The IFNL4 gene is a recently discovered type III interferon, which in a significant fraction of the human population harbours a frameshift mutation abolishing the IFNk4 ORF. The expression of IFNk4 is correlated with both poor spontaneous clearance of hepatitis C virus (HCV) and poor response to treatment with type I interferon. Here, we show that the IFNL4 gene encodes an active type III interferon, named IFNk4, which signals through the IFNkR1 and IL-10R2 receptor chains. Recombinant IFNk4 is antiviral against both HCV and coronaviruses at levels comparable to IFNk3. However, the secretion of IFNk4 is impaired compared to that of IFNk3, and this impairment is not due to a weak signal peptide, which was previously believed. We found that IFNk4 gets N-linked glycosylated and that this glycosylation is required for secretion. Nevertheless, this glycosylation is not required for activity. Together, these findings result in the paradox that IFNk4 is strongly antiviral but a disadvantage during HCV infection.

The IFNL4 gene is negatively associated with spontaneous and treatment-induced clearance of hepatitis C virus infection. The activity of IFNλ4 has an important causal role in the pathogenesis, but the molecular details are not fully understood. One possible reason for the detrimental effect of IFNλ4 could be a tissue-specific regulation of an unknown subset of genes. To address both tissue and subtype specificity in the interferon response, we treated primary human hepatocytes and airway epithelial cells with IFNα, IFNλ3 or IFNλ4 and assessed interferon mediated gene regulation using transcriptome sequencing. Our data show a surprisingly similar response to all three subtypes of interferon. We also addressed the tissue specificity of the response, and identified a subset of tissue-specific genes. However, the interferon response is robust in both tissues with the majority of the identified genes being regulated in hepatocytes as well as airway epithelial cells. Thus we provide an in-depth analysis of the liver interferon response seen over an array of interferon subtypes and compare it to the response in the lung epithelium.

Background Healthcare workers (HCWs) fighting against the COVID-19 pandemic are under incredible pressure, which puts them at risk of developing mental health problems. This study aimed to determine the prevalence of depression, anxiety, and stress among HCWs responding to COVID-19 and its associated factors. Methods A multi-country cross-sectional study was conducted during July–August 2020 among HCWs responding to COVID-19 in nine Eastern Mediterranean Region (EMR) countries. Data were collected using an online questionnaire administered using KoBo Toolbox. Mental problems were assessed using the Depression, Anxiety, and Stress Scale (DASS-21). Results A total of 1448 HCWs from nine EMR countries participated in this study. About 51.2% were male and 52.7% aged ≤ 30 years. Of all HCWs, 57.5% had depression, 42.0% had stress, and 59.1% had anxiety. Considering the severity, 19.2%, 16.1%, 26.6% of patients had severe to extremely severe depression, stress, and anxiety, respectively. Depression, stress, anxiety, and distress scores were significantly associated with participants’ residency, having children, preexisting psychiatric illness, and being isolated for COVID-19. Furthermore, females, those working in a teaching hospital, and specialists had significantly higher depression and stress scores. Married status, current smoking, diabetes mellitus, having a friend who died with COVID-19, and high COVID-19 worry scores were significantly associated with higher distress scores. Conclusions Mental problems were prevalent among HCWs responding to COVID-19 in EMR. Therefore, special interventions to promote mental well-being among HCWs responding to COVID-19 need to be immediately implemented.

The COVID-19 outbreak started as pneumonia in December 2019 in Wuhan, China. The subsequent pandemic was declared as the sixth public health emergency of international concern on January 30, 2020, by the World Health Organization. Pakistan could be a potential hotspot for COVID-19 owing to its high population of 204.65 million and its struggling health care and economic systems. Pakistan was able to tackle the challenge with relatively mild repercussions. The present analysis has been conducted to highlight the situation of the disease in Pakistan in 2020 and the measures taken by various stakeholders coupled with support from the community to abate the risk of catastrophic spread of the virus.

Background Since the first reports of COVID-19 infection, the foremost requirement has been to identify a treatment regimen that not only fights the causative agent but also controls the associated complications of the infection. Due to the time-consuming process of drug discovery, physicians have used readily available drugs and therapies for treatment of infections to minimize the death toll. Objective The aim of this study is to provide a snapshot analysis of the major drugs used in a cohort of 1562 Pakistani patients during the period from May to July 2020, when the first wave of COVID-19 peaked in Pakistan. Methods A retrospective observational study was performed to provide an overview of the major drugs used in a cohort of 1562 patients with COVID-19 admitted to the four major tertiary-care hospitals in the Rawalpindi-Islamabad region of Pakistan during the peak of the first wave of COVID-19 in the country (May-July 2020). Results Antibiotics were the most common choice out of all the therapies employed, and they were used as first line of treatment for COVID-19. Azithromycin was the most prescribed drug for treatment. No monthly trend was observed in the choice of antibiotics, and these drugs appeared to be a random but favored choice throughout the months of the study. It was also noted that even antibiotics used for multidrug resistant infections were prescribed irrespective of the severity or progression of the infection. The results of the analysis are alarming, as this approach may lead to antibiotic resistance and complications in immunocompromised patients with COVID-19. A total of 1562 patients (1064 male, 68.1%, and 498 female, 31.9%) with a mean age of 47.35 years (SD 17.03) were included in the study. The highest frequency of patient hospitalizations occurred in June (846/1562, 54.2%). Conclusions Guidelines for a targeted treatment regime are needed to control related complications and to limit the misuse of antibiotics in the management of COVID-19.