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1.
JMIR Public Health Surveill ; 2023 May 24.
Article in English | MEDLINE | ID: covidwho-20234741

ABSTRACT

BACKGROUND: The SARS-CoV-2 pandemic is characterized by a constant risk of a rapid increase in infection burden due to the emergence of new variants with higher transmissibility and immune escape. Monitoring the SARS-CoV-2 pandemic has so far mainly relied on passive surveillance, which yields biased epidemiological measures due to the disproportionate number of undetected asymptomatic cases. In contrast, active surveillance could provide more accurate estimates of the true SARS-CoV-2 prevalence that help to forecast the evolution of the pandemic, enabling evidence-based decision-making. OBJECTIVE: The objective of this study was to compare four different approaches of active SARS-CoV-2 surveillance, focusing on feasibility and epidemiological outcomes. METHODS: The randomized, two-factor factorial, multi-arm parallel trial was conducted in 2020 in a German district with 700,000 inhabitants. The epidemiological outcome comprised the SARS-CoV-2 prevalence and its precision. The four study arms combined two factors: i) individuals versus households, ii) direct testing versus testing conditioned on symptom pre-screening. Individuals seven years and older were eligible. Altogether, 27,908 addresses from general population representative samples of 51 municipalities were randomly allocated to the arms and 15 consecutive recruitment weekdays. Data collection and logistics were highly digitized, a website in five languages enabled low-barrier registration and tracking of results. Gargle sample collection kits were sent by post. Participants collected a gargle sample at home and mailed it to the laboratory. Samples were analyzed with RT-LAMP, positive/weak results were confirmed with RT-qPCR. RESULTS: Recruitment took place between 18 November and 11 December 2020. The response rates in the four arms varied between 34% and 41%. The pre-screening classified 17% as COVID-19 symptomatic. Altogether, 4,232 persons without pre-screening and 7,623 participating in the pre-screening provided 5,351 gargle samples, of which 5,319 (99%) could be analyzed, yielding 17 confirmed SARS-CoV-2 infections and a combined prevalence of 0.36% (95% CI [0.14%; 0.59%]) in the arms without, respectively 0.05% (95% CI [0.00%; 0.108%]) with pre-screening (initial contacts only). In more detail, we found a prevalence of 0.31% (95% CI [0.06; 0.58]), respectively 0.35% (95% CI [0.09; 0.6], household members included), and lower estimates with pre-screening (0.07% (95% CI [0.0; 0.15], respectively with household members 0.02 (95% CI [0.0; 0.06]). Asymptomatic infections occurred in 3/11 positive cases with symptom data. The two arms without pre-screening performed best regarding effectiveness and accuracy. CONCLUSIONS: This study has shown that the combination of postal mailing of gargle sample kits as well as returning home-based self-collected liquid gargle samples and a subsequent analysis with high-sensitivity RT-LAMP is generally a feasible way to conduct active SARS-CoV-2 population surveillance without burdening routine diagnostic testing. Efforts to improve participation rates and to facilitate integration into the public health system may increase the potential to effectively monitor the course of the pandemic. CLINICALTRIAL: The trial was registered (30 November 2020) at the German Clinical Trials Register, registration number DRKS00023271. INTERNATIONAL REGISTERED REPORT: RR2-10.1186/s13063-021-05619-5.

2.
J Clin Med ; 12(9)2023 May 04.
Article in English | MEDLINE | ID: covidwho-2314225

ABSTRACT

BACKGROUND: Critically ill patients, especially those who have undergone solid organ transplantation (SOT), are at risk of invasive pulmonary aspergillosis (IPA). The outcome relevance of adequately treated putative IPA (pIPA) is a matter of debate. The aim of this study is to assess the outcome relevance of pIPA in a cohort of critically ill patients with and without SOT. METHODS: Data from 121 surgical critically ill patients with pIPA (n = 30) or non-pIPA (n = 91) were included. Cox regression analysis was used to identify risk factors for mortality and unfavourable outcomes after 28 and 90 days. RESULTS: Mortality rates at 28 days were similar across the whole cohort of patients (pIPA: 31% vs. non-pIPA: 27%) and did not differ in the subgroup of patients after SOT (pIPA: 17% vs. non-pIPA: 22%). A higher Sequential Organ Failure Assessment (SOFA) score and evidence of bacteraemia were identified as risk factors for mortality and unfavourable outcome, whereas pIPA itself was not identified as an independent predictor for poor outcomes. CONCLUSIONS: Adequately treated pIPA did not increase the risk of death or an unfavourable outcome in this mixed cohort of critically ill patients with or without SOT, whereas higher disease severity and bacteraemia negatively affected the outcome.

3.
EMBO Rep ; 24(5): e57162, 2023 05 04.
Article in English | MEDLINE | ID: covidwho-2269718

ABSTRACT

Throughout the SARS-CoV-2 pandemic, limited diagnostic capacities prevented sentinel testing, demonstrating the need for novel testing infrastructures. Here, we describe the setup of a cost-effective platform that can be employed in a high-throughput manner, which allows surveillance testing as an acute pandemic control and preparedness tool, exemplified by SARS-CoV-2 diagnostics in an academic environment. The strategy involves self-sampling based on gargling saline, pseudonymized sample handling, automated RNA extraction, and viral RNA detection using a semiquantitative multiplexed colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay with an analytical sensitivity comparable with RT-qPCR. We provide standard operating procedures and an integrated software solution for all workflows, including sample logistics, analysis by colorimetry or sequencing, and communication of results. We evaluated factors affecting the viral load and the stability of gargling samples as well as the diagnostic sensitivity of the RT-LAMP assay. In parallel, we estimated the economic costs of setting up and running the test station. We performed > 35,000 tests, with an average turnover time of < 6 h from sample arrival to result announcement. Altogether, our work provides a blueprint for fast, sensitive, scalable, cost- and labor-efficient RT-LAMP diagnostics, which is independent of potentially limiting clinical diagnostics supply chains.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19 Testing , Clinical Laboratory Techniques/methods , Pandemics/prevention & control , Sensitivity and Specificity , RNA, Viral/genetics
5.
Nat Cancer ; 4(1): 96-107, 2023 01.
Article in English | MEDLINE | ID: covidwho-2186111

ABSTRACT

Patients with cancer are at high risk of severe coronavirus disease 2019 (COVID-19), with high morbidity and mortality. Furthermore, impaired humoral response renders severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines less effective and treatment options are scarce. Randomized trials using convalescent plasma are missing for high-risk patients. Here, we performed a randomized, open-label, multicenter trial ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001632-10/DE ) in hospitalized patients with severe COVID-19 (n = 134) within four risk groups ((1) cancer (n = 56); (2) immunosuppression (n = 16); (3) laboratory-based risk factors (n = 36); and (4) advanced age (n = 26)) randomized to standard of care (control arm) or standard of care plus convalescent/vaccinated anti-SARS-CoV-2 plasma (plasma arm). No serious adverse events were observed related to the plasma treatment. Clinical improvement as the primary outcome was assessed using a seven-point ordinal scale. Secondary outcomes were time to discharge and overall survival. For the four groups combined, those receiving plasma did not improve clinically compared with those in the control arm (hazard ratio (HR) = 1.29; P = 0.205). However, patients with cancer experienced a shortened median time to improvement (HR = 2.50; P = 0.003) and superior survival with plasma treatment versus the control arm (HR = 0.28; P = 0.042). Neutralizing antibody activity increased in the plasma cohort but not in the control cohort of patients with cancer (P = 0.001). Taken together, convalescent/vaccinated plasma may improve COVID-19 outcomes in patients with cancer who are unable to intrinsically generate an adequate immune response.


Subject(s)
COVID-19 , Neoplasms , Humans , COVID-19/therapy , SARS-CoV-2 , Immunization, Passive/adverse effects , Treatment Outcome , COVID-19 Serotherapy , Antibodies, Viral , Neoplasms/therapy
6.
Transplantation ; 107(5): 1139-1150, 2023 05 01.
Article in English | MEDLINE | ID: covidwho-2191236

ABSTRACT

BACKGROUND: The impaired immune response to coronavirus disease 2019 (COVID-19) vaccination in kidney transplant recipients (KTRs) leads to an urgent need for adapted immunization strategies. METHODS: Sixty-nine KTRs without seroconversion after ≥3 COVID-19 vaccinations were enrolled, and humoral response was determined after an additional full-dose mRNA-1273 vaccination by measuring severe acute respiratory syndrome coronavirus 2-specific antibodies and neutralizing antibody activity against the Delta and Omicron variants 1 and 3 mo postvaccination. T-cell response was analyzed 3 mo postvaccination by assessing interferon-γ release. Mycophenolic acid (MPA) was withdrawn in 41 KTRs 1 wk before until 4 wk after vaccination to evaluate effects on immunogenicity. Graft function, changes in donor-specific anti-HLA antibodies, and donor-derived cell-free DNA were monitored in KTRs undergoing MPA withdrawal. RESULTS: Humoral response to vaccination was significantly stronger in KTRs undergoing MPA withdrawal 1 mo postvaccination; however, overall waning humoral immunity was noted in all KTRs 3 mo after vaccination. Higher anti-S1 immunoglobulin G levels correlated with better neutralizing antibody activity against the Delta and Omicron variants, whereas no significant association was detected between T-cell response and neutralizing antibody activity. No rejection occurred during study, and graft function remained stable in KTRs undergoing MPA withdrawal. In 22 KTRs with Omicron variant breakthrough infections, neutralizing antibody activity was better against severe acute respiratory syndrome coronavirus 2 wild-type and the Delta variants than against the Omicron variant. CONCLUSIONS: MPA withdrawal to improve vaccine responsiveness should be critically evaluated because withdrawing MPA may be associated with enhanced alloimmune response, and the initial effect of enhanced seroconversion rates in KTRs with MPA withdrawal disappears 3 mo after vaccination.


Subject(s)
COVID-19 , Kidney Transplantation , Vaccines , Humans , Mycophenolic Acid , Kidney Transplantation/adverse effects , COVID-19/prevention & control , SARS-CoV-2 , Vaccination , Antibodies, Neutralizing , Antibodies, Viral , Immunity, Humoral , Transplant Recipients
7.
Front Med (Lausanne) ; 9: 958293, 2022.
Article in English | MEDLINE | ID: covidwho-2022776

ABSTRACT

Seroconversion rates after COVID-19 vaccination are significantly lower in kidney transplant recipients compared to healthy cohorts. Adaptive immunization strategies are needed to protect these patients from COVID-19. In this prospective observational cohort study, we enrolled 76 kidney transplant recipients with no seroresponse after at least three COVID-19 vaccinations to receive an additional mRNA-1273 vaccination (full dose, 100 µg). Mycophenolic acid was withdrawn in 43 selected patients 5-7 days prior to vaccination and remained paused for 4 additional weeks after vaccination. SARS-CoV-2-specific antibodies and neutralization of the delta and omicron variants were determined using a live-virus assay 4 weeks after vaccination. In patients with temporary mycophenolic acid withdrawal, donor-specific anti-HLA antibodies and donor-derived cell-free DNA were monitored before withdrawal and at follow-up. SARS-CoV-2 specific antibodies significantly increased in kidney transplant recipients after additional COVID-19 vaccination. The effect was most pronounced in individuals in whom mycophenolic acid was withdrawn during vaccination. Higher SARS-CoV-2 specific antibody titers were associated with better neutralization of SARS-CoV-2 delta and omicron variants. In patients with short-term withdrawal of mycophenolic acid, graft function and donor-derived cell-free DNA remained stable. No acute rejection episode occurred during short-term follow-up. However, resurgence of prior anti-HLA donor-specific antibodies was detected in 7 patients.

8.
Microbiol Spectr ; 10(5): e0122922, 2022 Oct 26.
Article in English | MEDLINE | ID: covidwho-2019781

ABSTRACT

Access to reverse transcription-PCR (RT-PCR) testing, the gold standard for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection, is limited throughout the world, due to restricted resources, available infrastructure, and high costs. Antigen-detecting rapid diagnostic tests (Ag-RDTs) overcome some of these barriers, but independent clinical validations in settings of intended use are scarce. To inform the World Health Organization's (WHO) emergency use listing (EUL) procedure and ensure affordable, high-quality Ag-RDTs, we assessed the performance and ease of use of the SureStatus for SARS-CoV-2. For this prospective, multicenter diagnostic accuracy study, we recruited unvaccinated participants with presumed SARS-CoV-2 infection in India and Germany from December 2020 to March 2021, when the Alpha (B.1.1.7) variant was predominantly circulating. Paired swabs were performed for (i) routine clinical RT-PCR testing (sampling was either nasopharyngeal [NP] or combined NP and oropharyngeal [NP/OP]) and (ii) Ag-RDT (sampling was NP). Performance of the Ag-RDT was compared to RT-PCR overall and by predefined subgroups, e.g., cycle threshold (CT) value, symptoms, and days from symptom onset. To understand the usability, a system usability scale (SUS) questionnaire and ease-of-use (EoU) assessment were performed. A total of 1,119 participants were included in the analysis, of whom 205 (18.3%) were RT-PCR positive. SureStatus detected 169 out of 205 RT-PCR-positive participants, reporting a sensitivity of 82.4% (95% confidence interval [CI]: 76.6% to 87.1%) and a specificity of 98.5% (95% CI: 97.4% to 99.1%). In the first 7 days post-symptom onset, the sensitivity was 90.7% (95% CI: 83.5% to 94.9%), when CT values were low and viral loads were high. The test was characterized as easy to use (SUS, 85/100) and considered suitable for point-of-care settings, although quality concerns were raised due to visibly contaminated packaging of swabs included in the test kits. The SureStatus diagnostic test can be considered a reliable test during the first week of SARS-CoV-2 infection, with high sensitivity in combination with excellent usability. IMPORTANCE Our manufacturer-independent, prospective diagnostic accuracy study assessed clinical performance in participants presumed to have a SARS-CoV-2 infection at three study sites in two countries. We assessed the accuracy overall and in predefined subgroups (CT values and symptom duration). SureStatus performed with high sensitivity. Its sensitivity was particularly high in the first 3 days after symptom onset and when CT values were low (i.e., the viral load was high). The system usability and ease-of-use assessment complements the accuracy assessment of the test and highlights critical factors to facilitate the widespread use of SureStatus in point-of-care settings. The high sensitivity demonstrated by the evaluated Ag-RDT within the first days of symptoms, when most transmission occurs, supports the role of Ag-RDTs for public health-relevant screening. Evidence from this study was used to inform the World Health Organization Emergency Use Listing procedure.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , COVID-19/diagnosis , Diagnostic Tests, Routine , Point-of-Care Systems , Prospective Studies , Sensitivity and Specificity , World Health Organization
9.
Clin Infect Dis ; 75(1): e1063-e1071, 2022 Aug 24.
Article in English | MEDLINE | ID: covidwho-2017768

ABSTRACT

BACKGROUND: At the entry site of respiratory virus infections, the oropharyngeal microbiome has been proposed as a major hub integrating viral and host immune signals. Early studies suggested that infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with changes of the upper and lower airway microbiome, and that specific microbial signatures may predict coronavirus disease 2019 (COVID-19) illness. However, the results are not conclusive, as critical illness can drastically alter a patient's microbiome through multiple confounders. METHODS: To study oropharyngeal microbiome profiles in SARS-CoV-2 infection, clinical confounders, and prediction models in COVID-19, we performed a multicenter, cross-sectional clinical study analyzing oropharyngeal microbial metagenomes in healthy adults, patients with non-SARS-CoV-2 infections, or with mild, moderate, and severe COVID-19 (n = 322 participants). RESULTS: In contrast to mild infections, patients admitted to a hospital with moderate or severe COVID-19 showed dysbiotic microbial configurations, which were significantly pronounced in patients treated with broad-spectrum antibiotics, receiving invasive mechanical ventilation, or when sampling was performed during prolonged hospitalization. In contrast, specimens collected early after admission allowed us to segregate microbiome features predictive of hospital COVID-19 mortality utilizing machine learning models. Taxonomic signatures were found to perform better than models utilizing clinical variables with Neisseria and Haemophilus species abundances as most important features. CONCLUSIONS: In addition to the infection per se, several factors shape the oropharyngeal microbiome of severely affected COVID-19 patients and deserve consideration in the interpretation of the role of the microbiome in severe COVID-19. Nevertheless, we were able to extract microbial features that can help to predict clinical outcomes.


Subject(s)
COVID-19 , Microbiota , Adult , Critical Illness , Cross-Sectional Studies , Dysbiosis , Haemophilus , Humans , Neisseria , SARS-CoV-2
11.
Am J Transplant ; 22(7): 1873-1883, 2022 07.
Article in English | MEDLINE | ID: covidwho-1807004

ABSTRACT

Seroconversion after COVID-19 vaccination is impaired in kidney transplant recipients. Emerging variants of concern such as the B.1.617.2 (delta) and the B.1.1.529 (omicron) variants pose an increasing threat to these patients. In this observational cohort study, we measured anti-S1 IgG, surrogate neutralizing, and anti-receptor-binding domain antibodies three weeks after a third mRNA vaccine dose in 49 kidney transplant recipients and compared results to 25 age-matched healthy controls. In addition, vaccine-induced neutralization of SARS-CoV-2 wild-type, the B.1.617.2 (delta), and the B.1.1.529 (omicron) variants was assessed using a live-virus assay. After a third vaccine dose, anti-S1 IgG, surrogate neutralizing, and anti-receptor-binding domain antibodies were significantly lower in kidney transplant recipients compared to healthy controls. Only 29/49 (59%) sera of kidney transplant recipients contained neutralizing antibodies against the SARS-CoV-2 wild-type or the B.1.617.2 (delta) variant and neutralization titers were significantly reduced compared to healthy controls (p < 0.001). Vaccine-induced cross-neutralization of the B.1.1.529 (omicron) variants was detectable in 15/35 (43%) kidney transplant recipients with seropositivity for anti-S1 IgG, surrogate neutralizing, and/or anti-RBD antibodies. Neutralization of the B.1.1.529 (omicron) variants was significantly reduced compared to neutralization of SARS-CoV-2 wild-type or the B.1.617.2 (delta) variant for both, kidney transplant recipients and healthy controls (p < .001 for all).


Subject(s)
COVID-19 , Kidney Transplantation , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunoglobulin G , RNA, Messenger , SARS-CoV-2 , Transplant Recipients , Vaccines, Synthetic , Viral Envelope Proteins/genetics , mRNA Vaccines
12.
Infection ; 50(5): 1281-1293, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-1783014

ABSTRACT

PURPOSE: The objective of this study was to develop a scalable approach for direct comparison of the analytical sensitivities of commercially available SARS-CoV-2 antigen point-of-care tests (AgPOCTs) to rapidly identify poor-performing products. METHODS: We present a methodology for quick assessment of the sensitivity of SARS-CoV-2 AgPOCTs suitable for quality evaluation of many different products. We established reference samples with high, medium, and low SARS-CoV-2 viral loads along with a SARS-CoV-2 negative control sample. Test samples were used to semi-quantitatively assess the analytical sensitivities of 32 different commercial AgPOCTs in a head-to-head comparison. RESULTS: Among 32 SARS-CoV-2 AgPOCTs tested, we observe sensitivity differences across a broad range of viral loads (9.8 × 108 to 1.8 × 105 SARS-CoV-2 genome copies per ml). 23 AgPOCTs detected the Ct25 test sample (1.6 × 106 copies/ml), while only five tests detected the Ct28 test sample (1.8 × 105 copies/ml). In the low-range of analytical sensitivity, we found three saliva spit tests only delivering positive results for the Ct21 sample (2.7 × 107 copies/ml). Comparison with published data supports our AgPOCT ranking. Importantly, we identified an AgPOCT widely offered, which did not reliably recognize the sample with the highest viral load (Ct16 test sample with 9.8 × 108 copies/ml) leading to serious doubts about its usefulness in SARS-CoV-2 diagnostics. CONCLUSION: The results show that the rapid sensitivity assessment procedure presented here provides useful estimations on the analytical sensitivities of 32 AgPOCTs and identified a widely-spread AgPOCT with concerningly low sensitivity.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , COVID-19 Testing , Clinical Laboratory Techniques/methods , Humans , Point-of-Care Systems , Point-of-Care Testing , Sensitivity and Specificity
13.
J Clin Med ; 11(6)2022 Mar 21.
Article in English | MEDLINE | ID: covidwho-1753642

ABSTRACT

BACKGROUND: To characterize humoral response after standard anti-SARS-CoV-2 vaccination in Rituximab-treated patients and to determine the optimal time point after last Rituximab treatment for appropriate immunization. METHODS: Sixty-four patients who received Rituximab within the last seven years prior to the first anti-SARS-CoV-2 vaccination were recruited in a prospective observational study. Anti-S1 IgG, SARS-CoV-2 specific neutralization, and various SARS-CoV-2 target antibodies were determined. A live virus assay was used to assess neutralizing antibody activity against B.1.617.2 (delta). In Rituximab-treated patients, CD19+ peripheral B-cells were quantified using flow cytometry. RESULTS: After second vaccination, all antibodies were significantly reduced compared to healthy controls. Neutralizing antibody activity against B.1.617.2 (delta) was detectable with a median (IQR) ID50 of 0 (0-1:20) compared to 1:320 (1:160-1:320) in healthy controls (for all p < 0.001). Longer time period since last Rituximab administration correlated with higher anti-SARS-CoV-2 antibody levels and a stronger neutralization of B.1.617.2 (delta). With one exception, only patients with a CD19+ cell proportion ≥ 1% had detectable neutralizing antibodies. CONCLUSION: Our data indicate that a reconstitution of the B-cell population to >1% seems crucial in developing neutralizing antibodies against SARS-CoV-2. We suggest that anti-SARS-CoV-2 vaccination should be administered at least 8-12 months after the last Rituximab treatment for sufficient humoral responses.

14.
Front Immunol ; 13: 840136, 2022.
Article in English | MEDLINE | ID: covidwho-1753372

ABSTRACT

Hemodialysis patients are at high risk for severe COVID-19, and impaired seroconversion rates have been demonstrated after COVID-19 vaccination. Humoral immunity wanes over time and variants of concern with immune escape are posing an increasing threat. Little is known about protection against the B.1.617.2 (delta) variant of concern in hemodialysis patients before and after third vaccination. We determined anti-S1 IgG, surrogate neutralizing, and IgG antibodies against different SARS-CoV-2 epitopes in 84 hemodialysis patients directly before and three weeks after a third vaccine dose with BNT162b2. Third vaccination was performed after a median (IQR) of 119 (109-165) days after second vaccination. In addition, neutralizing activity against the B.1.617.2 (delta) variant was assessed in 31 seroconverted hemodialysis patients before and after third vaccination. Triple seropositivity for anti-S1 IgG, surrogate neutralizing, and anti-RBD antibodies increased from 31/84 (37%) dialysis patients after second to 80/84 (95%) after third vaccination. Neutralizing activity against the B.1.617.2 (delta) variant was significantly higher after third vaccination with a median (IQR) ID50 of 1:320 (1:160-1:1280) compared with 1:20 (0-1:40) before a third vaccine dose (P<0.001). The anti-S1 IgG index showed the strongest correlation with the ID50 against the B.1.617.2 (delta) variant determined by live virus neutralization (r=0.91). We demonstrate low neutralizing activity against the B.1.617.2 (delta) variant in dialysis patients four months after standard two-dose vaccination but a substantial increase after a third vaccine dose. Booster vaccination(s) should be considered earlier than 6 months after the second vaccine dose in immunocompromised individuals.


Subject(s)
BNT162 Vaccine , COVID-19 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunoglobulin G , Renal Dialysis , SARS-CoV-2
17.
Vaccines (Basel) ; 10(2)2022 Feb 18.
Article in English | MEDLINE | ID: covidwho-1702700

ABSTRACT

The COVID-19 pandemic threatens patients with a compromised immune and endothelial system, including patients who underwent allogeneic stem cell transplantation (alloSCT). Thus, there is an unmet need for optimizing vaccination management in this high-risk cohort. Here, we monitored antibodies against SARS-CoV-2 spike protein (anti-S1) in 167 vaccinated alloSCT patients. Humoral immune responses were detectable in 81% of patients after two vaccinations with either mRNA-, vector-based, or heterologous regimens. Age, B-cell counts, time interval from vaccination, and the type of vaccine determined antibody titres in patients without systemic immunosuppression (sIS). Similar to a healthy control cohort, mRNA vaccine-based regimens induced higher titres than vector-based vaccines. Patients on two or more immunosuppressants rarely developed immunity. In contrast, 62% and 45% of patients without or on only one immunosuppressant, respectively, showed a strong humoral vaccination response (titre > 100). Exacerbation of cGVHD upon vaccination was observed in 6% of all patients and in 22% of patients receiving immunosuppression for cGVHD. cGVHD exacerbation and low antibody titres were both associated with higher angiopoietin-2 (ANG2) serum levels. In conclusion, mRNA-based vaccines elicit strong humoral responses in alloSCT patients in the absence of double sIS. Biomarkers such as ANG2 might help with weighing cGVHD risk versus beneficial responses.

18.
Clin Microbiol Infect ; 28(7): 1024.e7-1024.e12, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1664807

ABSTRACT

OBJECTIVES: Humoral immunity wanes over time after two-dose BNT162b2 vaccination. Emerging variants of concern, such as the B.1.617.2 (delta) variant, are increasingly responsible for breakthrough infections owing to their higher transmissibility and partial immune escape. Longitudinal data on neutralization against the B.1.617.2 (delta) variant are urgently needed to guide vaccination strategies. METHODS: In this prospective longitudinal observational study, anti-S1 IgG and surrogate neutralizing antibodies were measured in 234 collected samples from 60 health care workers after two-dose vaccination with BNT162b2 at five different time points over an 8-month period. In addition, antibodies against various severe acute respiratory syndrome coronavirus 2 epitopes, neutralization against wild-type, and cross-neutralization against the B.1.617.2 (delta) variant using a live virus assay were measured 6 weeks (second time point) and 8 months (last time point) after first vaccine dose. RESULTS: Median (interquartile range) anti-S1 IgG, surrogate neutralizing, and receptor-binding domain antibodies decreased significantly from a maximum level of 147 (102-298), 97 (96-98), and 20 159 (19 023-21 628) to 8 (4-13), 92 (80-96), and 15 324 (13 055-17 288) at the 8-month follow-up, respectively (p < 0.001 for all). Neutralization against the B.1.617.2 (delta) variant was detectable in all 36 (100%) participants at 6 weeks and in 50 of 53 (94%) participants 8 months after first vaccine dose. Median (interquartile) ID50 as determined by a live virus assay decreased from 160 (80-320) to 40 (20-40) (p < 0.001). DISCUSSION: Although humoral immunity wanes over time after two-dose BNT162b2 vaccination in healthy individuals, most individuals still had detectable neutralizing activity against the B.1.617.2 (delta) variant after 8 months.


Subject(s)
Antibodies, Neutralizing , COVID-19 , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , Health Personnel , Humans , Immunoglobulin G , Neutralization Tests , Prospective Studies , SARS-CoV-2 , Vaccination
19.
Eur J Radiol ; 144: 110002, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1605018

ABSTRACT

PURPOSE: To examine the performance of radiologists in differentiating COVID-19 from non-COVID-19 atypical pneumonia and to perform an analysis of CT patterns in a study cohort including viral, fungal and atypical bacterial pathogens. METHODS: Patients with positive RT-PCR tests for COVID-19 pneumonia (n = 90) and non-COVID-19 atypical pneumonia (n = 294) were retrospectively included. Five radiologists, blinded to the pathogen test results, assessed the CT scans and classified them as COVID-19 or non-COVID-19 pneumonia. For both groups specific CT features were recorded and a multivariate logistic regression model was used to calculate their ability to predict COVID-19 pneumonia. RESULTS: The radiologists differentiated between COVID-19 and non-COVID-19 pneumonia with an overall accuracy, sensitivity, and specificity of 88% ± 4 (SD), 79% ± 6 (SD), and 90% ± 6 (SD), respectively. The percentage of correct ratings was lower in the early and late stage of COVID-19 pneumonia compared to the progressive and peak stage (68 and 71% vs 85 and 89%). The variables associated with the most increased risk of COVID-19 pneumonia were band like subpleural opacities (OR 5.55, p < 0.001), vascular enlargement (OR 2.63, p = 0.071), and subpleural curvilinear lines (OR 2.52, p = 0.021). Bronchial wall thickening and centrilobular nodules were associated with decreased risk of COVID-19 pneumonia with OR of 0.30 (p = 0.013) and 0.10 (p < 0.001), respectively. CONCLUSIONS: Radiologists can differentiate between COVID-19 and non-COVID-19 atypical pneumonias at chest CT with high overall accuracy, although a lower performance was observed in the early and late stage of COVID 19 pneumonia. Specific CT features might help to make the correct diagnosis.


Subject(s)
COVID-19 , Influenza, Human , Humans , Lung , Radiologists , Retrospective Studies , SARS-CoV-2
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