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2.
Clin Immunol ; 230: 108821, 2021 09.
Article in English | MEDLINE | ID: covidwho-1525729

ABSTRACT

BACKGROUND: Information regarding inborn error of immunity (IEI) as a risk factor for severe COVID-19 is scarce. We aimed to determine if paediatric patients with moderate/severe IEI got COVID-19 at the same level as the general population, and to describe COVID-19 expression. MATERIAL AND METHODS: We included patients with moderate/severe IEI aged 0-21 years old: cross-sectional study (June2020) to determine the prevalence of COVID-19; prospective study (January2020-January2021) including IEI patients with COVID-19. Assays used: nasopharyngeal swab SARS-CoV-2 PCR and SARS-CoV-2-specific immunoglobulins. RESULTS: Seven from sixty-five patients tested positive (prevalence: 10.7% (7%-13%)) after the first SARS-COV-2 wave and 13/15 patients diagnosed with COVID-19 had an asymptomatic/mild course. CONCLUSIONS: In our area, prevalence of COVID-19 in moderate/severe IEI paediatric patients after the first wave was slightly higher than in the general population. The majority of patients presented a benign course, suggesting a possible protective factor related with age despite IEI.


Subject(s)
COVID-19/complications , Primary Immunodeficiency Diseases/complications , SARS-CoV-2 , Adolescent , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Infant , Male , Prevalence , Young Adult
3.
Cells ; 10(11)2021 10 27.
Article in English | MEDLINE | ID: covidwho-1488494

ABSTRACT

BACKGROUND: Patients with primary antibody deficiencies are at risk in the current COVID-19 pandemic due to their impaired response to infection and vaccination. Specifically, patients with common variable immunodeficiency (CVID) generated poor spike-specific antibody and T cell responses after immunization. METHODS: Thirty-four CVID convalescent patients after SARS-CoV-2 infection, 38 CVID patients immunized with two doses of the BNT162b2 vaccine, and 20 SARS-CoV-2 CVID convalescents later and immunized with BNT162b2 were analyzed for the anti-spike IgG production and the generation of spike-specific memory B cells and T cells. RESULTS: Spike-specific IgG was induced more frequently after infection than after vaccination (82% vs. 34%). The antibody response was boosted in convalescents by vaccination. Although immunized patients generated atypical memory B cells possibly by extra-follicular or incomplete germinal center reactions, convalescents responded to infection by generating spike-specific memory B cells that were improved by the subsequent immunization. Poor spike-specific T cell responses were measured independently from the immunological challenge. CONCLUSIONS: SARS-CoV-2 infection primed a more efficient classical memory B cell response, whereas the BNT162b2 vaccine induced non-canonical B cell responses in CVID. Natural infection responses were boosted by subsequent immunization, suggesting the possibility to further stimulate the immune response by additional vaccine doses in CVID.


Subject(s)
/immunology , COVID-19/immunology , Primary Immunodeficiency Diseases/immunology , SARS-CoV-2/immunology , Adult , Antibodies, Viral/immunology , COVID-19/complications , COVID-19/prevention & control , Convalescence , Female , Humans , Immunization , Immunoglobulin G/immunology , Male , Middle Aged , Primary Immunodeficiency Diseases/complications , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes/immunology
4.
Curr Opin Allergy Clin Immunol ; 21(6): 545-552, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1429315

ABSTRACT

PURPOSE OF REVIEW: Antisevere acute respiratory syndrome-corona virus 2 (SARS-CoV-2) vaccines may provide prompt, effective, and safe solution for the COVID-19 pandemic. Several vaccine candidates have been evaluated in randomized clinical trials (RCTs). Furthermore, data from observational studies mimicking real-life practice and studies on specific groups, such as pregnant women or immunocompromised patients who were excluded from RCTs, are currently available. The main aim of the review is to summarize and provide an immunologist's view on mechanism of action, efficacy and safety, and future challenges in vaccination against SARS-CoV-2. RECENT FINDINGS: mRNA and recombinant viral vector-based vaccines have been approved for conditional use in Europe and the USA. They show robust humoral and cellular responses, high with efficacy in prevention of COVID-19 infection (66.9 95%) and favorable safety profile in RCTs. High efficacy of 80-92% was observed in real-life practice. A pilot study also confirmed good safety profile of the mRNA vaccines in pregnant women. Unlike in those with secondary immunodeficiencies where postvaccination responses did not occur, encouraging results were obtained in patients with inborn errors of immunity. SUMMARY: Although both RCTs and observational studies suggest good efficacy and safety profiles of the vaccines, their long-term efficacy and safety are still being discussed. Despite the promising results, clinical evidence for specific groups such as children, pregnant and breastfeeding women, and immunocompromised patients, and for novel virus variants are lacking. VIDEO ABSTRACT: http://links.lww.com/COAI/A21.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Pandemics/prevention & control , Primary Immunodeficiency Diseases/immunology , SARS-CoV-2/immunology , COVID-19/epidemiology , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/adverse effects , Humans , Immunocompromised Host , Observational Studies as Topic , Pilot Projects , Primary Immunodeficiency Diseases/complications , Primary Immunodeficiency Diseases/genetics , Treatment Outcome , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/adverse effects
5.
Curr Opin Allergy Clin Immunol ; 21(6): 515-524, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1398151

ABSTRACT

PURPOSE OF REVIEW: The severe acute respiratory syndrome (SARS)-coronavirus 2 (CoV2)/COVID-19 pandemic has reminded us of the fundamental and nonredundant role played by the innate and adaptive immune systems in host defense against emerging pathogens. The study of rare 'experiments of nature' in the setting of inborn errors of immunity (IEI) caused by monogenic germline variants has revealed key insights into the molecular and cellular requirements for immune-mediated protection against infectious diseases. This review will provide an overview of the discoveries obtained from investigating severe COVID-19 in patients with defined IEI or otherwise healthy individuals. RECENT FINDINGS: Genetic, serological and cohort studies have provided key findings regarding host defense against SARS-CoV2 infection, and mechanisms of disease pathogenesis. Remarkably, the risk factors, severity of disease, and case fatality rate following SARS-CoV2 infection in patients with IEI were not too dissimilar to that observed for the general population. However, the type I interferon (IFN) signaling pathway - activated in innate immune cells in response to viral sensing - is critical for anti-SARS-CoV2 immunity. Indeed, genetic variants or autoAbs affecting type I IFN function account for up to 20% of all cases of life-threatening COVID-19. SUMMARY: The analysis of rare cases of severe COVID-19, coupled with assessing the impact of SARS-CoV2 infection in individuals with previously diagnosed IEI, has revealed fundamental aspects of human immunology, disease pathogenesis and immunopathology in the context of exposure to and infection with a novel pathogen. These findings can be leveraged to improve therapies for treating for emerging and established infectious diseases.


Subject(s)
COVID-19/immunology , Host-Pathogen Interactions/genetics , Primary Immunodeficiency Diseases/immunology , SARS-CoV-2/immunology , COVID-19/diagnosis , COVID-19/mortality , COVID-19/virology , Host-Pathogen Interactions/immunology , Humans , Primary Immunodeficiency Diseases/complications , Primary Immunodeficiency Diseases/genetics , Risk Factors , Severity of Illness Index
6.
J Allergy Clin Immunol ; 148(3): 739-749, 2021 09.
Article in English | MEDLINE | ID: covidwho-1253079

ABSTRACT

BACKGROUND: In mid-December 2020, Israel started a nationwide mass vaccination campaign against coronavirus disease 2019 (COVID-19). In the first few weeks, medical personnel, elderly citizens, and patients with chronic diseases were prioritized. As such, patients with primary and secondary immunodeficiencies were encouraged to receive the vaccine. Although the efficacy of RNA-based COVID-19 vaccines has been demonstrated in the general population, little is known about their efficacy and safety in patients with inborn errors of immunity (IEI). OBJECTIVE: Our aim was to evaluate the humoral and cellular immune response to COVID-19 vaccine in a cohort of patients with IEI. METHODS: A total of 26 adult patients were enrolled, and plasma and peripheral blood mononuclear cells were collected from them 2 weeks following the second dose of Pfizer-BioNTech COVID-19 vaccine. Humoral response was evaluated by testing anti-SARS-CoV-2 spike (S) receptor-binding domain and antinucleocapsid antibody titers and evaluating neutralizing ability by inhibition of receptor-binding domain-angiotensin-converting enzyme 2 binding. Cellular immune response was evaluated by using ELISpot, estimating IL-2 and IFN-γ secretion in response to pooled SARS-CoV-2 S- or M-peptides. RESULTS: Our cohort included 18 patients with a predominantly antibody deficiency, 2 with combined immunodeficiency, 3 with immune dysregulation, and 3 with other genetically defined diagnoses. Twenty-two of them were receiving immunoglobulin replacement therapy. Of the 26 patients, 18 developed specific antibody response, and 19 showed S-peptide-specific T-cell response. None of the patients reported significant adverse events. CONCLUSION: Vaccinating patients with IEI is safe, and most patients were able to develop vaccine-specific antibody response, S-protein-specific cellular response, or both.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunogenicity, Vaccine , Primary Immunodeficiency Diseases/complications , Adult , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/etiology , COVID-19/virology , Disease Susceptibility , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunity, Cellular , Male , Middle Aged , Primary Immunodeficiency Diseases/genetics , SARS-CoV-2/immunology , Young Adult
9.
J Infect Dis ; 223(1): 23-27, 2021 01 04.
Article in English | MEDLINE | ID: covidwho-1066344

ABSTRACT

We describe a case of chronic coronavirus disease 2019 (COVID-19) in a patient with lymphoma and associated B-cell immunodeficiency. Viral cultures and sequence analysis demonstrate ongoing replication of infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for at least 119 days. The patient had 3 admissions related to COVID-19 over a 4-month period and was treated twice with remdesivir and convalescent plasma with resolution of symptoms. The patient's lack of seroconversion and prolonged course illustrate the importance of humoral immunity in resolving SARS-CoV-2 infection. This case highlights challenges in managing immunocompromised hosts, who may act as persistent shedders and sources of transmission.


Subject(s)
COVID-19/virology , SARS-CoV-2/physiology , Virus Replication , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Antibodies, Viral/blood , COVID-19/diagnosis , Hospitalization , Humans , Immunity, Humoral , Immunocompromised Host , Lymphoma, Mantle-Cell/complications , Male , Middle Aged , Primary Immunodeficiency Diseases/complications , Seroconversion
10.
Front Immunol ; 11: 614086, 2020.
Article in English | MEDLINE | ID: covidwho-1058417

ABSTRACT

In the last few months the world has witnessed a global pandemic due to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection causing coronavirus disease 2019 (COVID-19). Obviously, this pandemic affected individuals differently, with a significant impact on populations considered to be at high-risk. One such population, was assumed to be patients with primary genetic defect involving components or pathways of the immune system. While human immunity against COVID-19 is not fully understood, it is, so far, well documented, that both adaptive and innate cells have a critical role in protection against SARS-CoV-2. Here, we aimed to summarize the clinical and laboratory data on primary immunodeficiency (PID) patients in Israel, who were tested positive for SARS-CoV-2, in order to estimate the impact of COVID-19 on such patients. Data was collected from mid-February to end-September. During this time Israel experienced two "waves" of COVID-19 diseases; the first, from mid-February to mid-May and the second from mid-June and still ongoing at the end of data collection. A total of 20 PID patients, aged 4 months to 60 years, were tested positive for SARS-CoV-2, all but one, were detected during the second wave. Fourteen of the patients were on routine monthly IVIG replacement therapy at the time of virus detection. None of the patients displayed severe illness and none required hospitalization; moreover, 7/20 patients were completely asymptomatic. Possible explanations for the minimal clinical impact of COVID-19 pandemic observed in our PID patients include high level of awareness, extra-precautions, and even self-isolation. It is also possible that only specific immune pathways (e.g. type I interferon signaling), may increase the risk for a more severe course of disease and these are not affected in many of the PID patients. In some cases, lack of an immune response actually may be a protective measure against the development of COVID-19 sequelae.


Subject(s)
COVID-19/complications , COVID-19/epidemiology , Primary Immunodeficiency Diseases/complications , Primary Immunodeficiency Diseases/epidemiology , SARS-CoV-2 , Adolescent , Adult , Child , Child, Preschool , Female , Health Impact Assessment , Humans , Infant , Israel/epidemiology , Male , Middle Aged , Public Health Surveillance , Young Adult
11.
Hematology Am Soc Hematol Educ Program ; 2020(1): 328-335, 2020 12 04.
Article in English | MEDLINE | ID: covidwho-1024352

ABSTRACT

An estimated 1 million people in the United States have functional or anatomic asplenia or hyposplenia. Infectious complications due to encapsulated organisms such as Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae can lead to fulminant sepsis and death, particularly in young children, in the period shortly after splenectomy, and in immunocompromised patients. Patients with asplenia are also at risk for less common infections due to Capnocytophaga, Babesia, and malaria. Antibiotic prophylaxis, vaccines, and patient and family education are the mainstays of prevention in these at-risk patients. Recommendations for antibiotic prophylaxis typically target high-risk periods, such as 1 to 3 years after splenectomy, children ≤5 years of age, or patients with concomitant immunocompromise. However, the risk for sepsis is lifelong, with infections occurring as late as 40 years after splenectomy. Currently available vaccines recommended for patients with asplenia include pneumococcal vaccines (13-valent pneumococcal conjugate vaccine followed by the 23-valent pneumococcal polysaccharide vaccine), meningococcal vaccines (meningococcal conjugate vaccines for serogroups A, C, Y and W-135 and serogroup B meningococcal vaccines), H. influenzae type b vaccines, and inactivated influenza vaccines. Ongoing booster doses are also recommended for pneumococcal and meningococcal vaccines to maintain protection. Despite the availability of prevention tools, adherence is often a challenge. Dedicated teams or clinics focused on patient education and monitoring have demonstrated substantial improvements in vaccine coverage rates for individuals with asplenia and reduced risk of infection. Future efforts to monitor the quality of care in patients with asplenia may be important to bridge the know-do gap in this high-risk population.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Infection Control , Infections/etiology , Primary Immunodeficiency Diseases/complications , Spleen/abnormalities , Vaccination , Adult , Bacterial Capsules , Bacterial Infections/chemically induced , Bacterial Infections/prevention & control , Child , Haemophilus Vaccines/therapeutic use , Humans , Meningococcal Vaccines/therapeutic use , Pneumococcal Vaccines/therapeutic use , Primary Immunodeficiency Diseases/pathology , Spleen/pathology , Splenectomy/adverse effects
13.
J Interferon Cytokine Res ; 40(12): 549-554, 2020 12.
Article in English | MEDLINE | ID: covidwho-990532

ABSTRACT

Coronavirus disease 2019 (COVID-19) has spread rapidly and become a pandemic. Caused by a novel human coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), severe COVID-19 is characterized by cytokine storm syndromes due to innate immune activation. Primary immunodeficiency (PID) cases represent a special patient population whose impaired immune system might make them susceptible to severe infections, posing a higher risk to COVID-19, but this could also lead to suppressed inflammatory responses and cytokine storm. It remains an open question as to whether the impaired immune system constitutes a predisposing or protective factor for PID patients when facing SARS-CoV-2 infection. After literature review, it was found that, similar to other patient populations with different comorbidities, PID patients may be susceptible to SARS-CoV-2 infection. Their varied immune status, however, may lead to different disease severity and outcomes after SARS-CoV-2 infection. PID patients with deficiency in antiviral innate immune signaling [eg, Toll-like receptor (TLR)3, TLR7, or interferon regulatory factor 7 (IRF7)] or interferon signaling (IFNAR2) may be linked to severe COVID-19. Because of its anti-infection, anti-inflammatory, and immunomodulatory effects, routine intravenous immunoglobulin therapy may provide some protective effects to the PID patients.


Subject(s)
COVID-19/complications , COVID-19/immunology , Immune System , Inflammation , Primary Immunodeficiency Diseases/complications , Primary Immunodeficiency Diseases/immunology , Comorbidity , Disease Susceptibility , Humans , Immunity, Innate , Immunoglobulins, Intravenous/metabolism , Interferon Regulatory Factor-7/metabolism , Pandemics , Receptor, Interferon alpha-beta/metabolism , Risk , Toll-Like Receptor 3/metabolism , Toll-Like Receptor 7/metabolism
14.
J Clin Immunol ; 41(2): 345-355, 2021 02.
Article in English | MEDLINE | ID: covidwho-954575

ABSTRACT

Although it is estimated that COVID-19 life-threatening conditions may be diagnosed in less than 1:1000 infected individuals below the age of 50, but the real impact of this pandemic on pediatric patients with different types of primary immunodeficiency (PID) is not elucidated. The current prospective study on a national registry of PID patients showed that with only 1.23 folds higher incidence of infections, these patients present a 10-folds higher mortality rate compared to population mainly in patients with combined immunodeficiency and immune dysregulation. Therefore, further management modalities against COVID-19 should be considered to improve the survival rate in these two PID entities using hematopoietic stem cell transplantation and immunomodulatory agents.


Subject(s)
COVID-19/complications , COVID-19/epidemiology , Health Impact Assessment , Primary Immunodeficiency Diseases/complications , Primary Immunodeficiency Diseases/epidemiology , SARS-CoV-2 , COVID-19/diagnosis , COVID-19/virology , Child, Preschool , Clinical Decision-Making , Comorbidity , Disease Management , Female , Humans , Infant , Male , Mortality , Primary Immunodeficiency Diseases/diagnosis , Public Health Surveillance , Severity of Illness Index
15.
Int J Med Sci ; 17(18): 2974-2986, 2020.
Article in English | MEDLINE | ID: covidwho-902898

ABSTRACT

In the ongoing COVID-19 pandemic, all COVID-19 patients are naïve patients as it is the first-time humans have been exposed to the SARS-CoV-2 virus. As with exposure to many viruses, individuals with pre-existing, compromised immune systems may be at increased risk of developing severe symptoms and/or dying because of (SARS-CoV-2) infection. To learn more about such individuals, we conducted a search and review of published reports on the clinical characteristics and outcomes of COVID-19 patients with pre-existing, compromised immune systems. Here we present our review of patients who possess pre-existing primary antibody deficiency (PAD) and those who are organ transplant recipients on maintenance immunosuppressants. Our review indicates different clinical outcomes for the patients with pre-existing PAD, depending on the underlying causes. For organ transplant recipients, drug-induced immune suppression alone does not appear to enhance COVID-19 mortality risk - rather, advanced age, comorbidities, and the development of secondary complications appears required.


Subject(s)
Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Immune System Diseases/complications , Immune System Diseases/diagnosis , Immunocompromised Host , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Betacoronavirus/immunology , Betacoronavirus/physiology , COVID-19 , Comorbidity , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Humans , Immunocompromised Host/immunology , Immunosuppressive Agents/therapeutic use , Mortality , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Primary Immunodeficiency Diseases/complications , Primary Immunodeficiency Diseases/diagnosis , Primary Immunodeficiency Diseases/immunology , Primary Immunodeficiency Diseases/mortality , Prognosis , SARS-CoV-2 , Transplant Recipients/statistics & numerical data
16.
J Infect Dis ; 223(1): 23-27, 2021 01 04.
Article in English | MEDLINE | ID: covidwho-889568

ABSTRACT

We describe a case of chronic coronavirus disease 2019 (COVID-19) in a patient with lymphoma and associated B-cell immunodeficiency. Viral cultures and sequence analysis demonstrate ongoing replication of infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for at least 119 days. The patient had 3 admissions related to COVID-19 over a 4-month period and was treated twice with remdesivir and convalescent plasma with resolution of symptoms. The patient's lack of seroconversion and prolonged course illustrate the importance of humoral immunity in resolving SARS-CoV-2 infection. This case highlights challenges in managing immunocompromised hosts, who may act as persistent shedders and sources of transmission.


Subject(s)
COVID-19/virology , SARS-CoV-2/physiology , Virus Replication , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Antibodies, Viral/blood , COVID-19/diagnosis , Hospitalization , Humans , Immunity, Humoral , Immunocompromised Host , Lymphoma, Mantle-Cell/complications , Male , Middle Aged , Primary Immunodeficiency Diseases/complications , Seroconversion
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