Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 15 de 15
Filter
1.
Clin Infect Dis ; 2022 Jul 23.
Article in English | MEDLINE | ID: covidwho-1961004

ABSTRACT

BACKGROUND: In the general population, illness after infection with the SARS-CoV-2 Omicron variant is less severe compared with previous variants. Data on the disease burden of Omicron in immunocompromised patients are lacking. We investigated the clinical characteristics and outcome of a cohort of immunocompromised patients with COVID-19 caused by Omicron. METHODS: Solid organ transplant recipients, patients on anti-CD20 therapy, and allogenic hematopoietic stem cell transplantation recipients on immunosuppressive therapy infected with the Omicron variant, were included. Patients were contacted regularly until symptom resolution. Clinical characteristics of consenting patients were collected through their electronic patient files. To identify possible risk factors for hospitalization, a univariate logistic analysis was performed. RESULTS: A total of 114 consecutive immunocompromised patients were enrolled. Eighty-nine percent had previously received three mRNA vaccinations. While only one patient died, 23 (20%) required hospital admission for a median of 11 days. A low SARS-CoV-2 IgG antibody response (<300 BAU/mL) at diagnosis, higher age, being a lung transplant recipient, more comorbidities and a higher frailty were associated with hospital admission (all p < 0.01). At the end of follow-up, 25% had still not fully recovered. Of the 23 hospitalized patients, 70% had a negative and 92% a low IgG (<300 BAU/mL) antibody response at admission. Sotrovimab was administered to 17 of them, of which one died. CONCLUSIONS: While the mortality in immunocompromised patients infected with Omicron was low, hospital admission was frequent and the duration of symptoms often prolonged. Besides vaccination, other interventions are needed to limit the morbidity from COVID-19 in immunocompromised patients.

2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335179

ABSTRACT

Background In the general population, illness after infection with the SARS-CoV-2 Omicron variant is less severe compared with previous variants. Data on the disease burden of Omicron in immunocompromised patients are lacking. We investigated the clinical characteristics and outcome of a cohort of immunocompromised patients with COVID-19 caused by Omicron. Methods Solid organ transplant recipients, patients on anti-CD20 therapy, and allogenic hematopoietic stem cell transplantation recipients on immunosuppressive therapy infected with the Omicron variant, were included. Patients were contacted regularly until symptom resolution. Clinical characteristics of consenting patients were collected through their electronic patient files. To identify possible risk factors for hospitalization, a univariate logistic analysis was performed. Results A total of 114 consecutive immunocompromised patients were enrolled. Eighty-nine percent had previously received three mRNA vaccinations. While only one patient died, 23 (20%) required hospital admission for a median of 11 days. A low SARS-CoV-2 IgG antibody response (<300 BAU/mL) at diagnosis, higher age, being a lung transplant recipient, more comorbidities and a higher frailty were associated with hospital admission (all p<0.01). At the end of follow-up, 25% had still not fully recovered. Of the 23 hospitalized patients, 70% had a negative and 92% a low IgG (<300 BAU/mL) antibody response at admission. Sotrovimab was administered to 17 of them, of which one died. Conclusions While the mortality in immunocompromised patients infected with Omicron was low, hospital admission was frequent and the duration of symptoms often prolonged. Besides vaccination, other interventions are needed to limit the morbidity from COVID-19 in immunocompromised patients. Summary COVID-19-associated morbidity and mortality in immunocompromised patients is unknown for the SARS-CoV-2 Omicron variant. This prospective registry, demonstrated low COVID-19-associated mortality in these vulnerable patients. However, morbidity remained substantial. Other interventions to abate COVID-19 severity are needed.

3.
Euro Surveill ; 27(8)2022 02.
Article in English | MEDLINE | ID: covidwho-1714940

ABSTRACT

BackgroundSARS-CoV-2 RT-PCR assays are more sensitive than rapid antigen detection assays (RDT) and can detect viral RNA even after an individual is no longer infectious. RDT can reduce the time to test and the results might better correlate with infectiousness.AimWe assessed the ability of five RDT to identify infectious COVID-19 cases and systematically recorded the turnaround time of RT-PCR testing.MethodsSensitivity of RDT was determined using a serially diluted SARS-CoV-2 stock with known viral RNA concentration. The probability of detecting infectious virus at a given viral load was calculated using logistic regression of viral RNA concentration and matched culture results of 78 specimens from randomly selected non-hospitalised cases. The probability of each RDT to detect infectious cases was calculated as the sum of the projected probabilities for viral isolation success for every viral RNA load found at the time of diagnosis in 1,739 confirmed non-hospitalised COVID-19 cases.ResultsThe distribution of quantification cycle values and estimated RNA loads for patients reporting to drive-through testing was skewed to high RNA loads. With the most sensitive RDT (Abbott and SD Biosensor), 97.30% (range: 88.65-99.77) of infectious individuals would be detected. This decreased to 92.73% (range: 60.30-99.77) for Coris BioConcept and GenBody, and 75.53% (range: 17.55-99.77) for RapiGEN. Only 32.9% of RT-PCR results were available on the same day as specimen collection.ConclusionThe most sensitive RDT detected infectious COVID-19 cases with high sensitivity and may considerably improve containment through more rapid isolation and contact tracing.


Subject(s)
COVID-19 , SARS-CoV-2 , Antigens, Viral/analysis , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19 Testing , Humans , Netherlands/epidemiology , SARS-CoV-2/genetics , Sensitivity and Specificity
4.
Clin Infect Dis ; 74(3): 521-524, 2022 02 11.
Article in English | MEDLINE | ID: covidwho-1684544

ABSTRACT

During COVID-19 lockdown, the in-hospital number of HIV indicator conditions decreased disproportionally compared with other non-COVID-19 diseases, which was accompanied by reduced HIV testing rates, number and proportion of positive HIV tests, and new HIV referrals, with more late presentation after lockdown cessation, indicating a significantly impacted HIV care continuum.


Subject(s)
COVID-19 , HIV Infections , Communicable Disease Control , Continuity of Patient Care , HIV , HIV Infections/drug therapy , HIV Infections/epidemiology , Hospitals , Humans , SARS-CoV-2
5.
PLoS One ; 16(11): e0259165, 2021.
Article in English | MEDLINE | ID: covidwho-1581791

ABSTRACT

The rapid, sensitive and specific detection of SARS-CoV-2 is critical in responding to the current COVID-19 outbreak. In this proof-of-concept study, we explored the potential of targeted mass spectrometry (MS) based proteomics for the detection of SARS-CoV-2 proteins in both research samples and clinical specimens. First, we assessed the limit of detection for several SARS-CoV-2 proteins by parallel reaction monitoring (PRM) MS in infected Vero E6 cells. For tryptic peptides of Nucleocapsid protein, the limit of detection was estimated to be in the mid-attomole range (9E-13 g). Next, this PRM methodology was applied to the detection of viral proteins in various COVID-19 patient clinical specimens, such as sputum and nasopharyngeal swabs. SARS-CoV-2 proteins were detected in these samples with high sensitivity in all specimens with PCR Ct values <24 and in several samples with higher CT values. A clear relationship was observed between summed MS peak intensities for SARS-CoV-2 proteins and Ct values reflecting the abundance of viral RNA. Taken together, these results suggest that targeted MS based proteomics may have the potential to be used as an additional tool in COVID-19 diagnostics.


Subject(s)
COVID-19/diagnosis , Proteomics , SARS-CoV-2/isolation & purification , Viral Proteins/isolation & purification , Animals , COVID-19/pathology , COVID-19/virology , Chlorocebus aethiops , Humans , Mass Spectrometry , Nucleocapsid/genetics , Nucleocapsid/isolation & purification , Phosphoproteins/genetics , Phosphoproteins/isolation & purification , Proteome/genetics , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Sputum/virology , Vero Cells , Viral Proteins/genetics
6.
J Virol Methods ; 300: 114397, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1540816

ABSTRACT

Here we describe a SARS-CoV-2 variant with diminished amplification of the ORF ORF1ab target in the Cobas® dual-target SARS-CoV-2 assay resulting in a discrepancy of Ct-values (Ct-value 20.7 for the E-gene and Ct-value 30.2 for ORF1ab). Five unique nucleotide mutations were identified in ORF1ab: C11450A (nsp10) C14178T (RdRp), G15006T (RdRp), G18394T (Hel), and G20995T (Hel). This case highlights the importance of surveillance of genomic regions used in molecular diagnostics and the importance of the public release of target regions used to update commercial and in-house developed SARS-CoV-2 PCR tests. This work underpins the importance of using dual-targets in molecular diagnostic assays to limit the change of false-negative results due to primer and/or probe mismatches.


Subject(s)
COVID-19 , SARS-CoV-2 , Diagnostic Tests, Routine , Humans , RNA, Viral , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and Specificity
7.
Int J Infect Dis ; 107: 34-36, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1300796

ABSTRACT

This report describes the first heart transplantation recipient with acute biventricular heart failure symptoms caused by a post-myocarditis state, late after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. No other viral pathogens could be detected. Computed tomography angiography did not show cardiac allograft vasculopathy, and myocardial biopsy demonstrated no clinically relevant rejection. Subsequent cardiovascular magnetic resonance imaging revealed extensive epicardial delayed enhancement without myocardial edema. Heart failure medication was initiated and an implantable cardioverter defibrillator was implanted (due to non-sustained ventricular tachycardias), leading to a partial recovery of the ejection fraction. Further studies are needed to investigate the number of heart transplant recipients with myocardial damage after a SARS-CoV-2 infection.


Subject(s)
COVID-19/complications , Heart Transplantation/adverse effects , Myocarditis/etiology , SARS-CoV-2 , Heart Failure/etiology , Humans , Middle Aged
8.
Biomark Insights ; 16: 11772719211021647, 2021.
Article in English | MEDLINE | ID: covidwho-1259132

ABSTRACT

Corticosteroids reduced mortality rate in patients with coronavirus disease 2019 (COVID-19). Previously, we hypothesized that corticosteroids mitigate the inflammation response resulting in reduced coagulation and thrombosis. In this retrospective study, we included 27 patients with COVID-19 that received high-dose corticosteroids (methylprednisolone 1000 mg i.v. daily for 3 days) for persistent respiratory failure or an excessive inflammation response. We found that inflammation, coagulation, and ventilation parameters improved significantly after methylprednisolone. The viral loads of SARS-CoV-2 remained stable or decreased. These results provides insight into the reduced mortality rate observed in patients with COVID-19 treated with corticosteroids.

9.
mSphere ; 6(3): e0031121, 2021 06 30.
Article in English | MEDLINE | ID: covidwho-1247323

ABSTRACT

COVID-19 is associated with a wide range of extrarespiratory complications, of which the pathogenesis is currently not fully understood. However, both systemic spread and systemic inflammatory responses are thought to contribute to the systemic pathogenesis. In this study, we determined the temporal kinetics of viral RNA in serum (RNAemia) and the associated inflammatory cytokines and chemokines during the course of COVID-19 in hospitalized patients. We show that RNAemia can be detected in 90% of the patients who develop critical disease, compared to 50% of the patients who develop moderate or severe disease. Furthermore, RNAemia lasts longer in patients who develop critical disease. Elevated levels of interleukin-10 (IL-10) and MCP-1-but not IL-6-are associated with viral load in serum, whereas higher levels of IL-6 in serum were associated with the development of critical disease. In conclusion, RNAemia is common in hospitalized patients, with the highest frequency and duration in patients who develop critical disease. The fact that several cytokines or chemokines are directly associated with the presence of viral RNA in the circulation suggests that the development of RNAemia is an important factor in the systemic pathogenesis of COVID-19. IMPORTANCE Severe COVID-19 can be considered a systemic disease as many extrarespiratory complications occur. However, the systemic pathogenesis is poorly understood. Here, we show that the presence of viral RNA in the blood (RNAemia) occurs more frequently in patients who develop critical disease, compared to patients with moderate or severe disease. In addition, RNAemia is associated with increased levels of inflammatory cytokines and chemokines, like MCP-1 and IL-10, in serum during the course of disease. This suggests that extrarespiratory spread of SARS-CoV-2 contributes to systemic inflammatory responses, which are an important factor in the systemic pathogenesis of COVID-19.


Subject(s)
COVID-19/immunology , Cytokines/blood , RNA, Viral/blood , SARS-CoV-2/genetics , COVID-19/etiology , COVID-19/virology , Hospitalization , Humans , Kinetics , Severity of Illness Index
10.
Nat Commun ; 12(1): 3189, 2021 05 27.
Article in English | MEDLINE | ID: covidwho-1246368

ABSTRACT

In a randomized clinical trial of 86 hospitalized COVID-19 patients comparing standard care to treatment with 300mL convalescent plasma containing high titers of neutralizing SARS-CoV-2 antibodies, no overall clinical benefit was observed. Using a comprehensive translational approach, we unravel the virological and immunological responses following treatment to disentangle which COVID-19 patients may benefit and should be the focus of future studies. Convalescent plasma is safe, does not improve survival, has no effect on the disease course, nor does plasma enhance viral clearance in the respiratory tract, influence SARS-CoV-2 antibody development or serum proinflammatory cytokines levels. Here, we show that the vast majority of patients already had potent neutralizing SARS-CoV-2 antibodies at hospital admission and with comparable titers to carefully selected plasma donors. This resulted in the decision to terminate the trial prematurely. Treatment with convalescent plasma should be studied early in the disease course or at least preceding autologous humoral response development.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/therapy , Cytokines/blood , SARS-CoV-2/immunology , Aged , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Blood Donors , COVID-19/blood , COVID-19/virology , Disease Progression , Female , Hospitalization , Humans , Immunization, Passive , Immunoglobulin G/blood , Kaplan-Meier Estimate , Male , Middle Aged , Spike Glycoprotein, Coronavirus/immunology , Treatment Outcome
11.
J Infect Dis ; 223(9): 1512-1521, 2021 05 20.
Article in English | MEDLINE | ID: covidwho-1238201

ABSTRACT

Lower respiratory tract (LRT) disease induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can deteriorate to acute respiratory distress syndrome (ARDS). Because the release of neutrophil extracellular traps (NETs) is implicated in ARDS pathogenesis, we investigated the presence of NETs and correlates of pathogenesis in blood and LRT samples of critically ill patients with COVID-19. Plasma NET levels peaked early after intensive care unit admission and were correlated with the SARS-CoV-2 RNA load in sputum and levels of neutrophil-recruiting chemokines and inflammatory markers in plasma samples. The baseline plasma NET quantity was correlated with disease severity but was not associated with soluble markers of thrombosis or with development of thrombosis. High NET levels were present in LRT samples and persisted during the course of COVID-19, consistent with the detection of NETs in bronchi and alveolar spaces in lung tissue from deceased patient with COVID-19. Thus, NETs are produced and retained in the LRT of critically ill patients with COVID-19 and could contribute to SARS-CoV-2-induced ARDS disease.


Subject(s)
Bronchoalveolar Lavage Fluid/virology , COVID-19/complications , COVID-19/pathology , Extracellular Traps/virology , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/pathology , SARS-CoV-2 , Adult , Aged , Biomarkers , Chemokines/blood , Cohort Studies , Computed Tomography Angiography , Critical Illness , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunohistochemistry , Male , Middle Aged , Netherlands/epidemiology , Prospective Studies , Severity of Illness Index , Thrombosis/virology , Viral Load
12.
Nat Commun ; 12(1): 267, 2021 01 11.
Article in English | MEDLINE | ID: covidwho-1019818

ABSTRACT

Key questions in COVID-19 are the duration and determinants of infectious virus shedding. Here, we report that infectious virus shedding is detected by virus cultures in 23 of the 129 patients (17.8%) hospitalized with COVID-19. The median duration of shedding infectious virus is 8 days post onset of symptoms (IQR 5-11) and drops below 5% after 15.2 days post onset of symptoms (95% confidence interval (CI) 13.4-17.2). Multivariate analyses identify viral loads above 7 log10 RNA copies/mL (odds ratio [OR] of 14.7 (CI 3.57-58.1; p < 0.001) as independently associated with isolation of infectious SARS-CoV-2 from the respiratory tract. A serum neutralizing antibody titre of at least 1:20 (OR of 0.01 (CI 0.003-0.08; p < 0.001) is independently associated with non-infectious SARS-CoV-2. We conclude that quantitative viral RNA load assays and serological assays could be used in test-based strategies to discontinue or de-escalate infection prevention and control precautions.


Subject(s)
COVID-19/diagnosis , COVID-19/virology , SARS-CoV-2 , Virus Shedding , Aged , COVID-19 Testing , Female , Humans , Male , Middle Aged , Multivariate Analysis , Odds Ratio , RNA, Viral , Respiratory System/virology , Viral Load
14.
Nat Commun ; 11(1): 3436, 2020 07 06.
Article in English | MEDLINE | ID: covidwho-630511

ABSTRACT

The world is entering a new era of the COVID-19 pandemic in which there is an increasing call for reliable antibody testing. To support decision making on the deployment of serology for either population screening or diagnostics, we present a detailed comparison of serological COVID-19 assays. We show that among the selected assays there is a wide diversity in assay performance in different scenarios and when correlated to virus neutralizing antibodies. The Wantai ELISA detecting total immunoglobulins against the receptor binding domain of SARS CoV-2, has the best overall characteristics to detect functional antibodies in different stages and severity of disease, including the potential to set a cut-off indicating the presence of protective antibodies. The large variety of available serological assays requires proper assay validation before deciding on deployment of assays for specific applications.


Subject(s)
Antibodies, Viral/blood , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Serologic Tests/standards , Antibodies, Neutralizing/blood , Betacoronavirus , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Enzyme-Linked Immunosorbent Assay , High-Throughput Screening Assays , Humans , Luminescent Measurements , Neutralization Tests , Pandemics , SARS-CoV-2 , Sensitivity and Specificity
15.
Transpl Int ; 33(9): 1099-1105, 2020 09.
Article in English | MEDLINE | ID: covidwho-381861

ABSTRACT

Solid organ transplant (SOT) recipients may be at risk for severe COVID-19. Data on the clinical course of COVID-19 in immunosuppressed patients are limited, and the effective treatment strategy for these patients is unknown. We describe our institutional experience with COVID-19 in SOT. Demographic, clinical, and treatment data were extracted from the electronic patient files. A total of 23 SOT transplant recipients suffering from COVID-19 were identified (n = 3 heart; n = 15 kidney; n = 1 kidney-after-heart; n = 3 lung, and n = 1 liver transplant recipient). The presenting symptoms were similar to nonimmunocompromised patients. Eighty-three percent (19/23) of the patients required hospitalization, but only two of these were transferred to the intensive care unit. Five patients died from COVID-19; all had high Clinical Frailty Scores. In four of these patients, mechanical ventilation was deemed futile. In 57% of patients, the immunosuppressive therapy was not changed and only three patients were treated with chloroquine. Most patients recovered without experimental antiviral therapy. Modification of the immunosuppressive regimen alone could be a therapeutic option for SOT recipients suffering from moderate to severe COVID-19. Pre-existent frailty is associated with death from COVID-19.


Subject(s)
COVID-19/epidemiology , Immunosuppression Therapy/adverse effects , Organ Transplantation/adverse effects , Transplant Recipients , Aged , Aged, 80 and over , COVID-19/immunology , COVID-19/therapy , Female , Humans , Male , Middle Aged , Netherlands/epidemiology , Pandemics , SARS-CoV-2 , Treatment Outcome , Young Adult
SELECTION OF CITATIONS
SEARCH DETAIL