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Herein, we report a case of an Italian male infected by Delta sublineage AY.4 harboring an atypical deletion, leading to a N gene target failure (NGTF) by a commercial molecular assay for SARS-CoV-2 diagnosis (AllplexTM SARS-CoV-2 Assay, Seegene). A 59-year-old unvaccinated patient was hospitalized for pulmonary embolism, with first negative results obtained by both molecular and antigen tests. After several days of viral negativity, he presented positive results for E and RdRP/S genes, but negative in N gene. Negativity in N gene was repeatedly confirmed in the following days. Suspecting an infection by the Omicron variant, SARS-CoV-2 genome sequencing was rapidly performed from nasopharyngeal swab by MiSeq and revealed the presence of the Delta sublineage AY.4 variant with an atypical deletion of six nucleotides, leading to G214-G215 deletion in the Nucleocapsid, thus responsible for NGTF. The analysis of GISAID sequences (N = 2,618,373 12 January 2022) showed that G214-G215 deletion is rarely occurring in most circulating Delta lineages and sublineages in the globe and Europe, with an overall prevalence never exceeding 0.2%. Hence, this study highlights the importance to perform SARS-CoV-2 sequencing and to characterize novel mutations/deletions that could jeopardize the proper interpretation of molecular diagnostic tests. Based on these assumptions, the role of deletions in the recently identified Omicron variant deserves further investigation.
RESUMEN
BACKGROUND: Cardiovascular diseases and insufficient levels of vitamin D are risk factors for adverse surgical outcomes, and they are both commonly present among older adults undergoing orthopaedic surgery. Giving the cardiovascular effects of vitamin D, pre-operative diagnosis of hypovitaminosis D would be a valuable step for the implementation of supplementation protocols. We investigated if the normalization of serum 25 [OH] D could ameliorate cardiac performance of older adults suffering from cardiovascular diseases. METHODS: We enrolled 47 older adults scheduled for major orthopaedic surgery and suffering from hypovitaminosis D. Patients underwent 6-months calcifediol supplementation with a starting dose at first post-operative day of 50 µg/die in liquid preparation. Down-titration to 20 µg/die at 3-months assessment was planned. Cardiac performance was evaluated by measuring left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) during pre-operative assessments and at 1-month, 3-months, 6-months follow-ups. RESULTS: Six months of calcifediol supplementation were associated with a significant improvement of both LVEF (+ 3.94%; 95% CI: -4.0789 to -0.8232; P < 0.01) and GLS (+ 18.56%; Z = -5.895; P < 0.0001). CONCLUSIONS: Calcifediol supplementation normalized serum 25 [OH] D concentration after 1-month treatment. GLS offered better insights into myocardial contractile amelioration than LVEF, thus being useful for detecting earlier subclinical changes that may anticipate hemodynamic modifications.