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1.
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.

2.
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.

4.
Hemasphere ; 6(1): e677, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1598646

ABSTRACT

The sustainability of coronavirus 19 (COVID-19) vaccine-induced immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to be determined to inform public health decisions on vaccination programs and prevention measures against COVID-19. The aim of the present study was to prospectively evaluate the kinetics of neutralizing antibodies (NAbs) and anti-S-receptor binding domain (RBD IgGs) against SARS-CoV-2 after full vaccination with the BNT162b2 mRNA vaccine for up to 9 months in healthy individuals (NCT04743388). The assessments were performed at the following time points after the second vaccination: 2 weeks, 1 month, 3 months, 6 months, and 9 months. The measurements were performed with the GenScript's cPassTM SARS-CoV-2 NAbs Detection Kit (GenScript, Inc.; Piscataway, NJ) and the Elecsys Anti-SARS-CoV-2 S assay (Roche Diagnostics GmbH; Mannheim, Germany). Three hundred nine participants with a median age of 48 years were included. A gradual decline in both NAbs and anti-S-RBD IgGs became evident from 2 weeks to 9 months postvaccination. Both NAbs and anti-S-RBD IgGs levels were significantly lower at 9 months compared with the previous timepoints. Interestingly, age was found to exert a statistically significant effect on NAbs elimination only during the first-trimester postvaccination, as older age was associated with a more rapid clearance of NAbs. Furthermore, simulation studies predicted that the median NAb value would fall from 66% at 9 months to 59% and 45% at 12 and 18 months postvaccination, respectively. This finding may reflect a declining degree of immune protection against COVID-19 and advocates for the administration of booster vaccine shots especially in areas with emerging outbreaks.

7.
Am J Hematol ; 97(1): 119-128, 2022 01 01.
Article in English | MEDLINE | ID: covidwho-1479374

ABSTRACT

Coronavirus disease 19 (COVID-19) is considered a multisystemic disease. Several studies have reported persistent symptoms or late-onset complications after acute COVID-19, including post-COVID-19 hematological disorders. COVID-19-induced coagulopathy, an immunothrombotic state, has been linked to thromboembolic and hemorrhagic events. Late-onset thrombocytopenia related to immune system dysregulation has also been reported as a rare manifestation post COVID-19. Close monitoring of laboratory dynamics is considered essential to identify timely abnormal values that need further investigation, providing supportive care whenever indicated. The role of hematologists is essential in terms of the multidisciplinary approach of long COVID-19. This review summarizes all the available evidence on post-acute COVID-19 hematological complications.


Subject(s)
COVID-19/complications , Hematologic Diseases/etiology , Animals , COVID-19/etiology , COVID-19/therapy , Disease Management , Hematologic Diseases/therapy , Hemorrhagic Disorders/etiology , Hemorrhagic Disorders/therapy , Humans , SARS-CoV-2/isolation & purification , Thrombocytopenia/etiology , Thrombocytopenia/therapy , Thromboembolism/etiology , Thromboembolism/therapy , Thrombosis/etiology , Thrombosis/therapy
8.
Vaccines (Basel) ; 9(10)2021 Oct 08.
Article in English | MEDLINE | ID: covidwho-1463855

ABSTRACT

OBJECTIVE: Vaccination for SARS-CoV-2 provides significant protection against the infection in the general population. However, limited data exist for cancer patients under systemic therapy. METHODS: In this cohort, we prospectively enrolled cancer patients treated with PARPi as well as healthy volunteers in order to study the kinetics of anti-SARS-CoV-2 antibodies (NAbs) after COVID-19 vaccination. Baseline demographics, co-morbidities, and NAb levels were compared between the two groups. RESULTS: The results of the cohort of 36 patients receiving PARP inhibitors are presented here. Despite no new safety issues being noticed, their levels of SARS-CoV-2 neutralizing antibodies were significantly lower in comparison to matched healthy volunteers up to day 30 after the second dose. CONCLUSIONS: These results suggest that maintaining precautions against COVID-19 is essential for cancer patients and should be taken into consideration for the patients under treatment, while further exploration is needed to reduce the uncertainty of SARS-CoV-2 immunity among cancer patients under treatment.

9.
Life (Basel) ; 11(10)2021 Oct 12.
Article in English | MEDLINE | ID: covidwho-1463742

ABSTRACT

Elucidating long-term immunity following COVID-19 vaccination is essential for decision-making regarding booster shots. The aim of this study was to investigate the kinetics of neutralizing antibodies (Nabs) against SARS-CoV-2 up to six months after the second vaccination dose with the BNT162b2 mRNA vaccine. Nabs levels were measured on days 1 (before the first vaccine shot), 8, 22 (before the second shot), 36, 50, and 3 and 6 months after the second vaccination (NCT04743388). Three hundred and eight healthy individuals without malignant disease were included in this study. At six months, 2.59% of the participants had a Nabs value less than 30%, while 11.9% had Nabs values of less than 50%. Importantly, 58% of the subjects had Nabs values of more than 75%. Nabs were initially eliminated at a relatively slow rate, but after three months their elimination was 5.7 times higher. Older age was inversely associated with Nabs levels at all examined timepoints. Interestingly, a population modeling analysis estimated that half of the subjects will have Nabs values less than 73.8% and 64.6% at 9 and 12 months, respectively, post vaccination completion. In conclusion, we found a persistent but declining anti-SARS-CoV-2 humoral immunity at six months following full vaccination with BNT162b2 in healthy individuals, which was more pronounced among older persons. These data may inform the public health policies regarding the prioritization of booster vaccine shots.

10.
Prostate Cancer Prostatic Dis ; 25(1): 117-118, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1461989

ABSTRACT

Data regarding the safety and efficacy of COVID-10 vaccines among cancer patients are lacking. Factors such as age, underlying disease and antineoplastic treatment confer negatively to the immune response due to vaccination. The degree of immunosuppression though may be lessen by targeted treatments like the androgen receptor-targeted agents (ARTA) that are commonly used in patients with metastatic prostate cancer. Herein, we report our data on 25 patients with prostate cancer under treatment with ARTA who were vaccinated for COVID-19. Our data suggest that these patients develop neutralizing antibodies against SARS-CoV-2 similarly to healthy volunteers. No safety issues were noted.


Subject(s)
Antineoplastic Agents , COVID-19 , Prostatic Neoplasms, Castration-Resistant , Androstenes , Antineoplastic Agents/therapeutic use , Benzamides , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Male , Nitriles , Phenylthiohydantoin , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/pathology , SARS-CoV-2 , Treatment Outcome , Vaccination
11.
Endocr Connect ; 10(9): R229-R239, 2021 Sep 20.
Article in English | MEDLINE | ID: covidwho-1448608

ABSTRACT

Endocrine system plays a vital role in controlling human homeostasis. Understanding the possible effects of COVID-19 on endocrine glands is crucial to prevent and manage endocrine disorders before and during hospitalization in COVID-19-infected patients as well as to follow them up properly upon recovery. Many endocrine glands such as pancreas, hypothalamus and pituitary, thyroid, adrenal glands, testes, and ovaries have been found to express angiotensin-converting enzyme 2 receptors, the main binding site of the virus. Since the pandemic outbreak, various publications focus on the aggravation of preexisting endocrine diseases by COVID-19 infection or the adverse prognosis of the disease in endocrine patients. However, data on endocrine disorders both during the phase of the infection (early complications) and upon recovery (late complications) are scarce. The aim of this review is to identify and discuss early and late endocrine complications of COVID-19. The majority of the available data refer to glucose dysregulation and its reciprocal effect on COVID-19 infection with the main interest focusing on the presentation of new onset of diabetes mellitus. Thyroid dysfunction with low triiodothyronine, low thyroid stimulating hormone, or subacute thyroiditis has been reported. Adrenal dysregulation and impaired spermatogenesis in affected men have been also reported. Complications of other endocrine glands are still not clear. Considering the recent onset of COVID-19 infection, the available follow-up data are limited, and therefore, long-term studies are required to evaluate certain effects of COVID-19 on the endocrine glands.

12.
Blood Adv ; 5(21): 4398-4405, 2021 11 09.
Article in English | MEDLINE | ID: covidwho-1416799

ABSTRACT

Immunocompromised patients with hematologic malignancies are more susceptible to COVID-19 and at higher risk of severe complications and worse outcomes compared with the general population. In this context, we evaluated the humoral response by determining the titers of neutralizing antibodies (NAbs) against SARS-CoV-2 in patients with Waldenström macroglobulinemia (WM) after vaccination with the BNT162b2 or AZD1222 vaccine. A US Food and Drug Administration-approved enzyme-linked immunosorbent assay-based methodology was implemented to evaluate NAbs on the day of the first vaccine shot, as well as on days 22 and 50 afterward. A total of 106 patients with WM (43% men; median age, 73 years) and 212 healthy controls (46% men; median age, 66 years) who were vaccinated during the same period at the same center were enrolled in the study (which is registered at www.clinicaltrials.gov as #NCT04743388). Our data indicate that vaccination with either 2 doses of the BNT162b2 or 1 dose of the AZD1222 vaccine leads to lower production of NAbs against SARS-CoV-2 in patients with WM compared with controls on days 22 and 50 (P < .001 for all comparisons). Disease-related immune dysregulation and therapy-related immunosuppression are involved in the low humoral response. Importantly, active treatment with either rituximab or Bruton's tyrosine kinase inhibitors was proven as an independent prognostic factor for suboptimal antibody response after vaccination. In conclusion, patients with WM have low humoral response after COVID-19 vaccination, which underlines the need for timely vaccination ideally during a treatment-free period and for continuous vigilance on infection control measures.


Subject(s)
COVID-19 , Waldenstrom Macroglobulinemia , Aged , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , Female , Humans , Male , Prospective Studies , SARS-CoV-2 , United States , Vaccination
13.
Br J Haematol ; 196(2): 356-359, 2022 01.
Article in English | MEDLINE | ID: covidwho-1412420

ABSTRACT

Patients with multiple myeloma (MM) have a suboptimal antibody response following vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and lower seroconversion rates following coronavirus disease 2019 (COVID-19) compared with healthy individuals. In this context, we evaluated the development of neutralising antibodies (NAbs) against SARS-CoV-2 in non-vaccinated patients with MM and COVID-19 compared with patients after vaccination with two doses of the BNT162b2 vaccine. Serum was collected either four weeks post confirmed diagnosis or four weeks post a second dose of BNT162b2. NAbs were measured with a Food and Drug Administration-approved enzyme-linked immunosorbent assay methodology. Thirty-five patients with COVID-19 and MM along with 35 matched patients were included. The two groups did not differ in age, sex, body mass index, prior lines of therapy, disease status, lymphocyte count, immunoglobulin levels and comorbidities. Patients with MM and COVID-19 showed a superior humoral response compared with vaccinated patients with MM. The median (interquartile range) NAb titre was 87·6% (71·6-94%) and 58·7% (21·4-91·8%) for COVID-19-positive and vaccinated patients, respectively (P = 0·01).Importantly, there was no difference in NAb production between COVID-19-positive and vaccinated patients who did not receive any treatment (median NAb 85·1% vs 91·7%, P = 0·14). In conclusion, our data indicate that vaccinated patients with MM on treatment without prior COVID-19 should be considered for booster vaccine doses.


Subject(s)
Antibodies, Neutralizing/biosynthesis , Antibodies, Viral/biosynthesis , COVID-19/immunology , Multiple Myeloma/immunology , SARS-CoV-2/immunology , Adult , Aged , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/complications , COVID-19/prevention & control , COVID-19 Serological Testing , Epitopes/immunology , Female , Humans , Immunization, Secondary , Immunocompromised Host , Immunogenicity, Vaccine , Male , Middle Aged , Multiple Myeloma/complications , Prospective Studies , Vaccination
14.
Cancers (Basel) ; 13(17)2021 Sep 06.
Article in English | MEDLINE | ID: covidwho-1390540

ABSTRACT

Emerging data suggest suboptimal antibody responses to COVID-19 vaccination in patients with hematological malignancies. We evaluated the humoral response following the BNT162b2 vaccine in patients with chronic lymphocytic leukemia (CLL), non-Hodgkin's lymphoma (NHL), and Hodgkin's lymphoma (HL). An FDA-approved, ELISA-based methodology was implemented to evaluate the titers of neutralizing antibodies (NAbs) against SARS-CoV-2 on day 1 of the first vaccine, and afterwards on day 22 and 50. One hundred and thirty-two patients with CLL/lymphomas and 214 healthy matched controls vaccinated during the same period, at the same center were enrolled in the study (NCT04743388). Vaccination with two doses of the BNT162b2 vaccine led to lower production of NAbs against SARS-CoV-2 in patients with CLL/lymphomas compared with controls both on day 22 and on day 50 (p < 0.001 for all comparisons). Disease-related immune dysregulation and therapy-related immunosuppression are involved in the low humoral response. Importantly, active treatment with Rituximab, Bruton's tyrosine kinase inhibitors, or chemotherapy was an independent prognostic factor for suboptimal antibody response. Patients with HL showed superior humoral responses to the NHL/CLL subgroups. In conclusion, patients with CLL/lymphomas have low humoral response following COVID-19 vaccination, underlining the need for timely vaccination ideally during a treatment-free period and for continuous vigilance on infection control measures.

15.
Breast ; 60: 58-61, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1372899

ABSTRACT

Undoubtedly, the development of COVID-19 vaccines displays a critical step towards ending this devastating pandemic, considering their protective benefits in the general population. Yet, data regarding their efficacy and safety in cancer patients are limited. Herein we provide the initial analysis of immune responses after the first dose of vaccination in 21 breast cancer patients receiving cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors. The levels of neutralizing antibodies post vaccination were similar to the matched healthy controls, whereas no safety issues have been raised. Further exploration is needed to reduce the uncertainty of SARS-CoV-2 immunity among cancer patients under treatment.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , Breast Neoplasms , COVID-19 Vaccines/immunology , COVID-19 , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , COVID-19/prevention & control , Cyclin-Dependent Kinase 4/antagonists & inhibitors , Cyclin-Dependent Kinase 6/antagonists & inhibitors , Female , Humans , SARS-CoV-2 , Vaccination
16.
Blood Cancer J ; 11(8): 138, 2021 08 02.
Article in English | MEDLINE | ID: covidwho-1338528

ABSTRACT

Recent data suggest a suboptimal antibody response to COVID-19 vaccination in patients with hematological malignancies. Neutralizing antibodies (NAbs) against SARS-CoV-2 were evaluated in 276 patients with plasma cell neoplasms after vaccination with either the BNT162b2 or the AZD1222 vaccine, on days 1 (before the first vaccine shot), 22, and 50. Patients with MM (n = 213), SMM (n = 38), and MGUS (n = 25) and 226 healthy controls were enrolled in the study (NCT04743388). Vaccination with either two doses of the BNT162b2 or one dose of the AZD1222 vaccine leads to lower production of NAbs in patients with MM compared with controls both on day 22 and on day 50 (p < 0.001 for all comparisons). Furthermore, MM patients showed an inferior NAb response compared with MGUS on day 22 (p = 0.009) and on day 50 (p = 0.003). Importantly, active treatment with either anti-CD38 monoclonal antibodies (Mabs) or belantamab mafodotin and lymphopenia at the time of vaccination were independent prognostic factors for suboptimal antibody response following vaccination. In conclusion, MM patients have low humoral response following SARS-CoV-2 vaccination, especially under treatment with anti-CD38 or belamaf. This underlines the need for timely vaccination, possibly during a treatment-free period, and for continuous vigilance on infection control measures in non-responders.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , COVID-19 , Multiple Myeloma , SARS-CoV-2 , Aged , Aged, 80 and over , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/blood , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Female , Humans , Male , Middle Aged , Multiple Myeloma/blood , Multiple Myeloma/immunology , Prospective Studies , SARS-CoV-2/immunology , SARS-CoV-2/metabolism
17.
Cells ; 10(8)2021 07 30.
Article in English | MEDLINE | ID: covidwho-1335013

ABSTRACT

The aim of this study was to investigate the kinetics of neutralizing antibodies (NAbs) and anti-SARS-CoV-2 anti-S-RBD IgGs up to three months after the second vaccination dose with the BNT162b2 mRNA vaccine. NAbs and anti-S-RBD levels were measured on days 1 (before the first vaccine shot), 8, 22 (before the second shot), 36, 50, and three months after the second vaccination (D111) (NCT04743388). 283 health workers were included in this study. NAbs showed a rapid increase from D8 to D36 at a constant rate of about 3% per day and reached a median (SD) of 97.2% (4.7) at D36. From D36 to D50, a slight decrease in NAbs values was detected and it became more prominent between D50 and D111 when the rate of decline was determined at -0.11 per day. The median (SD) NAbs value at D111 was 92.7% (11.8). A similar pattern was also observed for anti-S-RBD antibodies. Anti-S-RBDs showed a steeper increase during D22-D36 and a lower decline rate during D36-D111. Prior COVID-19 infection and younger age were associated with superior antibody responses over time. In conclusion, we found a persistent but declining anti-SARS-CoV-2 humoral immunity at 3 months following full vaccination with BNT162b2 in healthy individuals.


Subject(s)
Antibodies, Viral/immunology , COVID-19 Vaccines/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Adult , Aged , Antibodies, Viral/metabolism , Antibody Formation , Female , Humans , Kinetics , Male , Middle Aged , Young Adult
18.
Clin Exp Med ; 2021 Jul 20.
Article in English | MEDLINE | ID: covidwho-1317568

ABSTRACT

Vaccination against SARS-CoV-2 is considered as the most important preventive strategy against COVID-19, but its efficacy in patients with hematological malignancies is largely unknown. We investigated the development of neutralizing antibodies (NAbs) against SARS-CoV-2 in patients with Waldenstrom Macroglobulinemia (WM), Chronic Lymphocytic Leukemia (CLL) and Non-Hodgkin Lymphoma (NHL). After the first dose of the vaccine, on D22, WM/CLL/NHL patients had lower NAb titers compared to controls: the median NAb inhibition titer was 17% (range 0-91%, IQR 8-27%) for WM/CLL/NHL patients versus 32% (range 2-98%, IQR 19-48%) for controls (P < 0.001). Only 8 (14%) patients versus 114 (54%) controls developed NAb titers ≥ 30% on D22 (p < 0.001). Our data indicate that the first dose of both BNT162b2 and AZD1222 leads to lower production of NAbs against SARS-CoV-2 in patients with WM/CLL/NHL compared to controls of similar age and gender and without malignant disease. Even though the response rates were not optimal, vaccination is still considered essential and if possible should be performed before treatment initiation. These patients with suboptimal responses should be considered to be prioritized for booster doses.

19.
Eur J Neurol ; 28(11): 3826-3836, 2021 11.
Article in English | MEDLINE | ID: covidwho-1316884

ABSTRACT

Since the onset of the COVID-19 pandemic, a substantial proportion of COVID-19 patients had documented thrombotic complications and ischemic stroke. Several mechanisms related to immune-mediated thrombosis, the renin angiotensin system and the effect of SARS-CoV-2 in cardiac and brain tissue may contribute to the pathogenesis of ischemic stroke in patients with COVID-19. Simultaneously, significant strains on global healthcare delivery, including ischemic stroke management, have made treatment of stroke in the setting of COVID-19 particularly challenging. In this review, we summarize the current knowledge on epidemiology, clinical manifestation, and pathophysiology of ischemic stroke in patients with COVID-19 to bridge the gap from bench to bedside and clinical practice during the most challenging global health crisis of the last decades.


Subject(s)
Brain Ischemia , COVID-19 , Ischemic Stroke , Stroke , Brain Ischemia/complications , Brain Ischemia/epidemiology , Humans , Pandemics , SARS-CoV-2 , Stroke/epidemiology , Stroke/therapy
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