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Background The diversity in the clinical course of COVID-19 has been related to differences in innate and adaptative immune response mechanisms. Natural killer (NK) lymphocytes are critical protagonists of human host defense against viral infections. It would seem that reduced circulating levels of these cells have an impact on COVID-19 progression and severity. Their activity is strongly regulated by killer-cell immuno-globulin-like receptors (KIRs) expressed on the NK cell surface. The present study’s focus was to investigate the impact of KIRs and their HLA Class I ligands on SARS-CoV-2 infection. Methods KIR gene frequencies, KIR haplotypes, KIR ligands and combinations of KIRs and their HLA Class I ligands were investigated in 396 Sardinian patients with SARS-CoV-2 infection. Comparisons were made between 2 groups of patients divided according to disease severity: 240 patients were symptomatic or paucisymptomatic (Group A), 156 hospitalized patients had severe disease (Group S). The immunogenetic characteristics of patients were also compared to a population group of 400 individuals from the same geographical areas. Results Substantial differences were obtained for KIR genes, KIR haplotypes and KIR-HLA ligand combinations when comparing patients of Group S to those of Group A. Patients in Group S had a statistically significant higher frequency of the KIR A/A haplotype compared to patients in Group A [34.6% vs 23.8%, OR = 1.7 (95% CI 1.1–2.6); P = 0.02, Pc = 0.04]. Moreover, the KIR2DS2/HLA C1 combination was poorly represented in the group of patients with severe symptoms compared to those of the asymptomatic-paucisymptomatic group [33.3% vs 50.0%, OR = 0.5 (95% CI 0.3–0.8), P = 0.001, Pc = 0.002]. Multivariate analysis confirmed that, regardless of the sex and age of the patients, the latter genetic variable correlated with a less severe disease course [ORM = 0.4 (95% CI 0.3–0.7), PM = 0.0005, PMC = 0.005]. Conclusions The KIR2DS2/HLA C1 functional unit resulted to have a strong protective effect against the adverse outcomes of COVID-19. Combined to other well known factors such as advanced age, male sex and concomitant autoimmune diseases, this marker could prove to be highly informative of the disease course and thus enable the timely intervention needed to reduce the mortality associated with the severe forms of SARS-CoV-2 infection. However, larger studies in other populations as well as experimental functional studies will be needed to confirm our findings and further pursue the effect of KIR receptors on NK cell immune-mediated response to SARS-Cov-2 infection.

Summary Objectives Pregnant women represent a category at high risk of severe measles infection, that negatively affects the fetus as well. A systematic review of clinical outcomes of measles infection in gravid subjects and a meta-analysis of antibodies prevalence among pregnant women was conducted. Methods MEDLINE and EMBASE databases were searched up to 18 June 2018. The screening focused on: (i) articles describing the outcome of measles in pregnancy, synthesized in a descriptive fashion; (ii) articles addressing the measles seroprevalence in cohorts of gravid women, analysed quantitatively. Results Twenty-nine articles met inclusion criteria. A total of 420 cases of measles in gravid subjects were described, from 1941 to 2012. Among women, 18 deaths (4.3%) occurred, and the most frequent complication was pneumonia (75/420, 17.9%). Prematurity was the most important complication concerning fetal outcomes (55 out of 410 cases with available data, 13.4%). The random-effects pooled seroprevalence of measles in 20,546 gravid women worldwide was 89.3% (95% CI: 87.3–91.1%), that decreased, although not in a statistically significant way, over time (p = 0.54). Conclusions Measles infection in pregnancy is dangerous both for the mother and the foetus. Antibody seroprevalence among gravid women on a global scale is lower than the herd immunity threshold.