Rare predicted loss-of-function variants of type I IFN immunity genes are associated with critical COVID-19

BackgroundWe previously reported inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity in 1-5% of unvaccinated patients with life-threatening COVID-19, and auto-antibodies against type I IFN in another 15-20% of cases. MethodsWe report here a genome-wide rare variant burden association analysis in 3,269 unvaccinated patients with life-threatening COVID-19 (1,301 previously reported and 1,968 new patients), and 1,373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. A quarter of the patients tested had antibodies against type I IFN (234 of 928) and were excluded from the analysis. ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI:1.5-528.7, P=1.1x10-4), in analyses restricted to biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70 [95%CI:1.3-8.2], P=2.1x10-4). Adding the recently reported TYK2 COVID-19 locus strengthened this enrichment, particularly under a recessive model (OR=19.65 [95%CI:2.1-2635.4]; P=3.4x10-3). When these 14 loci and TLR7 were considered, all individuals hemizygous (n=20) or homozygous (n=5) for pLOF or bLOF variants were patients (OR=39.19 [95%CI:5.2-5037.0], P=4.7x10-7), who also showed an enrichment in heterozygous variants (OR=2.36 [95%CI:1.0-5.9], P=0.02). Finally, the patients with pLOF or bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10-5). ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.

The course of COVID-19 in patients with chronic spontaneous urticaria receiving omalizumab treatment

IntroductionAlthough there are case reports and guideline recommendations that states omalizumab can be used in chronic spontaneous urticaria (CSU) patients during SARS-CoV-2 pandemic, there are scarce studies showing the course of Coronavirus disease 2019 (COVID-19) in CSU patients receiving omalizumab. Materials and MethodsA total of 370 patients with chronic urticaria were included in the study between June 2020 and December 31, 2020. ResultsSixty patients (16.2%) became infected with the SARS-CoV-2. The rate of pneumonia and hospitalization were 4.1% and 1.9%. There was no significant difference was determined between the CSU patients with omalizumab treatment and the non-receivers in regard to the rate of SARS-CoV-2 (+) (p: 0.567) and in regard to the rate of SARS-CoV-2 related pneumonia and hospitalization (p: 0.331 and p: 0.690). Gender, duration of CSU, serum IgE levels, omalizumab treatment, and atopy were not found to be associated with an increased risk for SARS-CoV-2 positivity in patients with CSU. ConclusionOur study shows that the use of omalizumab does not increase the risk of COVID-19 infection, COVID-19-related pneumonia and hospitalizations in CSU patients and supports the views that omalizumab can be used safely in patients with CSU during the COVID-19 pandemic.

Are high urea values before intravenous immunoglobulin replacement a risk factor for COVID-related mortality?

ObjectiveSince the World Health Organization accepted The Coronavirus Disease 2019 (COVID-19) as a pandemic and there is still no effective treatment, it becomes crucial that the physicians interested in COVID-19 treatment share all the data they acquire, particularly in vulnerable patient groups, to reduce morbidity and mortality. MethodsThe study included 81 adult (Female: 27, Male: 54) COVID-19 patients who were hospitalized for the treatment of COVID-19 between April 2020 and September 2020 and were followed-up, treated and consulted in the immunology clinic for intravenous immunoglobulin (IVIG) treatment. ResultsThe univariate analysis found that the number of days of hospitalization in service, being intubated, number of IVIG treatment days, and the urea value before IVIG treatment were independent risk factors for mortality (p:0.043, p:0.001, p:0.074, p:0.004, respectively). As a result of multivariate analysis, being intubated and urea value before IVIG treatment were found to be independent risk factors for mortality (p:0.001 and p:0.009). It was found that for 60 mg/dL level of urea value before IVIG treatment, the sensitivity value for mortality in COVID-19 patients was 46.2%, and the specificity was 35.5% (p:0.029) ConclusionThe study found that urea values before IVIG treatment were a risk factor for mortality in patients who received IVIG treatment for COVID-19. This is important as it indicates that BUN values should be closely monitored in patients given IVIG treatment for COVID-19. It also suggests that when resources are limited and risk stratification is required in COVID-19 patients, BUN values can be helpful.

The course of COVID-19 in allergic rhinitis patients receiving allergen-specific immunotherapy

IntroductionThe aims of presenting study were trying to expose the course of SARS-CoV-2 (severe acute respiratory syndrome-related coronavirus) in patients with allergic rhinitis (AR), to compare the prevalence of SARS-CoV-2 infection, hospitalization and pneumonia rates in patients with AR receiving allergen immunotherapy (AIT) and patients did not receive AIT (non-receivers) and to define possible risk factors for SARS-CoV-2 positivity in patients with AR. Materials and MethodsA total of 419 patients with AR who were being followed up in a tertiary allergy clinic between 1 June 2020 and 31 December 2020, were selected for the study. Only patients who were receiving active-continuous treatment for allergic rhinitis during the study period, were included in the study. ResultsSeventy-nine patients (18.9%) became infected with the SARS-CoV-2 [32 patients (19.6%) in AR patients with AIT and 47 patients (19.0%) in non-receivers] and the rate of pneumonia was 2.4% [12.7% of SARS-CoV-2 (+) patients]. There was no significant difference was determined between the AR patients with AIT and the non-receivers in regard to the rate of SARS-CoV-2 infection, pneumonia, and hospitalization (p: 0.864, p: 0.081, p: 0.113). There was a significant difference between the groups in terms of gender, duration of disease, sensitivity to allergens (atopy), and serum IgE levels (p: 0.009, p: 0.001, p: 0.001, and p: 0.001). The accompanying comorbidities, eosinophil count, AIT, and duration of AIT were not found to be associated with an increased risk SARS-CoV-2 PCR positivity. However, the female gender was shown to be associated with a decreased risk for SARS-CoV-2 PCR positivity (OR, 0.571; 95% confidence interval, 0.330-0.987; p: 0.045) ConclusionThe course of SARS-CoV-2 is similar in patients with AR who underwent AIT and patients with AR who did not undergo AIT, and AIT does not seem to increase the risk for SARS-CoV-2 infection.

Are allergic diseases a risk factor for systemic side effects after COVID-19 vaccines?

Background/ aimMass vaccination seems to be the most effective way to turn back to the pre-pandemic period and end the pandemic. Unfortunately, COVID-19 vaccines have some side effects. In phase studies of currently-approved COVID-19 vaccines, patients with a known allergy or a history of anaphylaxis were excluded from the studies. This situation creates doubts about the course of atopy and the presence of allergic disease related to the side effects of COVID-19 vaccines in patients with allergic diseases. Therefore, our aim with this study was to evaluate local side effects (LSE) and systemic side effects (SSE) after COVID-19 vaccines in patients with allergic diseases and to determine possible risk factors. Materials and MethodsSix hundred forty-eight adult patients who received any COVID-19 vaccine between April 1, 2021 and September 30, 2021 and agreed to participate in the study were included in this case-control retrospective study. ResultsSix hundred forty-eight adult patients [Female: 446 (68.8%), Male: 202 (32.2%)] participated in the study. After the 1st dose of COVID-19 vaccine, 24.1% of patients reported SSE. After the 2nd dose of COVID-19 vaccine, 67 patients (12.3%) developed SSE. Female gender (OR: 1.757, 95%Cl: 1.143-2.702, p: 0.010), history of previous COVID-19 infection (OR: 1.762, 95%Cl: 1.068-2.906, p: 0.026), and COVID-19 vaccine type administered (OR: 4.443, 95% CI: 2.640-7.476, p<0.001) were found to be independent risk factors for SSE after COVID-19 vaccines. Premedication (OR: 0.454, 95% Cl: 0.281-0.733, p<0.001), was found to be a protective factor for SSE developing after COVID-19 vaccines. ConclusionCoronoVac and Pfizer-BioNTech COVID-19 vaccines are shown to be well tolerated. Patients with allergic disease do not have an increased risk for SSE that may develop after COVID-19 vaccines. Moreover, doubts or fears about possible side effects in the allergic patient group should not be an obstacle to COVID-19 vaccination.

The impact of SARS-CoV-2 transmission fear and COVID-19 pandemic on the mental health of patients with primary immunodeficiency disorders, severe asthma, and other high-risk groups

BackgroundThe adverse effects of COVID-19 pandemic on the mental health of high-risk group patients for morbidity and mortality and its impact on public health in the long term have not been clearly determined. ObjectiveTo determine the level of COVID-19 related transmission fear and anxiety in healthcare workers and patients with primary immunodeficiency disorder (PID), severe asthma, and the ones with other comorbidities. MethodsThe healthcare workers and patients with PID, severe asthma (all patients receiving biological agent treatment), malignancy, cardiovascular disease, hypertension (90% of patients receiving ACEI or ARB therapy), diabetes mellitus (42 % of patients receiving DPP-4 inhibitor therapy) were included in the study. A total of 560 participants, 80 individuals in each group, were provided. The hospital anxiety and depression scale (HADS) and Fear of illness and virus evaluation (FIVE) scales were applied to the groups with face to face interview methods. ResultsThe mean age was 49.30 {+/-} 13.74 years and 306 (55 %) were female. The FIVE Scale and HADS-A scale scores of health care workers were significantly higher than other groups scores (p = 0.001 and 0.006). The second-highest scores belonged to patients with PID. There was no significant difference between the groups for the HADS-D score (p=0.07). The lowest score in all scales was observed in patients with hypertension. ConclusionsThis study demonstrated that in the pandemic process, patients with primary immunodeficiency, asthma patients, and other comorbid patients, especially healthcare workers, should be referred to the centers for the detection and treatment of mental health conditions.