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2.
Front Immunol ; 13: 881259, 2022.
Article in English | MEDLINE | ID: covidwho-1903015

ABSTRACT

Critical respiratory manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are rare in children, and little is known about how immunocompromised children respond to the infection. We report a case of a 4-year-old boy with activated PI3K delta syndrome type 2 (APDS2) with a protracted and severe COVID-19 course with both inflammatory and acute respiratory features. He was treated with remdesivir, nitazoxanide, high-dose corticosteroids, and tocilizumab and made a full recovery. We propose that remdesivir may be used in combination with nitazoxanide to improve viral clearance and reduce the chance of resistance in treating acute SARS-CoV-2 infection.


Subject(s)
COVID-19 , Immunologic Deficiency Syndromes , Adrenal Cortex Hormones , Child , Child, Preschool , Humans , Immunocompromised Host , Male , SARS-CoV-2
3.
Sci Rep ; 12(1): 10369, 2022 Jun 20.
Article in English | MEDLINE | ID: covidwho-1900655

ABSTRACT

Rare variants affecting host defense against pathogens could be involved in COVID-19 severity and may help explain fatal outcomes in young and middle-aged patients. Our aim was to report the presence of rare genetic variants in certain genes, by using whole exome sequencing, in a selected group of COVID-19 patients under 65 years who required intubation or resulting in death (n = 44). To this end, different etiopathogenic mechanisms were explored using gene prioritization-based analysis in which genes involved in immune response, immunodeficiencies or blood coagulation were studied. We detected 44 different variants of interest, in 29 different patients (66%). Some of these variants were previously described as pathogenic and were located in genes mainly involved in immune response. A network analysis, including the 42 genes with candidate variants, showed three main components, consisting of 25 highly interconnected genes related to immune response and two additional networks composed by genes enriched in carbohydrate metabolism and in DNA metabolism and repair processes. In conclusion, we have detected candidate variants that may potentially influence COVID-19 outcome in our cohort of patients. Further studies are needed to confirm the ultimate role of the genetic variants described in the present study on COVID-19 severity.


Subject(s)
COVID-19 , Immunologic Deficiency Syndromes , Aged , COVID-19/genetics , Cohort Studies , Genetic Predisposition to Disease , Humans , Middle Aged , Whole Exome Sequencing
4.
Cell Rep Med ; 3(6): 100653, 2022 06 21.
Article in English | MEDLINE | ID: covidwho-1882624

ABSTRACT

Individuals with primary antibody deficiency (PAD) syndromes have poor humoral immune responses requiring immunoglobulin replacement therapy. We followed individuals with PAD after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination by evaluating their immunoglobulin replacement products and serum for anti-spike binding, Fcγ receptor (FcγR) binding, and neutralizing activities. The immunoglobulin replacement products tested have low anti-spike and receptor-binding domain (RBD) titers and neutralizing activity. In coronavirus disease 2019 (COVID-19)-naive individuals with PAD, anti-spike and RBD titers increase after mRNA vaccination but wane by 90 days. Those vaccinated after SARS-CoV-2 infection develop higher and more sustained responses comparable with healthy donors. Most vaccinated individuals with PAD have serum-neutralizing antibody titers above an estimated correlate of protection against ancestral SARS-CoV-2 and Delta virus but not against Omicron virus, although this is improved by boosting. Thus, some immunoglobulin replacement products likely have limited protective activity, and immunization and boosting of individuals with PAD with mRNA vaccines should confer at least short-term immunity against SARS-CoV-2 variants, including Omicron.


Subject(s)
COVID-19 , Immunologic Deficiency Syndromes , Viral Vaccines , Antibody Formation , COVID-19/prevention & control , Humans , SARS-CoV-2/genetics , Vaccines, Synthetic , Viral Vaccines/genetics , mRNA Vaccines
5.
BMC Infect Dis ; 22(1): 362, 2022 Apr 11.
Article in English | MEDLINE | ID: covidwho-1785144

ABSTRACT

BACKGROUND: The immune response to SARS-CoV-2 virus, the cause of COVID-19, is complex. Antibody mediated responses are important for viral clearance but may also drive hyperinflammation in severe COVID-19. We present a case of an individual with a genetic inability to produce antibodies and severe COVID-19, receiving no other specific anti-viral treatment than convalescent COVID-19 plasma, illustrating that hyperinflammation can occur in the absence of a humoral anti-viral response. In addition, the case illustrates that the assessment of SARS-CoV-2 T cell responses can facilitate clinical decision making in patients with COVID-19 and weak or absent humoral immune responses. CASE PRESENTATION: A male with X-linked agammaglobulinemia on regular immunoglobulin replacement therapy, hospitalized for 35 days due to severe COVID-19. Systemic inflammatory parameters were highly elevated. After treatment with convalescent COVID-19 plasma he became afebrile and the fatigue diminished. He was discharged on day 42 and nasopharyngeal SARS-CoV-2 PCR eventually was negative on day 49. Evidence of SARS-CoV-2 specific T cells prior to administration of plasma therapy suggested that antibodies were crucial for viral clearance. Regular assessment showed robust and persistent SARS-CoV-2 specific T-cell responses after recovery suggested that prophylactic administration of convalescent COVID-19 plasma was unnecessary. CONCLUSION: Assessment of SARS-CoV-2T-cell responses can facilitate the clinical management of COVID-19 patients with humoral immunodeficiencies.


Subject(s)
COVID-19 , Immunologic Deficiency Syndromes , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/therapy , Humans , Immunization, Passive , Male , SARS-CoV-2 , T-Lymphocytes
6.
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
8.
J Allergy Clin Immunol ; 149(2): 557-561.e1, 2022 02.
Article in English | MEDLINE | ID: covidwho-1670624

ABSTRACT

BACKGROUND: Patients with some types of immunodeficiency can experience chronic or relapsing infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This leads to morbidity and mortality, infection control challenges, and the risk of evolution of novel viral variants. The optimal treatment for chronic coronavirus disease 2019 (COVID-19) is unknown. OBJECTIVE: Our aim was to characterize a cohort of patients with chronic or relapsing COVID-19 disease and record treatment response. METHODS: We conducted a UK physician survey to collect data on underlying diagnosis and demographics, clinical features, and treatment response of immunodeficient patients with chronic (lasting ≥21 days) or relapsing (≥2 episodes) of COVID-19. RESULTS: We identified 31 patients (median age 49 years). Their underlying immunodeficiency was most commonly characterized by antibody deficiency with absent or profoundly reduced peripheral B-cell levels; prior anti-CD20 therapy, and X-linked agammaglobulinemia. Their clinical features of COVID-19 were similar to those of the general population, but their median duration of symptomatic disease was 64 days (maximum 300 days) and individual patients experienced up to 5 episodes of illness. Remdesivir monotherapy (including when given for prolonged courses of ≤20 days) was associated with sustained viral clearance in 7 of 23 clinical episodes (30.4%), whereas the combination of remdesivir with convalescent plasma or anti-SARS-CoV-2 mAbs resulted in viral clearance in 13 of 14 episodes (92.8%). Patients receiving no therapy did not clear SARS-CoV-2. CONCLUSIONS: COVID-19 can present as a chronic or relapsing disease in patients with antibody deficiency. Remdesivir monotherapy is frequently associated with treatment failure, but the combination of remdesivir with antibody-based therapeutics holds promise.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antibodies, Monoclonal/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/therapy , Immunologic Deficiency Syndromes/therapy , SARS-CoV-2/drug effects , Adenosine Monophosphate/therapeutic use , Adult , Aged , Aged, 80 and over , Alanine/therapeutic use , B-Lymphocytes/immunology , B-Lymphocytes/pathology , COVID-19/immunology , COVID-19/pathology , COVID-19/virology , Chronic Disease , Female , Humans , Immunization, Passive , Immunologic Deficiency Syndromes/immunology , Immunologic Deficiency Syndromes/pathology , Immunologic Deficiency Syndromes/virology , Lymphocyte Count , Male , Middle Aged , Recombinant Fusion Proteins/administration & dosage , Recurrence , SARS-CoV-2/pathogenicity , Treatment Failure
9.
J Am Soc Nephrol ; 33(2): 259-278, 2022 02.
Article in English | MEDLINE | ID: covidwho-1650730

ABSTRACT

Kidney disease is a known risk factor for poor outcomes of COVID-19 and many other serious infections. Conversely, infection is the second most common cause of death in patients with kidney disease. However, little is known about the underlying secondary immunodeficiency related to kidney disease (SIDKD). In contrast to cardiovascular disease related to kidney disease, which has triggered countless epidemiologic, clinical, and experimental research activities or interventional trials, investments in tracing, understanding, and therapeutically targeting SIDKD have been sparse. As a call for more awareness of SIDKD as an imminent unmet medical need that requires rigorous research activities at all levels, we review the epidemiology of SIDKD and the numerous aspects of the abnormal immunophenotype of patients with kidney disease. We propose a definition of SIDKD and discuss the pathogenic mechanisms of SIDKD known thus far, including more recent insights into the unexpected immunoregulatory roles of elevated levels of FGF23 and hyperuricemia and shifts in the secretome of the intestinal microbiota in kidney disease. As an ultimate goal, we should aim to develop therapeutics that can reduce mortality due to infections in patients with kidney disease by normalizing host defense to pathogens and immune responses to vaccines.


Subject(s)
COVID-19/etiology , Immunologic Deficiency Syndromes/etiology , Renal Insufficiency, Chronic/complications , Adaptive Immunity , Blood Platelets/immunology , COVID-19/immunology , COVID-19 Vaccines/immunology , Gastrointestinal Microbiome/immunology , Humans , Immunity, Innate , Immunologic Deficiency Syndromes/immunology , Immunologic Deficiency Syndromes/prevention & control , Immunophenotyping , Models, Immunological , Pandemics , Renal Insufficiency, Chronic/immunology , Risk Factors , SARS-CoV-2 , Seroconversion
10.
J Allergy Clin Immunol ; 149(2): 569-578, 2022 02.
Article in English | MEDLINE | ID: covidwho-1587444

ABSTRACT

Our understanding of risk factors and interventions influencing outcomes from coronavirus disease 2019 (COVID-19) has continued to evolve, revealing advances emerging from hypotheses formed at the start of the pandemic. Epidemiologic studies have shown that asthma control, rather than a diagnosis of asthma, is a determinant of COVID-19 severity. Clinical outcomes in patients with primary immunodeficiencies, even in those with impaired cellular immunity, are variable. IL-6 has emerged as a reliable biomarker of COVID-19 severity, and large clinical trials have shown the potential for improving outcomes through inhibition of IL-6 signaling in some patients. Studies of genetic risk factors for severe COVID-19 have also revealed the importance of interferon homeostasis in the defense against severe acute respiratory syndrome coronavirus 2. Because COVID-19 vaccines constitute the primary tool for ending this pandemic, strategies have been developed to address potential allergic and immune-mediated reactions. Here, we discuss advances in our understanding of COVID-19 risk factors and outcomes within the context of allergic and immunologic mechanisms.


Subject(s)
Antiviral Agents/therapeutic use , Asthma/therapy , Biological Products/therapeutic use , COVID-19/therapy , Immunologic Deficiency Syndromes/therapy , SARS-CoV-2/drug effects , Antibodies, Monoclonal/therapeutic use , Asthma/immunology , Asthma/mortality , Asthma/virology , Azetidines/therapeutic use , Biomarkers/metabolism , COVID-19/immunology , COVID-19/mortality , COVID-19/virology , COVID-19 Vaccines/administration & dosage , Humans , Immunologic Deficiency Syndromes/immunology , Immunologic Deficiency Syndromes/mortality , Immunologic Deficiency Syndromes/virology , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Interleukin-6/antagonists & inhibitors , Interleukin-6/genetics , Interleukin-6/immunology , Prognosis , Purines/therapeutic use , Pyrazoles/therapeutic use , Risk Factors , SARS-CoV-2/pathogenicity , Sulfonamides/therapeutic use , Survival Analysis , Treatment Outcome
11.
Curr Opin Pediatr ; 33(6): 657-675, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1546083

ABSTRACT

PURPOSE OF REVIEW: Primary immunodeficiency diseases (PIDs), also called inborn errors of immunity (IEI), are genetic disorders classically characterized by an increased susceptibility to infection and/or disruption in the regulation of an immunologic pathway. This review summarizes and highlights the new IEI disorders in the IUIS 2019 report and 2020 interim report and discusses the directions for the future management of PIDs. RECENT FINDINGS: Since 2017, the International Union of Immunologic Societies (IUIS) IEI committee has updated the IUIS classification of IEIs with 88 new gene defects and 75 new immune disorders. The increased utilization of genetic testing and advances in the strategic evaluation of genetic variants have identified, not only novel IEI disorders, but additional genetic causes for known IEI disorders. Investigation of potential immune susceptibilities during the ongoing COVID-19 pandemic suggests that defects in Type I interferon signalling may underlie more severe disease. SUMMARY: The rapid discovery of new IEIs reflects the growing trend of applying genetic testing modalities as part of medical diagnosis and management.In turn, elucidating the pathophysiology of these novel IEIs have enhanced our understanding of how genetic mutations can modulate the immune system and their consequential effect on human health and disease.


Subject(s)
COVID-19 , Immunologic Deficiency Syndromes , Primary Immunodeficiency Diseases , Humans , Immunologic Deficiency Syndromes/diagnosis , Immunologic Deficiency Syndromes/genetics , Immunologic Deficiency Syndromes/therapy , Pandemics , SARS-CoV-2
14.
J Allergy Clin Immunol ; 148(6): 1442-1450, 2021 12.
Article in English | MEDLINE | ID: covidwho-1474659

ABSTRACT

Recent advances in the field of inborn errors of immunity (IEIs) have been wide in scope, including progress in mechanisms of disease, diagnosis, and management. New gene defects affecting the immune response continue to be reported, as many as 26 in the year 2020. It was noted that the presentation of IEIs might not include recurrent infections in 9% of cases, and that current diagnostic methods can identify molecular causes in 92% of patients with severe combined immunodeficiency. Progress in immunopathogenesis explained mechanisms leading to symptoms of autosomal-recessive hyper-IgE syndrome. There was an emphasis on research in primary antibody deficiencies. The benefit of antibiotic prophylaxis to reduce the frequency of infections was demonstrated in these patients. The regimen of rituximab and azathioprine or mycophenolate was proven effective for chronic granulocytic interstitial pneumonia. The efficacy and adverse events of hematopoietic stem cell transplant in different IEI conditions were reported, as well as different strategies to improve outcomes, supporting its use in immunodeficiency and immunodysregulatory syndromes. The recent pandemic of coronavirus disease 2019 affected patients with IEIs, in particular those with deficiency in the interferon-mediated activation of the immune response. Initial data suggest that coronavirus disease 2019 vaccines might elicit anti-coronavirus disease 2019-neutralizing antibody responses in some patients with IEI conditions.


Subject(s)
COVID-19 , Genetic Diseases, Inborn , Immunologic Deficiency Syndromes , Primary Immunodeficiency Diseases , Humans , Metabolism, Inborn Errors , SARS-CoV-2
15.
J Clin Immunol ; 41(8): 1709-1722, 2021 11.
Article in English | MEDLINE | ID: covidwho-1474048

ABSTRACT

BACKGROUND: Data on immune responses to SARS-CoV-2 in patients with Primary Antibody Deficiencies (PAD) are limited to infected patients and to heterogeneous cohorts after immunization. METHODS: Forty-one patients with Common Variable Immune Deficiencies (CVID), six patients with X-linked Agammaglobulinemia (XLA), and 28 healthy age-matched controls (HD) were analyzed for anti-Spike and anti-receptor binding domain (RBD) antibody production, generation of Spike-specific memory B-cells, and Spike-specific T-cells before vaccination and one week after the second dose of BNT162b2 vaccine. RESULTS: The vaccine induced Spike-specific IgG and IgA antibody responses in all HD and in 20% of SARS-CoV-2 naive CVID patients. Anti-Spike IgG were detectable before vaccination in 4 out 7 CVID previously infected with SARS-CoV-2 and were boosted in six out of seven patients by the subsequent immunization raising higher levels than patients naïve to infection. While HD generated Spike-specific memory B-cells, and RBD-specific B-cells, CVID generated Spike-specific atypical B-cells, while RBD-specific B-cells were undetectable in all patients, indicating the incapability to generate this new specificity. Specific T-cell responses were evident in all HD and defective in 30% of CVID. All but one patient with XLA responded by specific T-cell only. CONCLUSION: In PAD patients, early atypical immune responses after BNT162b2 immunization occurred, possibly by extra-follicular or incomplete germinal center reactions. If these responses to vaccination might result in a partial protection from infection or reinfection is now unknown. Our data suggests that SARS-CoV-2 infection more effectively primes the immune response than the immunization alone, possibly suggesting the need for a third vaccine dose for patients not previously infected.


Subject(s)
Antibodies, Viral/blood , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunologic Deficiency Syndromes/immunology , SARS-CoV-2/immunology , Humans , Immunoglobulin G/blood , Immunologic Memory , Lymphocytes/immunology , Spike Glycoprotein, Coronavirus/immunology
16.
Signal Transduct Target Ther ; 6(1): 345, 2021 09 22.
Article in English | MEDLINE | ID: covidwho-1434094

ABSTRACT

The SARS-CoV-2 infection causes severe immune disruption. However, it is unclear if disrupted immune regulation still exists and pertains in recovered COVID-19 patients. In our study, we have characterized the immune phenotype of B cells from 15 recovered COVID-19 patients, and found that healthy controls and recovered patients had similar B-cell populations before and after BCR stimulation, but the frequencies of PBC in patients were significantly increased when compared to healthy controls before stimulation. However, the percentage of unswitched memory B cells was decreased in recovered patients but not changed in healthy controls upon BCR stimulation. Interestingly, we found that CD19 expression was significantly reduced in almost all the B-cell subsets in recovered patients. Moreover, the BCR signaling and early B-cell response were disrupted upon BCR stimulation. Mechanistically, we found that the reduced CD19 expression was caused by the dysregulation of cell metabolism. In conclusion, we found that SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolism, which may provide a new intervention target to cure COVID-19.


Subject(s)
Antigens, CD19/immunology , B-Lymphocytes/immunology , COVID-19/immunology , Down-Regulation/immunology , Immunologic Deficiency Syndromes/immunology , SARS-CoV-2/immunology , Animals , COVID-19/complications , Chlorocebus aethiops , Female , Humans , Immunologic Deficiency Syndromes/etiology , Immunologic Deficiency Syndromes/virology , Immunologic Memory , Male , Mice , Mice, Transgenic , Receptors, Antigen, B-Cell/immunology , Vero Cells
18.
Scand J Immunol ; 94(5): e13100, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1388399

ABSTRACT

The SARS-CoV-2 epidemic infections in Australia during 2020 were small in number in epidemiological terms and are well described. The SARS-CoV-2 genomic sequence data of many infected patients have been largely curated in a number of publicly available databases, including the corresponding epidemiological data made available by the Victorian Department of Health and Human Services. We have critically analysed the available SARS-CoV-2 haplotypes and genomic sequences in the context of putative deficits in innate immune APOBEC and ADAR deaminase anti-viral responses. It is now known that immune impaired elderly co-morbid patients display clear deficits in interferon type 1 (α/ß) and III (λ) stimulated innate immune gene cascades, of which APOBEC and ADAR induced expression are part. These deficiencies may help explain some of the clear genetic patterns in SARS-CoV-2 genomes isolated in Victoria, Australia, during the 2nd Wave (June-September, 2020). We tested the hypothesis that predicted lowered innate immune APOBEC and ADAR anti-viral deaminase responses in a significant proportion of elderly patients would be consistent with/reflected in a low level of observed mutagenesis in many isolated SARS-CoV-2 genomes. Our findings are consistent with this expectation. The analysis also supports the conclusions of the Victorian government's Department of Health that essentially one variant or haplotype infected Victorian aged care facilities where the great majority (79%) of all 820 SARS-CoV-2 associated deaths occurred. The implications of our data analysis for other localized epidemics and efficient coronavirus vaccine design and delivery are discussed.


Subject(s)
APOBEC Deaminases/genetics , Adenosine Deaminase/genetics , COVID-19 Vaccines/immunology , COVID-19/immunology , RNA-Binding Proteins/genetics , SARS-CoV-2/physiology , APOBEC Deaminases/metabolism , Adenosine Deaminase/metabolism , Age Factors , Aged, 80 and over , COVID-19/epidemiology , COVID-19/virology , Female , Gene Regulatory Networks , Haplotypes , Humans , Immunity, Innate , Immunologic Deficiency Syndromes , Interferon Type I/genetics , Male , RNA-Binding Proteins/metabolism , Victoria/epidemiology
19.
Front Immunol ; 12: 721738, 2021.
Article in English | MEDLINE | ID: covidwho-1378191

ABSTRACT

Here, we described the case of a B cell-deficient patient after CD19 CAR-T cell therapy for refractory B cell Non-Hodgkin Lymphoma with protracted coronavirus disease 2019 (COVID-19). For weeks, this patient only inefficiently contained the virus while convalescent plasma transfusion correlated with virus clearance. Interestingly, following convalescent plasma therapy natural killer cells matured and virus-specific T cells expanded, presumably allowing virus clearance and recovery from the disease. Our findings, thus, suggest that convalescent plasma therapy can activate cellular immune responses to clear SARS-CoV-2 infections. If confirmed in larger clinical studies, these data could be of general importance for the treatment of COVID-19 patients.


Subject(s)
B-Lymphocytes , COVID-19/immunology , COVID-19/therapy , Immunologic Deficiency Syndromes/immunology , Immunotherapy, Adoptive , Killer Cells, Natural/immunology , T-Lymphocytes/immunology , B-Lymphocytes/immunology , COVID-19/complications , Female , Humans , Immunization, Passive , Immunoglobulins, Intravenous , Immunologic Deficiency Syndromes/complications , Lymphocyte Activation , Lymphopoiesis , SARS-CoV-2 , Viral Load
20.
Allergy ; 77(1): 282-295, 2022 01.
Article in English | MEDLINE | ID: covidwho-1327507

ABSTRACT

BACKGROUND: Genetic deficiencies of immune system, referred to as inborn errors of immunity (IEI), serve as a valuable model to study human immune responses. In a multicenter prospective cohort, we evaluated the outcome of SARS-CoV-2 infection among IEI subjects and analyzed genetic and immune characteristics that determine adverse COVID-19 outcomes. METHODS: We studied 34 IEI patients (19M/15F, 12 [min: 0.6-max: 43] years) from six centers. We diagnosed COVID-19 infection by finding a positive SARS-CoV-2 PCR test (n = 25) and/or a lung tomography scoring (CORADS) ≥4 (n = 9). We recorded clinical and laboratory findings prospectively, fitted survival curves, and calculated fatality rates for the entire group and each IEI subclass. RESULTS: Nineteen patients had combined immune deficiency (CID), six with predominantly antibody deficiency (PAD), six immune dysregulation (ID), two innate immune defects, and one in the autoinflammatory class. Overall, 23.5% of cases died, with disproportionate fatality rates among different IEI categories. PAD group had a relatively favorable outcome at any age, but CIDs and IDs were particularly vulnerable. At admission, presence of dyspnea was an independent risk for COVID-related death (OR: 2.630, 95% CI; 1.198-5.776, p < .001). Concerning predictive roles of laboratory markers at admission, deceased subjects compared to survived had significantly higher CRP, procalcitonin, Troponin-T, ferritin, and total-lung-score (p = .020, p = .003, p = .014, p = .013, p = .020; respectively), and lower absolute lymphocyte count, albumin, and trough IgG (p = .012, p = .022, p = .011; respectively). CONCLUSION: Our data disclose a highly vulnerable IEI subgroup particularly disadvantaged for COVID-19 despite their youth. Future studies should address this vulnerability and consider giving priority to these subjects in SARS-Cov-2 therapy trials.


Subject(s)
COVID-19 , Immunologic Deficiency Syndromes , Primary Immunodeficiency Diseases , Adolescent , Humans , Prospective Studies , SARS-CoV-2
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