The End of the COVID-19 Pandemic—What Is Currently Known and What Could Have Been Useful Four Years Ago?

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: 31 May 2024 | Viewed by 13110

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Department of Neurodegeneration Diagnostics, Medical University of Bialystok, 15-269 Bialystok, Poland
Interests: neurodegenerative diseases; cancer; specific proteins; cytokines; biomarkers; non-invasive diagnosis
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Department of Biochemical Diagnostics, Medical University of Bialystok, Waszyngtona 15A St., 15-269 Bialystok, Poland
Interests: biomarkers; non-invasive diagnosis; inflammation; tumor biomarkers; neuroinflammation; specific proteins
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Special Issue Information

Dear Colleagues,

COVID-19 is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was identified in Wuhan, China, in December 2019. The disease spread worldwide, leading to an ongoing pandemic which was announced on March 11, 2020 by the World Health Organization (WHO). In the face of the growing number of patients affected by this disease, there was an urgent need to determine how to treat it and effectively detect infection. In one of the more severe stages of the pandemic, i.e., in May 2020, the highest mortality rate was observed in Italy, which was 14%.

In March 2020, scientists performed full sequencing of the new coronavirus, SARS-CoV-2, which contributed to the subsequent development of vaccines. The genome of the new coronavirus, SARS-CoV-2, shows 79% similarity to SARS-CoV-1 and 50% similarity to MERS-CoV. In addition, SARS-CoV-2, similarly to all coronaviruses, has a positive RNA strand. SARS-CoV-2 is mainly spread via droplet–air. Infection can also occur through the direct contact of mucous membranes with contaminated surfaces, e.g., through dirty hands. Infection occurs as a result of binding the SARS-CoV-2 S protein to, e.g., the ACE2 receptor, located, among other areas, on type 2 follicular epithelial cells. SARS-CoV-2 infection has a wide clinical spectrum; however, the course of the disease in most patients is mild and does not require hospitalization.

The first stage of the disease is often asymptomatic or with mild symptoms, e.g., fever, chills or cough. In some patients, especially young people, a loss of smell (anosmia) or loss of taste (ageusia) may be the only manifestation of the disease. In turn, in the elderly, the occurrence of unusual symptoms such as body temperature fluctuations, deliration and falls (associated with fatigue and weakness) may precede respiratory symptoms. After the acute phase of COVID-19, post COVID syndrome could occur (PC19, long-COVID). Its frequency, exact clinical picture and therapeutic recommendations are not yet fully known. Post COVID syndrome is assumed to include an abnormality 4 weeks after the onset of COVID-19. The most common complications are pulmonary tiredness, dyspnea, heart palpitations and olfactory and taste disturbances.

Despite the fact that on May 5, 2023, WHO declared the end of the COVID-19 global health emergency, we are still struggling with its consequences. However, during the pandemic, many studies and observations were carried out that expanded our knowledge about COVID-19. That is why this Special Issue aims to encourage continued comprehensive study in the field of biomolecular science connected with this disease over the past four years.

Dr. Monika Zajkowska
Dr. Monika Gudowska-Sawczuk
Guest Editors

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Keywords

  • COVID-19
  • SARS-CoV-2
  • pandemic
  • diagnosis
  • biomarkers
  • treatment
  • immunity
  • inflammation
  • cytokines
  • vaccine

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13 pages, 2067 KiB  
Article
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
Viewed by 429
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
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13 pages, 1289 KiB  
Article
SARS-CoV-2-Related Olfactory Dysfunction: Autopsy Findings, Histopathology, and Evaluation of Viral RNA and ACE2 Expression in Olfactory Bulbs
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
Viewed by 547
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
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17 pages, 1762 KiB  
Article
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 557
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
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12 pages, 1309 KiB  
Article
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
Viewed by 797
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
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13 pages, 728 KiB  
Article
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 1 | Viewed by 725
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
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15 pages, 1118 KiB  
Article
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
Viewed by 773
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
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14 pages, 2847 KiB  
Article
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
Viewed by 739
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
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12 pages, 1603 KiB  
Article
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
Viewed by 796
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
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12 pages, 1653 KiB  
Article
Treatment-Related Risk Factors for Adverse Outcomes of COVID-19 in Patients Treated for Lymphoid Malignancies in the Pre-Omicron Era—A Study of KroHem, the Croatian Group for Hematologic Diseases
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
Viewed by 664
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
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14 pages, 1620 KiB  
Article
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
Viewed by 826
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
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10 pages, 1777 KiB  
Article
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
Viewed by 1069
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
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12 pages, 2351 KiB  
Article
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 1 | Viewed by 895
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
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15 pages, 4698 KiB  
Article
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 1 | Viewed by 1234
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
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Review

Jump to: Research, Other

23 pages, 3270 KiB  
Review
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
Viewed by 1067
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
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Other

Jump to: Research, Review

11 pages, 422 KiB  
Brief 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
Viewed by 741
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
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