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1.
Biomark Insights ; 17: 11772719221112370, 2022.
Article in English | MEDLINE | ID: covidwho-1938207

ABSTRACT

Introduction: Predicting disease severity is important for treatment decisions in patients with COVID-19 in the intensive care unit (ICU). Different biomarkers have been investigated in COVID-19 as predictor of mortality, including C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), and soluble urokinase-type plasminogen activator receptor (suPAR). Using repeated measurements in a prediction model may result in a more accurate risk prediction than the use of single point measurements. The goal of this study is to investigate the predictive value of trends in repeated measurements of CRP, PCT, IL-6, and suPAR on mortality in patients admitted to the ICU with COVID-19. Methods: This was a retrospective single center cohort study. Patients were included if they tested positive for SARS-CoV-2 by PCR test and if IL-6, PCT, suPAR was measured during any of the ICU admission days. There were no exclusion criteria for this study. We used joint models to predict ICU-mortality. This analysis was done using the framework of joint models for longitudinal and survival data. The reported hazard ratios express the relative change in the risk of death resulting from a doubling or 20% increase of the biomarker's value in a day compared to no change in the same period. Results: A total of 107 patients were included, of which 26 died during ICU admission. Adjusted for sex and age, a doubling in the next day in either levels of PCT, IL-6, and suPAR were significantly predictive of in-hospital mortality with HRs of 1.523 (1.012-6.540), 75.25 (1.116-6247), and 24.45 (1.696-1057) respectively. With a 20% increase in biomarker value in a subsequent day, the HR of PCT, IL-6, and suPAR were 1.117 (1.03-1.639), 3.116 (1.029-9.963), and 2.319 (1.149-6.243) respectively. Conclusion: Joint models for the analysis of repeated measurements of PCT, suPAR, and IL-6 are a useful method for predicting mortality in COVID-19 patients in the ICU. Patients with an increasing trend of biomarker levels in consecutive days are at increased risk for mortality.

2.
J Clin Immunol ; 42(2): 232-239, 2022 02.
Article in English | MEDLINE | ID: covidwho-1838372

ABSTRACT

PURPOSE: To study the effect of interferon-α2 auto-antibodies (IFN-α2 Abs) on clinical and virological outcomes in critically ill COVID-19 patients and the risk of IFN-α2 Abs transfer during convalescent plasma treatment. METHODS: Sera from healthy controls, cases of COVID-19, and other respiratory illness were tested for IFN-α2 Abs by ELISA and a pseudo virus-based neutralization assay. The effects of disease severity, sex, and age on the risk of having neutralizing IFN-α2 Abs were determined. Longitudinal analyses were performed to determine association between IFN-α2 Abs and survival and viral load and whether serum IFN-α2 Abs appeared after convalescent plasma transfusion. RESULTS: IFN-α2 neutralizing sera were found only in COVID-19 patients, with proportions increasing with disease severity and age. In the acute stage of COVID-19, all sera from patients with ELISA-detected IFN-α2 Abs (13/164, 7.9%) neutralized levels of IFN-α2 exceeding physiological concentrations found in human plasma and this was associated with delayed viral clearance. Convalescent plasma donors that were anti-IFN-α2 ELISA positive (3/118, 2.5%) did not neutralize the same levels of IFN-α2. Neutralizing serum IFN-α2 Abs were associated with delayed viral clearance from the respiratory tract. CONCLUSIONS: IFN-α2 Abs were detected by ELISA and neutralization assay in COVID-19 patients, but not in ICU patients with other respiratory illnesses. The presence of neutralizing IFN-α2 Abs in critically ill COVID-19 is associated with delayed viral clearance. IFN-α2 Abs in COVID-19 convalescent plasma donors were not neutralizing in the conditions tested.


Subject(s)
Autoantibodies/immunology , COVID-19/immunology , COVID-19/therapy , Interferon alpha-2/immunology , Plasma/immunology , Adult , Aged , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Antiviral Agents/immunology , Blood Component Transfusion/methods , Critical Illness , Female , Humans , Immunization, Passive/methods , Immunoglobulin G/immunology , Male , Middle Aged , SARS-CoV-2/immunology
3.
J Allergy Clin Immunol ; 149(6): 1949-1957, 2022 06.
Article in English | MEDLINE | ID: covidwho-1783444

ABSTRACT

BACKGROUND: Patients with inborn errors of immunity (IEI) are at increased risk of severe coronavirus disease-2019 (COVID-19). Effective vaccination against COVID-19 is therefore of great importance in this group, but little is known about the immunogenicity of COVID-19 vaccines in these patients. OBJECTIVES: We sought to study humoral and cellular immune responses after mRNA-1273 COVID-19 vaccination in adult patients with IEI. METHODS: In a prospective, controlled, multicenter study, 505 patients with IEI (common variable immunodeficiency [CVID], isolated or undefined antibody deficiencies, X-linked agammaglobulinemia, combined B- and T-cell immunodeficiency, phagocyte defects) and 192 controls were included. All participants received 2 doses of the mRNA-1273 COVID-19 vaccine. Levels of severe acute respiratory syndrome coronavirus-2-specific binding antibodies, neutralizing antibodies, and T-cell responses were assessed at baseline, 28 days after first vaccination, and 28 days after second vaccination. RESULTS: Seroconversion rates in patients with clinically mild antibody deficiencies and phagocyte defects were similar to those in healthy controls, but seroconversion rates in patients with more severe IEI, such as CVID and combined B- and T-cell immunodeficiency, were lower. Binding antibody titers correlated well to the presence of neutralizing antibodies. T-cell responses were comparable to those in controls in all IEI cohorts, with the exception of patients with CVID. The presence of noninfectious complications and the use of immunosuppressive drugs in patients with CVID were negatively correlated with the antibody response. CONCLUSIONS: COVID-19 vaccination with mRNA-1273 was immunogenic in mild antibody deficiencies and phagocyte defects and in most patients with combined B- and T-cell immunodeficiency and CVID. Lowest response was detected in patients with X-linked agammaglobulinemia and in patients with CVID with noninfectious complications. The assessment of longevity of immune responses in these vulnerable patient groups will guide decision making for additional vaccinations.


Subject(s)
2019-nCoV Vaccine mRNA-1273 , Antibodies, Neutralizing , COVID-19 , Genetic Diseases, Inborn , Immunologic Deficiency Syndromes , 2019-nCoV Vaccine mRNA-1273/blood , 2019-nCoV Vaccine mRNA-1273/immunology , 2019-nCoV Vaccine mRNA-1273/therapeutic use , Adult , Agammaglobulinemia/genetics , Agammaglobulinemia/immunology , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/genetics , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/immunology , COVID-19 Vaccines/therapeutic use , Common Variable Immunodeficiency/genetics , Common Variable Immunodeficiency/immunology , Genetic Diseases, Inborn/blood , Genetic Diseases, Inborn/genetics , Genetic Diseases, Inborn/immunology , Genetic Diseases, X-Linked/genetics , Genetic Diseases, X-Linked/immunology , Humans , Immunologic Deficiency Syndromes/blood , Immunologic Deficiency Syndromes/genetics , Immunologic Deficiency Syndromes/immunology , Primary Immunodeficiency Diseases/genetics , Primary Immunodeficiency Diseases/immunology , Prospective Studies , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
4.
Sci Total Environ ; 755(Pt 2): 143182, 2021 Feb 10.
Article in English | MEDLINE | ID: covidwho-1768525

ABSTRACT

Current models for flu-like epidemics insufficiently explain multi-cycle seasonality. Meteorological factors alone, including the associated behavior, do not predict seasonality, given substantial climate differences between countries that are subject to flu-like epidemics or COVID-19. Pollen is documented to be allergenic, it plays a role in immuno-activation and defense against respiratory viruses, and seems to create a bio-aerosol that lowers the reproduction number of flu-like viruses. Therefore, we hypothesize that pollen may explain the seasonality of flu-like epidemics, including COVID-19, in combination with meteorological variables. We have tested the Pollen-Flu Seasonality Theory for 2016-2020 flu-like seasons, including COVID-19, in the Netherlands, with its 17.4 million inhabitants. We combined changes in flu-like incidence per 100 K/Dutch residents (code: ILI) with pollen concentrations and meteorological data. Finally, a predictive model was tested using pollen and meteorological threshold values, inversely correlated to flu-like incidence. We found a highly significant inverse correlation of r(224) = -0.41 (p < 0.001) between pollen and changes in flu-like incidence, corrected for the incubation period. The correlation was stronger after taking into account the incubation time. We found that our predictive model has the highest inverse correlation with changes in flu-like incidence of r(222) = -0.48 (p < 0.001) when average thresholds of 610 total pollen grains/m3, 120 allergenic pollen grains/m3, and a solar radiation of 510 J/cm2 are passed. The passing of at least the pollen thresholds, preludes the beginning and end of flu-like seasons. Solar radiation is a co-inhibitor of flu-like incidence, while temperature makes no difference. However, higher relative humidity increases with flu-like incidence. We conclude that pollen is a predictor of the inverse seasonality of flu-like epidemics, including COVID-19, and that solar radiation is a co-inhibitor, in the Netherlands.


Subject(s)
COVID-19 , Humans , Netherlands/epidemiology , Pollen , SARS-CoV-2 , Seasons
5.
Immun Inflamm Dis ; 10(4): e609, 2022 04.
Article in English | MEDLINE | ID: covidwho-1763241

ABSTRACT

INTRODUCTION: Myxovirus resistance protein 1 (MxA) is a biomarker that is elevated in patients with viral infections. The goal of this study was to evaluate the diagnostic value of MxA in diagnosing COVID-19 infections in the emergency department (ED) patients. METHODS: This was a single-center prospective observational cohort study including patients with a suspected COVID-19 infection. The primary outcome of this study was a confirmed COVID-19 infection by RT-PCR test. MxA was assessed using an enzyme immunoassay on whole blood and receiver operating chart and area under the curve (AUC) analysis was conducted. Sensitivity, specificity, negative predictive value, and positive predictive value of MxA on diagnosing COVID-19 at the optimal cut-off of MxA was determined. RESULTS: In 2021, 100 patients were included. Of these patients, 77 patients had COVID-19 infection and 23 were non-COVID-19. Median MxA level was significantly higher (p < .001) in COVID-19 patients compared to non-COVID-19 patients, respectively 1933 and 0.1 ng/ml. The AUC of MxA on a confirmed COVID-19 infection was 0.941 (95% CI: 0.867-1.000). The optimal cut-off point of MxA was 252 ng/ml. At this cut-off point, the sensitivity of MxA on a confirmed COVID-19 infection was 94% (95% CI: 85%-98%) and the specificity was 91% (95% CI: 72%-99%). CONCLUSION: MxA accurately distinguishes COVID-19 infections from bacterial infections and noninfectious diagnoses in the ED in patients with a suspected COVID-19 infection. If the results can be validated, MxA could improve the diagnostic workup and patient flow in the ED.


Subject(s)
COVID-19 , Orthomyxoviridae , COVID-19/diagnosis , Emergency Service, Hospital , Humans , Myxovirus Resistance Proteins , Prospective Studies
6.
J Thromb Haemost ; 20(6): 1412-1420, 2022 06.
Article in English | MEDLINE | ID: covidwho-1752627

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 infection is associated with an increased incidence of thrombosis. OBJECTIVES: By studying the fibrin network structure of coronavirus disease 2019 (COVID-19) patients, we aimed to unravel pathophysiological mechanisms that contribute to this increased risk of thrombosis. This may contribute to optimal prevention and treatment of COVID-19 related thrombosis. PATIENTS/METHODS: In this case-control study, we collected plasma samples from intensive care unit (ICU) patients with COVID-19, with and without confirmed thrombosis, between April and December 2020. Additionally, we collected plasma from COVID-19 patients admitted to general wards without thrombosis, from ICU patients with pneumococcal infection, and from healthy controls. Fibrin fiber diameters and fibrin network density were quantified in plasma clots imaged with stimulated emission depletion microscopy and confocal microscopy. Finally, we determined the sensitivity to fibrinolysis. RESULTS: COVID-19 ICU patients (n = 37) and ICU patients with pneumococcal disease (n = 7) showed significantly higher fibrin densities and longer plasma clot lysis times than healthy controls (n = 7). No differences were observed between COVID-19 ICU patients with and without thrombosis, or ICU patients with pneumococcal infection. At a second time point, after diagnosis of thrombosis or at a similar time point in patients without thrombosis, we observed thicker fibers and longer lysis times in COVID-19 ICU patients with thrombosis (n = 19) than in COVID-19 ICU patients without thrombosis (n = 18). CONCLUSIONS: Our results suggest that severe COVID-19 is associated with a changed fibrin network structure and decreased susceptibility to fibrinolysis. Because these changes were not exclusive to COVID-19 patients, they may not explain the increased thrombosis risk.


Subject(s)
COVID-19 , Pneumococcal Infections , Thrombosis , Case-Control Studies , Fibrin , Fibrin Clot Lysis Time , Fibrinolysis/physiology , Humans , Intensive Care Units , Pneumococcal Infections/complications
7.
BMC Infect Dis ; 22(1): 165, 2022 Feb 21.
Article in English | MEDLINE | ID: covidwho-1700326

ABSTRACT

BACKGROUND: Patients with a severe COVID-19 infection often require admission at an intensive care unit (ICU) when they develop acute respiratory distress syndrome (ARDS). Hyperinflammation plays an important role in the development of ARDS in COVID-19. Procalcitonin (PCT) is a biomarker which may be a predictor of hyperinflammation. When patients with COVID-19 are in the emergency department (ED), elevated PCT levels could be associated with severe COVID-19 infections. The goal of this study is to investigate the association between PCT levels and severe COVID-19 infections in the ED. METHODS: This was a retrospective cohort study including patients with a confirmed COVID-19 infection who visited the ED of Erasmus Medical Center in Rotterdam, the Netherlands, between March and December 2020. The primary outcome was a severe COVID-19 infection, which was defined as patients who required ICU admission, all cause in-hospital mortality and mortality within 30 days after hospital discharge. PCT levels were measured during the ED visit. We used logistic regression to calculate the odds ratio (OR) with 95% confidence interval (95% CI) and corresponding area under the curve (AUC) of PCT on a severe COVID-19 infection, adjusting for bacterial coinfections, age, sex, comorbidities, C-reactive protein (CRP) and D-dimer. RESULTS: A total of 332 patients were included in the final analysis of this study, of which 105 patients reached the composite outcome of a severe COVID-19 infection. PCT showed an unadjusted OR of 4.19 (95%CI: 2.52-7.69) on a severe COVID-19 infection with an AUC of 0.82 (95% CI: 0.76-0.87). Corrected for bacterial coinfection, the OR of PCT was 4.05 (95% CI: 2.45-7.41). Adjusted for sex, bacterial coinfection, age any comorbidity, CRP and D-dimer, elevated PCT levels were still significantly associated with a severe COVID-19 infection with an adjusted OR of 2.11 (95% CI: 1.36-3.61). The AUC of this multivariable model was 0.85 (95%CI: 0.81-0.90). CONCLUSION: High PCT levels are associated with high rates of severe COVID-19 infections in patients with a COVID-19 infection in the ED. The routine measurement of PCT in patients with a COVID-19 infection in the ED may assist physicians in the clinical decision making process regarding ICU disposition.


Subject(s)
COVID-19 , Procalcitonin , Biomarkers , C-Reactive Protein/analysis , Emergency Service, Hospital , Humans , Intensive Care Units , Prognosis , Retrospective Studies , SARS-CoV-2
8.
Journal of Clinical Investigation ; 131(21):1-13, 2021.
Article in English | ProQuest Central | ID: covidwho-1503264

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19). Little is known about the interplay between preexisting immunity to endemic seasonal coronaviruses and the development of a SARS-CoV-2-specific IgG response. We investigated the kinetics, breadth, magnitude, and level of cross-reactivity of IgG antibodies against SARS-CoV-2 and heterologous seasonal and epidemic coronaviruses at the clonal level in patients with mild or severe COVID-19 as well as in disease control patients. We assessed antibody reactivity to nucleocapsid and spike antigens and correlated this IgG response to SARS-CoV-2 neutralization. Patients with COVID-19 mounted a mostly type-specific SARS-CoV-2 response. Additionally, IgG clones directed against a seasonal coronavirus were boosted in patients with severe COVID-19. These boosted clones showed limited cross-reactivity and did not neutralize SARS-CoV-2. These findings indicate a boost of poorly protective CoV-specific antibodies in patients with COVID-19 that correlated with disease severity, revealing "original antigenic sin."

9.
J Clin Invest ; 131(21)2021 11 01.
Article in English | MEDLINE | ID: covidwho-1403157

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19). Little is known about the interplay between preexisting immunity to endemic seasonal coronaviruses and the development of a SARS-CoV-2-specific IgG response. We investigated the kinetics, breadth, magnitude, and level of cross-reactivity of IgG antibodies against SARS-CoV-2 and heterologous seasonal and epidemic coronaviruses at the clonal level in patients with mild or severe COVID-19 as well as in disease control patients. We assessed antibody reactivity to nucleocapsid and spike antigens and correlated this IgG response to SARS-CoV-2 neutralization. Patients with COVID-19 mounted a mostly type-specific SARS-CoV-2 response. Additionally, IgG clones directed against a seasonal coronavirus were boosted in patients with severe COVID-19. These boosted clones showed limited cross-reactivity and did not neutralize SARS-CoV-2. These findings indicate a boost of poorly protective CoV-specific antibodies in patients with COVID-19 that correlated with disease severity, revealing "original antigenic sin."


Subject(s)
B-Lymphocytes/immunology , B-Lymphocytes/virology , COVID-19/immunology , COVID-19/virology , Coronavirus/immunology , SARS-CoV-2/immunology , Adult , Aged , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Antibody Specificity , Case-Control Studies , Coronavirus Infections/immunology , Coronavirus Infections/virology , Coronavirus Nucleocapsid Proteins/immunology , Cross Reactions , Female , Host Microbial Interactions/immunology , Humans , Immunoglobulin G/blood , Longitudinal Studies , Male , Middle Aged , Pandemics , Phosphoproteins/immunology , Seasons , Severity of Illness Index , Spike Glycoprotein, Coronavirus/immunology
10.
Int J Environ Res Public Health ; 18(13)2021 06 30.
Article in English | MEDLINE | ID: covidwho-1302307

ABSTRACT

Public involvement in science has allowed researchers to collect large-scale and real-time data and also engage citizens, so researchers are adopting citizen science (CS) in many areas. One promising appeal is student participation in CS school programs. In this literature review, we aimed to investigate which school CS programs exist in the areas of (applied) life sciences and if any projects target infectious disease surveillance. This review's objectives are to determine success factors in terms of data quality and student engagement. After a comprehensive search in biomedical and social databases, we found 23 projects. None of the projects found focused on infectious disease surveillance, and the majority centered around species biodiversity. While a few projects had issues with data quality, simplifying the protocol or allowing students to resubmit data made the data collected more usable. Overall, students at different educational levels and disciplines were able to collect usable data that was comparable to expert data and had positive learning experiences. In this review, we have identified limitations and gaps in reported CS school projects and provided recommendations for establishing future programs. This review shows the value of using CS in collaboration with traditional research techniques to advance future science and increasingly engage communities.


Subject(s)
Citizen Science , Communicable Diseases , Biodiversity , Communicable Diseases/epidemiology , Humans , Schools , Students
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.
EClinicalMedicine ; 35: 100881, 2021 May.
Article in English | MEDLINE | ID: covidwho-1230446

ABSTRACT

BACKGROUND: As several COVID-19 vaccines are rolled-out globally, it has become important to develop an effective strategy for vaccine acceptance, especially in high-risk groups, such as elderly. Vaccine misconception was declared by WHO as one of the top 10 health issues in 2019. Here we test the effectiveness of applying debunking to combat vaccine misinformation, and reduce vaccine hesitancy. METHODS: Participants were recruited via a daily news show on Dutch Television, targeted to elderly viewers. The study was conducted in 980 elderly citizens during the October 2020 National Influenza Vaccination Campaign. Borrowing from the recent literature in behavioural science and psychology we conducted a two-arm randomized blinded parallel study, in which participants were allocated to exposure to a video containing social norms, vaccine information plus debunking of vaccination myths (intervention group, n = 505) or a video only containing vaccine information plus social norm (control group, n = 475). Participants who viewed either of the video's and completed both a pre- and post-intervention survey on vaccination trust and knowledge, were included in the analysis. The main outcomes of this study were improvement on vaccine knowledge and awareness. FINDINGS: Participants were recruited from the 13th of October 2020 till the 16th of October 2020 and could immediately participate in the pre-intervention survey. Subsequently, eligible participants were randomly assigned to an interventional video and the follow-up survey, distributed through email on the 18th of October 2020, and available for participation till the 24th of October 2020. We found that exposure to the video with addition of debunking strategies on top of social norm modelling and information resulted in substantially stronger rejection of vaccination misconceptions, including the belief that: (1) vaccinations can cause Autism Spectrum Disorders; (2) vaccinations weaken the immune system; (3) influenza vaccination would hamper the COVID-19 vaccine efficacy. Additionally, we observed that exposure to debunking in the intervention resulted in enhanced trust in government. INTERPRETATION: Utilizing debunking in media campaigns on top of vaccine information and social norm modeling is an effective means to combat misinformation and distrust associated with vaccination in elderly, and could help maximize grounds for the acceptance of vaccines, including the COVID-19 vaccines. FUNDING: Dutch Influenza Foundation.

13.
Res Pract Thromb Haemost ; 5(2): 278-290, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1120206

ABSTRACT

The incidence of venous thrombosis, mostly pulmonary embolism (PE), ranging from local immunothrombosis to central emboli, but also deep vein thrombosis (DVT) in people with coronavirus disease 2019 (COVID-19) is reported to be remarkably high. The relevance of better understanding, predicting, treating, and preventing COVID-19-associated venous thrombosis meets broad support, as can be concluded from the high number of research, review, and guideline papers that have been published on this topic. The Dutch COVID & Thrombosis Coalition (DCTC) is a multidisciplinary team involving a large number of Dutch experts in the broad area of venous thrombosis and hemostasis research, combined with experts on virology, critically ill patients, pulmonary diseases, and community medicine, across all university hospitals and many community hospitals in the Netherlands. Within the consortium, clinical data of at least 5000 admitted COVID-19-infected individuals are available, including substantial collections of biobanked materials in an estimated 3000 people. In addition to considerable experience in preclinical and clinical thrombosis research, the consortium embeds virology-hemostasis research models within unique biosafety facilities to address fundamental questions on the interaction of virus with epithelial and vascular cells, in relation to the coagulation and inflammatory system. The DCTC has initiated a comprehensive research program to answer many of the current questions on the pathophysiology and best anticoagulant treatment of COVID-19-associated thrombotic complications. The research program was funded by grants of the Netherlands Thrombosis Foundation and the Netherlands Organization for Health Research and Development. Here, we summarize the design and main aims of the research program.

14.
J Clin Med ; 10(4)2021 Feb 20.
Article in English | MEDLINE | ID: covidwho-1110450

ABSTRACT

Thrombocytopenia, which signifies a low platelet count usually below 150 × 109/L, is a common finding following or during many viral infections. In clinical medicine, mild thrombocytopenia, combined with lymphopenia in a patient with signs and symptoms of an infectious disease, raises the suspicion of a viral infection. This phenomenon is classically attributed to platelet consumption due to inflammation-induced coagulation, sequestration from the circulation by phagocytosis and hypersplenism, and impaired platelet production due to defective megakaryopoiesis or cytokine-induced myelosuppression. All these mechanisms, while plausible and supported by substantial evidence, regard platelets as passive bystanders during viral infection. However, platelets are increasingly recognized as active players in the (antiviral) immune response and have been shown to interact with cells of the innate and adaptive immune system as well as directly with viruses. These findings can be of interest both for understanding the pathogenesis of viral infectious diseases and predicting outcome. In this review, we will summarize and discuss the literature currently available on various mechanisms within the relationship between thrombocytopenia and virus infections.

15.
Infect Dis (Lond) ; 53(7): 488-497, 2021 07.
Article in English | MEDLINE | ID: covidwho-1091292

ABSTRACT

BACKGROUND: The first outbreak of coronavirus disease 2019 (COVID-19) occurred in March 2020 in Europe, which is normally the peak incidence period of human metapneumovirus (HMPV) infections, implying cocirculation and potentially causing competition between them. METHODS: We investigated differences in clinical characteristics and outcomes of HMPV infections in hospitalized patients before (January 2016-28 February, 2020) and HMPV and COVID-19 during part of the COVID-19 pandemic (28 February, 2020-1 April, 2020). RESULTS: A total of 239 HMPV patients and 303 COVID-19 patients were included. Incidence of HMPV peaked in March. Despite a 324% increase in HMPV testing during the COVID-19 outbreak, incidence of HMPV remained stable. Clinical characteristics showed 25 (11%) ICU admissions and 14 (6%) deaths. History of myocardial infarction, higher age and lower BMI were independently associated with increased 30-day mortality. Clinical characteristics of HMPV-infected patients did not differ between the non-COVID-19 period and the examined COVID-19 period except for length of hospital stay (7 vs. 5 days). HMPV infection and COVID-19 shared many clinical features but HMPV was associated with female gender, elderly patients and chronic conditions (COPD and chronic heart failure). Clinical outcomes did not differ between the viruses during the COVID-19 period. CONCLUSIONS: The clinical impact of HMPV infection did not change during the COVID-19 outbreak in terms of incidence and/or disease severity; hence, HMPV and SARS-CoV-2 are probably co-circulating independently. Despite the current clinical focus on the COVID-19 pandemic, clinicians should keep in mind that HMPV-infection may mimic COVID-19 and is also associated with serious adverse outcomes.


Subject(s)
COVID-19 , Metapneumovirus , Paramyxoviridae Infections , Respiratory Tract Infections , Aged , Europe , Female , Humans , Infant , Pandemics , Paramyxoviridae Infections/epidemiology , Respiratory Tract Infections/epidemiology , SARS-CoV-2
16.
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
17.
Vaccines (Basel) ; 8(3)2020 Aug 27.
Article in English | MEDLINE | ID: covidwho-824500

ABSTRACT

Vaccination uptake has decreased globally in recent years, with a subsequent rise of vaccine-preventable diseases. Travellers, immunocompromised patients (ICP), and healthcare workers (HCW) are groups at increased risk for (severe) infectious diseases due to their behaviour, health, or occupation, respectively. While targeted vaccination guidelines are available, vaccination uptake seems low. In this review, we give a comprehensive overview of determinants-based on the integrated change model-predicting vaccination uptake in these groups. In travellers, low perceived risk of infection and low awareness of vaccination recommendations contributed to low uptake. Additionally, ICP were often unaware of the recommended vaccinations. A physician's recommendation is strongly correlated with higher uptake. Furthermore, ICP appeared to be mainly concerned about the risks of vaccination and fear of deterioration of their underlying disease. For HCW, perceived risk of (the severity of) infection for themselves and for their patients together with perceived benefits of vaccination contribute most to their vaccination behaviour. As the determinants that affect uptake are numerous and diverse, we argue that future studies and interventions should be based on multifactorial health behaviour models, especially for travellers and ICP as only a limited number of such studies is available yet.

18.
JAMA Netw Open ; 3(7): e2014323, 2020 07 01.
Article in English | MEDLINE | ID: covidwho-635849

ABSTRACT

Importance: In the absence of a vaccine and therapeutic agent, personal hygiene and physical distancing are essential measures to contain the coronavirus disease 2019 pandemic. Objective: To determine whether a social media campaign, targeted at the gaps in behavior on personal hygiene and physical distancing and distributed nationwide via digital news media, may be an effective method to improve behavior and help to inhibit person-to-person transmission of severe acute respiratory syndrome coronavirus 2. Design, Setting, and Participants: This survey study was designed to uncover self-reported gaps in behavior regarding personal hygiene and physical distancing in the Netherlands. A diagnostic survey was distributed by a large national newspaper (De Telegraaf) and a popular social influencer (Govert Sweep) on March 17, 2020, and was completed by 16 072 participants. Analysis of these outcomes showed that coughing and sneezing in the elbow was done well, but that handwashing, face touching, and physical distancing showed serious gaps compared with advised behavior. This diagnostic information was used to design infographics and a video targeted at repairing these gaps in behavior. The video and infographics were distributed on a national level on March 21, 2020, followed by a postcampaign survey to measure the results on March 24, 2020. Data analysis was performed from March to April 2020. Exposure: Exposed participants were those who viewed the infographics and/or video. Main Outcomes and Measures: Improvement on the extent of handwashing in all areas, handwashing duration of 20 seconds or longer, awareness on face touching, and physical distancing were measured according to responses on the postcampaign survey. Results: A total of 17 189 participants (mean [SD] age, 47.61 [13.57] years; 9100 women [52.9%]) responded to the postcampaign survey. The news article in De Telegraaf was read more than 2 million times, and the influencer video was watched more than 80 000 times. Cross-sectional analysis of the postcampaign survey using logistic regression correcting for age, gender, and educational level showed that exposure to the video plus infographics (827 participants) (adjusted odds ratio [OR], 2.14; 95% CI, 1.83-2.50; P < .001) and to the infographics alone (11 348 participants) (adjusted OR, 1.31; 95% CI, 1.22-1.40; P < .001) were positively associated with washing hands in all areas compared with the unexposed group (4751 participants). In addition, exposure to the video plus infographics (adjusted OR, 1.86; 95% CI, 1.59-2.16; P < .001) and to the infographics alone (adjusted OR, 1.27; 95% CI, 1.19-1.36; P < .001) were positively associated with washing hands long enough compared with the unexposed group. Exposure to the video alone was not associated with improved handwashing. Compared with the unexposed group, exposure to the infographics alone and video plus infographics were associated with improvements in physical distancing when the participant had COVID-19 syptoms (infographics alone, adjusted OR, 1.10; 95% CI, 1.03-1.17; P = .006; video plus infographics, adjusted OR, 0.79; 95% CI, 0.69-0.91; P = .001) and face touching (infographics alone, adjusted OR, 1.29; 95% CI, 1.22-1.38; P < .001; infographics and video, adjusted OR, 1.49, 95% CI, 1.30-1.71; P < .001). Conclusions and Relevance: These findings suggest that a targeted behavioral change campaign, promoted by a news platform and social media, was associated with self-reported improvement in personal hygiene with the aim to prevent person-to-person transmission of severe acute respiratory syndrome coronavirus 2. This method of evidence-based campaigning may be an effective way to improve critical public health issues, such as the coronavirus disease 2019 pandemic.


Subject(s)
Coronavirus Infections/prevention & control , Hand Disinfection , Health Behavior , Health Promotion , Mass Media , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Public Health , Social Media , Adult , Aged , Betacoronavirus , COVID-19 , Female , Humans , Male , Middle Aged , Netherlands , Odds Ratio , SARS-CoV-2 , Surveys and Questionnaires , Young Adult
19.
Sci Immunol ; 5(48)2020 06 26.
Article in English | MEDLINE | ID: covidwho-617063

ABSTRACT

SARS-CoV-2 has been identified as the causative agent of a global outbreak of respiratory tract disease (COVID-19). In some patients the infection results in moderate to severe acute respiratory distress syndrome (ARDS), requiring invasive mechanical ventilation. High serum levels of IL-6, IL-10 and an immune hyperresponsiveness referred to as a 'cytokine storm' have been associated with poor clinical outcome. Despite the large numbers of COVID-19 cases and deaths, information on the phenotype and kinetics of SARS-CoV-2-specific T cells is limited. Here, we studied 10 COVID-19 patients who required admission to an intensive care unit and detected SARS-CoV-2-specific CD4+ and CD8+ T cells in 10 out of 10 and 8 out of 10 patients, respectively. We also detected low levels of SARS-CoV-2-reactive T cells in 2 out of 10 healthy controls not previously exposed to SARS-CoV-2, which is indicative of cross-reactivity due to past infection with 'common cold' coronaviruses. The strongest T-cell responses were directed to the spike (S) surface glycoprotein, and SARS-CoV-2-specific T cells predominantly produced effector and Th1 cytokines, although Th2 and Th17 cytokines were also detected. Furthermore, we studied T-cell kinetics and showed that SARS-CoV-2-specific T cells are present relatively early and increase over time. Collectively, these data shed light on the potential variations in T-cell responses as a function of disease severity, an issue that is key to understanding the potential role of immunopathology in the disease, and also inform vaccine design and evaluation.


Subject(s)
Betacoronavirus/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Coronavirus Infections/immunology , Phenotype , Pneumonia, Viral/immunology , Respiratory Distress Syndrome/immunology , Aged , COVID-19 , Cells, Cultured , Coronavirus Infections/blood , Coronavirus Infections/virology , Cytokines/metabolism , Female , Humans , Immunologic Memory , Kinetics , Longitudinal Studies , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/virology , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/virology , SARS-CoV-2 , Severity of Illness Index , Spike Glycoprotein, Coronavirus/immunology , Viral Load/immunology
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