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1.
BMC Anesthesiol ; 21(1): 280, 2021 11 13.
Article in English | MEDLINE | ID: covidwho-1515436

ABSTRACT

BACKGROUND: COVID-19 can induce acute respiratory distress syndrome (ARDS). In patients with congenital heart disease, established treatment strategies are often limited due to their unique cardiovascular anatomy and passive pulmonary perfusion. CASE PRESENTATION: We report the first case of an adult with single-ventricle physiology and bidirectional cavopulmonary shunt who suffered from severe COVID-19 ARDS. Treatment strategies were successfully adopted, and pulmonary vascular resistance was reduced, both medically and through prone positioning, leading to a favorable outcome. CONCLUSION: ARDS treatment strategies including ventilatory settings, prone positioning therapy and cannulation techniques for extracorporeal oxygenation must be adopted carefully considering the passive venous return in patients with single-ventricle physiology.


Subject(s)
COVID-19/diagnostic imaging , Cardiomegaly/diagnostic imaging , Cardiovascular Surgical Procedures/methods , Dextrocardia/diagnostic imaging , Extracorporeal Membrane Oxygenation/methods , Genetic Diseases, X-Linked/diagnostic imaging , Heterotaxy Syndrome/diagnostic imaging , Patient Positioning/methods , COVID-19/complications , COVID-19/therapy , Cardiomegaly/complications , Cardiomegaly/therapy , Dextrocardia/complications , Dextrocardia/therapy , Genetic Diseases, X-Linked/complications , Genetic Diseases, X-Linked/therapy , Heterotaxy Syndrome/complications , Heterotaxy Syndrome/therapy , Humans , Male , Middle Aged , Severity of Illness Index
2.
Pediatr Infect Dis J ; 40(12): e472-e474, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1447657

ABSTRACT

We present a case of a 17-year-old boy with X-linked agammaglobulinemia who had mild disease when initially infected with SARS-CoV-2 but after recovering from acute infection developed fevers and a raised erythrocyte sedimentation rate that persisted for several weeks without any ongoing respiratory symptoms. Multiple nasopharyngeal swabs were found to be negative for SARS-CoV-2 during the febrile period, but typical changes of COVID-19 on high resolution CT chest scan led to the detection of SARS-CoV-2 on RT-PCR in a sample from a bronchoalveolar lavage. His fevers completely resolved after a 5-day course of remdesivir.


Subject(s)
Agammaglobulinemia/complications , COVID-19/complications , Genetic Diseases, X-Linked/complications , Pneumonia, Viral/virology , SARS-CoV-2 , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adolescent , Alanine/analogs & derivatives , Alanine/therapeutic use , Antibodies, Viral/blood , Antiviral Agents/therapeutic use , Biomarkers/blood , Bronchoalveolar Lavage Fluid/virology , COVID-19/drug therapy , Fever , Humans , Inflammation/blood , Inflammation/metabolism , Male , Pneumonia, Viral/drug therapy , Pneumonia, Viral/pathology , SARS-CoV-2/isolation & purification
3.
Curr Opin Allergy Clin Immunol ; 21(6): 525-534, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1447630

ABSTRACT

PURPOSE OF REVIEW: The clinical outcomes from COVID-19 in monogenic causes of predominant antibody deficiency have pivotal implications for our understanding of the antiviral contribution of humoral immunity. This review summarizes the lessons learned from COVID-19 infection in X-linked agammaglobulinemia (XLA) due to genetic defects in Bruton's tyrosine kinase (BTK). RECENT FINDINGS: Key molecular pathways underlying the development of severe COVID-19 are emerging, highlighting the possible contribution of BTK to hyperinflammation. SARS-CoV-2 specific T-cell responses and complement activation appear insufficient to achieve viral clearance in some B-cell deficient individuals. Whilst appearing efficacious in this group, use of convalescent plasma has been recently associated with the evolution of viral escape variants. Early data suggests individuals with XLA can mount a viral-specific T-cell vaccine response, however, the clinical significance of this is still emerging. SUMMARY: In contrast to reports made early in the pandemic, we show XLA patients remain susceptible to severe disease. Persistent infection was common and is likely to carry a significant symptom burden and risk of novel variant evolution. COVID-19 infection in this vulnerable, antibody deficient group due to genetic, therapeutic or disease causes may require prompt and specific intervention for both patient and societal benefit.


Subject(s)
Agammaglobulinaemia Tyrosine Kinase/genetics , Agammaglobulinemia/complications , COVID-19/immunology , Genetic Diseases, X-Linked/complications , SARS-CoV-2/immunology , Agammaglobulinemia/genetics , Agammaglobulinemia/immunology , COVID-19/diagnosis , COVID-19/virology , Evolution, Molecular , Genetic Diseases, X-Linked/genetics , Genetic Diseases, X-Linked/immunology , Humans , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Severity of Illness Index
4.
Sci Immunol ; 6(62)2021 08 19.
Article in English | MEDLINE | ID: covidwho-1434876

ABSTRACT

Autosomal inborn errors of type I IFN immunity and autoantibodies against these cytokines underlie at least 10% of critical COVID-19 pneumonia cases. We report very rare, biochemically deleterious X-linked TLR7 variants in 16 unrelated male individuals aged 7 to 71 years (mean: 36.7 years) from a cohort of 1,202 male patients aged 0.5 to 99 years (mean: 52.9 years) with unexplained critical COVID-19 pneumonia. None of the 331 asymptomatically or mildly infected male individuals aged 1.3 to 102 years (mean: 38.7 years) tested carry such TLR7 variants (p = 3.5 × 10-5). The phenotypes of five hemizygous relatives of index cases infected with SARS-CoV-2 include asymptomatic or mild infection (n=2, 5 and 38 years), or moderate (n=1, 5 years), severe (n=1, 27 years), or critical (n=1, 29 years) pneumonia. Two boys (aged 7 and 12 years) from a cohort of 262 male patients with severe COVID-19 pneumonia (mean: 51.0 years) are hemizygous for a deleterious TLR7 variant. The cumulative allele frequency for deleterious TLR7 variants in the male general population is < 6.5x10-4 We also show that blood B cell lines and myeloid cell subsets from the patients do not respond to TLR7 stimulation, a phenotype rescued by wild-type TLR7 The patients' blood plasmacytoid dendritic cells (pDCs) produce low levels of type I IFNs in response to SARS-CoV-2. Overall, X-linked recessive TLR7 deficiency is a highly penetrant genetic etiology of critical COVID-19 pneumonia, in about 1.8% of male patients below the age of 60 years. Human TLR7 and pDCs are essential for protective type I IFN immunity against SARS-CoV-2 in the respiratory tract.


Subject(s)
COVID-19/complications , Genetic Diseases, X-Linked/complications , Immune System Diseases/complications , Toll-Like Receptor 7/deficiency , Adolescent , Adult , Aged , Aged, 80 and over , Alleles , Child , Child, Preschool , Humans , Infant , Male , Middle Aged , Pedigree , Penetrance , Toll-Like Receptor 7/genetics , Young Adult
5.
Pediatr Allergy Immunol Pulmonol ; 34(3): 115-118, 2021 09.
Article in English | MEDLINE | ID: covidwho-1398070

ABSTRACT

Introduction: The Centers for Disease Control and Prevention (CDC) has listed primary immunodeficiency disorders as being predisposed to severe coronavirus disease 2019 (COVID-19). However, patients affected with X-linked agammaglobulinemia (XLA) have shown contrary results. In this study, we present 2 boys in late adolescence from south India with XLA who were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as well as a review of cases reported in the literature. Case Presentation: Two patients with XLA had been diagnosed late and were started on regular immunoglobulin prophylaxis only during adolescence. Both of them had developed bronchiectasis, an irreversible suppurative lung disease. However, both patients made an uneventful recovery without the need for artificial ventilation or convalescent plasma. Conclusion: Successful outcomes of patients with XLA and COVID-19, except for delayed recovery, from our experience and from global reports are intriguing and the role of B cell depletion is being studied as well. Further research and clinical experience are necessary to fully elucidate the reasons for these observations.


Subject(s)
Agammaglobulinemia/complications , COVID-19/physiopathology , Genetic Diseases, X-Linked/complications , Adolescent , COVID-19/complications , COVID-19/therapy , Humans , Male , SARS-CoV-2 , Young Adult
6.
Sci Immunol ; 6(62)2021 08 19.
Article in English | MEDLINE | ID: covidwho-1367380

ABSTRACT

Autosomal inborn errors of type I IFN immunity and autoantibodies against these cytokines underlie at least 10% of critical COVID-19 pneumonia cases. We report very rare, biochemically deleterious X-linked TLR7 variants in 16 unrelated male individuals aged 7 to 71 years (mean: 36.7 years) from a cohort of 1,202 male patients aged 0.5 to 99 years (mean: 52.9 years) with unexplained critical COVID-19 pneumonia. None of the 331 asymptomatically or mildly infected male individuals aged 1.3 to 102 years (mean: 38.7 years) tested carry such TLR7 variants (p = 3.5 × 10-5). The phenotypes of five hemizygous relatives of index cases infected with SARS-CoV-2 include asymptomatic or mild infection (n=2, 5 and 38 years), or moderate (n=1, 5 years), severe (n=1, 27 years), or critical (n=1, 29 years) pneumonia. Two boys (aged 7 and 12 years) from a cohort of 262 male patients with severe COVID-19 pneumonia (mean: 51.0 years) are hemizygous for a deleterious TLR7 variant. The cumulative allele frequency for deleterious TLR7 variants in the male general population is < 6.5x10-4 We also show that blood B cell lines and myeloid cell subsets from the patients do not respond to TLR7 stimulation, a phenotype rescued by wild-type TLR7 The patients' blood plasmacytoid dendritic cells (pDCs) produce low levels of type I IFNs in response to SARS-CoV-2. Overall, X-linked recessive TLR7 deficiency is a highly penetrant genetic etiology of critical COVID-19 pneumonia, in about 1.8% of male patients below the age of 60 years. Human TLR7 and pDCs are essential for protective type I IFN immunity against SARS-CoV-2 in the respiratory tract.


Subject(s)
COVID-19/complications , Genetic Diseases, X-Linked/complications , Immune System Diseases/complications , Toll-Like Receptor 7/deficiency , Adolescent , Adult , Aged , Aged, 80 and over , Alleles , Child , Child, Preschool , Humans , Infant , Male , Middle Aged , Pedigree , Penetrance , Toll-Like Receptor 7/genetics , Young Adult
8.
Int J Infect Dis ; 106: 405-408, 2021 May.
Article in English | MEDLINE | ID: covidwho-1188640

ABSTRACT

OBJECTIVES: Multi-system inflammatory syndrome in children (MIS-C) is a post-viral inflammatory vasculopathy of children and adolescents following Covid-19 infection. Since the incidence of SARS-CoV-infections has been increasing in Germany since October 2020, we observe an increasing number of children presenting with MIS-C. DESIGN: We present detailed clinical characteristics of a cohort of nine children with MIS-C admitted to a tertiary PICU at the University Hospital of Cologne between March 2020 and February 2021. RESULTS: The clinical sings and symptoms are largely in line with recent reports. All but one patient had positive SARS-CoV-2 antibodies. Latency form infection to MIS-C was 4-6 weeks. Two children presented with unusual findings: A girl had encephalomyelitis and a boy developed MIS-C side to side with acute leukemia. CONCLUSION: MIS-C has been increasing in Germany paralell to SARS-CoV-2 infections. Rarely, unuasual findings may be associated with MIS-C.


Subject(s)
COVID-19/diagnosis , Systemic Inflammatory Response Syndrome/diagnosis , Abnormalities, Multiple , Adolescent , COVID-19/complications , COVID-19/therapy , Child , Cohort Studies , Female , Genetic Diseases, X-Linked/complications , Germany , Hospitalization , Humans , Ichthyosiform Erythroderma, Congenital/complications , Infant , Limb Deformities, Congenital/complications , Male , Systemic Inflammatory Response Syndrome/complications , Systemic Inflammatory Response Syndrome/therapy
9.
BMJ Case Rep ; 14(3)2021 Mar 04.
Article in English | MEDLINE | ID: covidwho-1136066

ABSTRACT

This report highlights the case of a patient with X-linked agammaglobulinaemia (XLA) and resultant bronchiectasis who was discharged from hospital after recovering from real-time reverse transcriptase-PCR positive COVID-19 infection having had a subsequent negative swab and resolution of symptoms, but was readmitted 3 weeks later with recrudescent symptoms and a further positive swab. Although there are reports of COVID-19 infection in XLA, for the first time we report a case of possible reinfection. Lessons learnt from this case include the potential for reinfection of COVID-19 in a patient with a weakened immune system and the importance of repeating COVID-19 swabs in inpatients. Extra caution needs to be taken when providing care in groups of patients who have a weakened or absent immune system.


Subject(s)
Agammaglobulinemia/complications , COVID-19/diagnosis , Genetic Diseases, X-Linked/complications , Reinfection/diagnosis , Reinfection/virology , Agammaglobulinemia/drug therapy , Anti-Bacterial Agents/therapeutic use , Anticoagulants/therapeutic use , Bronchiectasis/complications , COVID-19/complications , COVID-19/drug therapy , COVID-19 Nucleic Acid Testing/methods , Dexamethasone/therapeutic use , Fatal Outcome , Genetic Diseases, X-Linked/drug therapy , Humans , Male , Middle Aged , SARS-CoV-2/isolation & purification
10.
BMJ Case Rep ; 14(3)2021 Mar 04.
Article in English | MEDLINE | ID: covidwho-1119289

ABSTRACT

This report highlights the case of a patient with X-linked agammaglobulinaemia (XLA) and resultant bronchiectasis who was discharged from hospital after recovering from real-time reverse transcriptase-PCR positive COVID-19 infection having had a subsequent negative swab and resolution of symptoms, but was readmitted 3 weeks later with recrudescent symptoms and a further positive swab. Although there are reports of COVID-19 infection in XLA, for the first time we report a case of possible reinfection. Lessons learnt from this case include the potential for reinfection of COVID-19 in a patient with a weakened immune system and the importance of repeating COVID-19 swabs in inpatients. Extra caution needs to be taken when providing care in groups of patients who have a weakened or absent immune system.


Subject(s)
Agammaglobulinemia/complications , COVID-19/diagnosis , Genetic Diseases, X-Linked/complications , Reinfection/diagnosis , Reinfection/virology , Agammaglobulinemia/drug therapy , Anti-Bacterial Agents/therapeutic use , Anticoagulants/therapeutic use , Bronchiectasis/complications , COVID-19/complications , COVID-19/drug therapy , COVID-19 Nucleic Acid Testing/methods , Dexamethasone/therapeutic use , Fatal Outcome , Genetic Diseases, X-Linked/drug therapy , Humans , Male , Middle Aged , SARS-CoV-2/isolation & purification
13.
J Pediatr Gastroenterol Nutr ; 71(2): 153-155, 2020 08.
Article in English | MEDLINE | ID: covidwho-729245

ABSTRACT

Coronavirus disease 2019 (COVID-19) may lead to a severe inflammatory response referred to as a cytokine storm. We describe a case of severe COVID-19 infection in a recently diagnosed pediatric Crohn disease patient successfully treated with tumor necrosis factor-alpha (TNF-α) blockade. The patient presented with 5 days of fever, an erythematous maculopapular facial rash, and abdominal pain without respiratory symptoms. SARS-CoV-2 polymerase chain reaction was positive. Despite inpatient treatment for COVID-19 and a perianal abscess, the patient acutely decompensated, with worsening fever, tachycardia, fluid-refractory hypotension, elevation of liver enzymes, and transformation of the rash into purpura extending from the face to the trunk, upper and lower extremities, including the palmar and plantar surfaces of the hands and feet. Cytokine profile revealed rising levels of interleukin (IL)-6, IL-8, and TNF-α, higher than those described in either inflammatory bowel disease or severe COVID-19 alone. The patient was treated with infliximab for TNF-α blockade to address both moderately to severely active Crohn disease and multisystem inflammatory syndrome in children temporally related to COVID-19. Within hours of infliximab treatment, fever, tachycardia, and hypotension resolved. Cytokine profile improved with normalization of TNF-α, a decrease in IL-6, and IL-8 concentrations. This case supports a role for blockade of TNF-α in the treatment of COVID-19 inflammatory cascade. The role of anti-TNF agents in patients with multisystem inflammatory syndrome in children temporally related to COVID-19 requires further investigation.


Subject(s)
Coronavirus Infections/drug therapy , Crohn Disease/complications , Genetic Diseases, X-Linked/complications , Ichthyosiform Erythroderma, Congenital/complications , Infliximab/therapeutic use , Interleukin-6/blood , Interleukin-8/blood , Limb Deformities, Congenital/complications , Pneumonia, Viral/drug therapy , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Abnormalities, Multiple , Adolescent , Antirheumatic Agents/therapeutic use , Betacoronavirus , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/virology , Humans , Male , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/virology , SARS-CoV-2 , Tumor Necrosis Factor-alpha/blood
14.
Pediatr Allergy Immunol ; 31(5): 565-569, 2020 07.
Article in English | MEDLINE | ID: covidwho-102307

ABSTRACT

BACKGROUND: The recent SARS-CoV-2 pandemic, which has recently affected Italy since February 21, constitutes a threat to normal subjects, as the coronavirus disease-19 (COVID-19) can manifest with a broad spectrum of clinical phenotypes ranging from asymptomatic cases to pneumonia or even death. There is evidence that older age and several comorbidities can affect the risk to develop severe pneumonia and possibly the need of mechanic ventilation in subjects infected with SARS-CoV-2. Therefore, we evaluated the outcome of SARS-CoV-2 infection in patients with inborn errors of immunity (IEI) such as X-linked agammaglobulinemia (XLA). METHODS: When the SARS-CoV-2 epidemic has reached Italy, we have activated a surveillance protocol of patients with IEI, to perform SARS-CoV-2 search by nasopharyngeal swab in patients presenting with symptoms that could be a manifestation of COVID-19, such as fever, cough, diarrhea, or vomiting. RESULTS: We describe two patients with X-linked agammaglobulinemia (XLA) aged 34 and 26 years with complete absence of B cells from peripheral blood who developed COVID-19, as diagnosed by SARS-CoV-2 detection by nasopharyngeal swab, while receiving immunoglobulin infusions. Both patients developed interstitial pneumonia characterized by fever, cough, and anorexia and associated with elevation of CRP and ferritin, but have never required oxygen ventilation or intensive care. CONCLUSION: Our report suggests that XLA patients might present with high risk to develop pneumonia after SARS-CoV-2 infection, but can recover from infection, suggesting that B-cell response might be important, but is not strictly required to overcome the disease. However, there is a need for larger observational studies to extend these conclusions to other patients with similar genetic immune defects.


Subject(s)
Agammaglobulinemia/complications , Betacoronavirus , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Genetic Diseases, X-Linked/complications , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Adult , Agammaglobulinemia/therapy , Anti-Bacterial Agents/therapeutic use , COVID-19 , Enzyme Inhibitors/therapeutic use , Genetic Diseases, X-Linked/therapy , Humans , Hydroxychloroquine/therapeutic use , Immunization, Passive/methods , Italy , Male , Pandemics , SARS-CoV-2 , Treatment Outcome
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