Concomitant pulmonary nocardiosis and tuberculosis in a patient with rheumatoid arthritis: a new view point

A few case reports of coinfections with Nocardia and Mycobacterium tuberculosis (TB) have previously been published in the literature. We report on a case of concomitant pulmonary nocardiosis and tuberculosis, in a recently diagnosed 55-year-old woman, with rheumatoid arthritis, who had been taking a short course of a low dose corticosteroid. The patient was treated with a combination of amikacin and imipenem, as well as a Physiologic doses of corticosteroids might be a predisposing factor for opportunistic infections, such as nocardiosis or tuberculosis

Respiratory viral infections in otherwise healthy humans with inherited IRF7 deficiency.

Autosomal recessive IRF7 deficiency was previously reported in three patients with single critical influenza or COVID-19 pneumonia episodes. The patients' fibroblasts and plasmacytoid dendritic cells produced no detectable type I and III IFNs, except IFN-β. Having discovered four new patients, we describe the genetic, immunological, and clinical features of seven IRF7-deficient patients from six families and five ancestries. Five were homozygous and two were compound heterozygous for IRF7 variants. Patients typically had one episode of pulmonary viral disease. Age at onset was surprisingly broad, from 6 mo to 50 yr (mean age 29 yr). The respiratory viruses implicated included SARS-CoV-2, influenza virus, respiratory syncytial virus, and adenovirus. Serological analyses indicated previous infections with many common viruses. Cellular analyses revealed strong antiviral immunity and expanded populations of influenza- and SARS-CoV-2-specific memory CD4+ and CD8+ T cells. IRF7-deficient individuals are prone to viral infections of the respiratory tract but are otherwise healthy, potentially due to residual IFN-β and compensatory adaptive immunity

X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19

Publisher Copyright: Copyright © 2021Autosomal inborn errors of type I IFN immunity and autoantibodies against these cytokines underlie at least 10% of critical COVID-19 pneumonia cases. We report very rare, biochemically deleterious X-linked TLR7 variants in 16 unrelated male individuals aged 7 to 71 years (mean, 36.7 years) from a cohort of 1202 male patients aged 0.5 to 99 years (mean, 52.9 years) with unexplained critical COVID-19 pneumonia. None of the 331 asymptomatically or mildly infected male individuals aged 1.3 to 102 years (mean, 38.7 years) tested carry such TLR7 variants (P = 3.5 × 10−5). The phenotypes of five hemizygous relatives of index cases infected with SARS-CoV-2 include asymptomatic or mild infection (n = 2) or moderate (n = 1), severe (n = 1), or critical (n = 1) pneumonia. Two patients from a cohort of 262 male patients with severe COVID-19 pneumonia (mean, 51.0 years) are hemizygous for a deleterious TLR7 variant. The cumulative allele frequency for deleterious TLR7 variants in the male general population is <6.5 × 10−4. We show that blood B cell lines and myeloid cell subsets from the patients do not respond to TLR7 stimulation, a phenotype rescued by wild-type TLR7. The patients’ blood plasmacytoid dendritic cells (pDCs) produce low levels of type I IFNs in response to SARS-CoV-2. Overall, X-linked recessive TLR7 deficiency is a highly penetrant genetic etiology of critical COVID-19 pneumonia, in about 1.8% of male patients below the age of 60 years. Human TLR7 and pDCs are essential for protective type I IFN immunity against SARS-CoV-2 in the respiratory tract.Peer reviewe

Managing adult patients with infectious diseases in emergency departments: international ID-IRI study.

We aimed to explore factors for optimizing antimicrobial treatment in emergency departments. A single-day point prevalence survey was conducted on January 18, 2020, in 53 referral/tertiary hospitals in 22 countries. 1957 (17%) of 11557 patients presenting to EDs had infections. The mean qSOFA score was 0.37 ± 0.74. Sepsis (qSOFA ≥ 2) was recorded in 218 (11.1%) patients. The mean qSOFA score was significantly higher in low-middle (1.48 ± 0.963) compared to upper-middle (0.17 ± 0.482) and high-income (0.36 ± 0.714) countries (P < 0.001). Eight (3.7%) patients with sepsis were treated as outpatients. The most common diagnoses were upper-respiratory (n = 877, 43.3%), lower-respiratory (n = 316, 16.1%), and lower-urinary (n = 201, 10.3%) infections. 1085 (55.4%) patients received antibiotics. The most-commonly used antibiotics were beta-lactam (BL) and BL inhibitors (n = 307, 15.7%), third-generation cephalosporins (n = 251, 12.8%), and quinolones (n = 204, 10.5%). Irrational antibiotic use and inappropriate hospitalization decisions seemed possible. Patients were more septic in countries with limited resources. Hence, a better organizational scheme is required

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

We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. No 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 = 1.1 × 10 &lt;sup&gt;-4&lt;/sup&gt; ) for 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 = 2.1 × 10 &lt;sup&gt;-4&lt;/sup&gt; ). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1-2635.4], P = 3.4 × 10 &lt;sup&gt;-3&lt;/sup&gt; ), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3-8.4], P = 7.7 × 10 &lt;sup&gt;-8&lt;/sup&gt; ). Finally, the patients with pLOF/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 = 1.68 × 10 &lt;sup&gt;-5&lt;/sup&gt; ). Rare 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