State Responsibility, International Law and the COVID-19 Crisis

Disruptions caused by the global spread of COVID-19 have generated different types of responsibility claims at both the domestic and international levels. Alleged breaches of the law have resulted from the immediate reactions to the pandemic’s emergence and spread, as well as from less proximate adjustments made to the ongoing crisis. This contribution begins by briefly surveying the types of responsibility relevant to the crisis with a view to identifying systemic legal issues, particularly at the international level. It then focusses on the law of state responsibility for internationally wrongful acts, not to resolve the various claims that are or can be made, but in order to identify what this crisis reveals about the trends in the law of responsibility, the opportunities for its invocation, and indeed, state tactics in engaging with this body of law. Just as the pandemic has been revelatory of social trends, so too it has highlighted trends in the law and its operation.

Risk Stratification as a Predictive Factor for Cephalosporin Allergy: A Case-Controlled Study

<b><i>Background:</i></b> Compared to penicillin, cephalosporin allergies are less common in children, and their diagnostic approach is less standardized. A recent European Academy of Allergy and Clinical Immunology position paper provided a risk stratification system for patients with suspected β-lactam hypersensitivity reactions. <b><i>Objective:</i></b> This study aimed to evaluate risk stratification and predicting factors for confirmed cephalosporin hypersensitivity. <b><i>Methods:</i></b> The case-controlled study included patients with confirmed cephalosporin hypersensitivity (skin tests, <i>n</i> = 53; drug provocation, <i>n</i> = 19). For each patient, 2 age- and gender-matched control subjects were included in the study. Data were retrieved from patients’ records and analyzed retrospectively. Risk stratification was performed according to the severity of index reactions, which was initially divided as high and low risk and then further divided as immediate and nonimmediate. <b><i>Results:</i></b> According to risk stratification, the patient and control groups were divided as follows: high-risk immediate (66.7% vs. 13%, respectively), high-risk delayed (1.4% vs. 8.3%, respectively), low-risk immediate (16.7% vs. 16%, respectively), and low-risk delayed (15.3% vs. 62.9%, respectively). Immediate reactions (odds ratio [OR]: 12.1, 95% confidence interval [CI]: 9–24.8, <i>p</i> &#x3c; 0.001) and high-risk reactions (OR: 7.8, 95% CI: 4.1–14.6, <i>p</i> &#x3c; 0.001) were associated with confirmed cephalosporin hypersensitivity in univariate analysis. Multivariate regression analysis indicated that immediate reactions (OR: 7.5, 95% CI: 3.3–16.8, <i>p</i> &#x3c; 0.001) and high-risk reactions (OR: 5.2, 95% CI: 2.1–12.9, <i>p</i> &#x3c; 0.001) were significant risk factors for the prediction of cephalosporin hypersensitivity. <b><i>Conclusion:</i></b> This model can be applied in children with suspected cephalosporin allergy. Skin testing provides diagnostic information in high-risk patients with immediate reactions and reduces the need for drug provocation testing in these patients. It is highly likely to confirm the diagnosis of low-risk patients directly with provocation tests without skin tests. High-risk and immediate reactions were found to be predictive factors for confirmed cephalosporin allergy.

Next-Generation Sequencing and Genotype Association Studies Reveal the Association of HLA-DRB3*02:02 With Delayed Hypersensitivity to Penicillins

Background: Nonimmediate (delayed) allergic reactions to penicillins are common and some of them can be life-threatening. The genetic factors influencing these reactions are unknown/poorly known/poorly understood. We assessed the genetic predictors of a delayed penicillin allergy that cover the HLA loci. Methods: Using next-generation sequencing (NGS), we genotyped the MHC region in 24 patients with delayed hypersensitivity compared with 20 patients with documented immediate hypersensitivity to penicillins recruited in Italy. Subsequently, we analyzed in silico Illumina Immunochip genotyping data that covered the HLA loci in 98 Spanish patients with delayed hypersensitivity and 315 with immediate hypersensitivity compared to 1,308 controls. Results: The two alleles DRB3*02:02:01:02 and DRB3*02:02:01:01 were reported in twenty cases with delayed reactions (83%) and ten cases with immediate reactions (50%), but not in the Allele Frequency Net Database. Bearing at least one of the two alleles increased the risk of delayed reactions compared to immediate reactions, with an OR of 8.88 (95% CI, 3.37–23.32; P <0.0001). The haplotype (ACAA) from rs9268835, rs6923504, rs6903608, and rs9268838 genetic variants of the HLA-DRB3 genomic region was significantly associated with an increased risk of delayed hypersensitivity to penicillins (OR, 1.7; 95% CI: 1.06–1.92; P=0.001), but not immediate hypersensitivity. Conclusion: We showed that the HLA-DRB3 locus is strongly associated with an increased risk of delayed penicillin hypersensitivity, at least in Southwestern Europe. The determination of HLA-DRB3*02:02 alleles in the risk management of severe delayed hypersensitivity to penicillins should be evaluated further in larger population samples of different origins.

An Experimental Analogue Evaluation of Asian and Asian Americans’ Immediate Reactions to Therapist Microaggressions

Microaggressions are subtle, everyday exchanges that convey discriminatory messages. In psychotherapy, client reports of microaggressions are negatively associated with important therapeutic processes and outcomes. However, many studies are retrospective and correlational, and cannot establish the causal impact of specific therapist statements. In this study, Asian and Asian American participants recruited from Amazon Mechanical Turk ( N = 66) watched a brief animated counseling vignette, and were randomly assigned to four types of therapist responses to the client (control, subtle, moderate, and overt microaggressions). We assessed emotional reactions, perceptions of the session, and offensiveness of therapist statements. In general, moderate and overt microaggressions were rated much more negatively (Cohen’s d’s > 1.0) than subtle microaggressions or control statements (which were not significantly different from each other on any measure). We discuss implications for research, practice, and training.