Dear Editor, Recently, some cases of Guillain-Barré syndrome (GBS) and Miller Fisher (MF) have been reported, following COVID-19 infection [1][2][3]. We report two different clinical manifestations of COVID-19 related GBS; one is a GBS/MF overlap syndrome, the other one an Acute Motor Sensory Axonal Neuropathy (AMSAN) with massive vegetative impairment, both highly responsive to intravenous immunoglobulins. Case 1On March 2020, a 55-year-old man was hospitalized for severe respiratory syndrome preceded by anosmia and ageusia, fever, and cough, proven to be due to COVID-19 infection. Laboratory test on admission showed lymphocytopenia associated to the increase of inflammation biomarkers such as PRC, ferritin, and LDH. Oropharyngeal swab test searching for SARS-CoV-2 was positive. A therapy with idrossichlorochine, Arbidol, ritonavir, and lopinavir was promptly started, but for the worsening of respiratory function, after 3 days, the patient was moved to intensive care unit for invasive ventilation. After 20 days from admission, the patient showed acute onset of bilateral eyelid ptosis, dysphagia, and dysphonia. Neurological examination showed bilateral masseter weakness,

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Background The concentrations of the highly atherogenic lipoprotein(a) [Lp(a)] are mainly genetically determined by the LPA gene locus. However, up to 70% of the coding sequence is located in the complex so-called kringle IV type 2 (KIV-2) copy number variation, a region hardly accessible by common genotyping and sequencing technologies. Despite its size, little is known about genetic variants in this complex region. The R21X variant is a functional variant located in this region, but it has never been analyzed in large cohorts. Methods We typed R21X in 10,910 individuals from three European populations using a newly developed high-throughput allele-specific qPCR assay. R21X allelic location was determined by separating the LPA alleles using pulsed-field gel electrophoresis (PFGE) and typing them separately. Using GWAS data, we identified a proxy SNP located outside of the KIV-2. Linkage disequilibrium was determined both statistically and by long-range haplotyping using PFGE. Worldwide frequencies were determined by reanalyzing the sequencing data of the 1000 Genomes Project with a dedicated pipeline. Results R21X carriers (frequency 0.016–0.021) showed significantly lower mean Lp(a) concentrations (− 11.7 mg/dL [− 15.5; − 7.82], p = 3.39e−32). The variant is located mostly on medium-sized LPA alleles. In the 1000 Genome data, R21X mostly occurs in Europeans and South Asians, is absent in Africans, and shows varying frequencies in South American populations (0 to 0.022). Of note, the best proxy SNP was another LPA null mutation (rs41272114, D ′ = 0.958, R 2 = 0.281). D ′ was very high in all 1000G populations (0.986–0.996), although rs41272114 frequency varies considerably (0–0.182). Co-localization of both null mutations on the same allele was confirmed by PFGE-based long-range haplotyping. Conclusions We performed the largest epidemiological study on an LPA KIV-2 variant so far, showing that it is possible to assess LPA KIV-2 mutations on a large scale. Surprisingly, in all analyzed populations, R21X was located on the same haplotype as the splice mutation rs41272114, creating “double-null” LPA alleles. Despite being a nonsense variant, the R21X status does not provide additional information beyond the rs41272114 genotype. This has important implications for studies using LPA loss-of-function mutations as genetic instruments and emphasizes the complexity of LPA genetics.

Background Comorbidities including ischemic heart disease (IHD) worsen outcomes after SARS‐CoV‐2 infections. High lipoprotein(a) [Lp(a)] concentrations are a strong risk factor for IHD and possibly for thromboembolic events. We therefore evaluated whether SARS‐CoV‐2 infections modify the risk of high Lp(a) concentrations for IHD or thromboembolic events during the first 8.5 months follow‐up of the pandemic. Method Cohort study using data from the UK Biobank during the SARS‐CoV‐2 pandemic. Baseline Lp(a) was compared between SARS‐CoV‐2 positive patients and the population controls. UK Biobank received ethical approval from the North West Multi‐Centre Research Ethics Committee (REC reference: 11/NW/0382). All participants gave written informed consent before enrolment in the study, which was conducted in accordance with the principles of the Declaration of Helsinki. Results SARS‐CoV‐2 positive patients had Lp(a) concentrations similar to the population controls. The risk for IHD increased with higher Lp(a) concentrations in both, the population controls (n = 435,104) and SARS‐CoV‐2 positive patients (n = 6,937). The causality of the findings was supported by a genetic risk score for Lp(a). A SARS‐CoV‐2 infection modified the association with a steeper increase in risk for infected patients (interaction P‐value = 0.03). Although SARS‐CoV‐2 positive patients had a 5‐times higher frequency of thromboembolic events compared to the population controls (1.53% vs. 0.31%), the risk was not influenced by Lp(a). Conclusions SARS‐CoV‐2 infections enforce the association between high Lp(a) and IHD but the risk for thromboembolic events is not influenced by Lp(a). This article is protected by copyright. All rights reserved