Objectives Sofosbuvir and daclatasvir are direct-acting antivirals highly effective against hepatitis C virus. There is some in silico and in vitro evidence that suggests these agents may also be effective against SARS-CoV-2. This trial evaluated the effectiveness of sofosbuvir in combination with daclatasvir in treating patients with COVID-19. Methods Patients with a positive nasopharyngeal swab for SARS-CoV-2 on RT–PCR or bilateral multi-lobar ground-glass opacity on their chest CT and signs of severe COVID-19 were included. Subjects were divided into two arms with one arm receiving ribavirin and the other receiving sofosbuvir/daclatasvir. All participants also received the recommended national standard treatment which, at that time, was lopinavir/ritonavir and single-dose hydroxychloroquine. The primary endpoint was time from starting the medication until discharge from hospital with secondary endpoints of duration of ICU stay and mortality. Results Sixty-two subjects met the inclusion criteria, with 35 enrolled in the sofosbuvir/daclatasvir arm and 27 in the ribavirin arm. The median duration of stay was 5 days for the sofosbuvir/daclatasvir group and 9 days for the ribavirin group. The mortality in the sofosbuvir/daclatasvir group was 2/35 (6%) and 9/27 (33%) for the ribavirin group. The relative risk of death for patients treated with sofosbuvir/daclatasvir was 0.17 (95% CI 0.04–0.73, P = 0.02) and the number needed to treat for benefit was 3.6 (95% CI 2.1–12.1, P < 0.01). Conclusions Given these encouraging initial results, and the current lack of treatments proven to decrease mortality in COVID-19, further investigation in larger-scale trials seems warranted.

Objective To examine the associations between dietary intake and tissue biomarkers of alpha linolenic acid (ALA) and risk of mortality from all causes, cardiovascular disease (CVD), and cancer. Design Systematic review and meta-analysis of prospective cohort studies. Data sources PubMed, Scopus, ISI Web of Science, and Google Scholar to 30 April 2021. Study selection Prospective cohort studies that reported the risk estimates for death from all causes, CVD, and cancer. Data synthesis Summary relative risks and 95% confidence intervals were calculated for the highest versus lowest categories of ALA intake using random effects and fixed effects models. Linear and non-linear dose-response analyses were conducted to assess the dose-response associations between ALA intake and mortality. Results 41 articles from prospective cohort studies were included in this systematic review and meta-analysis, totalling 1 197 564 participants. During follow-up ranging from two to 32 years, 198 113 deaths from all causes, 62 773 from CVD, and 65 954 from cancer were recorded. High intake of ALA compared with low intake was significantly associated with a lower risk of deaths from all causes (pooled relative risk 0.90, 95% confidence interval 0.83 to 0.97, I 2 =77.8%, 15 studies), CVD (0.92, 0.86 to 0.99, I 2 =48.2%, n=16), and coronary heart disease (CHD) (0.89, 0.81 to 0.97, I 2 =5.6%, n=9), and a slightly higher risk of cancer mortality (1.06, 1.02 to 1.11, I 2 =3.8%, n=10). In the dose-response analysis, a 1 g/day increase in ALA intake (equivalent to one tablespoon of canola oil or 0.5 ounces of walnut) was associated with a 5% lower risk of all cause (0.95, 0.91 to 0.99, I 2 =76.2%, n=12) and CVD mortality (0.95, 0.91 to 0.98, I 2 =30.7%, n=14). The pooled relative risks for the highest compared with lowest tissue levels of ALA indicated a significant inverse association with all cause mortality (0.95, 0.90 to 0.99, I 2 =8.2%, n=26). Also, based on the dose-response analysis, each 1 standard deviation increment in blood concentrations of ALA was associated with a lower risk of CHD mortality (0.92, 0.86 to 0.98, I 2 =37.1%, n=14). Conclusions The findings show that dietary ALA intake is associated with a reduced risk of mortality from all causes, CVD, and CHD, and a slightly higher risk of cancer mortality, whereas higher blood levels of ALA are associated with a reduced risk of all cause and CHD mortality only. Systematic review registration PROSPERO CRD42021229487.

Data on the association of nut intake with risk of cancer and its mortality are conflicting. Although previous meta-analyses summarized available findings in this regard, some limitations may distort their findings. Moreover, none of these meta-analyses examined the dose-response associations of total nut intake with the risk of specific cancers as well as associations between specific types of nuts and cancer mortality. Therefore, this study aimed to summarize available findings on the associations of total nut (tree nuts and peanuts), tree nut (walnuts, pistachios, macadamia nuts, pecans, cashews, almonds, hazelnuts, and Brazil nuts), peanut (whole peanuts without considering peanut butter), and peanut butter consumption with risk of cancer and its mortality by considering the above-mentioned points. We searched the online databases until March 2020 to identify eligible articles. In total, 43 articles on cancer risk and 9 articles on cancer mortality were included in the current systematic review and meta-analysis. The summary effect size (ES) for risk of cancer, comparing the highest with lowest intakes of total nuts, was 0.86 (95% CI: 0.81, 0.92, P < 0.001, I2 = 58.1%; P < 0.01), indicating a significant inverse association. Such a significant inverse association was also seen for tree nut intake (pooled ES: 0.87, 95% CI: 0.78–0.96, P < 0.01, I2 = 15.8%; P = 0.28). Based on the dose-response analysis, a 5-g/d increase in total nut intake was associated with 3%, 6%, and 25% lower risks of overall, pancreatic, and colon cancers, respectively. In terms of cancer mortality, we found 13%, 18%, and 8% risk reductions with higher intakes of total nuts, tree nuts, and peanuts, respectively. In addition, a 5-g/d increase in total nut intake was associated with a 4% lower risk of cancer mortality. In conclusion, our findings support the protective association between total nut and tree nut intake and the risk of cancer and its mortality.

Background The combination of sofosbuvir and daclatasvir has a well-established safety profile and improves clinical outcomes in HCV patients. In silico and in vitro studies suggest that sofosbuvir/daclatasvir may show antiviral activity against SARS-CoV-2. Methods Three clinical trials comparing sofosbuvir/daclatasvir-based regimens with a comparator in hospitalized COVID-19 patients were combined in a meta-analysis. The primary outcomes measured were clinical recovery within 14 days of randomization, time to clinical recovery and all-cause mortality. A two-step approach was used to analyse individual-level patient data. The individual trial statistics were pooled using the random-effects inverse-variance model. Results Our search identified eight studies of which three met the inclusion criteria (n = 176 patients); two studies were randomized and one was non-randomized. Baseline characteristics were similar across treatment arms. Clinical recovery within 14 days of randomization was higher in the sofosbuvir/daclatasvir arms compared with control arms [risk ratio = 1.34 (95% CI = 1.05–1.71), P = 0.020]. Sofosbuvir/daclatasvir improves time to clinical recovery [HR = 2.04 (95% CI = 1.25–3.32), P = 0.004]. The pooled risk of all-cause mortality was significantly lower in the sofosbuvir/daclatasvir arms compared with control arms [risk ratio = 0.31 (95% CI = 0.12–0.78), P = 0.013]. Conclusions Available evidence suggests that sofosbuvir/daclatasvir improves survival and clinical recovery in patients with moderate to severe COVID-19. However, the sample size for analysis was relatively small, one of the trials was not randomized and the designs were not standardized. These results need to be confirmed in larger randomized controlled trials.

Vitamin D and zinc are important components of nutritional immunity. This study compared the serum concentrations of 25-hydroxyvitamin D (25(OH)D) and zinc in COVID-19 outpatients with those of potentially non-infected participants. The association of clinical symptoms with vitamin D and zinc status was also examined. A checklist and laboratory examination were applied to collect data in a cross-sectional study conducted on 53 infected outpatients with COVID-19 and 53 potentially non-infected participants. Serum concentration of 25(OH)D were not significantly lower in patients with moderate illness (19 ± 12 ng/mL) than patients with asymptomatic or mild illness (29 ± 18 ng/mL), with a trend noted for a lower serum concentration of 25(OH)D in moderate than asymptomatic or mild illness patients (p = 0.054). Infected patients (101 ± 18 µg/dL) showed a lower serum concentration of zinc than potentially non-infected participants (114 ± 13 µg/dL) (p = 0.01). Patients with normal (odds ratio (OR), 0.19; p ≤ 0.001) and insufficient (OR, 0.3; p = 0.007) vitamin D status at the second to seventh days of disease had decreased OR of general symptoms compared to patients with vitamin D deficiency. This study revealed the importance of 25(OH)D measurement to predict the progression of general and pulmonary symptoms and showed that infected patients had significantly lower zinc concentrations than potentially non-infected participants.