ABSTRACT
The Coronavirus Disease-19 (COVID-19) pandemic has caused more than 100,000,000 cases of coronavirus infection in the world in just a year, of which there were 2 million deaths. Its clinical picture is characterized by pulmonary involvement that culminates, in the most severe cases, in acute respiratory distress syndrome (ARDS). However, COVID-19 affects other organs and systems, including cardiovascular, urinary, gastrointestinal, and nervous systems. Currently, unique-drug therapy is not supported by international guidelines. In this context, it is important to resort to adjuvant therapies in combination with traditional pharmacological treatments. Among natural bioactive compounds, palmitoylethanolamide (PEA) seems to have potentially beneficial effects. In fact, the Food and Drug Administration (FDA) authorized an ongoing clinical trial with ultramicronized (um)-PEA as an add-on therapy in the treatment of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection. In support of this hypothesis, in vitro and in vivo studies have highlighted the immunomodulatory, anti-inflammatory, neuroprotective and pain-relieving effects of PEA, especially in its um form. The purpose of this review is to highlight the potential use of um-PEA as an adjuvant treatment in SARS-CoV-2 infection.
ABSTRACT
To date, there is still a paucity of data from Phase III trials concerning the efficacy of vaccines against COVID-19. Furthermore, no studies investigated the variables that may modulate the efficacy of vaccination. The aim of this analysis was to assess whether there are modifying factors that may potentially influence the clinical efficacy of COVID-19 vaccines. A quantitative synthesis of data from Phase III trials was performed via pairwise and network meta-analyses, along with meta-regression analysis. Data from Phase III trials are currently available only for AZD1222, BNT162b2, mRNA-1237, and Sputnik V. Vaccination resulted to be generally effective (90.0%, 95%CI 72.6-96.4;p < 0.001), although the efficacy of AZD1222 (62.1%) introduced a significant level of heterogeneity in the meta-analysis (I<sup>2</sup> 92.17%, p < 0.001). No significant modifying factors resulted from the meta-regression analysis. However, considering the mRNA-based vaccines, a trend toward significance (p = 0.081) resulted for age. The network meta-analysis provided the following rank of effectiveness: BNT162b2 mRNA-1273 > Sputnik V >> AZD1222. In conclusion, no modifying factors seem to modulate the efficacy of vaccines against COVID-19. This quantitative synthesis will need to be updated as soon as further clinical results on the efficacy profile are available from Phase III trials for further licensed COVID-19 vaccines.