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1.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-306553

ABSTRACT

This work investigates the use of interactively updated label suggestions to improve upon the efficiency of gathering annotations on the task of opinion mining in German Covid-19 social media data. We develop guidelines to conduct a controlled annotation study with social science students and find that suggestions from a model trained on a small, expert-annotated dataset already lead to a substantial improvement - in terms of inter-annotator agreement(+.14 Fleiss' $κ$) and annotation quality - compared to students that do not receive any label suggestions. We further find that label suggestions from interactively trained models do not lead to an improvement over suggestions from a static model. Nonetheless, our analysis of suggestion bias shows that annotators remain capable of reflecting upon the suggested label in general. Finally, we confirm the quality of the annotated data in transfer learning experiments between different annotator groups. To facilitate further research in opinion mining on social media data, we release our collected data consisting of 200 expert and 2,785 student annotations.

2.
Nature ; 600(7888): 295-301, 2021 12.
Article in English | MEDLINE | ID: covidwho-1626235

ABSTRACT

SARS-CoV-2 is a single-stranded RNA virus that causes COVID-19. Given its acute and often self-limiting course, it is likely that components of the innate immune system play a central part in controlling virus replication and determining clinical outcome. Natural killer (NK) cells are innate lymphocytes with notable activity against a broad range of viruses, including RNA viruses1,2. NK cell function may be altered during COVID-19 despite increased representation of NK cells with an activated and adaptive phenotype3,4. Here we show that a decline in viral load in COVID-19 correlates with NK cell status and that NK cells can control SARS-CoV-2 replication by recognizing infected target cells. In severe COVID-19, NK cells show defects in virus control, cytokine production and cell-mediated cytotoxicity despite high expression of cytotoxic effector molecules. Single-cell RNA sequencing of NK cells over the time course of the COVID-19 disease spectrum reveals a distinct gene expression signature. Transcriptional networks of interferon-driven NK cell activation are superimposed by a dominant transforming growth factor-ß (TGFß) response signature, with reduced expression of genes related to cell-cell adhesion, granule exocytosis and cell-mediated cytotoxicity. In severe COVID-19, serum levels of TGFß peak during the first two weeks of infection, and serum obtained from these patients severely inhibits NK cell function in a TGFß-dependent manner. Our data reveal that an untimely production of TGFß is a hallmark of severe COVID-19 and may inhibit NK cell function and early control of the virus.


Subject(s)
COVID-19/immunology , Killer Cells, Natural/immunology , SARS-CoV-2/immunology , Transforming Growth Factor beta/immunology , Atlases as Topic , Gene Expression Regulation/immunology , Humans , Immunity, Innate , Influenza, Human/immunology , Killer Cells, Natural/pathology , RNA-Seq , Single-Cell Analysis , Time Factors , Transforming Growth Factor beta/blood , Viral Load/immunology , Virus Replication/immunology
3.
Front Immunol ; 12: 722406, 2021.
Article in English | MEDLINE | ID: covidwho-1497073

ABSTRACT

Introduction: The COVID-19 pandemic dramatically disrupts health care for patients with chronic diseases including chronic spontaneous urticaria (CSU). As of now, it is unknown if the effects of the pandemic in CSU are different than in other chronic diseases. We also do not know, if different groups of CSU patients, for example female and male patients, are affected differently. Aim: To understand how CSU patients and subgroups are affected by the COVID-19 pandemic in their disease activity and control and treatment, using psoriasis as control. Patients and Methods: We analyzed 399 patients (450 visits) with CSU or psoriasis assessed during August 2019, i.e. before the pandemic, or August 2020, i.e. during the pandemic, for changes in disease activity, disease control, and the treatment they used, and how these changes are linked to age, gender, and disease duration. Results: Male but not female patients with CSU had markedly increased disease activity during the pandemic. CSU patients' age or disease duration were not linked to changes. Male and female patients with psoriasis showed similar increases in disease activity and decreases in disease control. The rate of omalizumab treatment, during the pandemic, was unchanged in male patients and increased in female patients with CSU. The efficacy of omalizumab treatment, during the pandemic, was reduced in male patients but not female patients with CSU. Conclusion: Male but not female CSU patients, during the COVID-19 pandemic, show loss of disease control linked to loss of omalizumab efficacy. The reasons for this need to be investigated.


Subject(s)
Chronic Urticaria/drug therapy , Adult , Anti-Allergic Agents/therapeutic use , COVID-19/epidemiology , Female , Humans , Male , Omalizumab/therapeutic use , Pandemics/prevention & control , Treatment Outcome
4.
Nature ; 600(7888): 295-301, 2021 12.
Article in English | MEDLINE | ID: covidwho-1483137

ABSTRACT

SARS-CoV-2 is a single-stranded RNA virus that causes COVID-19. Given its acute and often self-limiting course, it is likely that components of the innate immune system play a central part in controlling virus replication and determining clinical outcome. Natural killer (NK) cells are innate lymphocytes with notable activity against a broad range of viruses, including RNA viruses1,2. NK cell function may be altered during COVID-19 despite increased representation of NK cells with an activated and adaptive phenotype3,4. Here we show that a decline in viral load in COVID-19 correlates with NK cell status and that NK cells can control SARS-CoV-2 replication by recognizing infected target cells. In severe COVID-19, NK cells show defects in virus control, cytokine production and cell-mediated cytotoxicity despite high expression of cytotoxic effector molecules. Single-cell RNA sequencing of NK cells over the time course of the COVID-19 disease spectrum reveals a distinct gene expression signature. Transcriptional networks of interferon-driven NK cell activation are superimposed by a dominant transforming growth factor-ß (TGFß) response signature, with reduced expression of genes related to cell-cell adhesion, granule exocytosis and cell-mediated cytotoxicity. In severe COVID-19, serum levels of TGFß peak during the first two weeks of infection, and serum obtained from these patients severely inhibits NK cell function in a TGFß-dependent manner. Our data reveal that an untimely production of TGFß is a hallmark of severe COVID-19 and may inhibit NK cell function and early control of the virus.


Subject(s)
COVID-19/immunology , Killer Cells, Natural/immunology , SARS-CoV-2/immunology , Transforming Growth Factor beta/immunology , Atlases as Topic , Gene Expression Regulation/immunology , Humans , Immunity, Innate , Influenza, Human/immunology , Killer Cells, Natural/pathology , RNA-Seq , Single-Cell Analysis , Time Factors , Transforming Growth Factor beta/blood , Viral Load/immunology , Virus Replication/immunology
5.
Nat Commun ; 12(1): 1961, 2021 03 30.
Article in English | MEDLINE | ID: covidwho-1169399

ABSTRACT

The pathogenesis of severe COVID-19 reflects an inefficient immune reaction to SARS-CoV-2. Here we analyze, at the single cell level, plasmablasts egressed into the blood to study the dynamics of adaptive immune response in COVID-19 patients requiring intensive care. Before seroconversion in response to SARS-CoV-2 spike protein, peripheral plasmablasts display a type 1 interferon-induced gene expression signature; however, following seroconversion, plasmablasts lose this signature, express instead gene signatures induced by IL-21 and TGF-ß, and produce mostly IgG1 and IgA1. In the sustained immune reaction from COVID-19 patients, plasmablasts shift to the expression of IgA2, thereby reflecting an instruction by TGF-ß. Despite their continued presence in the blood, plasmablasts are not found in the lungs of deceased COVID-19 patients, nor does patient IgA2 binds to the dominant antigens of SARS-CoV-2. Our results thus suggest that, in severe COVID-19, SARS-CoV-2 triggers a chronic immune reaction that is instructed by TGF-ß, and is distracted from itself.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Transforming Growth Factor beta/immunology , Adult , Aged , Aged, 80 and over , COVID-19/virology , Female , Humans , Immunoglobulin A/immunology , Immunoglobulin G/immunology , Interleukins/immunology , Male , Middle Aged , Plasma Cells/immunology , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology
6.
Allergo J Int ; 30(2): 64-75, 2021.
Article in English | MEDLINE | ID: covidwho-1107918

ABSTRACT

BACKGROUND: Chronic urticaria (CU) is a common disease which represents a considerable burden for many patients. The current urticaria guideline describes the evidence-based diagnosis and treatment of CU. In addition, however, questions often arise in everyday practice that are not addressed by the guideline. METHODS: In May 2020, a digital meeting with German urticaria experts was held, in which practical aspects of CU treatment were discussed and supporting aids for everyday clinical treatment formulated. The resulting advice in this document focus on practical questions and the available literature and experiences of the participants. RESULTS: The diagnosis of CU can be made in a short time by means of a thorough anamnesis, a physical examination, and a basic laboratory chemical diagnosis. For this purpose, practical recommendations for everyday practice are given in this paper. An extended diagnosis is only indicated in a few cases and should always be carried out in parallel with an effective therapy. In general, CU should always be treated in the same way, regardless of whether wheals, angioedema or both occur. Symptomatic therapy should be carried out according to the treatment steps recommended by the guidelines. This publication provides practical advice on issues in everyday practice, such as the procedure in the current coronavirus disease 2019 (COVID-19) pandemic, the cardiac risk under higher dosed H1 antihistamines, the self-administration of omalizumab as well as vaccination under omalizumab therapy. In addition to treatment recommendations, topics such as documentation in the practice and family planning with urticaria will be discussed. DISCUSSION: These supporting treatment recommendations serve as an addendum to the current CU guideline and provide support in dealing with CU patients in everyday practice. The aim is to ensure that patients suffering from CU achieve complete freedom of symptoms with the help of an optimal therapy. SUPPLEMENTARY INFORMATION: The online version of this article (10.1007/s40629-021-00162-w) contains supplementary material, which is available to authorized users.

7.
Allergol Select ; 4: 53-68, 2020.
Article in English | MEDLINE | ID: covidwho-761024

ABSTRACT

BACKGROUND: Since the beginning of the COVID-19 pandemic, the treatment of patients with allergic and atopy-associated diseases has faced major challenges. Recommendations for "social distancing" and the fear of patients becoming infected during a visit to a medical facility have led to a drastic decrease in personal doctor-patient contacts. This affects both acute care and treatment of the chronically ill. The immune response after SARS-CoV-2 infection is so far only insufficiently understood and could be altered in a favorable or unfavorable way by therapy with monoclonal antibodies. There is currently no evidence for an increased risk of a severe COVID-19 course in allergic patients. Many patients are under ongoing therapy with biologicals that inhibit type 2 immune responses via various mechanisms. There is uncertainty about possible immunological interactions and potential risks of these biologicals in the case of an infection with SARS-CoV-2. MATERIALS AND METHODS: A selective literature search was carried out in PubMed, Livivo, and the internet to cover the past 10 years (May 2010 - April 2020). Additionally, the current German-language publications were analyzed. Based on these data, the present position paper provides recommendations for the biological treatment of patients with allergic and atopy-associated diseases during the COVID-19 pandemic. RESULTS: In order to maintain in-office consultation services, a safe treatment environment must be created that is adapted to the pandemic situation. To date, there is a lack of reliable study data on the care for patients with complex respiratory, atopic, and allergic diseases in times of an imminent infection risk from SARS-CoV-2. Type-2-dominant immune reactions, as they are frequently seen in allergic patients, could influence various phases of COVID-19, e.g., by slowing down the immune reactions. Theoretically, this could have an unfavorable effect in the early phase of a SARS-Cov-2 infection, but also a positive effect during a cytokine storm in the later phase of severe courses. However, since there is currently no evidence for this, all data from patients treated with a biological directed against type 2 immune reactions who develop COVID-19 should be collected in registries, and their disease courses documented in order to be able to provide experience-based instructions in the future. CONCLUSION: The use of biologicals for the treatment of bronchial asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, and spontaneous urticaria should be continued as usual in patients without suspected infection or proven SARS-CoV-2 infection. If available, it is recommended to prefer a formulation for self-application and to offer telemedical monitoring. Treatment should aim at the best possible control of difficult-to-control allergic and atopic diseases using adequate rescue and add-on therapy and should avoid the need for systemic glucocorticosteroids. If SARS-CoV-2 infection is proven or reasonably suspected, the therapy should be determined by weighing the benefits and risks individually for the patient in question, and the patient should be involved in the decision-making. It should be kept in mind that the potential effects of biologicals on the immune response in COVID-19 are currently not known. Telemedical offers are particularly desirable for the acute consultation needs of suitable patients.

8.
Allergol Select ; 4: 44-52, 2020.
Article in English | MEDLINE | ID: covidwho-613485

ABSTRACT

No abstract available.

9.
Allergo J ; 29(4): 14-27, 2020.
Article in German | MEDLINE | ID: covidwho-606497
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