Human Wharton's Jelly Mesenchymal Stem Cells Secretome Inhibits Human SARS-CoV-2 and Avian Infectious Bronchitis Coronaviruses.

Human SARS-CoV-2 and avian infectious bronchitis virus (IBV) are highly contagious and deadly coronaviruses, causing devastating respiratory diseases in humans and chickens. The lack of effective therapeutics exacerbates the impact of outbreaks associated with SARS-CoV-2 and IBV infections. Thus, novel drugs or therapeutic agents are highly in demand for controlling viral transmission and disease progression. Mesenchymal stem cells (MSC) secreted factors (secretome) are safe and efficient alternatives to stem cells in MSC-based therapies. This study aimed to investigate the antiviral potentials of human Wharton's jelly MSC secretome (hWJ-MSC-S) against SARS-CoV-2 and IBV infections in vitro and in ovo. The half-maximal inhibitory concentrations (IC50), cytotoxic concentration (CC50), and selective index (SI) values of hWJ-MSC-S were determined using Vero-E6 cells. The virucidal, anti-adsorption, and anti-replication antiviral mechanisms of hWJ-MSC-S were evaluated. The hWJ-MSC-S significantly inhibited infection of SARS-CoV-2 and IBV, without affecting the viability of cells and embryos. Interestingly, hWJ-MSC-S reduced viral infection by >90%, in vitro. The IC50 and SI of hWJ-MSC secretome against SARS-CoV-2 were 166.6 and 235.29 µg/mL, respectively, while for IBV, IC50 and SI were 439.9 and 89.11 µg/mL, respectively. The virucidal and anti-replication antiviral effects of hWJ-MSC-S were very prominent compared to the anti-adsorption effect. In the in ovo model, hWJ-MSC-S reduced IBV titer by >99%. Liquid chromatography-tandem mass spectrometry (LC/MS-MS) analysis of hWJ-MSC-S revealed a significant enrichment of immunomodulatory and antiviral proteins. Collectively, our results not only uncovered the antiviral potency of hWJ-MSC-S against SARS-CoV-2 and IBV, but also described the mechanism by which hWJ-MSC-S inhibits viral infection. These findings indicate that hWJ-MSC-S could be utilized in future pre-clinical and clinical studies to develop effective therapeutic approaches against human COVID-19 and avian IB respiratory diseases.

Interferon Beta-1b and Lopinavir-Ritonavir for Middle East Respiratory Syndrome.

BACKGROUND: Whether combined treatment with recombinant interferon beta-1b and lopinavir-ritonavir reduces mortality among patients hospitalized with Middle East respiratory syndrome (MERS) is unclear. METHODS: We conducted a randomized, adaptive, double-blind, placebo-controlled trial that enrolled patients at nine sites in Saudi Arabia. Hospitalized adults with laboratory-confirmed MERS were randomly assigned to receive recombinant interferon beta-1b plus lopinavir-ritonavir (intervention) or placebo for 14 days. The primary outcome was 90-day all-cause mortality, with a one-sided P-value threshold of 0.025. Prespecified subgroup analyses and safety analyses were conducted. Because of the pandemic of coronavirus disease 2019, the data and safety monitoring board requested an unplanned interim analysis and subsequently recommended the termination of enrollment and the reporting of the results. RESULTS: A total of 95 patients were enrolled; 43 patients were assigned to the intervention group and 52 to the placebo group. A total of 12 patients (28%) in the intervention group and 23 (44%) in the placebo group died by day 90. The analysis of the primary outcome, with accounting for the adaptive design, yielded a risk difference of -19 percentage points (upper boundary of the 97.5% confidence interval [CI], -3; one-sided P = 0.024). In a prespecified subgroup analysis, treatment within 7 days after symptom onset led to lower 90-day mortality than use of placebo (relative risk, 0.19; 95% CI, 0.05 to 0.75), whereas later treatment did not. Serious adverse events occurred in 4 patients (9%) in the intervention group and in 10 (19%) in the placebo group. CONCLUSIONS: A combination of recombinant interferon beta-1b and lopinavir-ritonavir led to lower mortality than placebo among patients who had been hospitalized with laboratory-confirmed MERS. The effect was greatest when treatment was started within 7 days after symptom onset. (Funded by the King Abdullah International Medical Research Center; MIRACLE ClinicalTrials.gov number, NCT02845843.).

Perception and attitude of healthcare workers in Saudi Arabia with regard to Covid-19 pandemic and potential associated predictors.

BACKGROUND: Healthcare workers (HCWs) face considerable mental and physical stress caring for patients with Covid-19. They are at higher risk of acquiring and transmitting this virus. This study aims to assess perception and attitude of HCWs in Saudi Arabia with regard to Covid-19, and to identify potential associated predictors. METHODS: In a cross-sectional study, HCWs at three tertiary hospitals in Saudi Arabia were surveyed via email with an anonymous link, by a concern scale about Covid-19 pandemic during 15-30 April, 2020. Concerns of disease severity, governmental efforts to contain it and disease outcomes were assessed using 32 concern statements in five distinct domains. Multiple regression analysis was used to identify predictors of high concern scores. RESULTS: A total of 844 HCW responded to the survey. Their average age was 40.4 ± 9.5 years, 40.3% were nurses, 58.2% had direct patient contact, and 77.3% were living with others. The majority of participants (72.1%) had overall concern scores of 55 or less out of a maximum score of 96 points, with an overall mean score of 48.5 ± 12.8 reflecting moderate level of concern. Three-fourth of respondents felt at risk of contracting Covid-19 infection at work, 69.1% felt threatened if a colleague contracted Covid-19, 69.9% felt obliged to care for patients infected with Covid-19 while 27.7% did not feel safe at work using the standard precautions available. Nearly all HCWs believed that the government should isolate patients with Covid-19 in specialized hospitals (92.9%), agreed with travel restriction to and/or from areas affected by Covid-19 (94.7%) and felt safe the government implemented curfew and movement restriction periods (93.6%). Predictors of high concern scores were; HCWs of Saudi nationality (p < 0.001), younger age (p = 0.003), undergraduate education (p = 0.044), living with others (p = 0.003) working in the western region (p = 0.003) and direct contact with patients (p = 0.018). CONCLUSIONS: This study highlights the high concern among HCWs about Covid-19 and identifies the predictors of those with highest concern levels. To minimize the potential negative impact of those concerns on the performance of HCWs during pandemics, measures are necessary to enhance their protection and to minimize the psychological effect of the perceived risk of infection.