Surfactant protein D (SP-D) as a biomarker of SARS-CoV-2 infection.

BACKGROUND: Surfactant protein-D (SP-D) is a lung-resident protein that has emerged as a potential biomarker for COVID-19. Previous investigations on acute respiratory distress syndrome patients demonstrated a significant increment of SP-D serum levels in pathological conditions. Since SP-D is not physiologically permeable to alveoli-capillary membrane and poorly expressed by other tissues, this enhancement is likely due to an impairment of the pulmonary barrier caused by prolonged inflammation. METHODS: A retrospective study on a relatively large cohort of patients of Hospital Pio XI of Desio was conducted to assess differences of the hematic SP-D concentrations among COVID-19 patients and healthy donors and if SP-D levels resulted a risk factor for disease severity and mortality. RESULTS: The first analysis, using an ANOVA-model, showed a significant difference in the mean of log SP-D levels between COVID-19 patients and healthy donors. Significant variations were also found between dead vs survived patients. Results confirm that SP-D concentrations were significantly higher for both hospitalized COVID-19 and dead patients, with threshold values of 150 and 250 ng/mL, respectively. Further analysis conducted with Logistic Mixed models, highlighted that higher SP-D levels at admission and increasing differences among follow-up and admission values resulted the strongest significant risk factors of mortality (model predictive accuracy, AUC = 0.844). CONCLUSIONS: The results indicate that SP-D can be a predictive marker of COVID-19 disease and its outcome. Considering its prognostic value in terms of mortality, the early detection of SP-D levels and its follow-up in hospitalized patients should be considered to direct the therapeutic intervention.

Role of Diet and Nutrients in SARS-CoV-2 Infection: Incidence on Oxidative Stress, Inflammatory Status and Viral Production.

Coronavirus illness (COVID-19) is an infectious pathology generated by intense severe respiratory syndrome coronavirus 2 (SARS-CoV-2). This infectious disease has emerged in 2019. The COVID-19-associated pandemic has considerably affected the way of life and the economy in the world. It is consequently crucial to find solutions allowing remedying or alleviating the effects of this infectious disease. Natural products have been in perpetual application from immemorial time given that they are attested to be efficient towards several illnesses without major side effects. Various studies have shown that plant extracts or purified molecules have a promising inhibiting impact towards coronavirus. In addition, it is substantial to understand the characteristics, susceptibility and impact of diet on patients infected with COVID-19. In this review, we recapitulate the influence of extracts or pure molecules from medicinal plants on COVID-19. We approach the possibilities of plant treatment/co-treatment and feeding applied to COVID-19. We also show coronavirus susceptibility and complications associated with nutrient deficiencies and then discuss the major food groups efficient on COVID-19 pathogenesis. Then, we covered emerging technologies using plant-based SARS-CoV-2 vaccine. We conclude by giving nutrient and plants curative therapy recommendations which are of potential interest in the COVID-19 infection and could pave the way for pharmacological treatments or co-treatments of COVID-19.

Role of Diet and Nutrients in SARS-CoV-2 Infection: Incidence on Oxidative Stress, Inflammatory Status and Viral Production

Coronavirus illness (COVID-19) is an infectious pathology generated by intense severe respiratory syndrome coronavirus 2 (SARS-CoV-2). This infectious disease has emerged in 2019. The COVID-19-associated pandemic has considerably affected the way of life and the economy in the world. It is consequently crucial to find solutions allowing remedying or alleviating the effects of this infectious disease. Natural products have been in perpetual application from immemorial time given that they are attested to be efficient towards several illnesses without major side effects. Various studies have shown that plant extracts or purified molecules have a promising inhibiting impact towards coronavirus. In addition, it is substantial to understand the characteristics, susceptibility and impact of diet on patients infected with COVID-19. In this review, we recapitulate the influence of extracts or pure molecules from medicinal plants on COVID-19. We approach the possibilities of plant treatment/co-treatment and feeding applied to COVID-19. We also show coronavirus susceptibility and complications associated with nutrient deficiencies and then discuss the major food groups efficient on COVID-19 pathogenesis. Then, we covered emerging technologies using plant-based SARS-CoV-2 vaccine. We conclude by giving nutrient and plants curative therapy recommendations which are of potential interest in the COVID-19 infection and could pave the way for pharmacological treatments or co-treatments of COVID-19.

Oxysterols as Reliable Markers of Quality and Safety in Cholesterol Containing Food Ingredients and Products.

Cholesterol is a lipid of high nutritional value that easily undergoes oxidation through enzymatic and non-enzymatic pathways, leading to a wide variety of cholesterol oxidation products (COPs), more commonly named oxysterols. The major oxysterols found in animal products are 7α-hydroxycholesterol, 7ß-hydroxycholesterol, 7-ketocholesterol, 5α,6α-epoxycholesterol, 5ß,6ß-epoxycholesterol, cholestan-3ß,5α,6ß-triol, and 25-hydroxycholesterol. They are all produced by cholesterol autoxidation, thus belonging to the non-enzymatic oxysterol subfamily, even if 7α-hydroxycholesterol and 25-hydroxycholesterol are, in part, generated enzymatically as well. A further oxysterol of the full enzymatic origin has recently been detected for the first time in milk of both human and bovine origin, namely 27-hydroxycholesterol. Nowadays, gas or liquid chromatography combined to mass spectrometry allows to measure all these oxysterols accurately in raw and in industrially processed food. While non-enzymatic oxysterols often exhibited in vitro relevant cytotoxicity, above all 7ß-hydroxycholesterol and 7-ketocholesterol, 27-hydroxycholesterol, as well as 25-hydroxycholesterol, shows a broad spectrum in vitro antiviral activity, inhibition of SARS-CoV-2 included, and might contribute to innate immunity. Quantification of oxysterols was afforded over the years, almost always focused on a few family's compounds. More comprehensive COPs measurements, also including oxysterols of enzymatic origin, are, nowadays, available, which better display the many advantages of systematically adopting this family of compounds as markers of quality, safety, and nutritional value in the selection of ingredients in processing and storage. Regarding foodstuff shelf life, COPs monitoring already provided useful hints for more suitable packaging. The identification of a subset of non-enzymatic and enzymatic oxysterols to be routinely assessed in food production and storage is proposed.

Antibody response after two doses of the SARS-CoV-2 Comirnaty vaccine in a Covid-19 positive and Covid-19 negative Italian healthcare workers cohort.

BACKGROUND: Extensive vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now universally regarded as one of the most effective strategies for counteracting the current pandemic. The durability of the immune response of available vaccines is not known, therefore the quantitative dynamics of serum anti-S antibodies after Comirnaty vaccine in health care workers (HCW) of Desio Hospital was conducted. METHODS: 51 previously infected and 198 not infected HCW, from Desio, Italy were enrolled in the study. Comirnaty double dose schedule was completed by each subject. Specific anti-S antibodies against the SARS-CoV-2 S protein were measured by ECLIA in sequential blood samples. RESULTS: A significant difference was observed beginning at pre priming dose (T0) of the anti-S antibodies between the two subgroups which persisted throughout the study (4 months). A significant reduction occurred after 4 months post-priming dose (T3). Finally, a subgroup of low and late responders with an increasing trend was found. CONCLUSIONS: Specific anti-S antibodies are significantly decreased 4 months post priming dose of Comirnaty vaccine although prior COVID-19 infection seems to escalate humoral response. Further evaluation concerning antibody persistence beyond this point, and the proportion of neutralizing antibodies with higher affinity towards SARS-CoV-2 is needed, especially in naїve and immunosuppressed subjects.

7-Ketocholesterol: Effects on viral infections and hypothetical contribution in COVID-19.

7-Ketocholesterol, which is one of the earliest cholesterol oxidization products identified, is essentially formed by the auto-oxidation of cholesterol. In the body, 7-ketocholesterol is both provided by food and produced endogenously. This pro-oxidant and pro-inflammatory molecule, which can activate apoptosis and autophagy at high concentrations, is an abundant component of oxidized Low Density Lipoproteins. 7-Ketocholesterol appears to significantly contribute to the development of age-related diseases (cardiovascular diseases, age-related macular degeneration, and Alzheimer's disease), chronic inflammatory bowel diseases and to certain cancers. Recent studies have also shown that 7-ketocholesterol has anti-viral activities, including on SARS-CoV-2, which are, however, lower than those of oxysterols resulting from the oxidation of cholesterol on the side chain. Furthermore, 7-ketocholesterol is increased in the serum of moderately and severely affected COVID-19 patients. In the case of COVID-19, it can be assumed that the antiviral activity of 7-ketocholesterol could be counterbalanced by its toxic effects, including pro-oxidant, pro-inflammatory and pro-coagulant activities that might promote the induction of cell death in alveolar cells. It is therefore suggested that this oxysterol might be involved in the pathophysiology of COVID-19 by contributing to the acute respiratory distress syndrome and promoting a deleterious, even fatal outcome. Thus, 7-ketocholesterol could possibly constitute a lipid biomarker of COVID-19 outcome and counteracting its toxic effects with adjuvant therapies might have beneficial effects in COVID-19 patients.

Baseline characteristics of COVID-19 Italian patients admitted to Desio Hospital, Lombardy: a retrospective study.

The correlation of clinical, radiological and laboratory findings of patients at admission in the Emergency Department (ED) with clinical severity and risk of mortality was investigated. Adult coronavirus disease 2019 (COVID-19) patients hospitalized in March 2020 in Desio Hospital, Lombardy, were retrospectively included in the study, and categorized in terms of disease severity and adverse outcome. Out of the 175 patients enrolled, 79% presented one or more comorbidities, with cardiovascular disease being the most frequent (62%). More than half of the patients showed lymphocytopenia and 20% thrombocytopenia. The patients in the severe group presented higher absolute neutrophil count (ANC), C-reactive protein (CRP), AST, LDH, procalcitonin (PCT) and BUN values compared to the non-severe group (p < .05). Increased odds of mortality associated with older age (OR = 22.43; 95% CI 5.22-96.27), partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FIO2) ratio < 200 (OR = 4.97; 95% CI 1.55-15.84), clinical severity (OR = 21.32; 95% CI 2.27-200.13), creatinine > 106.08 µmol/L (OR = 2.87; 95% CI 1.04-7.92) and creatine kinase > 2.90 µkat/L (OR = 3.80; 95% CI 1.31-10.9) were observed on admission (p < .05). The above findings may contribute to identify early risk factors of poor prognosis, and to select the most appropriate management for patients.

The cholesterol metabolite 27-hydroxycholesterol inhibits SARS-CoV-2 and is markedly decreased in COVID-19 patients.

There is an urgent need to identify antivirals against the coronavirus SARS-CoV-2 in the current COVID-19 pandemic and to contain future similar emergencies early on. Specific side-chain cholesterol oxidation products of the oxysterols family have been shown to inhibit a large variety of both enveloped and non-enveloped human viral pathogens. Here we report on the in vitro inhibitory activity of the redox active oxysterol 27-hydroxycholesterol against SARS-CoV-2 and against one of the common cold agents HCoV-OC43 human coronavirus without significant cytotoxicity. Interestingly, physiological serum levels of 27-hydroxycholesterol in SARS-CoV-2 positive subjects were significantly decreased compared to the matched control group, reaching a marked 50% reduction in severe COVID-19 cases. Moreover, no correlation at all was observed between 24-hydroxycholesterol and 25-hydroxycholesterol serum levels and the severity of the disease. Opposite to that of 27-hydroxycholesterol was the behaviour of two recognized markers of redox imbalance, i.e. 7-ketocholesterol and 7ß-hydroxycholesterol, whose serum levels were significantly increased especially in severe COVID-19. The exogenous administration of 27-hydroxycholesterol may represent in the near future a valid antiviral strategy in the worsening of diseases caused by present and emerging coronaviruses.