The disease severity of COVID-19, especially in the elderly and patients with co-morbidities, is characterized by hypercytokinemia, an exaggerated immune response associated with an uncontrolled and excessive release of proinflammatory cytokine mediators (cytokine storm). Flavonoids, important secondary metabolites of plants, have long been studied as therapeutic interventions in inflammatory diseases due to their cytokine-modulatory effects. In this review, we discuss the potential role of flavonoids in the modulation of signaling pathways that are crucial for COVID-19 disease, particularly those related to inflammation and immunity. The immunomodulatory ability of flavonoids, carried out by the regulation of inflammatory mediators, the inhibition of endothelial activation, NLRP3 inflammasome, toll-like receptors (TLRs) or bromodomain containing protein 4 (BRD4), and the activation of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2), might be beneficial in regulating the cytokine storm during SARS-CoV-2 infection. Moreover, the ability of flavonoids to inhibit dipeptidyl peptidase 4 (DPP4), neutralize 3-chymotrypsin-like protease (3CLpro) or to affect gut microbiota to maintain immune response, and the dual action of angiotensin-converting enzyme 2 (ACE-2) may potentially also be applied to the exaggerated inflammatory responses induced by SARS-CoV-2. Based on the previously proven effects of flavonoids in other diseases or on the basis of newly published studies associated with COVID-19 (bioinformatics, molecular docking), it is reasonable to assume positive effects of flavonoids on inflammatory changes associated with COVID-19. This review highlights the current state of knowledge of the utility of flavonoids in the management of COVID-19 and also points to the multiple biological effects of flavonoids on signaling pathways associated with the inflammation processes that are deregulated in the pathology induced by SARS-CoV-2. The identification of agents, including naturally occurring substances such as flavonoids, represents great approach potentially utilizable in the management of COVID-19. Although not clinically investigated yet, the applicability of flavonoids against COVID-19 could be a promising strategy due to a broad spectrum of their biological activities.

Background: Covid-19 is a disease with high morbidity and mortality among elderly residents of long-term care facilities (LTCF). During an outbreak of SARS-CoV-2 infection in the LTCF an effective screening tool is essential to identify the patients at risk for severe disease. We explored the role of interleukin 6 (IL-6) as a predictor for severe disease during the outbreak of Covid-19 in one LTCF in Slovakia. Methods: We conducted a retrospective data analysis of cases of COVID-19, diagnosed during the outbreak in one LTCF in Slovakia between April 11, 2020, and May 5, 2020. Within 24 h after the diagnosis of Covid-19, clinical and laboratory screening was performed in the LTCF to identify patients in need of hospitalization. Patients with oxygen saturation below 90% were immediately referred to the hospital. Patients staying in the LFTC were monitored daily and those that developed hypoxemia were transferred to the hospital. We analyzed the association between the IL-6 at the initial assessment and development of hypoxemia during follow up and determined the cut-off of the IL-6 able to predict the development of hypoxemia requiring oxygen therapy. Results: Fifty-three patients (11 men, 42 women) with diagnosed Covid-19 were included in the analysis. 19 (53%) patients developed hypoxemia during the disease. Patients with hypoxemia had significantly higher concentrations of IL-6, C-reactive protein, procalcitonin, fibrinogen, total bilirubin, aspartate aminotransferase and alanine aminotransferase at initial screening. ROC analyses identified IL-6 as the most robust predictor of hypoxemia. The concentration of IL-6 > 24 pg/mL predicted the development of hypoxemia with the sensitivity of 100% and specificity of 88.9%. The positive and negative predictive values were 76.9, and 100% respectively. Conclusions: The concentration of IL-6 > 24 pg/mL at initial assessment predicted the development of hypoxemia requiring hospitalization with excellent sensitivity and good specificity. IL-6 appears as a potential predictor for the development of the severe Covid-19 and might serve for early identification of patients in need of hospitalization. Further studies are needed to evaluate the robustness of the use of IL-6 as an effective screening tool for the severe course of Covid-19.

Body weight changes are associated with significant variations in blood pressure (BP). Body mass modifications may, therefore, influence hypertension control in primary care. Patients with a history of essential arterial hypertension were observed for 12 months. Anthropometric data and clinical BP were evaluated at the time of the recruitment and after 12 months of follow-up. The association between (body mass index) BMI change and BP control was analyzed by logistic regression. Sixteen thousand five hundred and sixty-four patients were recruited, while 13,631 patients (6336 men; 7295 women) finished the 1-year follow-up. In obese patients, a BMI decrease by at least 1 kg/m2 was negatively associated with uncontrolled hypertension at the end of the follow-up (men p < 0.0001, OR = 0.586, 0.481–0.713, women p < 0.001, OR = 0.732, 0.611–0.876). A similar association was observed in overweight patients (men p < 0.05, OR = 0. 804, 95% CI: 0.636–0.997, women p < 0.05, OR = 0.730, 95% CI: 0.568–0.937). A BMI increase of at least 1 kg/m2 was associated with a significantly higher odd of uncontrolled hypertension in obese (men p < 0.001, OR = 1.471, 1.087–1.991, women p < 0.001, OR = 1.422, 1.104–1.833) and overweight patients (men p < 0.0001, OR = 1.901, 95% CI: 1.463–2.470, women p < 0.0001, OR = 1.647, 95% CI: 1.304–2.080). Weight loss is inversely associated and weight increase is positively associated with the probability of uncontrolled hypertension in obese and overweight hypertensives.

The emergence of a novel SARS-CoV-2 B.1.1.7 variant sparked global alarm due to increased transmissibility, mortality, and uncertainty about vaccine efficacy, thus accelerating efforts to detect and track the variant. Current approaches to detect B.1.1.7 include sequencing and RT-qPCR tests containing a target assay that fails or results in reduced sensitivity towards the B.1.1.7 variant. Since many countries lack genomic surveillance programs and failed assays detect unrelated variants containing similar mutations as B.1.1.7, we used allele-specific PCR, and judicious placement of LNA-modified nucleotides to develop an RT-qPCR test that accurately and rapidly differentiates B.1.1.7 from other SARS-CoV-2 variants. We validated the test on 106 clinical samples with lineage status confirmed by sequencing and conducted a country-wide surveillance study of B.1.1.7 prevalence in Slovakia. Our multiplexed RT-qPCR test showed 97% clinical sensitivity and retesting 6,886 SARS-CoV-2 positive samples obtained during three campaigns performed within one month, revealed pervasive spread of B.1.1.7 with an average prevalence of 82%. Labs can easily implement this test to rapidly scale B.1.1.7 surveillance efforts and it is particularly useful in countries with high prevalence of variants possessing only the ΔH69/ΔV70 deletion because current strategies using target failure assays incorrectly identify these as putative B.1.1.7 variants.