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1.
Curr Opin Allergy Clin Immunol ; 21(6): 535-544, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1440659

ABSTRACT

PURPOSE OF REVIEW: In the general population, the risk of severe COVID-19 is associated with old age, male sex, hypertension, obesity and chronic diseases. Chronic lung diseases are listed as additional risk factors for hospitalization and ICU admission. The purpose of this review is to define whether chronic lung diseases, such as bronchiectasis and interstitial diseases, represent a risk for a severe SARS-CoV-2 infection in patients affected by common variable immunodeficiency (CVID), the most common symptomatic primary antibody defect. RECENT FINDINGS: CVID patients with SARS-CoV-2 infection have been reported since the beginning of the pandemic with a wide range of clinical presentations ranging from asymptomatic to mild/moderate and severe COVID-19. The meta-analysis of 88 CVID cases described in large cohorts and case reports demonstrated that CVID patients with chronic lung involvement have an increased risk for severe COVID-19 in comparison to CVID without lung diseases (50 vs. 28%, relative risk 1.75, 95% confidence interval 1.04--2.92, P = 0.043). Differently from the general population, age and metabolic comorbidities did not represent a risk factor for severe course in this patient's population. SUMMARY: Underlying chronic lung diseases but not age represent a risk factor for severe COVID-19 in CVID. Prompt therapeutic intervention should be adopted in SARS-CoV-2 positive CVID patients with chronic lung diseases independently of their age.


Subject(s)
Bronchiectasis/epidemiology , COVID-19/diagnosis , Common Variable Immunodeficiency/complications , Lung Diseases, Interstitial/epidemiology , Severity of Illness Index , Age Factors , Bronchiectasis/immunology , COVID-19/immunology , COVID-19/virology , Chronic Disease/epidemiology , Common Variable Immunodeficiency/immunology , Disease Susceptibility , Humans , Lung Diseases, Interstitial/immunology , Risk Factors , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification
4.
Genome Med ; 13(1): 64, 2021 04 20.
Article in English | MEDLINE | ID: covidwho-1195928

ABSTRACT

BACKGROUND: Immunosuppressive and anti-cytokine treatment may have a protective effect for patients with COVID-19. Understanding the immune cell states shared between COVID-19 and other inflammatory diseases with established therapies may help nominate immunomodulatory therapies. METHODS: To identify cellular phenotypes that may be shared across tissues affected by disparate inflammatory diseases, we developed a meta-analysis and integration pipeline that models and removes the effects of technology, tissue of origin, and donor that confound cell-type identification. Using this approach, we integrated > 300,000 single-cell transcriptomic profiles from COVID-19-affected lungs and tissues from healthy subjects and patients with five inflammatory diseases: rheumatoid arthritis (RA), Crohn's disease (CD), ulcerative colitis (UC), systemic lupus erythematosus (SLE), and interstitial lung disease. We tested the association of shared immune states with severe/inflamed status compared to healthy control using mixed-effects modeling. To define environmental factors within these tissues that shape shared macrophage phenotypes, we stimulated human blood-derived macrophages with defined combinations of inflammatory factors, emphasizing in particular antiviral interferons IFN-beta (IFN-ß) and IFN-gamma (IFN-γ), and pro-inflammatory cytokines such as TNF. RESULTS: We built an immune cell reference consisting of > 300,000 single-cell profiles from 125 healthy or disease-affected donors from COVID-19 and five inflammatory diseases. We observed a CXCL10+ CCL2+ inflammatory macrophage state that is shared and strikingly abundant in severe COVID-19 bronchoalveolar lavage samples, inflamed RA synovium, inflamed CD ileum, and UC colon. These cells exhibited a distinct arrangement of pro-inflammatory and interferon response genes, including elevated levels of CXCL10, CXCL9, CCL2, CCL3, GBP1, STAT1, and IL1B. Further, we found this macrophage phenotype is induced upon co-stimulation by IFN-γ and TNF-α. CONCLUSIONS: Our integrative analysis identified immune cell states shared across inflamed tissues affected by inflammatory diseases and COVID-19. Our study supports a key role for IFN-γ together with TNF-α in driving an abundant inflammatory macrophage phenotype in severe COVID-19-affected lungs, as well as inflamed RA synovium, CD ileum, and UC colon, which may be targeted by existing immunomodulatory therapies.


Subject(s)
COVID-19/immunology , Cytokines/immunology , Macrophages/immunology , SARS-CoV-2 , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/immunology , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/immunology , COVID-19/genetics , Colitis, Ulcerative/genetics , Colitis, Ulcerative/immunology , Colon/immunology , Crohn Disease/genetics , Crohn Disease/immunology , Humans , Inflammation/genetics , Inflammation/immunology , Lung/immunology , Lung Diseases, Interstitial/genetics , Lung Diseases, Interstitial/immunology , Lupus Erythematosus, Systemic/genetics , Lupus Erythematosus, Systemic/immunology , Phenotype , RNA-Seq
5.
Eur Rev Med Pharmacol Sci ; 24(22): 11960-11963, 2020 11.
Article in English | MEDLINE | ID: covidwho-962031

ABSTRACT

Though the exact etiology of autoimmune diseases still remains not completely known, there are various factors which are known to contribute to be trigger of autoimmune diseases. Viral infection is known to be among the other. It is known as the infection from severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) can be an autoimmune trigger, so, we suppose that SARS-Coronavirus (SARS-CoV-2) could be as well. Several authors have highlighted the temporal consequence between SARS-CoV-2 and autoimmune diseases. In this case report we described a patient admitted for COVID-19 pneumonia with completely negative autoimmunity at admission who developed major pulmonary interstitial disease. During the hospitalization the weaning difficulties from oxygen led us to the repetition of autoimmunity pattern which became positive (both during hospitalization then after two months from dismission) with marked positivity for specific antibodies for myositis even after the patient's infectious healing. In the follow-up, the patient continued to have asthenia and muscle weakness despite steroid therapy. She is still in follow-up and will be further evaluated over time. Can we therefore think that in this case the development of autoimmunity can persist beyond the infectious phase and determine over time the development of a real autoimmune myositis?


Subject(s)
Autoantibodies/immunology , Autoimmune Diseases/immunology , COVID-19/immunology , Lung Diseases, Interstitial/immunology , Muscle Weakness/immunology , Myositis/immunology , Aged , Antibodies, Antineutrophil Cytoplasmic/immunology , Antibodies, Antinuclear/immunology , Antigens, Nuclear/immunology , Asthenia/immunology , Autoimmune Diseases/drug therapy , Autoimmune Diseases/etiology , Autoimmune Diseases/physiopathology , COVID-19/complications , COVID-19/physiopathology , COVID-19/therapy , Female , Humans , Ku Autoantigen/immunology , Mi-2 Nucleosome Remodeling and Deacetylase Complex/immunology , Myositis/drug therapy , Myositis/etiology , Myositis/physiopathology
6.
Mod Rheumatol Case Rep ; 5(1): 101-107, 2021 01.
Article in English | MEDLINE | ID: covidwho-917630

ABSTRACT

Anti-melanoma differentiation-associated gene 5 juvenile dermatomyositis (anti-MDA5 JDM) is associated with high risk of developing rapidly progressive interstitial lung disease (RP-ILD). Here we report an 11-year-old girl with anti-MDA5 JDM and RP-ILD which led to a fatal outcome, further aggravated by SARS-CoV-2 infection. She was referred to our hospital after being diagnosed with anti-MDA5 JDM and respiratory failure due to RP-ILD. On admission, fibrobronchoscopy with bronchoalveolar lavage (BAL) revealed Pneumocystis jirovecii infection so treatment with intravenous trimethoprim-sulfamethoxazole was initiated. Due to RP-ILD worsening, immunosuppressive therapy was intensified using methylprednisolone pulses, cyclophosphamide, tofacitinib and intravenous immunoglobulin without response. She developed severe hypoxemic respiratory failure, pneumomediastinum and pneumothorax, further complicated with severe RP-ILD and cervical subcutaneous emphysema. Three real-time RT-PCR for SARS-CoV-2 were made with a negative result. In addition, she was complicated with a secondary hemophagocytic lymphohistiocytosis and a fourth real-time PCR for SARS-CoV-2 performed in BAS sample was positive. Despite aggressive treatment of RP-ILD due to anti-MDA5 JDM, there was no improvement of respiratory failure in the following days and patient developed refractory septic shock and died. Anti-MDA5 JDM patients with RP-ILD have a poor prognosis with a high mortality rate. For this reason, intensive immunosuppressive therapy is essential including the use of promising drugs such as tofacitinib. COVID-19 in children with underlying health conditions like anti-MDA5 JDM may still be at risk for disease and severe complications.


Subject(s)
COVID-19/complications , Dermatomyositis/complications , Immunosuppressive Agents/therapeutic use , Lung Diseases, Interstitial/complications , Lymphohistiocytosis, Hemophagocytic/etiology , Pneumonia, Pneumocystis/complications , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Anti-Bacterial Agents/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Antiviral Agents/therapeutic use , Autoantibodies/immunology , Bronchoscopy , COVID-19/therapy , COVID-19 Nucleic Acid Testing , Child , Cyclophosphamide/therapeutic use , Dermatomyositis/drug therapy , Dermatomyositis/immunology , Disease Progression , Fatal Outcome , Female , Humans , Hydroxychloroquine/therapeutic use , Immunocompromised Host , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Interferon-Induced Helicase, IFIH1/immunology , Lung/diagnostic imaging , Lung Diseases, Interstitial/diagnostic imaging , Lung Diseases, Interstitial/immunology , Lung Diseases, Interstitial/therapy , Lymphohistiocytosis, Hemophagocytic/immunology , Mediastinal Emphysema/etiology , Methylprednisolone/therapeutic use , Piperidines/therapeutic use , Pneumonia, Pneumocystis/immunology , Pneumothorax/etiology , Pyrimidines/therapeutic use , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy , Shock, Septic/etiology , Subcutaneous Emphysema/etiology , Tomography, X-Ray Computed , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use
7.
Front Immunol ; 11: 587517, 2020.
Article in English | MEDLINE | ID: covidwho-887608

ABSTRACT

Background and Objectives: Understanding the pathophysiology of respiratory failure in coronavirus disease 2019 (COVID-19) is indispensable for development of therapeutic strategies. Since we observed similarities between COVID-19 and interstitial lung disease in connective tissue disease (CTD-ILD), we investigated features of autoimmunity in SARS-CoV-2-associated respiratory failure. Methods: We prospectively enrolled 22 patients with RT-PCR-confirmed SARS-CoV-2 infection and 10 patients with non-COVID-19-associated pneumonia. Full laboratory testing was performed including autoantibody (AAB; ANA/ENA) screening using indirect immunofluorescence and immunoblot. Fifteen COVID-19 patients underwent high-resolution computed tomography. Transbronchial biopsies/autopsy tissue samples for histopathology and ultrastructural analyses were obtained from 4/3 cases, respectively. Results: Thirteen (59.1%) patients developed acute respiratory distress syndrome (ARDS), and five patients (22.7%) died from the disease. ANA titers ≥1:320 and/or positive ENA immunoblots were detected in 11/13 (84.6%) COVID-19 patients with ARDS, in 1/9 (11.1%) COVID-19 patients without ARDS (p = 0.002) and in 4/10 (40%) patients with non-COVID-19-associated pneumonias (p = 0.039). Detection of AABs was significantly associated with a need for intensive care treatment (83.3 vs. 10%; p = 0.002) and occurrence of severe complications (75 vs. 20%, p = 0.03). Radiological and histopathological findings were highly heterogeneous including patterns reminiscent of exacerbating CTD-ILD, while ultrastructural analyses revealed interstitial thickening, fibroblast activation, and deposition of collagen fibrils. Conclusions: We are the first to report overlapping clinical, serological, and imaging features between severe COVID-19 and acute exacerbation of CTD-ILD. Our findings indicate that autoimmune mechanisms determine both clinical course and long-term sequelae after SARS-CoV-2 infection, and the presence of autoantibodies might predict adverse clinical course in COVID-19 patients.


Subject(s)
Connective Tissue Diseases/pathology , Coronavirus Infections/pathology , Lung Diseases, Interstitial/pathology , Pneumonia, Viral/pathology , Severe Acute Respiratory Syndrome/pathology , Adult , Aged , Aged, 80 and over , Autoantibodies/blood , Betacoronavirus/immunology , COVID-19 , Connective Tissue Diseases/immunology , Coronavirus Infections/immunology , Female , Humans , Lung/pathology , Lung Diseases, Interstitial/immunology , Male , Middle Aged , Pandemics , Pneumonia, Viral/immunology , Prospective Studies , SARS-CoV-2 , Severe Acute Respiratory Syndrome/immunology
8.
Clin Rheumatol ; 39(11): 3171-3175, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-730357

ABSTRACT

We treated two patients with severe respiratory failure due to coronavirus disease 2019 (COVID-19). Case 1 was a 73-year-old woman, and Case 2 was a 65-year-old-man. Neither of them had a history of autoimmune disease. Chest computed tomography scans before the antiviral therapy showed bilateral multiple patchy ground-glass opacities (GGO) consistent with COVID-19 pneumonia. The GGO regressed over the course of the antiviral treatment; however, new non-segmental patchy consolidations emerged, which resembled those of interstitial lung disease (ILD), specifically collagen vascular disease-associated ILD. We tested the patients' sera for autoantibodies and discovered that both patients had high anti-SSA/Ro antibody titers. In Case 1, the patient recovered with antiviral therapy alone. However, in Case 2, the patient did not improve with antiviral therapy alone but responded well to corticosteroid therapy (methylprednisolone) and made a full recovery. The relationship between some immunological responses and COVID-19 pneumonia exacerbation has been discussed previously; our discovery of the elevation of anti-SSA/Ro antibodies suggests a contribution from autoimmunity functions of the immune system. Although it is unclear whether the elevation of anti-SSA/Ro antibodies was a cause or an outcome of aggravated COVID-19 pneumonia, we hypothesize that both patients developed aggravated the COVID-19 pneumonia due to an autoimmune response. In COVID-19 lung injury, there may be a presence of autoimmunity factors in addition to the known effects of cytokine storms. In patients with COVID-19, a high level of anti-SSA/Ro52 antibodies may be a surrogate marker of pneumonia severity and poor prognosis.


Subject(s)
Antibodies, Antinuclear/immunology , Coronavirus Infections/immunology , Lung Diseases, Interstitial/immunology , Pneumonia, Viral/immunology , Respiratory Insufficiency/immunology , Aged , Amides/therapeutic use , Antiviral Agents/therapeutic use , Benzamidines , Betacoronavirus , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/drug therapy , Female , Glucocorticoids/therapeutic use , Guanidines/therapeutic use , Humans , Hydroxychloroquine/therapeutic use , Lung Diseases, Interstitial/diagnostic imaging , Lung Diseases, Interstitial/drug therapy , Lung Diseases, Interstitial/etiology , Male , Methylprednisolone/therapeutic use , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/drug therapy , Pregnenediones/therapeutic use , Pyrazines/therapeutic use , Recovery of Function , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/immunology , Respiratory Insufficiency/etiology , SARS-CoV-2 , Severity of Illness Index , Tomography, X-Ray Computed
9.
Science ; 369(6505): 818-823, 2020 08 14.
Article in English | MEDLINE | ID: covidwho-631755

ABSTRACT

Coronavirus disease 2019 (COVID-19), which is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. It is unclear whether convalescing patients have a risk of reinfection. We generated a rhesus macaque model of SARS-CoV-2 infection that was characterized by interstitial pneumonia and systemic viral dissemination mainly in the respiratory and gastrointestinal tracts. Rhesus macaques reinfected with the identical SARS-CoV-2 strain during the early recovery phase of the initial SARS-CoV-2 infection did not show detectable viral dissemination, clinical manifestations of viral disease, or histopathological changes. Comparing the humoral and cellular immunity between primary infection and rechallenge revealed notably enhanced neutralizing antibody and immune responses. Our results suggest that primary SARS-CoV-2 exposure protects against subsequent reinfection in rhesus macaques.


Subject(s)
Betacoronavirus , Coronavirus Infections/immunology , Coronavirus Infections/virology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Anal Canal/virology , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , B-Lymphocyte Subsets/immunology , Betacoronavirus/immunology , Betacoronavirus/isolation & purification , Betacoronavirus/physiology , COVID-19 , Coronavirus Infections/pathology , Coronavirus Infections/physiopathology , Disease Models, Animal , Host Microbial Interactions , Immunity, Cellular , Immunity, Humoral , Lung/diagnostic imaging , Lung/immunology , Lung/pathology , Lung/virology , Lung Diseases, Interstitial/immunology , Lung Diseases, Interstitial/pathology , Lung Diseases, Interstitial/virology , Macaca mulatta , Nasopharynx/virology , Pandemics , Pneumonia, Viral/pathology , Pneumonia, Viral/physiopathology , Recurrence , SARS-CoV-2 , T-Lymphocyte Subsets/immunology , Viral Load , Virus Replication
11.
Science ; 369(6505): 812-817, 2020 08 14.
Article in English | MEDLINE | ID: covidwho-327276

ABSTRACT

An understanding of protective immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for vaccine and public health strategies aimed at ending the global coronavirus disease 2019 (COVID-19) pandemic. A key unanswered question is whether infection with SARS-CoV-2 results in protective immunity against reexposure. We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. After the initial viral clearance, animals were rechallenged with SARS-CoV-2 and showed 5 log10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa compared with after the primary infection. Anamnestic immune responses after rechallenge suggested that protection was mediated by immunologic control. These data show that SARS-CoV-2 infection induced protective immunity against reexposure in nonhuman primates.


Subject(s)
Betacoronavirus , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , Animals , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Betacoronavirus/immunology , Betacoronavirus/physiology , Bronchoalveolar Lavage Fluid/virology , COVID-19 , Coronavirus Infections/pathology , Coronavirus Infections/virology , Disease Models, Animal , Female , Immunity, Cellular , Immunity, Humoral , Immunologic Memory , Lung/immunology , Lung/pathology , Lung/virology , Lung Diseases, Interstitial/immunology , Lung Diseases, Interstitial/pathology , Lung Diseases, Interstitial/virology , Macaca mulatta , Male , Nasal Mucosa/virology , Pandemics , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Recurrence , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/immunology , Viral Load , Virus Replication
12.
Ann Rheum Dis ; 79(6): 724-726, 2020 06.
Article in English | MEDLINE | ID: covidwho-155085

ABSTRACT

Due to the frequent presence of interstitial lung disease and widespread use of immunosuppressive treatment, systemic sclerosis (SSc) patients may be considered at risk for a more severe disease course and higher mortality when they develop Severe Acute Respiratory Syndrome - Coronavirus - 2 (SARS-CoV-2) virus infection. Therefore, with World Scleroderma Foundation endorsement, experts from different specialties including rheumatology, virology and clinical immunology gathered virtually to answer to the main practical clinical questions regarding SARS-CoV-2 infection coming from both patients and physicians. This preliminary advice is aligned with other national and international recommendations, adapted for SSc patients.


Subject(s)
Coronavirus Infections/drug therapy , Coronavirus Infections/physiopathology , Pneumonia, Viral/drug therapy , Pneumonia, Viral/physiopathology , Scleroderma, Systemic/therapy , Scleroderma, Systemic/virology , Antibodies, Monoclonal, Humanized/therapeutic use , Betacoronavirus , COVID-19 , Coronavirus Infections/epidemiology , Humans , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects , Lung Diseases, Interstitial/immunology , Lung Diseases, Interstitial/virology , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/virology , SARS-CoV-2 , Scleroderma, Systemic/epidemiology , Scleroderma, Systemic/immunology
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