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1.
Clinical Immunology ; 246:109218, 2023.
Article in English | ScienceDirect | ID: covidwho-2165169

ABSTRACT

We aimed to develop a prediction model for intensive care unit (ICU) hospitalization of Coronavirus disease-19 (COVID-19) patients using artificial neural networks (ANN). We assessed 25 laboratory parameters at first from 248 consecutive adult COVID-19 patients for database creation, training, and development of ANN models. We developed a new alpha-index to assess association of each parameter with outcome. We used 166 records for training of computational simulations (training), 41 for documentation of computational simulations (validation), and 41 for reliability check of computational simulations (testing). The first five laboratory indices ranked by importance were Neutrophil-to-lymphocyte ratio, Lactate Dehydrogenase, Fibrinogen, Albumin, and D-Dimers. The best ANN based on these indices achieved accuracy 95.97%, precision 90.63%, sensitivity 93.55%. and F1-score 92.06%, verified in the validation cohort. Our preliminary findings reveal for the first time an ANN to predict ICU hospitalization accurately and early, using only 5 easily accessible laboratory indices.

6.
HemaSphere ; 6(8), 2022.
Article in English | EuropePMC | ID: covidwho-1970742

ABSTRACT

COVID-19 vaccination leads to a less intense humoral response in patients with multiple myeloma (MM) compared with healthy individuals, whereas the SARS-CoV-2-specific immunity fades over time. The purpose of this study was to explore the kinetics of SARS-CoV-2 neutralizing antibodies (NAbs) in patients with MM after vaccination with the BNT162b2 mRNA vaccine, focusing on their response before (B4D) and at 1 month after the fourth vaccination (M1P4D). Overall, 201 patients with a median age of 67 years were included, whereas 114 (56.7%) were men. The median NAbs levels B4D were 80.0% (±3.5%) and at M1P4D they increased to a median value of 96.1% (±3.7%). The NAb values at M1P4D were similar to those at 1 month post the third dose and superior to all previous timepoints. At M1P4D, the NAbs levels of all the treatment groups increased, apart from the anti-BCMA group. A significant increase in median NAbs values was observed for those receiving CD38-based treatment (n = 43, from 71.0% B4D to 96.0% at M1P4D) and those who did not receive CD38- or BCMA-targeted therapy (n = 137, from 89.6% B4D to 96.3% at M1P4D). Regarding the patients under BCMA-based therapy (n = 21), there was no remarkable increase in NAbs values following the second booster shot (from 3.0% B4D to 4.0% at M1P4D). In conclusion, booster vaccination with the BNT162b2 results in a substantially improved humoral response against SARS-CoV-2 in patients with MM. Anti-BCMA treatment remains an adverse predictive factor for NAbs response;thus, tailored prevention measures should be considered for this patient subgroup.

7.
Am J Hematol ; 97(10): 1300-1308, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-1955886

ABSTRACT

Patients with B-cell malignancies have suboptimal immune responses to SARS-CoV-2 vaccination and are a high-risk population for severe COVID19 disease. We evaluated the effect of a third booster BNT162b2 vaccine on the kinetics of anti- SARS-CoV-2 neutralizing antibody (NAbs) titers in patients with B-cell malignancies. Patients with NHL (n = 54) Waldenström's macroglobulinemia (n = 90) and chronic lymphocytic leukemia (n = 49) enrolled in the ongoing NCT04743388 study and compared against matched healthy controls. All patient groups had significantly lower NAbs compared to controls at all time points. 1 month post the third dose (M1P3D) NAbs increased significantly compared to previous time points (median NAbs 77.9%, p < .05 for all comparisons) in all patients. NAbs ≥ 50% were seen in 59.1% of patients, 34.5% of patients with suboptimal responses post-second dose, elicited a protective NAb titer ≥50%. Active treatment, rituximab, and BTKi treatment were the most important prognostic factors for a poor NAb response at 1MP3D; only 25.8% of patients on active treatment had NAbs ≥ 50%. No significant between-group differences were observed. Patients with B-cell malignancies have inferior humoral responses against SARS-CoV-2 and booster dose enhances the NAb response in a proportion of these patients.


Subject(s)
COVID-19 , Neoplasms , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines , Humans , SARS-CoV-2 , Vaccination
9.
Hemato ; 3(1):111, 2022.
Article in English | ProQuest Central | ID: covidwho-1818069

ABSTRACT

Background. Hypercoagulable state and endothelial cell activation are common alterations in patients with COVID-19. Nevertheless, the hypothesis of persistent hypercoagulability and endothelial cell activation following recovery from COVID-19 remains an unresolved issue. Objectives. To investigate the persistence of endothelial cell activation and hypercoagulability after recovery from COVID-19. Patients/Methods. COVID-19 survivors (n = 208) and 30 healthy individuals were enrolled in this study. The following biomarkers were measured: procoagulant phospholipid-dependent clotting time (PPL-ct), D-Dimer, fibrin monomers (FM), free Tissue factor pathway inhibitor (free-TFP)I, heparinase, and soluble thrombomodulin (sTM). Antibodies against SARS-CoV-2 (IgG and IgA) were also measured. Results. The median interval between symptom onset and screening for SARS-CoV-2 antibodies was 62 days (IQR = 22 days). Survivors showed significantly higher levels of D-Dimers, FM, TFPI, and heparanase as compared to that of the control group. Survivors had significantly shorter PPL-ct. Elevated D-dimer was associated with older age. Elevated FM was associated with female gender. Elevated heparanase was independently associated with male gender. Decreased Procoag-PPL clotting time was associated with female gender. One out of four of COVID-19 survivors showed increase at least one biomarker of endothelial cell activation or hypercoagulability. Conclusions. Two months after onset of COVID-19, a significant activation of endothelial cells and in vivo thrombin generation persists in at least one out of four survivors of COVID-19. The clinical relevance of these biomarkers in the diagnosis and follow-up of patients with long COVID-19 merits to be evaluated in a prospective clinical study.

10.
Trends Mol Med ; 28(7): 542-554, 2022 07.
Article in English | MEDLINE | ID: covidwho-1799776

ABSTRACT

Vaccination is a major tool for mitigating the coronavirus disease 2019 (COVID-19) pandemic, and mRNA vaccines are central to the ongoing vaccination campaign that is undoubtedly saving thousands of lives. However, adverse effects (AEs) following vaccination have been noted which may relate to a proinflammatory action of the lipid nanoparticles used or the delivered mRNA (i.e., the vaccine formulation), as well as to the unique nature, expression pattern, binding profile, and proinflammatory effects of the produced antigens - spike (S) protein and/or its subunits/peptide fragments - in human tissues or organs. Current knowledge on this topic originates mostly from cell-based assays or from model organisms; further research on the cellular/molecular basis of the mRNA vaccine-induced AEs will therefore promise safety, maintain trust, and direct health policies.


Subject(s)
COVID-19 , Viral Vaccines , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Liposomes , Nanoparticles , RNA, Messenger/genetics , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Vaccines, Synthetic , Viral Vaccines/genetics , mRNA Vaccines
11.
Front Endocrinol (Lausanne) ; 13: 840668, 2022.
Article in English | MEDLINE | ID: covidwho-1793031

ABSTRACT

Background: This is the first study, that aimed: a) to compare immune response, namely the kinetics of neutralizing antibodies (Nabs), after vaccination with BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech) between patients with autoimmune thyroiditis and controls, and b) to investigate changes in thyroid function in healthy subjects with no history of thyroid dysfunction before and after vaccination with BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech). Methods: The entire study consisted of two sub-studies. In the first sub-study, NAbs levels after BNT162b2 mRNA vaccination were compared between 56 patients with autoimmune thyroiditis and 56 age and gender-matched healthy controls from the day of the first dose until a period of up to three months after the second dose. In the second sub-study, thyroid hormones (T3, T4, TSH) and thyroid auto-antibodies levels (anti-TG, anti-TPO) of 72 healthy subjects with no history of thyroid disease were examined before (D1) and one month after completion of the second dose (D50). Results: Among patients with autoimmune thyroiditis, the median neutralizing inhibition on D22, immediately before second dose, was 62.5%. One month later (D50), values increased to 96.7%, while three months after the second dose NAbs titers remained almost the same (94.5%). In the healthy group, median NAbs levels at D22 were 53.6%. On D50 the median inhibition values increased to 95.1%, while after three months they were 89.2%. The statistical analysis did not show significant differences between two groups (p-values 0.164, 0.390, 0.105 for D22, D50 and three months). Regarding changes in thyroid function, the mean value for T4 before vaccination was 89.797 nmol/L and one month after the second dose was 89.11 nmol/L (p-value=0.649). On D1 the mean T3 value was 1.464 nmol/L, which dropped to 1.389 nmol/L on D50 (p-value = 0.004). For TSH, mean levels were 2.064 mIU/ml on D1 and fell to 1.840 mIU/ml one month after the second dose (p-value=0.037). Despite decrease, all thyroid hormone levels remained within the normal range. No changes were found for anti-TPO or anti-TG. Conclusions: This study provided evidence that patients with autoimmune thyroiditis present similar immunological response to COVID-19 BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech) with healthy subjects, while vaccination may affect thyroid function.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Thyroiditis, Autoimmune/immunology , Adult , Autoantibodies/blood , Autoantibodies/immunology , /genetics , COVID-19/prevention & control , COVID-19/virology , Case-Control Studies , Female , Follow-Up Studies , Healthy Volunteers , Humans , Male , Middle Aged , SARS-CoV-2/genetics , Thyroid Gland/metabolism , Thyroid Hormones/blood , Thyroid Hormones/metabolism , Thyroiditis, Autoimmune/metabolism , Vaccination
12.
Viruses ; 14(4)2022 04 05.
Article in English | MEDLINE | ID: covidwho-1776360

ABSTRACT

In-depth understanding of the immune response provoked by SARS-CoV-2 infection is necessary, as there is a great risk of reinfection and a difficulty in achieving herd immunity due to a decline in both antibody concentration and avidity. Avidity testing, however, could overcome variability in the immune response associated with sex or clinical symptoms, and thus differentiate between recent and past infections. In this context, here, we analyzed SARS-CoV-2 antibody kinetics and avidity in Greek hospitalized (26%) and non-hospitalized (74%) COVID-19 patients (N = 71) in the course of up to 15 months after their infection to improve the accuracy of the serological diagnosis in dating the onset of the infection. The results showed that IgG-S1 levels decline significantly at four months (p = 0.0239) in both groups of patients and are higher in hospitalized ones (up to 2.1-fold, p < 0.001). Additionally, hospitalized patients' titers drop greatly and are equalized to non-hospitalized ones only at a time-point of twelve to fifteen months. Antibody levels of women in total remain more stable months after infection, compared to men. Furthermore, we examined the differential maturation of IgG avidity after SARS-CoV-2 infection, showing an incomplete maturation of avidity that results in a plateau at four months after infection. We also defined 38.2% avidity (sensitivity: 58.9%, specificity: 90.91%) as an appropriate "cut-off" that could be used to determine the stage of infection before avidity reaches a plateau.


Subject(s)
COVID-19 , Antibodies, Viral , Antibody Formation , COVID-19/diagnosis , Female , Greece , Humans , Immunoglobulin G , Kinetics , Male , SARS-CoV-2
13.
Cells ; 11(7)2022 04 06.
Article in English | MEDLINE | ID: covidwho-1776140

ABSTRACT

Vaccination is currently the most effective strategy for the mitigation of the COVID-19 pandemic. mRNA vaccines trigger the immune system to produce neutralizing antibodies (NAbs) against SARS-CoV-2 spike proteins. However, the underlying molecular processes affecting immune response after vaccination remain poorly understood, while there is significant heterogeneity in the immune response among individuals. Metabolomics have often been used to provide a deeper understanding of immune cell responses, but in the context of COVID-19 vaccination such data are scarce. Mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR)-based metabolomics were used to provide insights based on the baseline metabolic profile and metabolic alterations induced after mRNA vaccination in paired blood plasma samples collected and analysed before the first and second vaccination and at 3 months post first dose. Based on the level of NAbs just before the second dose, two groups, "low" and "high" responders, were defined. Distinct plasma metabolic profiles were observed in relation to the level of immune response, highlighting the role of amino acid metabolism and the lipid profile as predictive markers of response to vaccination. Furthermore, levels of plasma ceramides along with certain amino acids could emerge as predictive biomarkers of response and severity of inflammation.


Subject(s)
COVID-19 Vaccines , COVID-19 , Antibodies, Neutralizing , Antibodies, Viral , Biomarkers , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Immunity , Metabolomics , Pandemics , Plasma , SARS-CoV-2 , Vaccination
14.
Br J Haematol ; 197(5): 576-579, 2022 06.
Article in English | MEDLINE | ID: covidwho-1741343

ABSTRACT

Patients with transfusion-dependent thalassaemia (TDT) are considered an at increased-risk population for severe and/or morbid coronavirus disease 2019 (COVID-19) infection. Timely vaccination is the main preventive method for severe COVID-19. Different adverse events and reactions after vaccination have been reported, with severe ones being extremely rare. Patients with TDT may have altered immunity due to chronic transfusions, iron overload and chelation therapy, and splenic dysfunction. Here, we show that adult patients with TDT following vaccination with the novel messenger RNA vaccines have mild adverse events and can produce protective antibodies comparable to the healthy population.


Subject(s)
COVID-19 , Thalassemia , Adult , Antibodies, Viral , COVID-19/prevention & control , Humans , Immunity , SARS-CoV-2 , Thalassemia/complications , Thalassemia/therapy , Vaccination/adverse effects
15.
Frontiers in endocrinology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-1733325

ABSTRACT

Background This is the first study, that aimed: a) to compare immune response, namely the kinetics of neutralizing antibodies (Nabs), after vaccination with BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech) between patients with autoimmune thyroiditis and controls, and b) to investigate changes in thyroid function in healthy subjects with no history of thyroid dysfunction before and after vaccination with BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech). Methods The entire study consisted of two sub-studies. In the first sub-study, NAbs levels after BNT162b2 mRNA vaccination were compared between 56 patients with autoimmune thyroiditis and 56 age and gender-matched healthy controls from the day of the first dose until a period of up to three months after the second dose. In the second sub-study, thyroid hormones (T3, T4, TSH) and thyroid auto-antibodies levels (anti-TG, anti-TPO) of 72 healthy subjects with no history of thyroid disease were examined before (D1) and one month after completion of the second dose (D50). Results Among patients with autoimmune thyroiditis, the median neutralizing inhibition on D22, immediately before second dose, was 62.5%. One month later (D50), values increased to 96.7%, while three months after the second dose NAbs titers remained almost the same (94.5%). In the healthy group, median NAbs levels at D22 were 53.6%. On D50 the median inhibition values increased to 95.1%, while after three months they were 89.2%. The statistical analysis did not show significant differences between two groups (p-values 0.164, 0.390, 0.105 for D22, D50 and three months). Regarding changes in thyroid function, the mean value for T4 before vaccination was 89.797 nmol/L and one month after the second dose was 89.11 nmol/L (p-value=0.649). On D1 the mean T3 value was 1.464 nmol/L, which dropped to 1.389 nmol/L on D50 (p-value = 0.004). For TSH, mean levels were 2.064 mIU/ml on D1 and fell to 1.840 mIU/ml one month after the second dose (p-value=0.037). Despite decrease, all thyroid hormone levels remained within the normal range. No changes were found for anti-TPO or anti-TG. Conclusions This study provided evidence that patients with autoimmune thyroiditis present similar immunological response to COVID-19 BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech) with healthy subjects, while vaccination may affect thyroid function.

16.
Hemato ; 3(1):204-219, 2022.
Article in English | MDPI | ID: covidwho-1732001

ABSTRACT

In some patients, SARS-CoV-2 infection induces cytokine storm, hypercoagulability and endothelial cell activation leading to worsening of COVID-19, intubation and death. Prompt identification of patients at risk of intubation is an urgent need. Objectives. To derive a prognostic score for the risk of intubation or death in patients with COVID-19 admitted in intensive care unit (ICU), by assessing biomarkers of hypercoagulability, endothelial cell activation and inflammation and a large panel of clinical analytes. Design, Setting and Participants. A prospective, observational study enrolled 118 patients with COVID-19 admitted in the ICU. On the first day of ICU admission, all patients were assessed for biomarkers (protein C, protein S, antithrombin, D-Dimer, fibrin monomers, FVIIa, FV, FXII, FXII, FVIII, FvW antigen, fibrinogen, procoagulant phospholipid dependent clotting time, TFPI, thrombomodulin, P-selectin, heparinase, microparticles exposing TF, IL-6, complement C3a, C5a, thrombin generation, PT, aPTT, hemogram, platelet count) and clinical predictors. Main Outcomes and Measures. The clinical outcomes were intubation and mortality during hospitalization in ICU. Results: The intubation and mortality rates were 70% and 18%, respectively. The COMPASS-COVID-19-ICU score composed of P-Selectin, D-Dimer, free TFPI, TF activity, IL-6 and FXII, age and duration of hospitalization predicted the risk of intubation or death with high sensitivity and specificity (0.90 and 0.92, respectively). Conclusions and Relevance. COVID-19 is related to severe endothelial cell activation and hypercoagulability orchestrated in the context of inflammation. The COMPASS-COVID-19-ICU risk assessment model is accurate for the evaluation of the risk of mechanical ventilation and death in patients with critical COVID-19. The COMPASS-COVID-19-ICU score is feasible in tertiary hospitals and could be placed in the diagnostic procedure of personalized medical management and prompt therapeutic intervention.

17.
Front Endocrinol (Lausanne) ; 13: 780663, 2022.
Article in English | MEDLINE | ID: covidwho-1731765

ABSTRACT

There seems to be a bidirectional interplay between Diabetes mellitus (DM) and coronavirus disease 2019 (COVID-19). On the one hand, people with diabetes are at higher risk of fatal or critical care unit-treated COVID-19 as well as COVID-19 related health complications compared to individuals without diabetes. On the other hand, clinical data so far suggest that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may result in metabolic dysregulation and in impaired glucose homeostasis. In addition, emerging data on new onset DM in previously infected with SARS-CoV-2 patients, reinforce the hypothesis of a direct effect of SARS-CoV-2 on glucose metabolism. Attempting to find the culprit, we currently know that the pancreas and the endothelium have been found to express Angiotensin-converting enzyme 2 (ACE2) receptors, the main binding site of the virus. To move from bench to bedside, understanding the effects of COVID-19 on metabolism and glucose homeostasis is crucial to prevent and manage complications related to COVID-19 and support recovering patients. In this article we review the potential underlying pathophysiological mechanisms between COVID-19 and glucose dysregulation as well as the effects of antidiabetic treatment in patients with diabetes and COVID-19.


Subject(s)
COVID-19/complications , Diabetes Complications/virology , Diabetes Mellitus/etiology , COVID-19/epidemiology , COVID-19/metabolism , COVID-19/pathology , Causality , Comorbidity , Diabetes Complications/epidemiology , Diabetes Complications/metabolism , Diabetes Mellitus/epidemiology , Diabetes Mellitus/pathology , Humans , Patient Acuity , Risk Factors , SARS-CoV-2/pathogenicity
19.
Biomedicines ; 10(2)2022 Feb 01.
Article in English | MEDLINE | ID: covidwho-1667045

ABSTRACT

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

20.
Biomedicines ; 10(2)2022 Jan 18.
Article in English | MEDLINE | ID: covidwho-1625623

ABSTRACT

Vaccination against SARS-CoV-2 with BNT162b2 mRNA vaccine plays a critical role in COVID-19 prevention. Although BNT162b2 is highly effective against COVID-19, a time-dependent decrease in neutralizing antibodies (NAbs) is observed. The aim of this study was to identify the individual features that may predict NAbs levels after vaccination. Machine learning techniques were applied to data from 302 subjects. Principal component analysis (PCA), factor analysis of mixed data (FAMD), k-means clustering, and random forest were used. PCA and FAMD showed that younger subjects had higher levels of neutralizing antibodies than older subjects. The effect of age is strongest near the vaccination date and appears to decrease with time. Obesity was associated with lower antibody response. Gender had no effect on NAbs at nine months, but there was a modest association at earlier time points. Participants with autoimmune disease had lower inhibitory levels than participants without autoimmune disease. K-Means clustering showed the natural grouping of subjects into five categories in which the characteristics of some individuals predominated. Random forest allowed the characteristics to be ordered by importance. Older age, higher body mass index, and the presence of autoimmune diseases had negative effects on the development of NAbs against SARS-CoV-2, nine months after full vaccination.

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