12(1), 42; https://doi.org/10.3390/biomedicines12010042 - 22 Dec 2023

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Abstract

SARS-CoV-2 (Severe Acute Respiratory Syndrome-related CoronaVirus 2) activates the immune system, causing thrombin dysregulation and tissue damage and reduces endothelium anticoagulant function, leading to excessive thrombin formation. Hypercoagulability, which causes multiple organ failure in critically ill COVID-19 (COronaVIrus Disease 2019) patients, can be [...] Read more.

SARS-CoV-2 (Severe Acute Respiratory Syndrome-related CoronaVirus 2) activates the immune system, causing thrombin dysregulation and tissue damage and reduces endothelium anticoagulant function, leading to excessive thrombin formation. Hypercoagulability, which causes multiple organ failure in critically ill COVID-19 (COronaVIrus Disease 2019) patients, can be detected by viscoelastic tests like thromboelastography and rotational thromboelastometry (ROTEM). We aimed to assess the coagulation system status and fibrinolytic activity using ROTEM thromboelastometry in patients with COVID-19 and convalescents. The observational prospective study included 141 patients with COVID-19: Group 1—patients with mild (n = 39), Group 2—patients with moderate (n = 65), and Group 3—patients with severe (n = 37) COVID-19. The coagulation status was assessed twice—during the disease and in convalescence. The male gender, age > 56 years, overweight, and obesity were risk factors for developing severe COVID-19. During the disease in patients with moderate and severe COVID-19, the hemostatic system was characterized by a procoagulant status, which persists during the period of convalescence. Fibrinolysis shutdown was detected in both moderate and severe patients with COVID-19. The procoagulant status of the coagulation system and the shutdown of fibrinolysis are typical for patients with moderate to severe COVID-19. In convalescents, activation of coagulation remains, which indicates the need to monitor the hemostatic system after Illness. Full article

(This article belongs to the Special Issue The End of the COVID-19 Pandemic—What Is Currently Known and What Could Have Been Useful Four Years Ago?)

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10 pages, 1777 KiB

Open AccessEditor’s ChoiceArticle

Application of a Receptor-Binding-Domain-Based Simple Immunoassay for Assessing Humoral Immunity against Emerging SARS-CoV-2 Virus Variants

by Orsolya Mózner, Judit Moldvay, Kata Sára Szabó, Dorottya Vaskó, Júlia Domján, Dorottya Ács, Zoltán Ligeti, Csaba Fehér, Edit Hirsch, László Puskás, Cordula Stahl, Manfred Frey and Balázs Sarkadi

Biomedicines 2023, 11(12), 3193; https://doi.org/10.3390/biomedicines11123193 - 1 Dec 2023

Cited by 1 | Viewed by 1777

Abstract

We have developed a simple, rapid, high-throughput RBD-based ELISA to assess the humoral immunity against emerging SARS-CoV-2 virus variants. The cDNAs of the His-tagged RBD proteins of the virus variants were stably engineered into HEK cells secreting the protein into the supernatant, and [...] Read more.

We have developed a simple, rapid, high-throughput RBD-based ELISA to assess the humoral immunity against emerging SARS-CoV-2 virus variants. The cDNAs of the His-tagged RBD proteins of the virus variants were stably engineered into HEK cells secreting the protein into the supernatant, and RBD purification was performed by Ni-chromatography and buffer exchange by membrane filtration. The simplified assay uses single dilutions of sera from finger-pricked native blood samples, purified RBD in 96-well plates, and a chromogenic dye for development. The results of this RBD-ELISA were confirmed to correlate with those of a commercial immunoassay measuring antibodies against the Wuhan strain, as well as direct virus neutralization assays assessing the cellular effects of the Wuhan and the Omicron (BA.5) variants. Here, we document the applicability of this ELISA to assess the variant-specific humoral immunity in vaccinated and convalescent patients, as well as to follow the time course of selective vaccination response. This simple and rapid assay, easily modified to detect humoral immunity against emerging SARS-CoV-2 virus variants, may help to assess the level of antiviral protection after vaccination or infection. Full article

(This article belongs to the Special Issue The End of the COVID-19 Pandemic—What Is Currently Known and What Could Have Been Useful Four Years Ago?)

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12 pages, 2351 KiB

Open AccessArticle

Characterisation of Ferritin–Lymphocyte Ratio in COVID-19

by Alexander Liu, Robert Hammond, Kenneth Chan, Chukwugozie Chukwuenweniwe, Rebecca Johnson, Duaa Khair, Eleanor Duck, Oluwaseun Olubodun, Kristian Barwick, Winston Banya, James Stirrup, Peter D. Donnelly, Juan Carlos Kaski and Anthony R. M. Coates

Biomedicines 2023, 11(10), 2819; https://doi.org/10.3390/biomedicines11102819 - 18 Oct 2023

Cited by 3 | Viewed by 1482

Abstract

Introduction: The ferritin–lymphocyte ratio (FLR) is a novel inflammatory biomarker for the assessment of acute COVID-19 patients. However, the prognostic value of FLR for predicting adverse clinical outcomes in COVID-19 remains unclear, which hinders its clinical translation. Methods: We characterised the prognostic value [...] Read more.

Introduction: The ferritin–lymphocyte ratio (FLR) is a novel inflammatory biomarker for the assessment of acute COVID-19 patients. However, the prognostic value of FLR for predicting adverse clinical outcomes in COVID-19 remains unclear, which hinders its clinical translation. Methods: We characterised the prognostic value of FLR in COVID-19 patients, as compared to established inflammatory markers. Results: In 217 study patients (69 years [IQR: 55–82]; 60% males), FLR was weakly correlated with CRP (R = 0.108, p = 0.115) and white cell count (R = −0.144; p = 0.034). On ROC analysis, an FLR cut-off of 286 achieved a sensitivity of 86% and a specificity of 30% for predicting inpatient mortality (AUC 0.60, 95% CI: 0.53–0.67). The negative predictive values of FLR for ruling out mortality, non-invasive ventilation requirement and critical illness (intubation and/or ICU admission) were 86%, 85% and 93%, respectively. FLR performed similarly to CRP (AUC 0.60 vs. 0.64; p = 0.375) for predicting mortality, but worse than CRP for predicting non-fatal outcomes (all p < 0.05). On Kaplan–Meier analysis, COVID-19 patients with FLR values > 286 had worse inpatient survival than patients with FLR ≤ 286, p = 0.041. Conclusions: FLR has prognostic value in COVID-19 patients, and appears unrelated to other inflammatory markers such as CRP and WCC. FLR exhibits high sensitivity and negative predictive values for adverse clinical outcomes in COVID-19, and may be a good “rule-out” test. Further work is needed to improve the sensitivity of FLR and validate its role in prospective studies for guiding clinical management. Full article

(This article belongs to the Special Issue The End of the COVID-19 Pandemic—What Is Currently Known and What Could Have Been Useful Four Years Ago?)

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15 pages, 4698 KiB

Open AccessArticle

Thrombosis in Multisystem Inflammatory Syndrome Associated with COVID-19 in Children: Retrospective Cohort Study Analysis and Review of the Literature

by Liudmila V. Bregel, Olesya S. Efremova, Kirill Y. Kostyunin, Natalya Y. Rudenko, Yury A. Kozlov, Vadim V. Albot, Natalya А. Knyzeva, Olga V. Tolmacheva, Svetlana V. Ovanesyan, Alexander O. Barakin, Ki O. Pak, Liudmila V. Belousova, Tatyana S. Korinets and Mikhail M. Kostik

Biomedicines 2023, 11(8), 2206; https://doi.org/10.3390/biomedicines11082206 - 6 Aug 2023

Cited by 4 | Viewed by 1767

Abstract

Background: The causative agent of the new coronavirus infection SARS-CoV-2 has unique properties causing hyperinflammatory syndrome and cytokine storm, as well as widespread endotheliitis and thrombotic microangiopathy, initially detected in the lungs of adult patients who died from a severe form of the [...] Read more.

Background: The causative agent of the new coronavirus infection SARS-CoV-2 has unique properties causing hyperinflammatory syndrome and cytokine storm, as well as widespread endotheliitis and thrombotic microangiopathy, initially detected in the lungs of adult patients who died from a severe form of the disease. Venous and arterial thrombosis in adults were identified as common causes of severe complications and deaths in new coronavirus infections. There are very few reports of thrombotic events in children with COVID-19 in the literature. Methods: We conducted a retrospective analysis of the histories of 60 patients in the Irkutsk Regional Children’s Clinical Hospital from November 2020 to November 2022 with a MIS-C diagnosis established according to WHO criteria, of which 8 (13.3%) were diagnosed with venous and/or arterial thrombosis, confirmed by laboratory and ultrasound and/or X-ray methods. Results: The average age of children with thrombosis (Me) was 7.5 years (min 4 months, max 17 years), with a M:F ratio of 3.0. Venous thrombosis was detected in six of the eight patients, including in the deep veins of the lower extremities in four. Pulmonary embolism occurred in two (one of them was fatal), and cerebral venous sinus thrombosis and thrombosis of the branches of the upper and lower vena cava were found in one patient. Extensive bilateral stroke due to thrombosis of the large cerebral arteries occurred in two patients, including one in combination with distal gangrene. Secondary thrombotic renal microangiopathy took place in three of the eight patients. Among these three, atypical HUS was diagnosed in one case. Multiple thrombosis involving the venous and arterial bed was detected in four of the eight patients. High levels of D-dimer, thrombocytopenia, increased NT-proBNP, cerebral coma, and aseptic meningitis were the events most often associated with thrombosis. All patients received immunomodulatory therapy (immunoglobulin, dexamethasone/methylprednisolone), pathogenetic therapy for multiorgan failure, anticoagulant therapy with heparin/LMWH, and acetylsalicylic acid. Biologics were used in two patients. Conclusions: The main predictors of thrombosis in children with MIS-C were increased D-dimer, thrombocytopenia, hospitalization in the ICU, and noncardiogenic pulmonary edema. Thrombosis of the deep veins of the lower extremities, large cerebral arteries, and secondary thrombotic microangiopathy was common. There was a single death (12.5% of the eight patients), associated with PE. Full article

(This article belongs to the Special Issue The End of the COVID-19 Pandemic—What Is Currently Known and What Could Have Been Useful Four Years Ago?)

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Review

Jump to: Research, Other

26 pages, 3634 KiB

Open AccessReview

Addressing Post-Acute COVID-19 Syndrome in Cancer Patients, from Visceral Obesity and Myosteatosis to Systemic Inflammation: Implications in Cardio-Onco-Metabolism

by Vincenzo Quagliariello, Maria Laura Canale, Irma Bisceglia, Carlo Maurea, Domenico Gabrielli, Luigi Tarantini, Andrea Paccone, Alessandro Inno, Stefano Oliva, Christian Cadeddu Dessalvi, Concetta Zito, Michele Caraglia, Massimiliano Berretta, Giuseppe D’Aiuto and Nicola Maurea

Biomedicines 2024, 12(8), 1650; https://doi.org/10.3390/biomedicines12081650 - 24 Jul 2024

Cited by 1 | Viewed by 1452

Abstract

Cardiovascular disease and cancer are the two leading causes of morbidity and mortality in the world. The emerging field of cardio-oncology described several shared risk factors that predispose patients to both cardiovascular disease and cancer. Post-acute COVID-19 syndrome is a chronic condition that [...] Read more.

Cardiovascular disease and cancer are the two leading causes of morbidity and mortality in the world. The emerging field of cardio-oncology described several shared risk factors that predispose patients to both cardiovascular disease and cancer. Post-acute COVID-19 syndrome is a chronic condition that occurs in many patients who have experienced a SARS-CoV-2 infection, mainly based on chronic fatigue, sedentary lifestyle, cramps, breathing difficulties, and reduced lung performance. Post-acute COVID-19 exposes patients to increased visceral adiposity, insulin resistance, myosteatosis, and white adipose tissue content (surrounded by M1 macrophages and characterized by a Th1/Th17 phenotype), which increases the risk of cardiovascular mortality and cancer recurrence. In this review, the main metabolic affections of post-acute COVID-19 syndrome in cancer patients at low and high risk of cardiomyopathies will be summarized. Furthermore, several non-pharmacological strategies aimed at reducing atherosclerotic and cardiac risk will be provided, especially through anti-inflammatory nutrition with a low insulin and glycemic index, appropriate physical activity, and immune-modulating bioactivities able to reduce visceral obesity and myosteatosis, improving insulin-related signaling and myocardial metabolism. Full article

(This article belongs to the Special Issue The End of the COVID-19 Pandemic—What Is Currently Known and What Could Have Been Useful Four Years Ago?)

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12 pages, 532 KiB

Open AccessReview

The Impact of COVID-19 on the Guillain–Barré Syndrome Incidence

by Magdalena Kopańko, Magdalena Zabłudowska, Monika Zajkowska, Monika Gudowska-Sawczuk, Mateusz Mucha and Barbara Mroczko

Biomedicines 2024, 12(6), 1248; https://doi.org/10.3390/biomedicines12061248 - 4 Jun 2024

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Abstract

Despite the fact that the global COVID-19 pandemic has officially ended, we continue to feel its effects and discover new correlations between SARS-CoV-2 infection and changes in the organism that have occurred in patients. It has been shown that the disease can be [...] Read more.

Despite the fact that the global COVID-19 pandemic has officially ended, we continue to feel its effects and discover new correlations between SARS-CoV-2 infection and changes in the organism that have occurred in patients. It has been shown that the disease can be associated with a variety of complications, including disorders of the nervous system such as a characteristic loss of smell and taste, as well as less commonly reported incidents such as cranial polyneuropathy or neuromuscular disorders. Nervous system diseases that are suspected to be related to COVID-19 include Guillain–Barré syndrome, which is frequently caused by viruses. During the course of the disease, autoimmunity destroys peripheral nerves, which despite its rare occurrence, can lead to serious consequences, such as symmetrical muscle weakness and deep reflexes, or even their complete abolition. Since the beginning of the pandemic, case reports suggesting a relationship between these two disease entities have been published, and in some countries, the increasing number of Guillain–Barré syndrome cases have also been reported. This suggests that previous contact with SARS-CoV-2 may have had an impact on their occurrence. This article is a review and summary of the literature that raises awareness of the neurological symptoms’ prevalence, including Guillain–Barré syndrome, which may be impacted by the commonly occurring COVID-19 disease or vaccination against it. The aim of this review was to better understand the mechanisms of the virus’s action on the nervous system, allowing for better detection and the prevention of its complications. Full article

(This article belongs to the Special Issue The End of the COVID-19 Pandemic—What Is Currently Known and What Could Have Been Useful Four Years Ago?)

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23 pages, 3270 KiB

Open AccessReview

COVID-19 on Oral Health: A New Bilateral Connection for the Pandemic

by Luigi Bellocchio, Gianna Dipalma, Angelo Michele Inchingolo, Alessio Danilo Inchingolo, Laura Ferrante, Gaetano Del Vecchio, Giuseppina Malcangi, Andrea Palermo, Andis Qendro and Francesco Inchingolo

Biomedicines 2024, 12(1), 60; https://doi.org/10.3390/biomedicines12010060 - 26 Dec 2023

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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and transmission are generally known to be produced by respiratory droplets and aerosols from the oral cavity (O.C.) of infected subjects, as stated by the World Health Organization. Saliva also retains the viral particles and [...] Read more.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and transmission are generally known to be produced by respiratory droplets and aerosols from the oral cavity (O.C.) of infected subjects, as stated by the World Health Organization. Saliva also retains the viral particles and aids in the spread of COVID-19. Angiotensin-converting enzyme Type 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are two of the numerous factors that promote SARS-CoV-2 infection, expressed by O.C. structures, various mucosa types, and the epithelia of salivary glands. A systemic SARS-CoV-2 infection might result from viral replication in O.C. cells. On the other hand, cellular damage of different subtypes in the O.C. might be associated with various clinical signs and symptoms. Factors interfering with SARS-CoV-2 infection potential might represent fertile ground for possible local pharmacotherapeutic interventions, which may confine SARS-CoV-2 virus entry and transmission in the O.C., finally representing a way to reduce COVID-19 incidence and severity. Full article

(This article belongs to the Special Issue The End of the COVID-19 Pandemic—What Is Currently Known and What Could Have Been Useful Four Years Ago?)

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Other

Jump to: Research, Review

11 pages, 422 KiB

Open AccessBrief Report

Using HScore for Evaluation of Hemophagocytosis in Multisystem Inflammatory Syndrome Associated with COVID-19 in Children

by Ilia S. Avrusin, Natalia N. Abramova, Konstantin E. Belozerov, Liudmila V. Bregel, Olesya S. Efremova, Alla A. Vilnits, Julia E. Konstantinova, Eugenia A. Isupova, Tatiana L. Kornishina, Vera V. Masalova, Olga V. Kalashnikova, Vyacheslav G. Chasnyk, Yuriy S. Aleksandrovich, Dmitri O. Ivanov and Mikhail M. Kostik

Biomedicines 2024, 12(2), 294; https://doi.org/10.3390/biomedicines12020294 - 27 Jan 2024

Cited by 2 | Viewed by 1255

Abstract

Hemophagocytic syndrome is a key point in the pathogenesis of severe forms of multisystem inflammatory syndrome associated with COVID-19 in children (MIS-C). The factors associated with hemophagocytosis in patients with MIS-C were assessed in the present study of 94 boys and 64 girls [...] Read more.

Hemophagocytic syndrome is a key point in the pathogenesis of severe forms of multisystem inflammatory syndrome associated with COVID-19 in children (MIS-C). The factors associated with hemophagocytosis in patients with MIS-C were assessed in the present study of 94 boys and 64 girls ranging in age from 4 months to 17 years, each of whose HScore was calculated. In accordance with a previous analysis, patients with HScore ≤ 91 (n = 79) and HScore > 91 (n = 79) were compared. Patients with HScore > 91 had a higher frequency of symptoms such as cervical lymphadenopathy, dry cracked lips, bright mucous, erythema/swelling of hands and feet, peeling of fingers, edematous syndrome, hepatomegaly, splenomegaly, and hypotension/shock. They also had a higher erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and D-dimer levels, and a tendency to anemia, thrombocytopenia, and hypofibrinogenemia. They more often needed acetylsalicylic acid and biological treatment and were admitted to ICU in 70.9% of cases. Conclusion: The following signs of severe MIS-C were associated with HScore > 91: myocardial involvement, pericarditis, hypotension/shock, and ICU admission. Full article

(This article belongs to the Special Issue The End of the COVID-19 Pandemic—What Is Currently Known and What Could Have Been Useful Four Years Ago?)

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