Outcome of SARS-CoV-2 Infection in 121 Patients with Inborn Errors of Immunity: A Cross-Sectional Study.

PURPOSE: There is still scarce data on SARS-CoV-2 infection in patients with Inborn Errors of Immunity (IEI) and many unresolved questions. We aimed to describe the clinical outcome of SARS-CoV-2 infection in Brazilian IEI patients and identify factors influencing the infection. METHODS: We did a cross-sectional, multicenter study that included patients of any age affected by IEI and SARS-CoV-2 infection. The variables studied were sex, age, type of IEI, comorbidities (number and type), treatment in use for IEI, clinical manifestations and severity of SARS-CoV-2 infection. RESULTS: 121 patients were included: 55.4% female, ages from six months to 74 yo (median age = 25.1 yo). Most patients had predominantly antibody deficiency (n = 53). The infection was mostly asymptomatic (n = 21) and mild (n = 66), and one child had multisystem inflammatory syndrome (MIS-C). We could not observe sex-related susceptibility, and there was a weak correlation between age and severity of infection. The number of comorbidities was higher in severe cases, particularly bronchiectasis and cardiopathy. There were no severe cases in hereditary angioedema patients. Six patients aged 2 to 74 years died, three of them with antibody deficiency. CONCLUSION: The outcome was mild in most patients, but the Case Fatality Ratio was higher than in the general population. However, the type of IEI was not a determining factor for severity, except for complement deficiencies linked to milder COVID-19. The severity of SARS-CoV-2 infection seems to be more related to older age, a higher number of comorbidities and type of comorbidities (bronchiectasis and cardiopathy).

Socialization During the COVID-19 Pandemic: The Role of Social and Scientific Networks During Social Distancing.

In the COVID-19 era, while we are encouraged to be physically far away from each other, social and scientific networking is needed more than ever. The dire consequences of social distancing can be diminished by social networking. Social media, a quintessential component of social networking, facilitates the dissemination of reliable information and fighting against misinformation by health authorities. Distance learning, telemedicine, and telehealth are among the most prominent applications of networking during this pandemic. Additionally, the COVID-19 pandemic highlights the importance of collaborative scientific efforts. In this chapter, we summarize the advantages of harnessing both social and scientific networking in minimizing the harms of this pandemic. We also discuss the extra collaborative measures we can take in our fight against COVID-19, particularly in the scientific field.

Laboratory diagnosis of COVID-19.

OBJECTIVES: This was a non-systematic review of the literature on the laboratory diagnosis of COVID-19. DATA SOURCES: Searches in PubMed and Google Scholar for articles made available in 2020, using the terms "diagnosis" OR "diagnostic" OR "diagnostic tests" OR "tests" AND "COVID-19" OR "SARS-CoV-2" in the title. SUMMARY OF FINDINGS: Tests for the etiological agent identify genetic material of SARS-CoV-2 or humoral responses to it. The gold standard for diagnosis is the identification of viral genome targets by real-time polymerase chain reaction (RT-PCR) in respiratory tract materials during the first week of symptoms. Serological tests should be indicated from the second week of symptoms onwards. A wide range of different tests is available, with variable sensitivity and specificity, most of which require validation. Laboratory tests such as complete blood count, C-reactive protein (CRP), D-dimer, clotting tests, lactic dehydrogenase (LDH), ferritin, and procalcitonin identify risk of disease with greater severity, thromboembolic complications, myocardial damage, and/or worse prognosis. Imaging tests may be useful for diagnosis, especially when there is a compatible clinical picture, and other tests presented negative results or were unavailable. CONCLUSIONS: The identification of genetic material of the virus by RT-PCR is the gold standard test, but its sensitivity is not satisfactory. The diagnosis of COVID-19 should be based on clinical data, epidemiological history, tests for etiological diagnosis, and tests to support the diagnosis of the disease and/or its complications. New diagnostic methods with higher sensitivity and specificity, as well as faster results, are necessary.

Auto-antibodies to type I IFNs can underlie adverse reactions to yellow fever live attenuated vaccine.

Yellow fever virus (YFV) live attenuated vaccine can, in rare cases, cause life-threatening disease, typically in patients with no previous history of severe viral illness. Autosomal recessive (AR) complete IFNAR1 deficiency was reported in one 12-yr-old patient. Here, we studied seven other previously healthy patients aged 13 to 80 yr with unexplained life-threatening YFV vaccine-associated disease. One 13-yr-old patient had AR complete IFNAR2 deficiency. Three other patients vaccinated at the ages of 47, 57, and 64 yr had high titers of circulating auto-Abs against at least 14 of the 17 individual type I IFNs. These antibodies were recently shown to underlie at least 10% of cases of life-threatening COVID-19 pneumonia. The auto-Abs were neutralizing in vitro, blocking the protective effect of IFN-α2 against YFV vaccine strains. AR IFNAR1 or IFNAR2 deficiency and neutralizing auto-Abs against type I IFNs thus accounted for more than half the cases of life-threatening YFV vaccine-associated disease studied here. Previously healthy subjects could be tested for both predispositions before anti-YFV vaccination.

BCG vaccine: Worrying proposal for COVID-19.

Bacille Calmette-Guérin (BCG) vaccine is proven to be effective in protecting against severe tuberculosis. It has been suggested to be able to exert a non-specific beneficial effect as protection against other infectious diseases. The duration of protection against tuberculosis is estimated to be from 10 to 15 years, but the duration of the protection against other infections is not known, maybe up to 20 years, maybe much shorter than that. We don't know it for sure. BCG induced trained immunity paradigm is based on experimental models, cohort studies with low number of individuals, and some epidemiological data in which other possible interfering factors are not controlled. The titles and scopes of scientific articles should be cautiously considered as they can promote indications of getting vaccinated or revaccinated with BCG, before its effectiveness is confirmed and recommendations are published. Besides, revaccination with BCG can put at serious risk patients with primary or secondary immunodeficiency. Maybe BCG vaccine is effective in preventing COVID-19 deaths or reducing its severity, but may the effect of this vaccine be relevant even with poor health politics and assistance? It is very difficult to compare the epidemiologic data about COVID-19 in different countries. There are countless factors, mainly social and related to the healthcare system, which can be more decisive than the hypothesis of trained immunity induced by BCG. Until now, we can say that BCG's protective role is, at least, insufficient, given many other factors that corroborate SARS-CoV-2 infection and/or its severity.

Immunity and inflammatory biomarkers in COVID-19: A systematic review.

Coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Patients can be asymptomatic or present respiratory and gastrointestinal symptoms, and even multiple-organ failure which can lead to death. The balance between an effective antiviral response and dysregulated immune response is the key factor determining the severity of COVID-19 progression. A systematic review was performed using the NCBI-PubMed database to find the articles related to COVID-19 immunity and inflammatory response published from 1 December 2019 to 15 April 2020. Haematological, immunological and biochemical parameters were extracted and correlated with disease severity, age and presence of comorbidities. Twelve articles were analysed comprising a total of 1042 hospitalized patients infected with SARS-CoV-2 and 95 different parameters. Total lymphocyte count and levels of CD3+ and CD4+ T cells were decreased in severe and critical cases. Neutrophilia was found in patients who progressed to acute respiratory distress syndrome (ARDS). Interleukin-six (IL-6) was high in mild and severe patients regardless of comorbidities. Erythrocyte sedimentation rate (ESR) and count and C-reactive protein (CRP) levels were increased regardless of disease severity or presence of comorbidities. High levels of D-dimer and lactate dehydrogenase were present in diabetic patients and patients who developed ARDS. Procalcitonin levels were elevated to varying degrees in severe and critical patients. We conclude that the total lymphocyte count, CD3+ and CD4+ T cells are low, especially in severe and critical COVID-19 patients; ESR, CRP and IL-6 were elevated, independent of the severity of disease. Understanding the inflammatory response of COVID-19 patients is essential for the development of better therapeutic and management strategies.

All together to Fight COVID-19.

Novel coronavirus disease (COVID-19), named a pandemic by the WHO, is the current global health crisis. National and international collaboration are indispensable for combating COVID-19 and other similar potential outbreaks. International efforts to tackle this complex problem have led to remarkable scientific advances. Yet, as a global society, we can and must take additional measures to fight this pandemic. Undoubtedly, our approach toward COVID-19 was not perfect, and testing has not been deployed fast enough to arrest the epidemic early on. It is critical that we revise our approaches to be more prepared for pandemics as a united body by promoting global cooperation and commitment.