Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease 2019 (COVID-19), has already infected over 200 million individuals and claimed at least 2 million lives. Global presentation of this infection varied with different individuals, different geographical regions, different genders, age groups, and comorbidities, while its severity level ranged from asymptomatic infection to life-threatening disease. The observed difference in the immune response to SARS-COV-2 could be due to variation in one of more of host factors including the genetic make-up, immune system age, and immune-metabolic balance.
Moreover, Inborn errors of immunity (IEI) are classified as rare diseases and cause a vulnerability to infections by bacteria, viruses, fungi, and protozoa. Consequently, IEI patients are considered a priori to be a population at risk of developing severe coronavirus disease 2019. There is uncertainty about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in individuals with IEI. This is relevant not only for these patients but also for the general population. Indeed, studies on IEIs can reveal key immunity requirements since these patients can be considered as human Knock Out models for genes involved in host defense.
COVID-19 pathogenesis is characterized by pounced inflammation, muted interferon and antiviral immunity, ineffective viral clearance, T cell exhaustion, and delayed adaptive response. This immune imbalance is exaggerated in immunocompromised patients, aged patients with higher levels of immunosenescent, and those with cardio-metabolic-associated inflammation and pre-mature immune aging. Moreover, viral immune derangement could lead to loss of tolerance to self-peptide and result in triggering pre-existing or de-novo autoimmune diseases.
Besides the known at-risk groups, the additional otherwise healthy group was found to have variability in response to SARS-COV-2 infection ranging from asymptomatic presentation to an exaggerated infection leading to ICU admission and death outcomes. Further studies have associated severe infection to genetic defects in interferon production, while others with intact interferon production were found to have neutralizing autoantibodies against these interferons; early interferon treatment has shown promising outcomes in these patients.
Understanding the genetic basis and molecular mechanism underpinning the immunity predisposing to severe infection could guide toward more effective personalized treatment, and potentially pave the way for novel therapeutic interventions.
Moreover, the pandemic crisis has also influenced the clinical management of subjects living with IEI. Strategies to protect IEI patients are not clear since SARSCov2 vaccines may not work for patients with IEIs. Due to the immune defect, many patients cannot react to vaccine antigens and will not develop protective T and/or B cell immunity. Proposed alternative strategies may include monoclonal or polyclonal antibodies against SARSCov2 or polyvalent immunoglobulins containing protective antibodies against the virus.
We welcome submissions of Original Research, Review, and Mini Review related to immune dysregulation predisposing to severe infection, including but not limited to:
• Immune checkpoint dysregulation during SARS-CoV-2 infection
• Inborn error of immunity and their contribution to COVID-19 pathogenesis.
• De-novo or pre-existing autoantibody reactivities during COVID-19
• Summarizing updated clinical and immunological features of SARS-Cov2 infections in IEIs.
• Characterize response of IEI patients to COVID19 vaccines.
• Summarizing therapeutical approach of COVID-19 in IEIs, including mechanism and therapeutics of monoclonal antibodies
• Immuno-metabolic dysregulation predisposing to severe COVID19.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease 2019 (COVID-19), has already infected over 200 million individuals and claimed at least 2 million lives. Global presentation of this infection varied with different individuals, different geographical regions, different genders, age groups, and comorbidities, while its severity level ranged from asymptomatic infection to life-threatening disease. The observed difference in the immune response to SARS-COV-2 could be due to variation in one of more of host factors including the genetic make-up, immune system age, and immune-metabolic balance.
Moreover, Inborn errors of immunity (IEI) are classified as rare diseases and cause a vulnerability to infections by bacteria, viruses, fungi, and protozoa. Consequently, IEI patients are considered a priori to be a population at risk of developing severe coronavirus disease 2019. There is uncertainty about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in individuals with IEI. This is relevant not only for these patients but also for the general population. Indeed, studies on IEIs can reveal key immunity requirements since these patients can be considered as human Knock Out models for genes involved in host defense.
COVID-19 pathogenesis is characterized by pounced inflammation, muted interferon and antiviral immunity, ineffective viral clearance, T cell exhaustion, and delayed adaptive response. This immune imbalance is exaggerated in immunocompromised patients, aged patients with higher levels of immunosenescent, and those with cardio-metabolic-associated inflammation and pre-mature immune aging. Moreover, viral immune derangement could lead to loss of tolerance to self-peptide and result in triggering pre-existing or de-novo autoimmune diseases.
Besides the known at-risk groups, the additional otherwise healthy group was found to have variability in response to SARS-COV-2 infection ranging from asymptomatic presentation to an exaggerated infection leading to ICU admission and death outcomes. Further studies have associated severe infection to genetic defects in interferon production, while others with intact interferon production were found to have neutralizing autoantibodies against these interferons; early interferon treatment has shown promising outcomes in these patients.
Understanding the genetic basis and molecular mechanism underpinning the immunity predisposing to severe infection could guide toward more effective personalized treatment, and potentially pave the way for novel therapeutic interventions.
Moreover, the pandemic crisis has also influenced the clinical management of subjects living with IEI. Strategies to protect IEI patients are not clear since SARSCov2 vaccines may not work for patients with IEIs. Due to the immune defect, many patients cannot react to vaccine antigens and will not develop protective T and/or B cell immunity. Proposed alternative strategies may include monoclonal or polyclonal antibodies against SARSCov2 or polyvalent immunoglobulins containing protective antibodies against the virus.
We welcome submissions of Original Research, Review, and Mini Review related to immune dysregulation predisposing to severe infection, including but not limited to:
• Immune checkpoint dysregulation during SARS-CoV-2 infection
• Inborn error of immunity and their contribution to COVID-19 pathogenesis.
• De-novo or pre-existing autoantibody reactivities during COVID-19
• Summarizing updated clinical and immunological features of SARS-Cov2 infections in IEIs.
• Characterize response of IEI patients to COVID19 vaccines.
• Summarizing therapeutical approach of COVID-19 in IEIs, including mechanism and therapeutics of monoclonal antibodies
• Immuno-metabolic dysregulation predisposing to severe COVID19.