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1.
Crit Rev Clin Lab Sci ; : 1-15, 2022 Mar 15.
Article in English | MEDLINE | ID: covidwho-1740611

ABSTRACT

A plethora of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostic tests are available, each with different performance specifications, detection methods, and targets. This narrative review aims to summarize the diagnostic technologies available and how they are best selected to tackle SARS-CoV-2 infection as the pandemic evolves. Seven key settings have been identified where diagnostic tests are being deployed: symptomatic individuals presenting for diagnostic testing and/or treatment of COVID-19 symptoms; asymptomatic individuals accessing healthcare for planned non-COVID-19-related reasons; patients needing to access emergency care (symptom status unknown); patients being discharged from healthcare following hospitalization for COVID-19; healthy individuals in both single event settings (e.g. airports, restaurants, hotels, concerts, and sporting events) and repeat access settings (e.g. workplaces, schools, and universities); and vaccinated individuals. While molecular diagnostics remain central to SARS-CoV-2 testing strategies, we have offered some discussion on the considerations for when other tools and technologies may be useful, when centralized/point-of-care testing is appropriate, and how the various additional diagnostics can be deployed in differently resourced settings. As the pandemic evolves, molecular testing remains important for definitive diagnosis, but increasingly widespread point-of-care testing is essential to the re-opening of society.

2.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327108

ABSTRACT

After the implementation of broad vaccination programs, there is an urgent need to understand how the population immunity affects the dynamics of the COVID-19 pandemic in presence of the protection waning and of the emergence of new variants of concern. In the current Omicron wave that is propagating across Europe, assessing the risk of saturation of the healthcare systems is crucial for pandemic management, as it allows us to support the transition towards the endemic course of SARS-CoV-2 and implement more refined mitigation strategies that shield the most vulnerable groups and protect the healthcare systems. We investigated the current pandemic dynamics by means of compartmental models that describe the age-stratified social-mixing, and consider vaccination status, vaccine types, and their waning efficacy. Our goal is to provide insight into the plausible scenarios that are likely to be seen in Switzerland and Germany in the coming weeks and help take informed decisions. Despite the huge numbers of new positive cases, our results suggest that the current wave is unlikely to create an overwhelming healthcare demand: owing to the lower hospitalization rate of the novel variant and the effectiveness of the vaccines. Our findings are robust with respect to the plausible variability of the main parameters that govern the severity and the progression of the Omicron infection. In a broader context, our framework can be applied also to future endemic scenarios, offering quantitative support for refined public health interventions in response to recurring COVID-19 waves.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-321361

ABSTRACT

Background: Since December 2019, coronavirus disease 2019 (COVID-19), as an infectious disease with cytokine storm, has become an emerging global challenge. To assess the duration of SARS-COV-2 viral shedding and associated risk factors in COVID-19 patients. Methods: : COVID-19 patients with interleukin (IL)-1b, soluble interleukin-2 receptor (sIL-2R), IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α cytokines data consecutively admitted to Tongji Hospital from January 27, 2020 through February 5, 2020 were enrolled and been followed up until March 24, 2020. We utilized Kaplan-Meier method and Cox proportional hazards regression analysis to assess the duration of viral shedding and risk factors affecting virus clearance. Results: : 246 inpatients with laboratory confirmed COVID-19 were enrolled. The median duration of viral shedding was 24 days, ranging from 6 to 63 days. Age, severity of COVID-19, albumin, lactate dehydrogenase (LDH), D-dimer, ferritin and sIL-2R were associated with duration of viral shedding. Administration of lopinavir-ritonavir, arbidol, oseltamivir and intravenous immunoglobulin did not shorten viral shedding time. Multivariate cox regression analysis revealed that sIL-2R, LDH and severity of COVID-19 were independent factors associated with duration of viral shedding. At stratified analysis, the viral shedding time was positively correlated with age, sIL-2R and LDH in non-corticosteroid subgroup, while negatively correlated with lymphocyte count in corticosteroid group. Conclusions: : The present study demonstrated that elevated sIL-2R, increased LDH and severe status were related to prolongation of viral shedding in COVID-19 inpatients. Further research is urgent to investigate the mechanism of immune reaction involved in the virus clearance process and aim to the optimal antiviral therapy.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-320071

ABSTRACT

Background: We investigated machine learning based identification of the pre-symptomatic coronavirus disease 2019 (COVID-19) and detection of infection-related changes in physiology using a wearable device (the Ava bracelet).Methods: Participants from an ongoing cohort study (GAPP) of the general population in Liechtenstein were included in the current sub-study (COVI-GAPP). Nightly they wore the fertility bracelet that measured every ten seconds skin temperature, heart rate, respiratory rate, skin perfusion, and heart rate variability. Participants reported daily symptoms in a complementary app. Laboratory reverse transcription polymerase chain reaction (RT-PCR) and/or COVID-19 serology samples were collected from all participants. Long short-term memory (LSTM) based recurrent neural networks (RNN) were chosen for the binary classification of an individual as healthy or infected on a given day in a derivation and validation procedure.Findings: A total of 1ž5 million hours of physiological data were recorded from 1163 participants (mean age 44 +/- 5ž5 years). COVID-19 was confirmed in 127 participants. Of these, 66 (52%) had worn their device from baseline to symptom onset and were included in the analysis and RNN. Multi-level modelling revealed significantly different values in pre- versus post-symptomatic respiratory rate, temperature, heart rate, heart rate variability ratio, and skin perfusion. The developed RNN algorithm had a recall of 0ž73 in the training set and 0ž68 in the testing set (overall recall of 0ž71) when detecting COVID-19 up to two days prior to symptom onset.Interpretation: Our proposed RNN algorithm identified 71% of COVID-19 positive participants two days prior to symptom onset. Wearable sensor technology can therefore enable COVID-19’ detection during the pre-symptomatic period.Funding: IMI grant agreement number 101005177, the Princely House of the Principality of Liechtenstein, the government of the Principality of Liechtenstein, and the Hanela Foundation in Switzerland.Declaration of Interest: Lorenz Risch, and Martin Risch are key shareholders of the Dr Risch Medical Laboratory. David Conen has received consulting fees from Roche Diagnostics, outside of the current work. The other authors have no financial or personal conflicts of interest to declare.Ethical Approval: The local ethics committee approved the study protocol, andwritten informed consent was obtained from each participant (BASEC 2020-00786).

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-306228

ABSTRACT

The outbreak of the new Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a public health emergency. Asthma does not represent a risk factor for COVID-19 in several published cohorts. We hypothesized that the SARS-CoV-2 proteome contains T cell epitopes, which are potentially cross-reactive to allergen epitopes. We aimed at identifying homologous peptide sequences by means of two distinct complementary bioinformatics approaches. Pipeline 1 included prediction of MHC Class I and Class II epitopes contained in the SARS-CoV-2 proteome and allergens along with alignment and elaborate ranking approaches. Pipeline 2 involved alignment of SARS-CoV-2 overlapping peptides with known allergen-derived T cell epitopes. Our results indicate a large number of MHC Class I epitope pairs including known as well as de novo predicted allergen T cell epitopes with high probability for cross-reactivity. Allergen sources, such as Aspergillus fumigatus , Phleum pratense and Dermatophagoides species are of particular interest due to their association with multiple cross-reactive candidate peptides, independently of the applied bioinformatic approach. In contrast, peptides derived from food allergens, as well as MHC class II epitopes did not achieve high in silico ranking and were therefore not further investigated. Our findings warrant further experimental confirmation along with examination of the functional importance of such cross-reactive responses.

6.
Nat Commun ; 12(1): 5417, 2021 09 14.
Article in English | MEDLINE | ID: covidwho-1410404

ABSTRACT

COVID-19 is associated with a wide range of clinical manifestations, including autoimmune features and autoantibody production. Here we develop three protein arrays to measure IgG autoantibodies associated with connective tissue diseases, anti-cytokine antibodies, and anti-viral antibody responses in serum from 147 hospitalized COVID-19 patients. Autoantibodies are identified in approximately 50% of patients but in less than 15% of healthy controls. When present, autoantibodies largely target autoantigens associated with rare disorders such as myositis, systemic sclerosis and overlap syndromes. A subset of autoantibodies targeting traditional autoantigens or cytokines develop de novo following SARS-CoV-2 infection. Autoantibodies track with longitudinal development of IgG antibodies recognizing SARS-CoV-2 structural proteins and a subset of non-structural proteins, but not proteins from influenza, seasonal coronaviruses or other pathogenic viruses. We conclude that SARS-CoV-2 causes development of new-onset IgG autoantibodies in a significant proportion of hospitalized COVID-19 patients and are positively correlated with immune responses to SARS-CoV-2 proteins.


Subject(s)
Autoantibodies/immunology , COVID-19/immunology , Immunoglobulin G/immunology , SARS-CoV-2/immunology , Aged , Antibodies, Antinuclear/blood , Antibodies, Antinuclear/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Autoantibodies/blood , Autoantigens/immunology , Connective Tissue Diseases/immunology , Cytokines/immunology , Female , Hospitalization , Humans , Immunoglobulin G/blood , Male , Middle Aged , SARS-CoV-2/pathogenicity , Viral Proteins/immunology
9.
J Allergy Clin Immunol ; 148(3): 679-688, 2021 09.
Article in English | MEDLINE | ID: covidwho-1322161

ABSTRACT

In addition to being a source of nutrients for the developing newborn, human milk contains thousands of bioactive compounds, which influence infant health in the short-term as exemplified by its major benefits on infectious disease prevention. Many of the human milk compounds also have the required characteristics to instruct immune development and guide long-term health. Prebiotics, probiotics, and varied antimicrobial molecules all have the potential to shape the composition and function of the establishing gut microbiota, which is known to be a major determinant of immune function. Another and less explored way human milk can instruct long-term immunity is through antigen shedding. Here, we will review the evidence that antigens from maternal environment and more specifically from allergen sources are found in human milk. We will discuss data from rodent models and birth cohorts showing that allergen shedding in breast milk may influence long-term allergy risk. We will uncover the variables that may underlie heterogeneity in oral tolerance induction and allergy prevention in children breast-fed by allergen-exposed mothers. We will focus on the parameters that control antigen transfer to breast milk, on the unique biological characteristics of allergens in breast milk, and on the milk bioactive compounds that were found to influence immune response in offspring. We propose this understanding is fundamental to guide maternal interventions leading to lifelong allergen tolerance.


Subject(s)
Allergens/immunology , Hypersensitivity/prevention & control , Milk, Human/immunology , Animals , Female , Humans , Hypersensitivity/epidemiology , Immune System , Immune Tolerance , Risk
10.
J Allergy Clin Immunol ; 148(3): 843-857.e6, 2021 09.
Article in English | MEDLINE | ID: covidwho-1213300

ABSTRACT

BACKGROUND: Prenatal exposure to infections can modify immune development. These environmental disturbances during early life potentially alter the incidence of inflammatory disorders as well as priming of immune responses. Infection with the helminth Schistosoma mansoni is widely studied for its ability to alter immune responsiveness and is associated with variations in coinfection, allergy, and vaccine efficacy in endemic populations. OBJECTIVE: Exposure to maternal schistosomiasis during early life, even without transmission of infection, can result in priming effects on offspring immune responses to bystander antigenic challenges as related to allergic responsiveness and vaccination, with this article seeking to further clarify the effects and underlying immunologic imprinting. METHODS: Here, we have combined a model of chronic maternal schistosomiasis infection with a thorough analysis of subsequent offspring immune responses to allergy and vaccination models, including viral challenge and steady-state changes to immune cell compartments. RESULTS: We have demonstrated that maternal schistosomiasis alters CD4+ responses during allergic sensitization and challenge in a skewed IL-4/B-cell-dominant response to antigenic challenge associated with limited inflammatory response. Beyond that, we have uncovered previously unidentified alterations to CD8+ T-cell responses during immunization that are dependent on vaccine formulation and have functional impact on the efficacy of vaccination against viral infection in a murine hepatitis B virus model. CONCLUSION: In addition to steady-state modifications to CD4+ T-cell polarization and B-cell priming, we have traced these modified CD8+ responses to an altered dendritic cell phenotype sustained into adulthood, providing evidence for complex priming effects imparted by infection via fetomaternal cross talk.


Subject(s)
Prenatal Exposure Delayed Effects/immunology , Respiratory Hypersensitivity/immunology , Schistosomiasis/immunology , Allergens/immunology , Animals , B-Lymphocytes/immunology , Cells, Cultured , Dendritic Cells/immunology , Female , Fetus/immunology , Gene Expression Profiling , Immunization , Lung/immunology , Lymph Nodes/immunology , Male , Mice, Inbred BALB C , Mice, Inbred C57BL , Ovalbumin/immunology , Pregnancy , Respiratory Hypersensitivity/genetics , Schistosoma mansoni , Spleen/immunology , T-Lymphocytes/immunology
11.
Sci Rep ; 11(1): 4792, 2021 02 26.
Article in English | MEDLINE | ID: covidwho-1104550

ABSTRACT

The outbreak of the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a public health emergency. Asthma does not represent a risk factor for COVID-19 in several published cohorts. We hypothesized that the SARS-CoV-2 proteome contains T cell epitopes, which are potentially cross-reactive to allergen epitopes. We aimed at identifying homologous peptide sequences by means of two distinct complementary bioinformatics approaches. Pipeline 1 included prediction of MHC Class I and Class II epitopes contained in the SARS-CoV-2 proteome and allergens along with alignment and elaborate ranking approaches. Pipeline 2 involved alignment of SARS-CoV-2 overlapping peptides with known allergen-derived T cell epitopes. Our results indicate a large number of MHC Class I epitope pairs including known as well as de novo predicted allergen T cell epitopes with high probability for cross-reactivity. Allergen sources, such as Aspergillus fumigatus, Phleum pratense and Dermatophagoides species are of particular interest due to their association with multiple cross-reactive candidate peptides, independently of the applied bioinformatic approach. In contrast, peptides derived from food allergens, as well as MHC class II epitopes did not achieve high in silico ranking and were therefore not further investigated. Our findings warrant further experimental confirmation along with examination of the functional importance of such cross-reactive responses.


Subject(s)
Allergens/immunology , COVID-19/immunology , Immunity, Heterologous , SARS-CoV-2/immunology , T-Lymphocytes/immunology , Asthma/immunology , Computational Biology , Epitopes, T-Lymphocyte/immunology , HLA Antigens/immunology , Humans , Immunity, Cellular , Viral Proteins/immunology
13.
Dis Markers ; 2021: 8810196, 2021.
Article in English | MEDLINE | ID: covidwho-1039930

ABSTRACT

Several tests based on chemiluminescence immunoassay techniques have become available to test for SARS-CoV-2 antibodies. There is currently insufficient data on serology assay performance beyond 35 days after symptoms onset. We aimed to evaluate SARS-CoV-2 antibody tests on three widely used platforms. A chemiluminescent microparticle immunoassay (CMIA; Abbott Diagnostics, USA), a luminescence immunoassay (LIA; Diasorin, Italy), and an electrochemiluminescence immunoassay (ECLIA; Roche Diagnostics, Switzerland) were investigated. In a multigroup study, sensitivity was assessed in a group of participants with confirmed SARS-CoV-2 (n = 145), whereas specificity was determined in two groups of participants without evidence of COVID-19 (i.e., healthy blood donors, n = 191, and healthcare workers, n = 1002). Receiver operating characteristic (ROC) curves, multilevel likelihood ratios (LR), and positive (PPV) and negative (NPV) predictive values were characterized. Finally, analytical specificity was characterized in samples with evidence of the Epstein-Barr virus (EBV) (n = 9), cytomegalovirus (CMV) (n = 7), and endemic common-cold coronavirus infections (n = 12) taken prior to the current SARS-CoV-2 pandemic. The diagnostic accuracy was comparable in all three assays (AUC 0.98). Using the manufacturers' cut-offs, the sensitivities were 90%, 95% confidence interval [84,94] (LIA), 93% [88,96] (CMIA), and 96% [91,98] (ECLIA). The specificities were 99.5% [98.9,99.8] (CMIA), 99.7% [99.3,99.9] (LIA), and 99.9% [99.5,99.98] (ECLIA). The LR at half of the manufacturers' cut-offs were 60 (CMIA), 82 (LIA), and 575 (ECLIA) for positive and 0.043 (CMIA) and 0.035 (LIA, ECLIA) for negative results. ECLIA had higher PPV at low pretest probabilities than CMIA and LIA. No interference with EBV or CMV infection was observed, whereas endemic coronavirus in some cases provided signals in LIA and/or CMIA. Although the diagnostic accuracy of the three investigated assays is comparable, their performance in low-prevalence settings is different. Introducing gray zones at half of the manufacturers' cut-offs is suggested, especially for orthogonal testing approaches that use a second assay for confirmation.


Subject(s)
Antibodies, Viral/blood , COVID-19/diagnosis , Luminescent Measurements/methods , SARS-CoV-2/immunology , Adult , COVID-19 Testing , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Sensitivity and Specificity
14.
Allergol Select ; 5: 1-25, 2021.
Article in English | MEDLINE | ID: covidwho-1022168

ABSTRACT

With the advent of biologicals, more and more therapeutics are available that specifically address specific switch points in the pathomechanism of immunologically dominated diseases. Thus, the focus of diagnostics and therapy (precision medicine) is more on the individual disease characteristics of the individual patient. Regarding the different phenotypes of atopic diseases, severe asthma was the first entity for which biologicals were approved, followed by urticaria, and finally atopic dermatitis and chronic rhinosinusitis with nasal polyps. Experience in the treatment of severe bronchial asthma has shown that the intensity of the response to biological therapy depends on the quality of clinical and immunological phenotyping of the patients. This also applies to different diseases of the atopic form, as patients can suffer from several atopic diseases at the same time, each with different characteristics. Biologics are already emerging that may represent a suitable therapy for allergic bronchial asthma, which often occurs together with severe neurodermatitis, and chronic rhinosinusitis with nasal polyps. In practice, however, the question of possible combinations of biologicals for the therapy of complex clinical pictures of individual patients is increasingly arising. In doing so, the side effect profile must be taken into account, including hypersensitivity reactions, whose diagnostic and logistical management must aim at a safe and efficient therapy of the underlying disease. Increased attention must also be paid to biological therapy in pregnancy and planned (predictable) vaccinations as well as existing infections, such as SARS-CoV-2 infection. Before starting a biological therapy, the immune status should be checked with regard to chronic viral and bacterial infections and, if necessary, the vaccination status should be refreshed or missing vaccinations should be made up for before starting therapy. Currently, reliable data on the effect of biologicals on the immunological situation of SARS-CoV-2 infection and COVID-19 are not available. Therefore, research and development of suitable diagnostic methods for detection of immunologically caused side effects as well as detection of potential therapy responders and non-responders is of great importance.

15.
J Clin Med ; 9(12)2020 Dec 09.
Article in English | MEDLINE | ID: covidwho-969190

ABSTRACT

Pan-immunoglobulin assays can simultaneously detect IgG, IgM and IgA directed against the receptor binding domain (RBD) of the S1 subunit of the spike protein (S) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 S1-RBD Ig). In this work, we aim to evaluate a quantitative SARS-CoV-2 S1-RBD Ig electrochemiluminescence immunoassay (ECLIA) regarding analytical, diagnostic, operational and clinical characteristics. Our work takes the form of a population-based study in the principality of Liechtenstein, including 125 cases with clinically well-described and laboratory confirmed SARS-CoV-2 infection and 1159 individuals without evidence of coronavirus disease 2019 (COVID-19). SARS-CoV-2 cases were tested for antibodies in sera taken with a median of 48 days (interquartile range, IQR, 43-52) and 139 days (IQR, 129-144) after symptom onset. Sera were also tested with other assays targeting antibodies against non-RBD-S1 and -S1/S2 epitopes. Sensitivity was 97.6% (95% confidence interval, CI, 93.2-99.1), whereas specificity was 99.8% (95% CI, 99.4-99.9). Antibody levels linearly decreased from hospitalized patients to symptomatic outpatients and SARS-CoV-2 infection without symptoms (p < 0.001). Among cases with SARS-CoV-2 infection, smokers had lower antibody levels than non-smokers (p = 0.04), and patients with fever had higher antibody levels than patients without fever (p = 0.001). Pan-SARS-CoV-2 S1-RBD Ig in SARS-CoV-2 infection cases significantly increased from first to second follow-up (p < 0.001). A substantial proportion of individuals without evidence of past SARS-CoV-2 infection displayed non-S1-RBD antibody reactivities (248/1159, i.e., 21.4%, 95% CI, 19.1-23.4). In conclusion, a quantitative SARS-CoV-2 S1-RBD Ig assay offers favorable and sustained assay characteristics allowing the determination of quantitative associations between clinical characteristics (e.g., disease severity, smoking or fever) and antibody levels. The assay could also help to identify individuals with antibodies of non-S1-RBD specificity with potential clinical cross-reactivity to SARS-CoV-2.

17.
Biomed Res Int ; 2020: 9878453, 2020.
Article in English | MEDLINE | ID: covidwho-934159

ABSTRACT

Knowledge of the sensitivities of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests beyond 35 days after the clinical onset of COVID-19 is insufficient. We aimed to describe positivity rate of SARS-CoV-2 assays employing three different measurement principles over a prolonged period. Two hundred sixty-eight samples from 180 symptomatic patients with COVID-19 and a reverse transcription polymerase chain reaction (RT-PCR) test followed by serological investigation of SARS-CoV-2 antibodies were included. We conducted three chemiluminescence (including electrochemiluminescence assay (ECLIA)), four enzyme-linked immunosorbent assay (ELISA), and one lateral flow immunoassay (LFIA) test formats. Positivity rates, as well as positive (PPVs) and negative predictive values (NPVs), were calculated for each week after the first clinical presentation for COVID-19. Furthermore, combinations of tests were assessed within an orthogonal testing approach employing two independent assays and predictive values were calculated. Heat maps were constructed to graphically illustrate operational test characteristics. During a follow-up period of more than 9 weeks, chemiluminescence assays and one ELISA IgG test showed stable positivity rates after the third week. With the exception of ECLIA, the PPVs of the other chemiluminescence assays were ≥95% for COVID-19 only after the second week. ELISA and LFIA had somewhat lower PPVs. IgM exhibited insufficient predictive characteristics. An orthogonal testing approach provided PPVs ≥ 95% for patients with a moderate pretest probability (e.g., symptomatic patients), even for tests with a low single test performance. After the second week, NPVs of all but IgM assays were ≥95% for patients with low to moderate pretest probability. The confirmation of negative results using an orthogonal algorithm with another assay provided lower NPVs than the single assays. When interpreting results from SARS-CoV-2 tests, the pretest probability, time of blood draw, and assay characteristics must be carefully considered. An orthogonal testing approach increases the accuracy of positive, but not negative, predictions.


Subject(s)
Antibodies, Viral/immunology , Betacoronavirus/immunology , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , Antibodies, Viral/blood , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques/methods , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Enzyme-Linked Immunosorbent Assay/methods , Female , Humans , Immunoassay/methods , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Reverse Transcriptase Polymerase Chain Reaction/methods , SARS-CoV-2 , Sensitivity and Specificity , Serologic Tests/methods
18.
J Allergy Clin Immunol ; 146(6): 1295-1301, 2020 12.
Article in English | MEDLINE | ID: covidwho-812091

ABSTRACT

The newly described severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for a pandemic (coronavirus disease 2019 [COVID-19]). It is now well established that certain comorbidities define high-risk patients. They include hypertension, diabetes, and coronary artery disease. In contrast, the context with bronchial asthma is controversial and shows marked regional differences. Because asthma is the most prevalent chronic inflammatory lung disease worldwide and SARS-CoV-2 primarily affects the upper and lower airways leading to marked inflammation, the question arises about the possible clinical and pathophysiological association between asthma and SARS-CoV-2/COVID-19. Here, we analyze the global epidemiology of asthma among patients with COVID-19 and propose the concept that patients suffering from different asthma endotypes (type 2 asthma vs non-type 2 asthma) present with a different risk profile in terms of SARS-CoV-2 infection, development of COVID-19, and progression to severe COVID-19 outcomes. This concept may have important implications for future COVID-19 diagnostics and immune-based therapy developments.


Subject(s)
Asthma , COVID-19 , SARS-CoV-2/immunology , Asthma/epidemiology , Asthma/immunology , Asthma/pathology , COVID-19/epidemiology , COVID-19/immunology , COVID-19/pathology , Humans , Pandemics
19.
Clin Chem Lab Med ; 58(12): 2131-2140, 2020 08 31.
Article in English | MEDLINE | ID: covidwho-737632

ABSTRACT

Objectives The sensitivity of molecular and serological methods for COVID-19 testing in an epidemiological setting is not well described. The aim of the study was to determine the frequency of negative RT-PCR results at first clinical presentation as well as negative serological results after a follow-up of at least 3 weeks. Methods Among all patients seen for suspected COVID-19 in Liechtenstein (n=1921), we included initially RT-PCR positive index patients (n=85) as well as initially RT-PCR negative (n=66) for follow-up with SARS-CoV-2 antibody testing. Antibodies were detected with seven different commercially available immunoassays. Frequencies of negative RT-PCR and serology results in individuals with COVID-19 were determined and compared to those observed in a validation cohort of Swiss patients (n=211). Results Among COVID-19 patients in Liechtenstein, false-negative RT-PCR at initial presentation was seen in 18% (12/66), whereas negative serology in COVID-19 patients was 4% (3/85). The validation cohort showed similar frequencies: 2/66 (3%) for negative serology, and 16/155 (10%) for false negative RT-PCR. COVID-19 patients with negative follow-up serology tended to have a longer disease duration (p=0.05) and more clinical symptoms than other patients with COVID-19 (p<0.05). The antibody titer from quantitative immunoassays was positively associated with the number of disease symptoms and disease duration (p<0.001). Conclusions RT-PCR at initial presentation in patients with suspected COVID-19 can miss infected patients. Antibody titers of SARS-CoV-2 assays are linked to the number of disease symptoms and the duration of disease. One in 25 patients with RT-PCR-positive COVID-19 does not develop antibodies detectable with frequently employed and commercially available immunoassays.


Subject(s)
Betacoronavirus/genetics , Betacoronavirus/immunology , Real-Time Polymerase Chain Reaction , Serologic Tests , Adult , False Positive Reactions , Female , Humans , Male , Middle Aged , SARS-CoV-2 , Time Factors , Young Adult
20.
Diagnostics (Basel) ; 10(8)2020 Aug 14.
Article in English | MEDLINE | ID: covidwho-717706

ABSTRACT

While lateral flow test formats can be utilized with whole blood and low sample volumes, their diagnostic characteristics are inferior to immunoassays based on chemiluminescence immunoassay (CLIA) or enzyme-linked immunosorbent assay (ELISA) technology. CLIAs and ELISAs can be automated to a high degree but commonly require larger serum or plasma volumes for sample processing. We addressed the suitability of EDTA-anticoagulated whole blood as an alternative sample material for antibody testing against SARS-CoV-2 by electro-CLIA (ECLIA; Roche, Rotkreuz, Switzerland) and ELISA (IgG and IgA; Euroimmun, Germany). Simultaneously drawn venous serum and EDTA-anticoagulated whole blood samples from 223 individuals were included. Correction of the whole blood results for hematocrit led to a good agreement with the serum results for weakly to moderately positive antibody signals. In receiver-operating characteristic curve analysis, all three assays displayed comparable diagnostic accuracy (area under the curve (AUC)) using corrected whole blood and serum (AUCs: 0.97 for ECLIA and IgG ELISA; 0.84 for IgA ELISA). In conclusion, our results suggest that the investigated assays can reliably detect antibodies against SARS-CoV-2 in hemolyzed whole blood anticoagulated with EDTA. Correction of these results for hematocrit is suggested. This study demonstrates that the automated processing of whole blood for identification of SARS-CoV-2 antibodies with common ECLIA and ELISA methods is accurate and feasible.

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