Saliva metabolomic profile of COVID-19 patients associates with disease severity.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is strongly linked to dysregulation of various molecular, cellular, and physiological processes that change abundance of different biomolecules including metabolites that may be ultimately used as biomarkers for disease progression and severity. It is important at early stage to readily distinguish those patients that are likely to progress to moderate and severe stages. OBJECTIVES: This study aimed to investigate the utility of saliva and plasma metabolomic profiles as a potential parameter for risk stratifying COVID-19 patients. METHOD: LC-MS/MS-based untargeted metabolomics were used to profile the changes in saliva and plasma metabolomic profiles of COVID-19 patients with different severities. RESULTS: Saliva and plasma metabolites were screened in 62 COVID-19 patients and 18 non-infected controls. The COVID-19 group included 16 severe, 15 moderate, 16 mild, and 15 asymptomatic cases. Thirty-six differential metabolites were detected in COVID-19 versus control comparisons. SARS-CoV-2 induced metabolic derangement differed with infection severity. The metabolic changes were identified in saliva and plasma, however, saliva showed higher intensity of metabolic changes. Levels of saliva metabolites such as sphingosine and kynurenine were significantly different between COVID-19 infected and non-infected individuals; while linoleic acid and Alpha-ketoisovaleric acid were specifically increased in severe compared to non-severe patients. As expected, the two prognostic biomarkers of C-reactive protein and D-dimer were negatively correlated with sphingosine and 5-Aminolevulinic acid, and positively correlated with L-Tryptophan and L-Kynurenine. CONCLUSION: Saliva disease-specific and severity-specific metabolite could be employed as potential COVID-19 diagnostic and prognostic biomarkers.

Interleukin-17, a salivary biomarker for COVID-19 severity.

OBJECTIVES: T-helper 17 cell-mediated response and their effector IL-17 cytokine induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a major cause of COVID-19 disease severity and death. Therefore, the study aimed to determine if IL-17 level in saliva mirrors its circulatory level and hence can be used as a non-invasive biomarker for disease severity. METHODS: Interleukin-17 (IL-17) level was evaluated by ELISA in saliva and blood of 201 adult COVID-19 patients with different levels of severity. The IL-17 saliva level was also associated with COVID-19 disease severity, and need for mechanical ventilation and/or death within 29 days after admission of severe COVID-19 patients. RESULTS: We found that IL-17 level in saliva of COVID-19 patients reflected its circulatory level. High IL-17 level in saliva was associated with COVID-19 severity (P<0.001), need for mechanical ventilation (P = 0.002), and/or death by 29 days (P = 0.002), after adjusting for patients' demographics, comorbidity, and COVID-19 serum severity markers such as D-Dimer, C-reactive protein, and ferritin. CONCLUSION: We propose that saliva IL-17 level could be used as a biomarker to identify patients at risk of developing severe COVID-19.

Vitamin D modulates systemic inflammation in patients with severe COVID-19.

AIMS: The ability of vitamin D (VitD) to modulate immune responses in the clinical setting of COVID-19 infection is not well investigated. This study aimed to evaluate the ability of VitD to attenuate inflammatory responses in patients with severe COVID-19. MATERIALS AND METHODS: Blood samples and nasopharyngeal swabs were obtained from patients with severe COVID-19 who had been treated (20 patients), or not (25 patients), with VitD, during their stay in the intensive care unit. Western blotting was used to evaluate the expressions of STAT3, JNK and AKT signaling pathways and ELISA was used to measure levels of IL-6, IL-17, and IL-1ß in blood of these patients. KEY FINDINGS: Reduced levels of STAT3, JNK and AKT pathways and lower levels of proinflammatory cytokines such as IL-6, IL-17, and IL-1ß were observed in VitD treated patients (50,000 IU of cholecalciferol weekly for 3 weeks), and in vitro following treatment of poly I:C stimulated PBMCs with VitD (50 nM of calcitriol). Moreover, lower circulatory levels of these proinflammatory cytokines following treatment with VitD were associated with lower serum levels of COVID-19-related severity markers such as D-dimer and C-reactive proteins (P < 0.001) which in overall resulted in shorter length of ICU stay for VitD treated compared to untreated patients (18 days for VitD treated vs. 28 days for VitD untreated; P = 0.01). SIGNIFICANCE: This study reveals that VitD plays immunomodulatory role during COVID-19 infection, which further emphasizes the importance of maintaining a normal level of this vitamin for the prevention of hyperinflammatory conditions associated with COVID-19.

Determinants of healthcare workers perceptions, acceptance and choice of COVID-19 vaccines: a cross-sectional study from the United Arab Emirates.

Acceptance of COVID-19 vaccine among health-care workers (HCWs) is crucial for controlling the pandemic and ensuring HCW and patient safety. Information on the acceptance of different COVID-19 vaccines is lacking. Despite the United Arab Emirates (UAE) having vaccinated most of its population, vaccine acceptance still raises concerns. This study explores COVID-19 vaccine acceptance, vaccine choice, and associated factors among HCWs in the UAE. An online national cross-sectional study was conducted among 517 HCWs. Acceptance and choice of COVID-19 vaccines were assessed, and logistic regression analysis identified predictors for vaccine acceptance. More than half (58%) of HCWs were willing to take the vaccine and give it to their family. Reasons for taking the vaccine were concerns for families contracting COVID-19 (67%) and social responsibility (64%). Reasons for refusals included concerns with side-effects (61%). Most HCWs knew of the Pfizer (79%) and Sinopharm (57%) vaccines; however, acceptance was higher for Pfizer (35%) and AstraZeneca (21%) vaccines. Being male and being influenza vaccinated predicted willingness to take the vaccine (aOR: 2.34; 95% CI:1.34-4.08; p ≤ 0.001) and (aOR: 2.13; 95% CI: 1.29-3.51; p ≤ 0.001), respectively. HCWs who expressed concerns with inadequate safety data were less likely to take the vaccine (aOR: 0.17; 95% CI: 0.10-0.30; p ≤ 0.001). Additionally, side effects, perception of risk, and level of trust of company and country of manufacture predicted acceptance and choice of vaccines. Effective vaccine policy campaigns to improve acceptance should target HCW's knowledge and awareness of perceived risks of COVID-19, safety data, social responsibility, and individual preferences for vaccine choice.