Clinical characteristics, risk factors and antiviral treatments of influenza in immunosuppressed inpatients in Beijing during the 2015–2020 influenza seasons

Background Compared with immunocompetent patients, immunosuppressed patients have higher morbidity and mortality, a longer duration of viral shedding, more frequent complications, and more antiviral resistance during influenza infections. However, few data on this population in China have been reported. We analysed the clinical characteristics, effects of antiviral therapy, and risk factors for admission to the intensive care unit (ICU) and death in this population after influenza infections and explored the influenza vaccination situation for this population. Methods We analysed 111 immunosuppressed inpatients who were infected with influenza virus during the 2015–2020 influenza seasons. Medical data were collected through the electronic medical record system and analysed. Univariate analysis and multivariate logistics analysis were used to identify risk factors. Results The most common cause of immunosuppression was malignancies being treated with chemotherapy (64.0%, 71/111), followed by haematopoietic stem cell transplantation (HSCT) (23.4%, 26/111). The most common presenting symptoms were fever and cough. Dyspnoea, gastrointestinal symptoms and altered mental status were more common in HSCT patients than in patients with immunosuppression due to other causes. Approximately 14.4% (16/111) of patients were admitted to the ICU, and 9.9% (11/111) of patients died. Combined and double doses of neuraminidase inhibitors did not significantly reduce the risk of admission to the ICU or death. Risk factors for admission to the ICU were dyspnoea, coinfection with other pathogens and no antiviral treatment within 48 h. The presence of dyspnoea and altered mental status were independently associated with death. Only 2.7% (3/111) of patients less than 12 months old had received a seasonal influenza vaccine. Conclusion Fever and other classic symptoms of influenza may be absent in immunosuppressed recipients, especially in HSCT patients. Conducting influenza virus detection at the first presentation seems to be a good choice for early diagnosis. Clinicians should pay extra attention to immunosuppressed patients with dyspnoea, altered mental status, coinfection with other pathogens and no antiviral treatment within 48 h because these patients have a high risk of severe illness. Inactivated influenza vaccines are recommended for immunosuppressed patients.

Features of patients who developed hepatocellular carcinoma after direct-acting antiviral treatment for hepatitis C Virus

Background The features of hepatitis C virus patients with a sustained virologic response (SVR) who developed hepatocellular carcinoma (HCC) after direct-acting antiviral (DAA) therapy are unclear. Methods The study population included 1494 DAA-SVR patients without a history of HCC. The cumulative carcinogenesis rate after the end of treatment (EOT) and factors related to HCC were analyzed. Results Sixty (4.0%) patients developed HCC during a median observation period of 47.6 months. At four years, the cumulative carcinogenesis rate was 4.7%. A Cox proportional hazards analysis showed that age ≥73 years (hazard ratio [HR]: 2.148), male sex (HR: 3.060), hyaluronic acid (HA) ≥75 ng/mL (HR: 3.996), alpha-fetoprotein at EOT (EOT-AFP) ≥5.3 ng/mL (HR: 4.773), and albumin at EOT (EOT-Alb) <3.9 g/dL (HR: 2.305) were associated with HCC development. Especially, EOT-AFP ≥5.3 ng/mL was associated with HCC development after 3 years from EOT (HR: 6.237). Among patients who developed HCC, AFP did not increase in patients with EOT-AFP <5.3 ng/mL at the onset of HCC. Of these 5 factors, EOT-AFP ≥5.3 ng/mL was scored as 2 points; the others were scored as 1 point. The 4-year cumulative carcinogenesis rate for patients with total scores of 0–2, 3–4, and 5–6 points were 0.6%, 11.9%, and 27.1%, respectively (p<0.001). Conclusions EOT-AFP ≥5.3 ng/mL is useful for predicting HCC development after an SVR. However, AFP does not increase in patients with EOT-AFP <5.3 ng/mL at the onset of HCC. The combination of EOT-AFP, age, sex, HA, and EOT-Alb is important for predicting carcinogenesis.

Favipiravir, umifenovir and camostat mesylate: a comparative study against SARS-CoV-2

Since the first cases the coronavirus disease caused by SARS-CoV-2 (COVID-19) reported in December 2019, worldwide continuous efforts have been placed both for the prevention and treatment of this infectious disease. As new variants of the virus emerge, the need for an effective antiviral treatment continues. The concept of preventing SARS-CoV-2 on both pre-entry and post-entry stages has not been much studied. Therefore, we compared the antiviral activities of three antiviral drugs which have been currently used in the clinic. In silico docking analyses and in vitro viral infection in Vero E6 cells were performed to delineate their antiviral effectivity when used alone or in combination. Both in silico and in vitro results suggest that the combinatorial treatment by favipiravir and umifenovir or camostat mesylate has more antiviral activity against SARS-CoV-2 rather than single drug treatment. These results suggest that inhibiting both viral entry and viral replication at the same time is much more effective for the antiviral treatment of SARS-CoV-2.

Efficacy of Antiviral Treatment in Hepatitis C Virus (HCV)-Driven Monoclonal Gammopathies Including Myeloma

Multiple myeloma (MM) remains an incurable plasma cell malignancy. While its origin is enigmatic, an association with infectious pathogens including hepatitis C virus (HCV) has been suggested. Here we report nine patients with monoclonal gammopathy of undetermined significance (MGUS) or MM with previous HCV infection, six of whom received antiviral treatment. We studied the evolution of the gammopathy disease, according to anti-HCV treatment and antigen specificity of purified monoclonal immunoglobulin, determined using the INNO-LIA™ HCV Score assay, dot-blot assays, and a multiplex infectious antigen microarray. The monoclonal immunoglobulin from 6/9 patients reacted against HCV. Four of these patients received antiviral treatment and had a better evolution than untreated patients. Following antiviral treatment, one patient with MM in third relapse achieved complete remission with minimal residual disease negativity. For two patients who did not receive antiviral treatment, disease progressed. For the two patients whose monoclonal immunoglobulin did not react against HCV, antiviral treatment was not effective for MGUS or MM disease. Our results suggest a causal relationship between HCV infection and MGUS and MM progression. When HCV was eliminated, chronic antigen-stimulation disappeared, allowing control of clonal plasma cells. This opens new possibilities of treatment for MGUS and myeloma.

The Presence of Non-organ-specific Autoantibodies in Chronic Hepatitis C Treatment-naive Patients

Background: In the patients with hepatitis C virus (HCV) various immune mediated phenomena are described, and non organ specific autoantibodies (NOSAs) in particular are common. The aim of the present study was to investigate the NOSAs prevalence in chronic hepatitis C treatment naive patients. Patients and Methods: Sera of 76 consecutive HCV treatment naive patients were considered to be eligible for this study for evaluation of Antinuclear, antismooth muscle, antimitochondrial, antineutrophil cytoplasmatic and antiliver kidney microsomal antibodies. Criteria of eligibility were serum antiHCV antibody and HCV RNA positivity, chronic inflammation revealed by histological analysis of the liver, genotyping, treatment naive patients, and no have the diagnosis of probable or definite autoimmune hepatitis. Results: Mean chronological age for the 76 patients (44 females and 32 males) was 51.3 years (range: 20 to 67 years). Nineteen patients (25.0%) infected with HCV had detectable levels of NOSAs at before combined antiviral treatment. SMA was present in 16 (21.0%) of 76 patients, ANA in 2 patients (2.6%), and pANCA (perinuclear ANCA) in 1 patients (1.3%). No patient had specimens reactive to AMA, LMK, or cANCA (cytoplasmic ANCA). Conclusions: In this study, we show the NOSAs positivity in chronic hepatitis c treatment naive patients. Assigned to high prevalence of SMA positivity is associated with high METAVIR score, and HCV genotype 1 and 1b, may reflect a release of intracellular antigens at the time of hepatocellular injury triggering immune responses in the form of autoantibody production or a direct infection of immunocytes by the HCV. Keywords: hepatitis C, treatment naive, non organ specific antibodies, chronic liver disease

Effectiveness of Positive Deviance, an Asset-Based Behavior Change Approach, to Improve Knowledge, Attitudes, and Practices Regarding Dengue in Low-Income Communities (Slums) of Islamabad, Pakistan: A Mixed-Method Study

Dengue is a mosquito-borne, viral disease that has emerged as a global health concern in recent years. In the absence of specific antiviral treatment and vaccines, prevention remains the key strategy for dengue control. Therefore, innovative and community-driven approaches are required to improve the vector control practices. This study applied and evaluated the positive deviance (PD) approach on dengue prevention and control in selected slums of Islamabad during June–October 2020. The two most dengue-affected slums, the Faisal colony and France colony, were purposively selected as intervention and control groups, respectively. A total of 112 participants (56 for the intervention and 56 for the control group) participated in the study. The intervention group was exposed for two months to locally identified role model behaviors through weekly interactive sessions, dengue sketch competitions, and role plays. Another two months enabled the community to practice these behaviors without any external support in order to explore the intervention’s sustainability. Three surveys were conducted: before the intervention, after two months, and after four months, to assess any changes in the knowledge, attitudes, and practices of participating communities. Results found that the PD intervention had a significant positive impact on dengue knowledge, attitudes, and practices in the intervention group. PD could offer an empowering and efficient community engagement tool for future dengue prevention and control, both in Pakistan and more globally.

Middle East respiratory syndrome coronavirus infection in camelids

Middle East respiratory syndrome coronavirus (MERS-CoV) is the cause of a severe respiratory disease with a high case fatality rate in humans. Since its emergence in mid-2012, 2578 laboratory-confirmed cases in 27 countries have been reported by the World Health Organization, leading to 888 known deaths due to the disease and related complications. Dromedary camels are considered the major reservoir host for this virus leading to zoonotic infection in humans. Dromedary camels, llamas, and alpacas are susceptible to MERS-CoV, developing a mild-to-moderate upper respiratory tract infection characterized by epithelial hyperplasia as well as infiltration of neutrophils, lymphocytes, and some macrophages within epithelium, lamina propria, in association with abundant viral antigen. The very mild lesions in the lower respiratory tract of these camelids correlate with absence of overt illness following MERS-CoV infection. Unfortunately, there is no approved antiviral treatment or vaccine for MERS-CoV infection in humans. Thus, there is an urgent need to develop intervention strategies in camelids, such as vaccination, to minimize virus spillover to humans. Therefore, the development of camelid models of MERS-CoV infection is key not only to assess vaccine prototypes but also to understand the biologic mechanisms by which the infection can be naturally controlled in these reservoir species. This review summarizes information on virus-induced pathological changes, pathogenesis, viral epidemiology, and control strategies in camelids, as the intermediate hosts and primary source of MERS-CoV infection in humans.

Acute HBV Related ALF- Successful Outcome with Oral Antiviral Treatment

Case report: We present a young female of fourteen years who was admitted to the hospital with short duration of Icterus, malaise, vomiting and diagnosed to be having acute hepatitis B. She went into acute liver failure as evidenced by development of hepatic encephalopathy and coagulopathy. She was managed on lines of hepatic encephalopathy along with oral antiviral treatment. She recovered successfully and was discharged after two weeks in heamodynamically stable condition. After a gap of six months, she became Hepatitis B surface (HbsAg) & hepatitis B e-antigen (HbeAg) negative and Hepatitis B Virus DNA (HBV DNA) was undetectable with normal liver function tests. She is on regular follow up for last one year and is absolutely normal. Conclusion: Acute hepatitis B can go into acute liver failure in 1% of cases, treatment for which includes liver transplantation and oral antiviral treatment which is especially helpful in cases who cannot afford liver transplantation, as was in our case.