Fu Jen Catholic University

Lai C., Liu Y.H., Wang C., Wang Y., Hsueh S., Yen M., Ko W., Hsueh P.

Since the emergence of coronavirus disease 2019 (COVID-19) (formerly known as the 2019 novel coronavirus [2019-nCoV]) in Wuhan, China in December 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), more than 75,000 cases have been reported in 32 countries/regions, resulting in more than 2000 deaths worldwide. Despite the fact that most COVID-19 cases and mortalities were reported in China, the WHO has declared this outbreak as the sixth public health emergency of international concern. The COVID-19 can present as an asymptomatic carrier state, acute respiratory disease, and pneumonia. Adults represent the population with the highest infection rate; however, neonates, children, and elderly patients can also be infected by SARS-CoV-2. In addition, nosocomial infection of hospitalized patients and healthcare workers, and viral transmission from asymptomatic carriers are possible. The most common finding on chest imaging among patients with pneumonia was ground-glass opacity with bilateral involvement. Severe cases are more likely to be older patients with underlying comorbidities compared to mild cases. Indeed, age and disease severity may be correlated with the outcomes of COVID-19. To date, effective treatment is lacking; however, clinical trials investigating the efficacy of several agents, including remdesivir and chloroquine, are underway in China. Currently, effective infection control intervention is the only way to prevent the spread of SARS-CoV-2.

Zupanc A., Zhulanov V., Zhukova V., Zhou X., Zhang Y., Zhang Y., Zhang J., Zeyrek M., Zani L., Zakharov S., Yusa Y., Yuan C.Z., Yuan W., Yoshinobu T., Yonenaga M., et. al.

Lai C., Wang C., Hsueh P.

Co-infection has been reported in patients with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome, but there is limited knowledge on co-infection among patients with coronavirus disease 2019 (COVID-19). The prevalence of co-infection was variable among COVID-19 patients in different studies, however, it could be up to 50% among non-survivors. Co-pathogens included bacteria, such as Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumonia , Legionella pneumophila and Acinetobacter baumannii ; Candida species and Aspergillus flavus ; and viruses such as influenza, coronavirus, rhinovirus/enterovirus, parainfluenza, metapneumovirus, influenza B virus, and human immunodeficiency virus. Influenza A was one of the most common co-infective viruses, which may have caused initial false-negative results of real-time reverse-transcriptase polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Laboratory and imaging findings alone cannot help distinguish co-infection from SARS-CoV-2 infection. Newly developed syndromic multiplex panels that incorporate SARS-CoV-2 may facilitate the early detection of co-infection among COVID-19 patients. By contrast, clinicians cannot rule out SARS-CoV-2 infection by ruling in other respiratory pathogens through old syndromic multiplex panels at this stage of the COVID-19 pandemic. Therefore, clinicians must have a high index of suspicion for coinfection among COVID-19 patients. Clinicians can neither rule out other co-infections caused by respiratory pathogens by diagnosing SARS-CoV-2 infection nor rule out COVID-19 by detection of non-SARS-CoV-2 respiratory pathogens. After recognizing the possible pathogens causing co-infection among COVID-19 patients, appropriate antimicrobial agents can be recommended.

Bala S., Garg D., Thirumalesh B.V., Sharma M., Sridhar K., Inbaraj B.S., Tripathi M.

Environmental pollution brought on by xenobiotics and other related recalcitrant compounds have recently been identified as a major risk to both human health and the natural environment. Due to their toxicity and non-biodegradability, a wide range of pollutants, such as heavy metals, polychlorinated biphenyls, plastics, and various agrochemicals are present in the environment. Bioremediation is an effective cleaning technique for removing toxic waste from polluted environments that is gaining popularity. Various microorganisms, including aerobes and anaerobes, are used in bioremediation to treat contaminated sites. Microorganisms play a major role in bioremediation, given that it is a process in which hazardous wastes and pollutants are eliminated, degraded, detoxified, and immobilized. Pollutants are degraded and converted to less toxic forms, which is a primary goal of bioremediation. Ex situ or in situ bioremediation can be used, depending on a variety of factors, such as cost, pollutant types, and concentration. As a result, a suitable bioremediation method has been chosen. This review focuses on the most recent developments in bioremediation techniques, how microorganisms break down different pollutants, and what the future holds for bioremediation in order to reduce the amount of pollution in the world.

Verweij P.E., Rijnders B.J., Brüggemann R.J., Azoulay E., Bassetti M., Blot S., Calandra T., Clancy C.J., Cornely O.A., Chiller T., Depuydt P., Giacobbe D.R., Janssen N.A., Kullberg B., Lagrou K., et. al.

Invasive pulmonary aspergillosis is increasingly reported in patients with influenza admitted to the intensive care unit (ICU). Classification of patients with influenza-associated pulmonary aspergillosis (IAPA) using the current definitions for invasive fungal diseases has proven difficult, and our aim was to develop case definitions for IAPA that can facilitate clinical studies. A group of 29 international experts reviewed current insights into the epidemiology, diagnosis and management of IAPA and proposed a case definition of IAPA through a process of informal consensus. Since IAPA may develop in a wide range of hosts, an entry criterion was proposed and not host factors. The entry criterion was defined as a patient requiring ICU admission for respiratory distress with a positive influenza test temporally related to ICU admission. In addition, proven IAPA required histological evidence of invasive septate hyphae and mycological evidence for Aspergillus. Probable IAPA required the detection of galactomannan or positive Aspergillus culture in bronchoalveolar lavage (BAL) or serum with pulmonary infiltrates or a positive culture in upper respiratory samples with bronchoscopic evidence for tracheobronchitis or cavitating pulmonary infiltrates of recent onset. The IAPA case definitions may be useful to classify patients with COVID-19-associated pulmonary aspergillosis (CAPA), while awaiting further studies that provide more insight into the interaction between Aspergillus and the SARS-CoV-2-infected lung. A consensus case definition of IAPA is proposed, which will facilitate research into the epidemiology, diagnosis and management of this emerging acute and severe Aspergillus disease, and may be of use to study CAPA.

Lai C., Wang C., Wang Y., Hsueh S., Ko W., Hsueh P.

• As of 29 Feb. 2020, COVID-19 has affected 85 403 patients in 57 countries/territories and caused 2924 deaths in 9 countries. • The incidence (per 1 000 000 people) ranged from 61.4 in Republic of Korea to 0.0002 in India. • Daily cumulative index (DCI) of COVID-19 (cumulative cases/no. of days between first reported case and 29 Feb. 2020) was greatest in China (1320.85). • High DCIs were also seen in the Republic of Korea (78.78), Iran (43.11) and Italy (30.62). • The incidence and mortality were correlated with the DCI. It has been 2 months since the first case of coronavirus disease 2019 (COVID-19) was reported in Wuhan, China. So far, COVID-19 has affected 85 403 patients in 57 countries/territories and has caused 2924 deaths in 9 countries. However, epidemiological data differ between countries. Although China had higher morbidity and mortality than other sites, the number of new daily cases in China has been lower than outside of China since 26 February 2020. The incidence ranged from 61.44 per 1 000 000 people in the Republic of Korea to 0.0002 per 1 000 000 people in India. The daily cumulative index (DCI) of COVID-19 (cumulative cases/no. of days between the first reported case and 29 February 2020) was greatest in China (1320.85), followed by the Republic of Korea (78.78), Iran (43.11) and Italy (30.62). However, the DCIs in other countries/territories were

Gong N., Zhang Y., Teng X., Wang Y., Huo S., Qing G., Ni Q., Li X., Wang J., Ye X., Zhang T., Chen S., Wang Y., Yu J., Wang P.C., et. al.

Cancer vaccines hold great promise for improved cancer treatment. However, endosomal trapping and low immunogenicity of tumour antigens usually limit the efficiency of vaccination strategies. Here, we present a proton-driven nanotransformer-based vaccine, comprising a polymer–peptide conjugate-based nanotransformer and loaded antigenic peptide. The nanotransformer-based vaccine induces a strong immune response without substantial systemic toxicity. In the acidic endosomal environment, the nanotransformer-based vaccine undergoes a dramatic morphological change from nanospheres (about 100 nanometres in diameter) into nanosheets (several micrometres in length or width), which mechanically disrupts the endosomal membrane and directly delivers the antigenic peptide into the cytoplasm. The re-assembled nanosheets also boost tumour immunity via activation of specific inflammation pathways. The nanotransformer-based vaccine effectively inhibits tumour growth in the B16F10-OVA and human papilloma virus-E6/E7 tumour models in mice. Moreover, combining the nanotransformer-based vaccine with anti-PD-L1 antibodies results in over 83 days of survival and in about half of the mice produces complete tumour regression in the B16F10 model. This proton-driven transformable nanovaccine offers a robust and safe strategy for cancer immunotherapy. A shape-changing pH-responsive cancer vaccine delivers antigenic peptides directly to the cytoplasm and boosts the cellular immune response upon activation of the inflammasome pathway, efficiently inhibiting tumour growth and extending survival in animal tumour models.

Tantai X., Liu Y., Yeo Y.H., Praktiknjo M., Mauro E., Hamaguchi Y., Engelmann C., Zhang P., Jeong J.Y., van Vugt J.L., Xiao H., Deng H., Gao X., Ye Q., Zhang J., et. al.

Background & AimsThe association between sarcopenia and prognosis in patients with cirrhosis remains to be determined. In this study, we aimed to quantify the association between sarcopenia and the risk of mortality in patients with cirrhosis, stratified by sex, underlying liver disease etiology, and severity of hepatic dysfunction.MethodsPubMed, Web of Science, EMBASE, and major scientific conference sessions were searched without language restriction through 13 January 2021 with an additional manual search of bibliographies of relevant articles. Cohort studies of ≥100 patients with cirrhosis and ≥12 months of follow-up that evaluated the association between sarcopenia, muscle mass and the risk of mortality were included.ResultsTwenty-two studies involving 6,965 patients with cirrhosis were included. The pooled prevalence of sarcopenia in patients with cirrhosis was 37.5% overall (95% CI 32.4%-42.8%), and was higher in male patients, those with alcohol-associated liver disease, those with Child-Pugh grade C cirrhosis, and when sarcopenia was defined by L3-SMI (third lumbar-skeletal muscle index). Sarcopenia was associated with an increased risk of mortality in patients with cirrhosis (adjusted hazard ratio [aHR] 2.30, 95% CI 2.01-2.63), with similar findings in a sensitivity analysis of patients with cirrhosis without hepatocellular carcinoma (aHR 2.35, 95% CI 1.95-2.83) and in subgroups stratified by sex, liver disease etiology, and severity of hepatic dysfunction. The association between quantitative muscle mass index and mortality further supports the association between sarcopenia and poor prognosis (aHR 0.95, 95% CI 0.93-0.98). There was no significant heterogeneity in any of our analyses.ConclusionsSarcopenia was highly and independently associated with higher risk of mortality in patients with cirrhosis.Lay summaryThe prevalence of sarcopenia and its association with death in patients with cirrhosis remain unclear. This meta-analysis indicated that sarcopenia affected about one-third of patients with cirrhosis and up to 50% of patients with alcohol-related liver disease or Child-Pugh class C cirrhosis. Sarcopenia was independently associated with an ∼2-fold higher risk of mortality in patients with cirrhosis. The mortality rate increased with greater severity or longer durations of sarcopenia. Increasing awareness about the importance of sarcopenia in patients with cirrhosis among stakeholders must be prioritized.

Zupanc A., Zhulanov V., Zhukova V., Zhou X., Zhang Y., Zhang Y., Zhang J., Zeyrek M., Zani L., Zakharov S., Yusa Y., Yuan C.Z., Yuan W., Yoshinobu T., Yonenaga M., et. al.

In the original version of this manuscript, an error was introduced on pp352. '2.7nb:1.6nb' has been corrected to '2.4nb:1.3nb' in the current online and printed version. doi:10.1093/ptep/ptz106.

Lai H., Lin T., Chen T., Kuo Y., Chang C., Wu T., Shu C., Tsai Y., Swift S., Lu C.

ObjectiveChronic obstructive pulmonary disease (COPD) is a global disease characterised by chronic obstruction of lung airflow interfering with normal breathing. Although the microbiota of respiratory tract is established to be associated with COPD, the causality of gut microbiota in COPD development is not yet established. We aimed to address the connection between gut microbiota composition and lung COPD development, and characterise bacteria and their derived active components for COPD amelioration.DesignA murine cigarette smoking (CS)-based model of COPD and strategies evaluating causal effects of microbiota were performed. Gut microbiota structure was analysed, followed by isolation of target bacterium. Single cell RNA sequencing, together with sera metabolomics analyses were performed to identify host responsive molecules. Bacteria derived active component was isolated, followed by functional assays.ResultsGut microbiota composition significantly affects CS-induced COPD development, and faecal microbiota transplantation restores COPD pathogenesis. A commensal bacterium Parabacteroides goldsteinii was isolated and shown to ameliorate COPD. Reduction of intestinal inflammation and enhancement of cellular mitochondrial and ribosomal activities in colon, systematic restoration of aberrant host amino acids metabolism in sera, and inhibition of lung inflammations act as the important COPD ameliorative mechanisms. Besides, the lipopolysaccharide derived from P. goldsteinii is anti-inflammatory, and significantly ameliorates COPD by acting as an antagonist of toll-like receptor 4 signalling pathway.ConclusionThe gut microbiota–lung COPD axis was connected. A potentially benefial bacterial strain and its functional component may be developed and used as alternative agents for COPD prevention or treatment.