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1.
Pulmonologiya ; 31(6):792-798, 2021.
Article in Russian | EMBASE | ID: covidwho-2033501

ABSTRACT

The main focus in the course of COVID-19 goes on assessing the overall immune response. The role of mucosal immunity in this disease has not been studied sufficiently. The study aimed to analyze published data about secretory IgA as a significant indicator of the mucosal immune response of the respiratory tract in the context of the COVID-19 pandemic. Methods. Articles were identified via PubMed bibliographic database. The time-span of research was two years (2020, 2021). Results. The search identified 54 articles. There is evidence that secretory IgA (sIgA) is the main antibody isotype of the mucosal immunity. It is produced in quantities significantly higher than those of all other isotypes of immunoglobulins combined. sIgA antibodies are effective against various pathogens, including the SARS-CoV-2 virus, due to mechanisms such as neutralization, suppression of adhesion to the mucosal surface and invasion of epithelial cells, agglutination and facilitating the removal of pathogenic microorganisms with the mucosal secretions. Virus-specific IgA antibodies in the blood serum are detected in patients with COVID-19 as early as two days after the first symptoms, while IgM or IgG class antibodies appear only after 5 days. We accessed the efficacy of intranasal immunization as to induction of predominant production of sIgA in the upper and lower respiratory tract. Conclusion. The current information on the local immune response of the respiratory mucosa is important for understanding the pathophysiological mechanisms of the disease, diagnosis, and development of new methods of treatment and prevention of COVID-19.

2.
Medical News of North Caucasus ; 17(2):202-204, 2022.
Article in English | EMBASE | ID: covidwho-2033430

ABSTRACT

The study determined the etiological structure and sensitivity to antibacterial agents of pathogens of uncomplicated and complicated forms of pneumonia in children treated in a multidisciplinary hospital. According to the study, that timely bacteriological diagnosis in the treatment of pneumonia in childhood with an adequate selection of effective antibacterial agents helps reduce hospitalizations and the development of complicated forms of pneumonia.

3.
Frontiers in Immunology ; 13, 2022.
Article in English | EMBASE | ID: covidwho-2032772

ABSTRACT

Hydroa vacciniforme-like lymphoproliferative disorder (HV-LPD) is a cutaneous form of chronic active Epstein-Barrvirus (EBV) infection, which can develop into the extremely rare systemic lymphoma. Patients with Inborn errors of immunity (IEI), such as common variable immunodeficiency (CVID), are at higher risk of developing a severe course of infections especially viral and malignancies than the general population. The aim of the study was to present complex diagnostic and therapeutic management of HV-LPD. The clinical diagnosis was confirmed at the histological and molecular level with next generation sequencing. HV-LPD was diagnosed in a patient with CVID and chronic active Epstein–Barr virus (CAEBV) infection. The patient was refractory to CHOP chemotherapy and immunosuppressive treatment in combination with antiviral drugs (prednisone, bortezomib, gancyclovir). The third-party donor EBV-specific cytotoxic T cells (EBV-CTL, tabelecleucel) were used, which stabilised the disease course. Finally, matched unrelated donor hematopoietic cell transplantation (MUD-HCT) was performed followed by another cycle of EBV-CTL.

4.
ASAIO Journal ; 68:64, 2022.
Article in English | EMBASE | ID: covidwho-2032182

ABSTRACT

Background and aims: Acute Kidney Injury (AKI) is the most frequent complication after respiratory failure in COVID-19 patients. AKI increases mortality risk, length of hospital stay and healthcare costs with possibile progression toward CKD. Study aims: 1) evaluation of AKI incidence in 1020 COVID-19 hospitalized patients;2) comparison of AKI incidence in COVID-19 vs. pre-pandemic period;3) establishment of out-patient follow-up for monitoring kidney, lung, motor and immune function;4) creation of a biobank for biomarker discovery studies. Methods: AKI incidence was calculated matching laboratory and administrative data of 26214 hospitalized patients in 2018-2019 and in 1020 COVID-19 patients in 2020-2021: KDIGO algorithms were applied for AKI grading. After 12 months from discharge, 232 COVID AKI patients and relative controls matched for age and gender were evaluated for kidney (eGFR, biomarkers of tubular damage NGAL, CCl-14, DKK-3), lung (DLCO, CT scan) and neuro-motor (SPPB, 2-min walking test, post-traumatic stress test-IES) function. Results: Before pandemic, in-hospital AKI incidence was 18% (10% KDIGO 1, 5% KDIGO 2, 3% KDIGO 3): median age of AKI patients was 69. In-hospital mortality was 3.5 % in non-AKI group vs. 15% in AKI group in accordance with KDIGO stages. In COVID patients, AKI incidence increased to 37% (20% KDIGO 1,11% KDIGO 2, 6% KDIGO 3): median age of patients was 54. In-hospital mortality was 31 % in AKI group. After 12 months from hospital discharge, COVID AKI patients showed a persistent reduction of respiratory function (severe DLCO impairment <60%) related to the extent of CT scan abnormalities. AKI patients also presented motor function impairment and a worse posttraumatic stress response. GFR reduction was 1.8 ml/min in non AKI vs. 9.7 ml/min in AKI COVID patients not related to age. Urinary DKK-3 and CCL-14 were also higher in the AKI group. Last, IgG response after SARS-CoV-2 vaccination was significantly lower in the AKI group. Conclusion: AKI incidence was significantly increased during COVID-19 in respect to pre-pandemic period with an association with higher mortality in class 2-3 KDIGO. In the post-COVID follow-up, AKI was associated with lung and neuro-motor function impairment, a defective antibody response and a sudden GFR decline concomitant to the persistence of tubular injury biomarkers. These results suggest the importance of a nephrological and multidisciplinary follow-up of frail patients who developed AKI during hospitalization for COVID-19.

5.
HemaSphere ; 6:2974-2975, 2022.
Article in English | EMBASE | ID: covidwho-2032158

ABSTRACT

Background: SARS-COV2 infection is associated with inflammation, hypercoagulability and endothelial damage. Anti-SARS-COV2 vaccines have radically changed the course of the pandemic, however, reports on rare thrombotic events raise concern in the scientific community and the general population. Aims: In a prospectively enrolled cohort of adult subjects undergoing mRNA or adenovirus vector vaccination, we wanted to longitudinally evaluate the changes in levels of hemostatic biomarkers (i.e. activation of blood coagulation and perturbance of endothelium and fibrinolysis), together with the serological response, and occurrence of manifest thrombotic complications. Methods: Peripheral venous blood samples were collected at enrollment (day 0, D0) before the 1st vaccine dose, and on 15 (D15), 60 (D60), 90 (D90) and 180 (D180) days after the 1st dose. At each time point, hemostatic markers (i.e., fibrinogen, D-dimer, FVIII, von Willebrand Factor [vWF] antigen and activity, F1+2, thrombomodulin, protein C, protein S, FXIII, tPA, and PAI-1), and anti-Spike receptor-binding-domain protein (anti-S/RBD) IgG were measured. Follow up is currently continuing. Results: Fifty-three subjects (57% males) with a median age of 50 years (range 23-86) were enrolled into the study and followed-up for 6 months: 36 (68%) received BNT162b2, 6 (11%) mRNA-1273, and 8 (15%) ChAdOx1 nCoV-19 vaccines, in 2 doses over 21, 30 and 77 days, respectively;while 3 (6%) subjects received Ad26.COV2.S as single shot. Twenty individuals (38%) reported previous history of COVID-19, with a mean time from infection to vaccination of 10 months (4-18);only 1 required Hospitalization. Nine subjects presented cardiovascular risk factors and 4 a prior, non-active, cancer;3 were on anticoagulation for atrial fibrillation. The evaluation of the hemostatic biomarkers at the different time points showed variations in some of the parameters evaluated, with median values remaining within normal range levels. Specifically, compared to baseline, we observed a significant increase in thrombomodulin at D90 (p=0.001) and D180 (p=0.03), in parallel to a significant decrease in fibrinogen (D60), vWFAg (D60 and D180), FVIII (D60, D90 and D180), and TPA (D60 and D90) levels. The reduction of these biomarkers was particularly evident in individuals with a history of COVID-19. Of interest, this group of subjects was also characterized by significantly lower levels of PAI-1 both at baseline (7.18 ng/mL vs 17.53 ng/mL;p<0.0001), and at other time points (p<0.0001), and by an increase in F1+2 at D90 (p=0.02). The association between lower baseline PAI-1 levels with history of COVID-19 was confirmed by linear regression analysis (B= -10.351, p=0.013), and was independent by the time of infection resolution. Notably, no differences were observed in the hemostatic biomarkers according to vaccine types. All subjects positively responded to vaccination with a significant increase in anti-S/RBD IgG from baseline (D0) to each time point, especially COVID-19 subjects (D15, D60, and D90:p<0.0001;D180:p=0.031). No thrombotic or cardiovascular complications occurred during follow-up. Summary/Conclusion: No hypercoagulable state elicited by COVID-19 vaccination was observed, contrarily we detected an overall persistent reduction of coagulation activation over time. Subjects with previous SARS-COV2 infection had persistently low levels of PAI-1, supporting enhanced fibrinolysis activation. Compared with recent studies, our results provide a longer observation follow-up with all vaccine types and reassure on the safety of anti- SARS-COV2 vaccination.

6.
HemaSphere ; 6:1071-1072, 2022.
Article in English | EMBASE | ID: covidwho-2032136

ABSTRACT

Background: Patients with chronic lymphocytic leukemia (CLL) show high infection-related morbidity and mortality due to variable degree of humoral and cellular immune deficiency. High Covid-related mortality and reduced response to the SARS-Cov-2 vaccine have been reported in this patient population. Aims: We carried out a prospective multicenter study to define the rate of CLL patients with an appropriate immune response after the mRNA SARS-CoV2 vaccine (Pfizer-BioNTech;Moderna). Methods: Two-hundred patients with CLL received the first dose of the SARS-CoV-2 vaccine between February and August 2021. Centralized assessment of the anti-SARS-Cov-2 IgG levels (Sero Index, Kantaro Quantitative SARS-CoV-2 IgG Antibody, RUO-R&D System) was performed at the Istituto Superiore di Sanità of Rome, Italy. The median followup of this study is 10.7 months (range 1-12.9). Results: The median age of patients was 70 years, the median IgG level was 635 mg/dl, 61% of patients were IGHV unmutated, and 34% showed TP53 disruption. The majority of patients, 83.5%, were previously treated. Prior treatment included chemoimmunotherapy in 20 (10%) patients, ibrutinib-based therapy in 72 (36%;front-line, 21%;advanced line, 15%), venetoclax-based therapy in 75 (37.5%;front-line, 13.5%;advanced line, 24%). Overall, 135 (77.5%) patients had been previously treated with rituximab, 33 (16.5%) of them within 12 months before vaccination. We assessed the serologic response after the second dose of the SARS-CoV2 vaccine in 195 patients while five were excluded from the analysis (positive test before vaccination, 3 patients;lost to the follow-up, 1;Richter syndrome, 1). Adequate levels of anti-SARS-Cov-2 IgG were detected in 76/195 (39%) patients. Age (<70 vs.≥ 70 years;p <0.0001), CIRS value (<6 vs. ≥6;p=0.005), beta-2 microglobulin (<3.5 vs. ≥ 3.5mg/dl;p=0.04), IgG levels (<550 vs. ≤ 550 mg/dl;p <0.0001), prior treatment (p=0.0001), number of prior treatments (0+1 vs. ≥ 2;p=0.002) and the time between prior rituximab and vaccination (>12 vs. ≤12 month;p=0.001) showed a significant impact on the humoral response. In multivariate analysis only age (OR: 0.92 [95% CI: 0.92-0.97] p=0.0001), IgG levels (OR: 0.28 [95% CI: 0.13-0.58] p<0.001), and the time between prior rituximab and vaccination (OR: 0.10 [95% CI: 0.03-0.37] p=0.001), revealed a significant and independent impact on response. When the analysis was restricted to patients who received targeted therapy, in addition to the younger age (OR: 0.96 [95% CI: 0.92-0.99] p=0.04), higher IgG levels at baseline (OR: 0.31 [95% CI: 0.12-0.79] p=0.014), longer time between the start of ibrutinib or venetoclax-based therapy and vaccination (<18 vs.≥18 months;OR: 0.17 [95% CI: 0.06-0.44], p <0.0001) showed a favorable and independent impact on response. Ninety-three% (182/195) of patients received a third dose of the vaccine. A significant increase in the rate of serologic responses, 51.5% (85/165 evaluated patients, p=0.019), was observed after the booster dose. Moreover, a response was detected in 25% (26/103 evaluated patients) of previously seronegative patients. Summary/Conclusion: In this prospective, multicenter, centralized study, we recorded an effective immune response to the SARS-CoV-2 vaccine in about a third of patients with CLL. Younger age, higher IgG levels, no prior treatment, or stable disease after targeted therapy that suggest preserved immunocompetence were associated with a greater likelihood of achieving an effective immune response. A booster dose of the SARS-CoV-2 vaccine proved beneficial also in previously seronegative patients.

7.
HemaSphere ; 6:291-292, 2022.
Article in English | EMBASE | ID: covidwho-2032117

ABSTRACT

Background: The ongoing COVID-19 pandemic has resulted in more than 419 million cases and more than 5.9 million deaths. Preious studies hae indicated inferior responses to SARS-CoV-2 accination across different hematological diseases. Through this prospectie cohort study, we examined the deelopment and durability of anti-receptor binding domain (RBD) IgG after two doses of BNT162b2 in 179 patients with either multiple myeloma (MM) or Chronic Lymphatic B-cell Leukemia (B-CLL) six months after accination and compared to immunocompetent controls. Aims: We aimed to inestigate the durability of immune responses to COVID-19 accination in patients with MM or B-CLL compared to healthy controls, and to identify risk factors for humoral non-response, including type of diagnosis. Methods: We measured anti-receptor binding domain (RBD) IgG after two doses of BNT162b2 in 179 patients (MM: n=78, B-CLL: n=101) and 179 age and sex matched healthy controls up to six months after first accination. Anti- RBD IgG leels and neutralizing capacity of antibodies were measured at first and second dose of BNT162b2 and two and six months after first dose. Humoral response was defined as anti-RBD IgG > 225 AU/mL with a neutralizing index ≥ 25%. Humoral non-response was defined as the absence of a humoral response. T-cell responses were assessed six months after the first dose using an ELISA-based interferon-gamma release assay. A positie T-cell response was defined as IFN-γ release > 200 mIU/mL. Data on diagnoses were obtained through medical records, and data on accination status were obtained from the Danish Vaccination Register. Results: In patients with MM or B-CLL, the geometric mean concentration (GMC) of anti-RBD IgG increased from baseline 1.49 AU/mL (95% CI: 1.21-1.84) to three weeks after the first accine dose 15.10 AU/mL (95% CI: 9.39- 24.29) and after receiing the second dose 1179.60 AU/mL (95% CI: 727.78-1919.85). From two to six months after first accine there was a significant decline in the GMC of anti-RBD IgG to 252.75 AU/mL (95% CI: 159.17-403.43). The mean neutralizing capacity in patients with MM or B-CLL was lower than in controls at all time points after the first accine dose. Six months after first accine dose, 79 of 179 (44.1%) patients with MM or B-CLL had a positie humoral response, while this was the case for 170 of 179 controls (95.0%), p<0.001. Haing MM or B-CLL was significantly associated with risk of humoral non-response. This was most pronounced in B-CLL patients who had an age and sex adjusted risk ratio (RR) of 12.25 (95% CI: 6.42-23.38, p< 0.001) of humoral non-response compared to healthy controls. For MM patients the RR was 4.65 (95% CI: 2.21-9.80, p< 0.001). T-cell response was assessed in a subset of 48 patients with MM (n=28) or B-CLL (n=20) and 26 controls, six months after first accine dose. A total of 21 (43.8%) patients with MM (12/28) or B-CLL (9/20) and 14 (53.8%) controls had a positie T-cell response (p =0.56). Seen of 20 (35.0%) patients with MM or B-CLL who did not deelop a humoral response, deeloped a T-cell response (MM: 3/8, B-CLL: 4/12), while 14 of 28 (50.0%) patients with MM or B-CLL who deeloped a humoral response deeloped a T-cell response (p =0.46, MM: 9/11, B-CLL: 5/8). In healthy controls 14 of 25 (56.0%) people who deeloped a humoral response also deeloped a T-cell response. Summary/Conclusion: Humoral response to BNT162b2 was impaired in patients with MM or B-CLL compared to healthy controls. Both patients with MM and B-CLL were at higher risk of humoral non-response compared to healthy controls.

8.
HemaSphere ; 6:1862-1863, 2022.
Article in English | EMBASE | ID: covidwho-2032105

ABSTRACT

Background: In patients (pts) with hematological malignancies, COVID-19 is considered to be associated with a high risk of severe morbidity and mortality. While anti-COVID-19 vaccination of such pts has become the standard of care, pts undergoing lymphodepleting therapy fail to generate protective serological response due to either the nature of their underlying disease or exposure to therapy. Aims: This study aimed to assess serological response to vaccination with BNT162b2 (Pfizer) as well as COVID-19-related morbidity and mortality in Hodgkin lymphoma (HL) pts. Methods: The above vaccine was available in Israel from January 2021 and all pts with hematological malignancies were recommended to undergo vaccination with 2 doses of this vaccine, injected 21 days apart. Six months later a 3rd dose was recommended and in another 3 months a 4th dose was available for pts at risk. Serology tests were performed at least 2 weeks after the 2nd vaccination. The SARS-CoV-2 IgG II Quant (Abbott©) assay was used to measure levels of IgG antibodies (Abs) against the SARS-CoV-2 spike protein. A result was considered positive if the IgG level was ≥150 AU/ml, which was defined as an adequate serological response. Results: The current non-interventional single-center study evaluated the outcome of 55 HL pts (median age 46 years, 53% females);51% of pts had advanced HL. Study participants received 1-9 lines of therapy (median 1 line). Six pts had COVID-19 prior to vaccination, 49 were vaccinated: 9 with 2 doses, 36 with 3 doses and 4 with 4 doses of BNT162b2. Following initial 2 vaccine doses and after a 3rd dose Ab levels >150 AU/ml were developed in 85% and 89.5% of pts, respectively. At a median of 95 days post-2nd vaccination, Ab levels were 2024 (1-29400) and 4 (0-7539) in 48 patients with no background disease versus 7 pts treated with lymphodepleting drugs or having a background disease, respectively. During the follow-up, 5 vaccinated pts were diagnosed with COVID-19 when the Delta variant was prevalent and 9-during the Omicron wave. Notably, similar Ab levels were observed in those infected with Omicron and in non-infected pts, reflecting the genetic drift of this variant. A further analysis was performed to compare findings in a subgroup of 7 pts who had an additional background disease along with HL, such as chronic lymphocytic leukemia, s/p kidney transplantation, solid tumor, or those who were heavily pretreated, including therapy with bendamustine, versus the values observed in the rest 48 pts. The median age in the former subgroup was 58 (31-80) years, which was significantly older than in the remaining pts [median 45 (18-78) years] and median Ab levels were 4 (0-7539) AU/ml and 2024 (1-2940) AU/ml, respectively. Notably, after the 3rd vaccination, the median Ab level in both groups was 7000 AU/ml. Summary/Conclusion: The results of the current study show that at least 85% of HL pts develop a high titer of anti-spike antibodies after vaccination with 2 BNT162b2 doses. These titers substantially increased post the 3rd vaccine dose. Only a minority of HL pts who had additional background diseases or were heavily pretreated, failed to develop an adequate serological response;however, some of them had high Ab titers post-3rd and 4th vaccinations. In this study, morbidity and mortality rates of HL pts infected with COVID-19 were lower than those reported in pts with other lymphoma types.

9.
HemaSphere ; 6:2679-2681, 2022.
Article in English | EMBASE | ID: covidwho-2032097

ABSTRACT

Background: Autoimmune haemolytic anaemia (AIHA) during pregnancy is a rare finding, and few is known about maternal and foetal outcomes. AIHA may either develop or relapse during gestation and postpartum or be an issue in a patient on active therapy who becomes pregnant. AIHA management during pregnancy and lactation is not standardized and drug use is often limited by safety concerns. Aims: We studied AIHA impact on pregnancy focusing on disease severity, treatment need and maternal/foetal outcome. Methods: Through a multicentric retrospective cohort study, we identified 38 pregnancies occurred in 28 women from 1997 to 2021 in 10 European centres in Italy, Denmark, France, the Netherlands, USA, and Spain. All included patients had a previous AIHA history or developed/exacerbated AIHA during gestation or postpartum. AIHA was classified according to the direct antiglobulin test. Results: We registered 18 warm AIHA (10 IgG;8 IgG+C3d), 2 cold agglutinin disease, 3 mixed and 5 atypical forms (Table 1). Evans syndrome (i.e., association of AIHA and immune thrombocytopenia or neutropenia) was present in 4. Mean age at AIHA diagnosis was 27 (3-39) and at pregnancy 32 (21-41) years. AIHA diagnosis predated pregnancy in 15 women and had required at least 1 therapy line in all of them, and >2 lines in 12 (rituximab, N=7;cytotoxic immunosuppressants, N=6;splenectomy, N=5). Among these 15 patients, 6 had a relapse during pregnancy, 3 during postpartum and 9 were on active treatment at the time of pregnancy (steroids, N=8;cyclosporine, N=1;azathioprine, N=1;the latter stopped after positive pregnancy test). A patient with a previous AIHA, relapsed as immune thrombocytopenic purpura during pregnancy. Further 8 patients had an AIHA onset during gestation and 2 postpartum. A patient had AIHA onset during the postpartum of the 1st pregnancy and relapsed during the 2nd one. In the 20 women experiencing AIHA during pregnancy/postpartum, median Hb and LDH levels were 6,4 g/dL (3,1 - 8,7) and 588 UI/L (269-1631), respectively. Management consisted in blood transfusions (N=10) and prompt establishment of steroid therapy+/-IVIG (N=20), all with response (complete N=13, partial N=7). After delivery, rituximab was necessary in 4 patients and cyclosporine was added in one. Anti-thrombotic prophylaxis was given in 7 patients. Overall, we registered 10 obstetric complications (10/38, 26%), including 4 early miscarriages, a premature rupture of membranes, a placental detachment, 2 preeclampsia, a postpartum infection and a biliary colic. Apart from the case of biliary colic and one of the two cases of preeclampsia, 8/10 complications occurred during active haemolysis and treatment for AIHA. Nine foetal adverse events (9/38, 24%) were reported: a transitory respiratory distress of the new-born in a mother with active AIHA, 3 cases of foetal growth restriction, a preterm birth, an infant reporting neurologic sequelae, a case of AIHA of the new-born requiring intravenous immunoglobulins, blood transfusions and plasma exchange, and 2 perinatal deaths. The latter both occurred in women on active AIHA therapy and were secondary to a massive placental detachment and a symptomatic SARS-CoV-2 infection. (Figure Presented ) Summary/Conclusion: AIHA developing/reactivating during pregnancy or postpartum is rare (about 5%) but mainly severe requiring steroid therapy and transfusions. Importantly, severe maternal and foetal complications may occur in up to 26% of cases mostly associated with active disease, pinpointing the importance of maintaining a high level of awareness. Passive maternal autoantibodies transfer to the foetus seems a rare event.

10.
Mayo Clin Proc Innov Qual Outcomes ; 2022.
Article in English | ScienceDirect | ID: covidwho-2031555

ABSTRACT

Objective: To assess clinical and immunological benefits of passive immunization using convalescent plasma therapy (CPT) we performed sub-group analyses on a completed randomised control trial (RCT) on CPT in severe COVID-19. Patients: A series of subclass analyses were performed on the previously published outcome data and accompanying clinical metadata from a completed RCT (Clinical Trial Registry of India, No. CTRI/2020/05/025209). Methods: The subclass analyses were performed on the outcome data and accompanying clinical metadata from a completed randomized control trial. Data on the plasma abundance of a large panel of cytokines from the same cohort of patients were also utilised to characterize the heterogeneity of the putative anti-inflammatory function of convalescent plasma (CP) in addition to passively providing neutralizing antibodies. Results: While across all age-groups primary clinical outcomes were not significantly different in the RCT, significant immediate mitigation of hypoxia, reduction in hospital stay as well as significant survival benefit were registered in younger (<67 years in our cohort) severe COVID-19 patients with ARDS on receiving CPT. In addition to neutralizing antibody content of convalescent plasma, its anti-inflammatory proteome on attenuation of systemic cytokine deluge, significantly contributed to the clinical benefits of CPT. Conclusion: The sub-group analyses revealed that clinical benefit of CPT in severe COVID-19 is linked to the anti-inflammatory protein content of CP, apart from the anti-SARS-CoV-2 neutralizing antibody content.

11.
Cadernos de Saude Publica ; 38(8):e00021022, 2022.
Article in English | MEDLINE | ID: covidwho-2029826

ABSTRACT

This serological survey, conducted in five Brazilian municipalities, evaluated the use of dried blood spots (DBS), obtained from newborns and their mothers, to detect SARS-CoV-2 IgG antibodies. DBS were obtained from 4,803 neonates aged up to seven days and their mothers, both asymptomatic, at public health care clinics during newborn screening. DBS were processed by ELISA to detect IgG antibodies against SARS-CoV-2 nucleocapsid antigen. Mothers of seropositive neonates were interviewed about sociodemographic characteristics and clinical and laboratory antecedents. Non-satisfactory samples, dyads with incomplete data, and vaccinated mothers were excluded. Of the 1,917 DBS dyads samples analyzed, 14.7% of neonates showed IgG antibodies against SARS-CoV-2. Among seropositive neonates, 73.2% of their mothers were also seropositive. More than half of the mothers with seropositive neonates denied clinical or laboratory suspicion of COVID-19 during pregnancy. Suspicion occurred in the third trimester for 24.6% of the mothers. This study tested an innovative strategy to improve the understanding of COVID-19 antibody dynamics during pregnancy and suggests the feasibility of a universal serological survey in puerperal women and neonates.

12.
JAMA Network Open ; 5(9):e2231334, 2022.
Article in English | MEDLINE | ID: covidwho-2027278

ABSTRACT

Importance: West Virginia prioritized SARS-CoV-2 vaccine delivery to nursing home facilities because of increased risk of severe illness in elderly populations. However, the persistence and protective role of antibody levels remain unclear. Objective: To examine the persistence of humoral immunity after COVID-19 vaccination and the association of SARS-CoV-2 antibody levels and subsequent infection among nursing home residents and staff. Design, Setting, and Participants: In this cross-sectional study, blood samples were procured between September 13 and November 30, 2021, from vaccinated residents and staff at participating nursing home facilities in the state of West Virginia for measurement of SARS-CoV-2 antibody (anti-receptor binding domain [RBD] IgG). SARS-CoV-2 infection and vaccination history were documented during specimen collection and through query of the state SARS-CoV-2 surveillance system through January 16, 2022. Exposure: SARS-CoV-2 vaccination (with BNT162b2, messenger RNA-1273, or Ad26.COV2.S). Main Outcomes and Measures: Anti-RBD IgG levels were assessed using multivariate analysis to examine associations between time since vaccination or infection, age, sex, booster doses, and vaccine type. Antibody levels from participants who became infected after specimen collection were compared with those without infection to correlate antibody levels with subsequent infection. Results: Among 2139 SARS-CoV-2 vaccinated residents and staff from participating West Virginia nursing facilities (median [range] age, 67 [18-103] years;1660 [78%] female;2045 [96%] White), anti-RBD IgG antibody levels decreased with time after vaccination or infection (mean [SE] estimated coefficient, -0.025 [0.0015];P < .001). Multivariate regression modeling of participants with (n = 608) and without (n = 1223) a known history of SARS-CoV-2 infection demonstrated significantly higher mean (SE) antibody indexes with a third (booster) vaccination (with infection: 11.250 [1.2260];P < .001;without infection: 8.056 [0.5333];P < .001). Antibody levels (calculated by dividing the sample signal by the mean calibrator signal) were significantly lower among participants who later experienced breakthrough infection during the Delta surge (median, 2.3;95% CI, 1.8-2.9) compared with those without breakthrough infection (median, 5.8;95% CI, 5.5-6.1) (P = .002);however, no difference in absorbance indexes was observed in participants with breakthrough infections occurring after specimen collection (median, 5.9;95% CI, 3.7-11.1) compared with those without breakthrough infection during the Omicron surge (median, 5.8;95% CI, 5.6-6.2) (P = .70). Conclusions and Relevance: In this cross-sectional study, anti-RBD IgG levels decreased after vaccination or infection. Higher antibody responses were found in individuals who received a third (booster) vaccination. Although lower antibody levels were associated with breakthrough infection during the Delta surge, no significant association was found between antibody level and infection observed during the Omicron surge. The findings of this cross-sectional study suggest that among nursing home residents, COVID-19 vaccine boosters are important and updated vaccines effective against emerging SARS-CoV-2 variants are needed.

13.
The Ethiopian Journal of Health Development ; 35(4):367, 2021.
Article in English | ProQuest Central | ID: covidwho-2026938

ABSTRACT

Background: Anti-SARS-CoV-2 antibody tests are increasingly used for sero-epidemiological purposes to provide a better understanding of the extent of the infection in the community, and to monitor the progression of the COVID-19 epidemic. A sero-prevalence study was conducted to estimate prior infections with SARS-CoV-2 in Addis Ababa. Methods: A cross-sectional study was conducted from April 23 to 28, 2020 among 301 randomly selected residents of Addis Ababa;sub-city health offices, health facilities and health extension workers were contacted, to obtain a population profile and to conduct the random selection of study participants. Participants were selected, who had not been in direct contact with people who had contracted COVID-19, to maintain consistency among the study population. Interviews on socio demographic and behavioural risk factors, followed by serological tests were performed for SARS-CoV-2 IgM, and IgG antibodies, using the COVID-19 IgG/IgM Rapid Test Cassette. Based on the manufacturer information, the test has a sensitivity of 87·9% and specificity of 100% for lgM;and a sensitivity of 97·2% and specificity of 100% for IgG. A Polymerase chain reaction (RT-PCR) test was also done on combined nasopharyngeal and oropharengeal swabs. Findings: The unadjusted antibody-based crude SARS-CoV-2 prevalence was 7·6% and the adjusted (weighted average) SARS-CoV-2 prevalence was estimated at 8·8% (95% CI 5·5%-11·6%) for the study population. Higher sero-prevalence were observed for males (9.0%), age below 50 years (8.2%), students and unemployed (15.6%), as well as those with primary education (12.1%), educated above high school (37·9%), non- smokers (78·7%), with no history of regular alcohol (53·8%), no chat (70·8%), and no shisha use (94·7%). According to the findings, a significantly higher number of individuals had been infected in Addis Ababa as compared to what was being detected and reported by the RT-PCR test, which is suggestive of community transmission.

14.
Viruses ; 14(8):1742, 2022.
Article in English | ProQuest Central | ID: covidwho-2024286

ABSTRACT

In West Africa, research on the hepatitis E virus (HEV) is barely covered, despite the recorded outbreaks. The low level of access to safe water and adequate sanitation is still one of the main factors of HEV spread in developing countries. HEV infection induces acute or sub-clinical liver diseases with a mortality rate ranging from 0.5 to 4%. The mortality rate is more alarming (15 to 25%) among pregnant women, especially in the last trimester of pregnancy. Herein, we conducted a multicentric socio-demographic and seroepidemiological survey of HEV in Senegal among pregnant women. A consecutive and non-redundant recruitment of participants was carried out over the period of 5 months, from March to July 2021. A total of 1227 consenting participants attending antenatal clinics responded to a standard questionnaire. Plasma samples were collected and tested for anti-HEV IgM and IgG by using the WANTAI HEV-IgM and IgG ELISA assay. The overall HEV seroprevalence was 7.8% (n = 96), with 0.5% (n = 6) and 7.4% (n = 91) for HEV IgM and HEV IgG, respectively. One of the participant samples was IgM/IgG-positive, while four were declared indeterminate to anti-HEV IgM as per the manufacturer’s instructions. From one locality to another, the seroprevalence of HEV antibodies varied from 0 to 1% for HEV IgM and from 1.5 to 10.5% for HEV IgG. The data also showed that seroprevalence varied significantly by marital status (p < 0.0001), by the regularity of income (p = 0.0043), and by access to sanitation services (p = 0.0006). These data could serve as a basis to setup national prevention strategies focused on socio-cultural, environmental, and behavioral aspects for a better management of HEV infection in Senegal.

15.
Viruses ; 14(8):1716, 2022.
Article in English | ProQuest Central | ID: covidwho-2024282

ABSTRACT

The rapid transmission of measles poses a great challenge for measles elimination. Thus, rapid testing is required to screen the health status in the population during measles outbreaks. A pseudotype-based virus neutralisation assay was used to measure neutralising antibody titres in serum samples collected from healthcare workers in Sheffield during the measles outbreak in 2016. Vesicular stomatitis virus (VSV) pseudotypes bearing the haemagglutinin and fusion glycoproteins of measles virus (MeV) and carrying a luciferase marker gene were prepared;the neutralising antibody titre was defined as the dilution resulting in 90% reduction in luciferase activity. Spearman’s correlation coefficients between IgG titres and neutralising antibody levels ranged from 0.40 to 0.55 (p < 0.05) or from 0.71 to 0.79 (p < 0.0001) when the IgG titres were obtained using different testing kits. In addition, the currently used vaccine was observed to cross-neutralise most circulating MeV genotypes. However, the percentage of individuals being “well-protected” was lower than 95%, the target rate of vaccination coverage to eliminate measles. These results demonstrate that the level of clinical protection against measles in individuals could be inferred by IgG titre, as long as a precise correlation has been established between IgG testing and neutralisation assay;moreover, maintaining a high vaccination coverage rate is still necessary for measles elimination.

16.
International Journal of Molecular Sciences ; 23(17):9604, 2022.
Article in English | ProQuest Central | ID: covidwho-2023744

ABSTRACT

Understanding the biological mechanisms underlying the pH-dependent nature of FcRn binding, as well as the various factors influencing the affinity to FcRn, was concurrent with the arrival of the first recombinant IgG monoclonal antibodies (mAbs) and IgG Fc-fusion proteins in clinical practice. IgG Fc–FcRn became a central subject of interest for the development of these drugs for the comfort of patients and good clinical responses. In this review, we describe (i) mAb mutations close to and outside the FcRn binding site, increasing the affinity for FcRn at acidic pH and leading to enhanced mAb half-life and biodistribution, and (ii) mAb mutations increasing the affinity for FcRn at acidic and neutral pH, blocking FcRn binding and resulting, in vivo, in endogenous IgG degradation. Mutations modifying FcRn binding are discussed in association with pH-dependent modulation of antigen binding and (iii) anti-FcRn mAbs, two of the latest innovations in anti-FcRn mAbs leading to endogenous IgG depletion. We discuss the pharmacological effects, the biological consequences, and advantages of targeting IgG–FcRn interactions and their application in human therapeutics.

17.
Frontiers in Immunology ; 13, 2022.
Article in English | Scopus | ID: covidwho-2022745

ABSTRACT

Influenza vaccines remain the most effective tools to prevent flu and its complications. Trivalent or quadrivalent inactivated influenza vaccines primarily elicit antibodies towards haemagglutinin and neuraminidase. These vaccines fail to induce high protective efficacy, in particular in older adults and immunocompromised individuals and require annual updates to keep up with evolving influenza strains (antigenic drift). Vaccine efficacy declines when there is a mismatch between its content and circulating strains. Current correlates of protection are merely based on serological parameters determined by haemagglutination inhibition or single radial haemolysis assays. However, there is ample evidence showing that these serological correlates of protection can both over- or underestimate the protective efficacy of influenza vaccines. Next-generation universal influenza vaccines that induce cross-reactive cellular immune responses (CD4+ and/or CD8+ T-cell responses) against conserved epitopes may overcome some of the shortcomings of the current inactivated vaccines by eliciting broader protection that lasts for several influenza seasons and potentially enhances pandemic preparedness. Assessment of cellular immune responses in clinical trials that evaluate the immunogenicity of these new generation vaccines is thus of utmost importance. Moreover, studies are needed to examine whether these cross-reactive cellular immune responses can be considered as new or complementary correlates of protection in the evaluation of traditional and next-generation influenza vaccines. An overview of the assays that can be applied to measure cell-mediated immune responses to influenza with their strengths and weaknesses is provided here. Copyright © 2022 Janssens, Joye, Waerlop, Clement, Leroux-Roels and Leroux-Roels.

18.
Frontiers in Immunology ; 13:939311, 2022.
Article in English | MEDLINE | ID: covidwho-2022716

ABSTRACT

Background: Owing to the coronavirus disease 2019 (COVID-19) pandemic and the emergency use of different types of COVID-19 vaccines, there is an urgent need to consider the effectiveness and persistence of different COVID-19 vaccines. Methods: We investigated the immunogenicity of CoronaVac and Covilo, two inactivated vaccines against COVID-19 that each contain inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The levels of neutralizing antibodies to live SARS-CoV-2 and the inhibition rates of neutralizing antibodies to pseudovirus, as well as the immunoglobulin (Ig)G and IgM responses towards the spike (S) and nucleocapsid (N) protein of SARS-CoV-2 at 180 days after two-dose vaccination were detected. Results: The CoronaVac and Covilo vaccines induced similar antibody responses. Regarding neutralizing antibodies to live SARS-CoV-2, 77.9% of the CoronaVac vaccine recipients and 78.3% of the Covilo vaccine recipients (aged 18-59 years) seroconverted by 28 days after the second vaccine dose. Regarding SARS-CoV-2-specific antibodies, 97.1% of the CoronaVac vaccine recipients and 95.7% of the Covilo vaccine recipients seroconverted by 28 days after the second vaccine dose. The inhibition rates of neutralizing antibody against a pseudovirus of the SARS-CoV-2 Delta variant were significantly lower compared with those against a pseudovirus of wildtype SARS-CoV-2. Associated with participant characteristics and antibody levels, persons in the older age group and with basic disease, especially a chronic respiratory disease, tended to have lower anti-SARS-CoV-2 antibody seroconversion rates. Conclusion: Antibodies that were elicited by these two inactivated COVID-19 vaccines appeared to wane following their peak after the second vaccine dose, but they persisted at detectable levels through 6 months after the second vaccine dose, and the effectiveness of these antibodies against the Delta variant of SARS-CoV-2 was lower than their effectiveness against wildtype SARS-CoV-2, which suggests that attention must be paid to the protective effectiveness, and its persistence, of COVID-19 vaccines on SARS-CoV-2 variants.

19.
Frontiers in Cellular and Infection Microbiology ; 12, 2022.
Article in English | Web of Science | ID: covidwho-2022655

ABSTRACT

The World Health Organization declared a public health emergency of international concern in January 2020. The Delta variant became the main epidemic strain on 11 May 2021. Vaccines were proven highly effective in controlling hospitalization and deaths associated with severe acute respiratory syndrome coronavirus 2 infections. Real data on vaccine efficacy against B.1.617.2 infection in the Chinese population were currently limited. This study aimed to evaluate the protective effect of inactivated vaccine injection and immunoglobulin (Ig) G levels in coronavirus disease 2019 (COVID-19) severity. This retrospective study included patients with COVID-19 in Xi'an Chest Hospital from December 2021 to January 2022. The protective effect of inactivated vaccine injection and IgG levels on COVID-19 severity was analyzed using multiple logistic regressions. A total of 580 patients were included in the study, of whom 158 (27.24%) were mild, 412 (71.03%) were moderate, 5 (0.9%) were severe, and 5 (0.86%) were critical. Severe case (including severe and critical) rates were 1.72% (10/580). Compared with the unvaccinated group, the vac+IgG- group had a 0.21 (0.02-2.05)-fold risk of suffering from severe cases, and the vac+IgG+ group had a 0.05 (0-0.63)-fold risk of suffering from severe cases. Of the 10 severe cases, 8 were older than 60 years, 8 were men, 8 had underlying diseases, 6 were in the unvaccinated group, and 2 were in the vac+IgG- group. Vaccination and sufficient IgG antibody production can protect patients with COVID-19 from severe cases. Booster vaccine injection can produce a stronger immune response and protection.

20.
Allergy & Asthma Proceedings ; 43(5):419-430, 2022.
Article in English | MEDLINE | ID: covidwho-2022489

ABSTRACT

Background: Secretory immunoglobulin A (sIgA) plays an important role in antiviral protective immunity. Although salivary testing has been used for many viral infections, including severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS), its use has not yet been well established with the SARS coronavirus 2 (SARS-CoV-2). Quantification of salivary IgA and IgG antibodies can elucidate mucosal and systemic immune responses after natural infection or vaccination. Here, we report the development and validation of a rapid enzyme-linked immunosorbent assay (ELISA) for anti-SARS-CoV-2 salivary IgA and serum IgG antibodies, and present quantitative results for immunized subjects both prior to or following COVID-19 infections. Objective: Total and serum SARS-CoV-2 spike-specific IgG responses were compared with salivary spike-specific IgA and IgG responses in samples obtained from patients recently infected with SARS-CoV-2 and from subjects recently immunized with COVID-19 vaccines.

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