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1.
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.

2.
Trends Mol Med ; 2022 Apr 21.
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.

3.
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
4.
In Vivo ; 36(2): 954-960, 2022.
Article in English | MEDLINE | ID: covidwho-1732570

ABSTRACT

BACKGROUND/AIM: Multiple reports from all over the world link COVID-19 with endothelial/coagulation disorders as well as a dysregulated immune response. This study tested the hypothesis that immunostimulation will be greater in COVID-19 patients than in patients with H1N1 infection or bacterial sepsis. Also, whether an increase in immune stimulation will be accompanied by a more severely affected endothelium/coagulation system was examined. PATIENTS AND METHODS: Twenty-three septic patients, admitted in the Intensive Care Unit (ICU), were enrolled (9 with SARS-CoV-2, 5 with H1N1 pneumonia, 9 with bacterial sepsis). Myeloperoxidase (MPO) activity along with certain endothelial/coagulation factors were assessed on admission (time point 1) and at either improvement or deterioration (time point 2). RESULTS: MPO levels were significantly higher in COVID-19 patients compared to both other groups. Furthermore, in patients with COVID-19, vWF levels did not differ significantly, fVIII levels were lower while ADAMTS-13 activity was higher compared to patients with H1N1 pneumonia and bacterial sepsis (a trend in the latter). CONCLUSION: Increased immunostimulation was noted in COVID-19 patients compared to other septic patients; however, this was not accompanied by greater disturbance of the clotting system and/or more severe endothelial injury.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Influenza A Virus, H1N1 Subtype , Sepsis , Blood Coagulation Disorders/etiology , COVID-19/complications , Humans , Immunization , SARS-CoV-2 , Sepsis/complications
5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-318682

ABSTRACT

Currently, there are no effective treatments for novel corona virus disease 2019 (COVID-19). In this study, we report the preliminary results on the efficacy and safety of convalescent plasma (CP) infusion, as monotherapy in 9 patients with severe COVID-19 disease. The median time from symptom onset to CP transfusion was 6 days. All symptoms improved significantly after a median of 8 days. In 6/9 patients, symptomatic improvement was observed already after the 1 st dose of CP transfusion. Laboratory parameters associated with disease severity tended to significantly decrease over time and lymphocyte counts significantly increased on day 14. All patients exhibited significant increases in SARS-CoV-2 IgA and IgG antibodies starting on day 7 through day 21 after CP infusion with concurrent reduction of SARS-CoV-2 RNA on days 7 and 14 with 44.4% % of the patients having undetectable SARS-CoV-2 RNA on day 14. After a median follow-up of 66 days, all patients remain alive. Eight patients recovered completely and were discharged from hospital after a median duration of hospitalization of 21 days. No severe adverse events were observed. In conclusion, this preliminary report suggests that CP infusion monotherapy administered early in the disease course may be a safe and effective strategy for patients with severe COVID-19 disease. Trial registration: NCT04408209. Registered 05 May 2020- Retrospectively registered, (https://clinicaltrials.gov/ct2/show/ NCT04408209 ?term=NCT04408209&draw=2&rank=1).

6.
J Cell Mol Med ; 26(5): 1445-1455, 2022 03.
Article in English | MEDLINE | ID: covidwho-1642687

ABSTRACT

There is an unmet need of models for early prediction of morbidity and mortality of Coronavirus disease-19 (COVID-19). We aimed to a) identify complement-related genetic variants associated with the clinical outcomes of ICU hospitalization and death, b) develop an artificial neural network (ANN) predicting these outcomes and c) validate whether complement-related variants are associated with an impaired complement phenotype. We prospectively recruited consecutive adult patients of Caucasian origin, hospitalized due to COVID-19. Through targeted next-generation sequencing, we identified variants in complement factor H/CFH, CFB, CFH-related, CFD, CD55, C3, C5, CFI, CD46, thrombomodulin/THBD, and A Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS13). Among 381 variants in 133 patients, we identified 5 critical variants associated with severe COVID-19: rs2547438 (C3), rs2250656 (C3), rs1042580 (THBD), rs800292 (CFH) and rs414628 (CFHR1). Using age, gender and presence or absence of each variant, we developed an ANN predicting morbidity and mortality in 89.47% of the examined population. Furthermore, THBD and C3a levels were significantly increased in severe COVID-19 patients and those harbouring relevant variants. Thus, we reveal for the first time an ANN accurately predicting ICU hospitalization and death in COVID-19 patients, based on genetic variants in complement genes, age and gender. Importantly, we confirm that genetic dysregulation is associated with impaired complement phenotype.


Subject(s)
COVID-19/genetics , COVID-19/mortality , Neural Networks, Computer , COVID-19/epidemiology , Complement Activation/genetics , Complement Factor H/genetics , Complement System Proteins/genetics , Female , Greece/epidemiology , Hospitalization/statistics & numerical data , Humans , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Models, Genetic , Morbidity , Polymorphism, Single Nucleotide , Thrombomodulin/genetics
7.
Viruses ; 13(9)2021 09 15.
Article in English | MEDLINE | ID: covidwho-1411088

ABSTRACT

COVID-19 is an ongoing pandemic with high morbidity and mortality. Despite meticulous research, only dexamethasone has shown consistent mortality reduction. Convalescent plasma (CP) infusion might also develop into a safe and effective treatment modality on the basis of recent studies and meta-analyses; however, little is known regarding the kinetics of antibodies in CP recipients. To evaluate the kinetics, we followed 31 CP recipients longitudinally enrolled at a median of 3 days post symptom onset for changes in binding and neutralizing antibody titers and viral loads. Antibodies against the complete trimeric Spike protein and the receptor-binding domain (Spike-RBD), as well as against the complete Nucleocapsid protein and the RNA binding domain (N-RBD) were determined at baseline and weekly following CP infusion. Neutralizing antibody (pseudotype NAb) titers were determined at the same time points. Viral loads were determined semi-quantitatively by SARS-CoV-2 PCR. Patients with low humoral responses at entry showed a robust increase of antibodies to all SARS-CoV-2 proteins and Nab, reaching peak levels within 2 weeks. The rapid increase in binding and neutralizing antibodies was paralleled by a concomitant clearance of the virus within the same timeframe. Patients with high humoral responses at entry demonstrated low or no further increases; however, virus clearance followed the same trajectory as in patients with low antibody response at baseline. Together, the sequential immunological and virological analysis of this well-defined cohort of patients early in infection shows the presence of high levels of binding and neutralizing antibodies and potent clearance of the virus.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/virology , Nucleocapsid/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Viral Load , Aged , Aged, 80 and over , Antibody Formation/immunology , COVID-19/therapy , Female , Host-Pathogen Interactions , Humans , Immunization, Passive , Kinetics , Male , Middle Aged
8.
Blood ; 136(Supplement 1):1-2, 2020.
Article in English | PMC | ID: covidwho-1338965

ABSTRACT

Introduction: Convalescent plasma is a promising therapeutic option for corona virus disease 2019 (COVID-19). A recent study in 34 COVID-19 patients showed a reduction of recovered patients antibodies within 3 months of infection. The aim on this analysis was to evaluate the antibody titers and explore possible correlations with disease characteristics in volunteer donors, who participated in a phase 2 study for the use of convalescent plasma for the treatment of severe COVID-19 infection.Patients and Methods: This in an ongoing phase 2 study (NCT04408209) for the use of convalescent plasma for severe COVID-19. This analysis reports the results of the first part of the study, regarding the presence of anti-SARS-CoV-2 antibodies in volunteer plasma donors and their correlation with disease characteristics. The main Inclusion criteria for plasma donors included: (i) confirmed SARS-CoV-2 infection by PCR of the nasal/pharyngeal swab;(ii) interval of at least 14 days after complete recovery from COVID-19;(iii) presence of anti-SARS-CoV-2 antibodies;(iv) two negative SARS-CoV-2 PCR results (the second at least 7 days prior to plasmapheresis). For the detection of anti-SARS-CoV-2 antibodies we used two commercially developed assays: one ELISA assay (Euroimmun Medizinische Labordiagnostika AG, Lubeck, Germany), which detects antibodies against the recombinant Spike protein of the virus (S1 domain) and a multiplex assay (ProtATonce Ltd, Athens, Greece) based on the Luminex® xMAP™ technology that detects total antibodies (IgG/IgM/IgA) and individual antibody isotypes IgG, IgM and IgA against 3 SARS-CoV-2 antigens (S1, basic nucleocapsid (N) protein and receptor-binding domain (RBD).Results: To-date, 260 (137M/123F) possible plasma donors were tested for the presence of anti-SARS-CoV-2 antibodies. At the time of their COVID-19 diagnosis, 20 (7.7%) were asymptomatic, 157 (60.3%) were symptomatic but did not need hospitalization and 83 (32%) were hospitalized. Median time from the day of their first symptom or PCR+ (for asymptomatic patients) till the day of screening was 62 (range: 14-104) days. Anti-SARS-CoV-2 antibodies were detected in 229 (88%) donors with the Euroimmun assay and in 238 (91.5%) with the multiplex assay (including the 229 who had antibodies with the Euroimmun method). Univariate analysis showed that donors who had asymptomatic COVID-19 had lower antibody titer compared to those who had symptomatic disease but did not need hospitalization or those who hospitalized (Fig. A-D). Donors <50 years had lower antibody titer compared with older patients [for Euroimmun method, median (IQR): 3.94 (5.10) vs. 7.34 (6.16);p<0.0001], while patients who were tested within 60 days from the first day of symptom or PCR+ (for asymptomatic patients) had higher antibody titer [6.09 (6.52) vs. 4.68 (6.12);p=0.024]. The multivariate analysis showed that age ≥50 years (OR 2.88, 95% CI:1.60-5.18;p<0.001) and need for hospitalization (OR 4.11, 95% CI:2.13-7.90;p<0.001) correlated with higher antibody titers, while asymptomatic phase (OR 0.10, 95% CI:0,01-0.82;p<0.001) and testing within ≥60 days post symptoms onset (OR 0.36, 95% CI:0.20-0.66;p=0.001) correlated with lower antibody titers. In the multivariate logistic regression analysis examining associations between individual symptoms and antibody levels, there was strong correlation between anti-SARS-CoV-2 antibodies and anosmia (OR 11.14, 95% CI:3.92-31.67;p<0.001), loss of taste (OR 5.50, 95% CI:2.23-13.56;p<0.001), fever (OR 4.25, 95% CI:1.90-9.51;p<0.001), and headache (OR 2.34, 95% CI:1.09-5.03;p=0.029). To-date, plasmapheresis was performed in 74 patients with anti-SARS-CoV-2 antibodies, within a median time of 12 (8-19) days after screening;the respective median time (range) from the first day of symptoms or PCR+ was 52 (14-84) days. Interestingly, there was a significant reduction in the antibody titers between the day of screening and the day of plasmapheresis [Fig. E].Conclusion: Lower anti-SARS-CoV-2 antibody titers, against all studied epitopes, are found in asymptomatic patients, in patients <50 years and in those who were tested ≥60 days post onset of first symptoms. The rapid reduction of anti-SARS-CoV-2 antibodies in our cohort reveals a time pattern of reduction, although we do not know if neutralizing antibodies share the same trend or if this reduction affects the host immunity against SARS-CoV-2.

9.
Eur J Intern Med ; 89: 87-96, 2021 07.
Article in English | MEDLINE | ID: covidwho-1313078

ABSTRACT

Elucidating the characteristics of human immune response against SARS-CoV-2 is of high priority and relevant for determining vaccine strategies. We report the results of a follow-up evaluation of anti-SARS-CoV-2 antibodies in 148 convalescent plasma donors who participated in a phase 2 study at a median of 8.3 months (range 6.8-10.5 months) post first symptom onset. Monitoring responses over time, we found contraction of antibody responses for all four antigens tested, with Spike antibodies showing higher persistence than Nucleocapsid antibodies. A piecewise linear random-effects multivariate regression analysis showed a bi-phasic antibody decay with a more pronounced decrease during the first 6 months post symptoms onset by analysis of two intervals. Interestingly, antibodies to Spike showed better longevity whereas their neutralization ability contracted faster. As a result, neutralizing antibodies were detected in only 76% of patients at the last time point. In a multivariate analysis, older age and hospitalization were independently associated with higher Spike, Spike-RBD, Nucleocapsid, N-RBD antibodies and neutralizing antibody levels. Results on persistence and neutralizing ability of anti-SARS-CoV-2 antibodies, especially against Spike and Spike-RBD, should be considered in the design of future vaccination strategies.


Subject(s)
COVID-19 , SARS-CoV-2 , Aged , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/therapy , Humans , Immunization, Passive , Kinetics , Spike Glycoprotein, Coronavirus
10.
Vaccines (Basel) ; 9(7)2021 Jul 01.
Article in English | MEDLINE | ID: covidwho-1289048

ABSTRACT

It is unclear whether the ChAdOx1 nCov-19 vaccine can induce the development of anti-PF4 antibodies in vaccinated individuals who have not developed thrombosis. The aim of this prospective study was to evaluate the presence of antibodies against heparin/PF4 in adults who received a first dose of the ChAdOx1 nCov-19 vaccine, and correlate them with clinical data and antibody responses to the vaccine. We detected non-platelet activating anti-PF4 antibodies in 67% (29/43) of the vaccinated individuals on day 22 following the first dose of the ChAdOx1 nCov-19 vaccine, though these were detected in low titers. Furthermore, there was no correlation between the presence of anti-PF4 IgG antibodies and the baseline clinical characteristics of the patients. Our findings suggest that the ChAdOx1 nCov-19 vaccine can elicit anti-PF4 antibody production even in recipients without a clinical manifestation of thrombosis. The presence of anti-PF4 antibodies was not sufficient to provoke clinically evident thrombosis. Our results offer an important insight into the ongoing investigations regarding the underlying multifactorial pathophysiology of thrombotic events induced by the ChAdOx1 nCov-19 vaccine.

11.
Microorganisms ; 9(4)2021 Apr 11.
Article in English | MEDLINE | ID: covidwho-1178363

ABSTRACT

COVID-19 is a global pandemic associated with increased morbidity and mortality. Convalescent plasma (CP) infusion is a strategy of potential therapeutic benefit. We conducted a multicenter phase II study to evaluate the efficacy and safety of CP in patients with COVID-19, grade 4 or higher. To evaluate the efficacy of CP, a matched propensity score analysis was used comparing the intervention (n = 59) to a control group (n = 59). Sixty patients received CP within a median time of 7 days from symptom onset. During a median follow-up of 28.5 days, 56/60 patients fully recovered and 1 patient remained in the ICU. The death rate in the CP group was 3.4% vs. 13.6% in the control group. By multivariate analysis, CP recipients demonstrated a significantly reduced risk of death [HR: 0.04 (95% CI: 0.004-0.36), p: 0.005], significantly better overall survival by Kaplan-Meir analysis (p < 0.001), and increased probability of extubation [OR: 30.3 (95% CI: 2.64-348.9), p: 0.006]. Higher levels of antibodies in the CP were independently associated with significantly reduced risk of death. CP infusion was safe with only one grade 3 adverse event (AE), which easily resolved. CP used early may be a safe and effective treatment for patients with severe COVID-19 (trial number NCT04408209).

12.
Sci Rep ; 11(1): 6614, 2021 03 23.
Article in English | MEDLINE | ID: covidwho-1147848

ABSTRACT

There is a plethora of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) serological tests based either on nucleocapsid phosphoprotein (N), S1-subunit of spike glycoprotein (S1) or receptor binding domain (RBD). Although these single-antigen based tests demonstrate high clinical performance, there is growing evidence regarding their limitations in epidemiological serosurveys. To address this, we developed a Luminex-based multiplex immunoassay that detects total antibodies (IgG/IgM/IgA) against the N, S1 and RBD antigens and used it to compare antibody responses in 1225 blood donors across Greece. Seroprevalence based on single-antigen readouts was strongly influenced by both the antigen type and cut-off value and ranged widely [0.8% (95% CI 0.4-1.5%)-7.5% (95% CI 6.0-8.9%)]. A multi-antigen approach requiring partial agreement between RBD and N or S1 readouts (RBD&N|S1 rule) was less affected by cut-off selection, resulting in robust seroprevalence estimation [0.6% (95% CI 0.3-1.1%)-1.2% (95% CI 0.7-2.0%)] and accurate identification of seroconverted individuals.


Subject(s)
Antigens/immunology , COVID-19/diagnosis , Serologic Tests/methods , Adolescent , Adult , Aged , Antibodies, Viral/blood , COVID-19/virology , Coronavirus Nucleocapsid Proteins/immunology , Female , Humans , Immunoassay , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged , Phosphoproteins/immunology , SARS-CoV-2/isolation & purification , Sensitivity and Specificity , Spike Glycoprotein, Coronavirus/immunology , Young Adult
13.
Vaccines (Basel) ; 9(3)2021 Mar 02.
Article in English | MEDLINE | ID: covidwho-1124925

ABSTRACT

Between June and November 2020, we assessed plasma antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein in 4996 participants (aged 18-82 years, 34.5% men) from the National and Kapodistrian University of Athens. The weighted overall prevalence was 1.6% and monthly prevalence correlated with viral RNA-confirmed SARS-CoV-2 infections in Greece, in the same period. Notably, 49% of seropositive cases reported no history of SARS-CoV-2 infection-related clinical symptoms and 33% were unsuspected of their previous infection. Additionally, levels of anti-SARS-CoV-2 antibodies against the spike-protein receptor-binding domain were similar between symptomatic and asymptomatic individuals, irrespective of age and gender. Using Food and Drug Administration Emergency Use Authorization-approved assays, these results support the need for such studies on pandemic evaluation and highlight the development of robust humoral immune responses even among asymptomatic individuals. The high percentage of unsuspected/asymptomatic active cases, which may contribute to community transmission for more days than that of cases who are aware and self-isolate, underscores the necessity of measures across the population for the efficient control of the pandemic.

14.
Viruses ; 13(1)2020 12 25.
Article in English | MEDLINE | ID: covidwho-1043520

ABSTRACT

Immune profiling of patients with COVID-19 has shown that SARS-CoV-2 causes severe lymphocyte deficiencies (e.g., lymphopenia, decreased numbers, and exhaustion of T cells) and increased levels of pro-inflammatory monocytes. Peripheral blood (PB) samples from convalescent plasma (CP) donors, COVID-19 patients, and control subjects were analyzed by multiparametric flow cytometry, allowing the identification of a wide panel of immune cells, comprising lymphocytes (T, B, natural killer (NK) and NKT cells), monocytes, granulocytes, and their subsets. Compared to active COVID-19 patients, our results revealed that the immune profile of recovered donors was restored for most subpopulations. Nevertheless, even 2 months after recovery, CP donors still had reduced levels of CD4+ T and B cells, as well as granulocytes. CP donors with non-detectable levels of anti-SARS-CoV-2-specific antibodies in their serum were characterized by higher Th9 and Th17 cells, which were possibly expanded at the expense of Th2 humoral immunity. The most noticeable alterations were identified in previously hospitalized CP donors, who presented the lowest levels of CD8+ regulatory T cells, the highest levels of CD56+CD16- NKT cells, and a promotion of a Th17-type phenotype, which might be associated with a prolonged pro-inflammatory response. A longer follow-up of CP donors will eventually reveal the time needed for full recovery of their immune system competence.


Subject(s)
Antibodies, Viral/blood , COVID-19/therapy , Plasma/immunology , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Aged, 80 and over , B-Lymphocytes , CD4-Positive T-Lymphocytes , CD8-Positive T-Lymphocytes , COVID-19/immunology , Female , Humans , Immunity, Humoral , Immunization, Passive , Male , Middle Aged , Th1 Cells , Th17 Cells , Th2 Cells , Time Factors , Young Adult
15.
Viruses ; 13(1):26, 2021.
Article in English | ScienceDirect | ID: covidwho-984663

ABSTRACT

Immune profiling of patients with COVID-19 has shown that SARS-CoV-2 causes severe lymphocyte deficiencies (e.g., lymphopenia, decreased numbers, and exhaustion of T cells) and increased levels of pro-inflammatory monocytes. Peripheral blood (PB) samples from convalescent plasma (CP) donors, COVID-19 patients, and control subjects were analyzed by multiparametric flow cytometry, allowing the identification of a wide panel of immune cells, comprising lymphocytes (T, B, natural killer (NK) and NKT cells), monocytes, granulocytes, and their subsets. Compared to active COVID-19 patients, our results revealed that the immune profile of recovered donors was restored for most subpopulations. Nevertheless, even 2 months after recovery, CP donors still had reduced levels of CD4+ T and B cells, as well as granulocytes. CP donors with non-detectable levels of anti-SARS-CoV-2-specific antibodies in their serum were characterized by higher Th9 and Th17 cells, which were possibly expanded at the expense of Th2 humoral immunity. The most noticeable alterations were identified in previously hospitalized CP donors, who presented the lowest levels of CD8+ regulatory T cells, the highest levels of CD56+CD16−NKT cells, and a promotion of a Th17-type phenotype, which might be associated with a prolonged pro-inflammatory response. A longer follow-up of CP donors will eventually reveal the time needed for full recovery of their immune system competence.

16.
Microorganisms ; 8(12)2020 Nov 28.
Article in English | MEDLINE | ID: covidwho-948911

ABSTRACT

We evaluated the antibody responses in 259 potential convalescent plasma donors for Covid-19 patients. Different assays were used: a commercial ELISA detecting antibodies against the recombinant spike protein (S1); a multiplex assay detecting total and specific antibody isotypes against three SARS-CoV-2 antigens (S1, basic nucleocapsid (N) protein and receptor-binding domain (RBD)); and an in-house ELISA detecting antibodies to complete spike, RBD and N in 60 of these donors. Neutralizing antibodies (NAb) were also evaluated in these 60 donors. Analyzed samples were collected at a median time of 62 (14-104) days from the day of first symptoms or positive PCR (for asymptomatic patients). Anti-SARS-CoV-2 antibodies were detected in 88% and 87.8% of donors using the ELISA and the multiplex assay, respectively. The multivariate analysis showed that age ≥50 years (p < 0.001) and need for hospitalization (p < 0.001) correlated with higher antibody titers, while asymptomatic status (p < 0.001) and testing >60 days after symptom onset (p = 0.001) correlated with lower titers. Interestingly, pseudotype virus-neutralizing antibodies (PsNAbs) significantly correlated with spike and with RBD antibodies by ELISA. Sera with high PsNAb also showed a strong ability to neutralize active SARS-CoV-2 virus, with hospitalized patients showing higher titers. Therefore, convalescent plasma donors can be selected based on the presence of high RBD antibody titers.

17.
Hemasphere ; 4(3): e409, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-894676

ABSTRACT

Various agents are currently under evaluation as potential treatments in the fight against coronavirus disease 2019 (COVID-19). Plasma from patients that have overcome COVID-19 infection, referred to as convalescent plasma, is a treatment option with considerable background in viral diseases such as Spanish influenza, H1N1, Ebola, Severe Acute Respiratory Syndrome (SARS), and Middle East Respiratory Syndrome (MERS). Although convalescent plasma has historically proven beneficial in the treatment of some viral diseases, its use is still explorative in the context of COVID-19. To date, preliminary evidence from case series is favorable as significant clinical, biochemical improvement and hospital discharge have been reported. A detailed overview of randomized as well non-randomized trials of treatment with convalescent plasma, which have been registered worldwide, is provided in this review. Based on these studies, data from thousands of patients is anticipated in the near future. Convalescent plasma seems to be a safe option, but potential risks such as transfusion-related acute lung injury and antibody-dependent enhancement are discussed. Authorities including the Food and Drug Administration (FDA), and scientific associations such as the International Society of Blood Transfusion (ISBT) and the European Blood Alliance (EBA), have provided guidance into the selection criteria for donors and recipients. A debatable, pivotal issue pertains to the optimal timing of convalescent plasma transfusion. This treatment should be administered as early as possible to maximize efficacy, but at the same time be reserved for severe cases. Emerging risk stratification algorithms integrating clinical and biochemical markers to trace the cases at risk of significant deterioration can prove valuable in this direction.

19.
Am J Hematol ; 95(7): 834-847, 2020 07.
Article in English | MEDLINE | ID: covidwho-46110

ABSTRACT

COVID-19 is a systemic infection with a significant impact on the hematopoietic system and hemostasis. Lymphopenia may be considered as a cardinal laboratory finding, with prognostic potential. Neutrophil/lymphocyte ratio and peak platelet/lymphocyte ratio may also have prognostic value in determining severe cases. During the disease course, longitudinal evaluation of lymphocyte count dynamics and inflammatory indices, including LDH, CRP and IL-6 may help to identify cases with dismal prognosis and prompt intervention in order to improve outcomes. Biomarkers, such high serum procalcitonin and ferritin have also emerged as poor prognostic factors. Furthermore, blood hypercoagulability is common among hospitalized COVID-19 patients. Elevated D-Dimer levels are consistently reported, whereas their gradual increase during disease course is particularly associated with disease worsening. Other coagulation abnormalities such as PT and aPTT prolongation, fibrin degradation products increase, with severe thrombocytopenia lead to life-threatening disseminated intravascular coagulation (DIC), which necessitates continuous vigilance and prompt intervention. So, COVID-19 infected patients, whether hospitalized or ambulatory, are at high risk for venous thromboembolism, and an early and prolonged pharmacological thromboprophylaxis with low molecular weight heparin is highly recommended. Last but not least, the need for assuring blood donations during the pandemic is also highlighted.


Subject(s)
Betacoronavirus , Coronavirus Infections/blood , Lymphopenia/etiology , Pneumonia, Viral/blood , Thrombophilia/etiology , Anticoagulants/therapeutic use , Biomarkers , Blood Coagulation Tests , Blood Donors/supply & distribution , C-Reactive Protein/analysis , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/etiology , Cytokines/blood , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/etiology , Early Diagnosis , Ferritins/blood , Fibrin Fibrinogen Degradation Products/analysis , Humans , Meta-Analysis as Topic , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Risk , SARS-CoV-2 , Thrombophilia/blood , Thrombophilia/drug therapy , Venous Thromboembolism/blood , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control
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