The reason behind the high inter-individual variability in response to SARS-CoV-2 infection and patient’s outcome is poorly understood. The present study targets the sphingolipid profile of twenty-four healthy controls and fifty-nine COVID-19 patients with different disease severity. Sera were analyzed by untargeted and targeted mass spectrometry and ELISA. Results indicated a progressive increase in dihydrosphingosine, dihydroceramides, ceramides, sphingosine, and a decrease in sphingosine-1-phosphate. These changes are associated with a serine palmitoyltransferase long chain base subunit 1 (SPTLC1) increase in relation to COVID-19 severity. Severe patients showed a decrease in sphingomyelins and a high level of acid sphingomyelinase (aSMase) that influences monosialodihexosyl ganglioside (GM3) C16:0 levels. Critical patients are characterized by high levels of dihydrosphingosine and dihydroceramide but not of glycosphingolipids. In severe and critical patients, unbalanced lipid metabolism induces lipid raft remodeling, leads to cell apoptosis and immunoescape, suggesting active sphingolipid participation in viral infection. Furthermore, results indicated that the sphingolipid and glycosphingolipid metabolic rewiring promoted by aSMase and GM3 is age-dependent but also characteristic of severe and critical patients influencing prognosis and increasing viral load. AUCs calculated from ROC curves indicated ceramides C16:0, C18:0, C24:1, sphingosine and SPTLC1 as putative biomarkers of disease evolution.

Objectives Limited data are available regarding the occurrence and the extent of cardiac rhythm disturbances in patients with COVID-19 treated with Remdesivir. Methods Here we present a case series of 52 patients who underwent daily electrocardiogram (ECG) examination after Remdesivir administration. Results Compared to baseline, a significant heart rate reduction was observed after initiation of Remdesivir; no case of severe bradycardia or arrhythmias leading to significant clinical complications or Remdesivir discontinuation however occurred. Heart rate reduction was proportional to baseline heart rate values (r=0.75, p<0.001). At multivariate analysis less severe clinical presentation of Covid-19 (beta=0.47, p<0.01) was related to lower heart rate levels observed after Remdesivir administration. Conclusions. Despite a significant reduction in heart rate observed after Remdesivir administration, no serious cardiovascular toxicity was observed in Covid-19 patients, even in case of cardiovascular comorbidities.

Few data are available regarding the incidence and the evolution of neuropsychiatric manifestations in children with a history of COVID-19. We herein report five consequent cases of pediatric patients with psychiatric and neurological symptoms of long COVID-19. All patients, mainly males, reported asymptomatic-to-mild COVID-19 and underwent home self-isolation. Abnormal movements, anxiety, and emotional dysregulation were the most recurrent symptoms observed from a few weeks to months after the resolution of the acute infection. A later onset was observed in younger patients. Blood tests and brain imaging resulted in negative results in all subjects; pharmacological and cognitive behavioral therapy was set. A multifactorial etiology could be hypothesized in these cases, as a result of a complex interplay between systemic and brain inflammation and environmental stress in vulnerable individuals. Longer follow-up is required to observe the evolution of neuropsychiatric manifestation in the present cohort and other young patients with previous SARS-CoV-2 infection.

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BackgroundSARS-CoV-2 transmission mainly occurs through exposure of the upper airway mucosa to infected secretions such as saliva, which are excreted by an infected person. Thus, oral mucosal immunity plays a central role in the prevention of and early defense against SARS-CoV-2 infection. Although virus-specific antibody response has been extensively investigated in blood samples of SARS-CoV-2-infected patients and vaccinees, local humoral immunity in the oral cavity and its relationship to systemic antibody levels needs to be further addressed.Material and MethodsWe fine-tuned a virus neutralization assay (vNTA) to measure the neutralizing activity (NA) of plasma and saliva samples from 20 SARS-CoV-2-infected (SI), 40 SARS-CoV-2-vaccinated (SV), and 28 SARS-CoV-2-vaccinated subjects with a history of infection (SIV) using the “wild type” SARS-CoV-2 lineage B.1 (EU) and the Delta (B.1.617.2) strains. To validate the vNTA results, the presence of neutralizing antibodies (NAbs) to the spike receptor binding domain (RBD) was evaluated with an ELISA assay.ResultsNA to SARS-CoV-2 lineage B.1 (EU) was present in plasma samples from all the tested subjects, with higher titers in SIV compared to both SI and SV. Conversely, NA was detected in saliva samples from 10.3% SV, 45% SI, and 92.6% SIV, with significantly lower titers in SV compared to both SI and SIV. The detection of NAbs in saliva reflected its reduced NA in SV.DiscussionThe difference in NA of plasma vs. saliva was confirmed in a vNTA where the SARS-CoV-2 B.1 and Delta strains were tested head-to-head, which also revealed a reduced NA of both specimens compared to the B.1 variant.ConclusionsThe administration of SARS-CoV-2 vaccines was associated with limited virus NA in the oral cavity, as measured in saliva and in comparison to plasma. This difference was more evident in vaccinees without a history of SARS-CoV-2 infection, possibly highlighting the importance of local exposure at the site of virus acquisition to effectively prevent the infection and block its spread. Nevertheless, the presence of immune escape mutations as possibly represented by the SARS-CoV-2 Delta variant negatively affects both local and systemic efficacy of NA associated with vaccination.