Impacts of androgen deprivation therapy on the risks and outcomes of SARS-CoV-2 infection in patients with prostate cancer.

Studies have investigated the effects of androgen deprivation therapy (ADT) use on the incidence and clinical outcomes of coronavirus disease 2019 (COVID-19); however, the results have been inconsistent. We searched the PubMed, Medline, Cochrane, Scopus, and Web of Science databases from inception to March 2022; 13 studies covering 84 003 prostate cancer (PCa) patients with or without ADT met the eligibility criteria and were included in the meta-analysis. We calculated the pooled risk ratios (RRs) with 95% confidence intervals (CIs) to explore the association between ADT use and the infection risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and severity of COVID-19. After synthesizing the evidence, the pooled RR in the SARS-CoV-2 positive group was equal to 1.17, and the SARS-CoV-2 positive risk in PCa patients using ADT was not significantly different from that in those not using ADT (P = 0.544). Moreover, no significant results concerning the beneficial effect of ADT on the rate of intensive care unit admission (RR = 1.04, P = 0.872) or death risk (RR = 1.23, P = 0.53) were found. However, PCa patients with a history of ADT use had a markedly higher COVID-19 hospitalization rate (RR = 1.31, P = 0.015) than those with no history of ADT use. These findings indicate that ADT use by PCa patients is associated with a high risk of hospitalization during infection with SARS-CoV-2. A large number of high quality studies are needed to confirm these results.

Ultrarapid and ultrasensitive detection of SARS-CoV-2 antibodies in COVID-19 patients via a 3D-printed nanomaterial-based biosensing platform.

Rapid detection of antibodies during infection and after vaccination is critical for the control of infectious outbreaks, understanding immune response, and evaluating vaccine efficacy. In this manuscript, we evaluate a simple ultrarapid test for SARS-CoV-2 antibodies in COVID-19 patients, which gives quantitative results (i.e., antibody concentration) in 10-12 s using a previously reported nanomaterial-based three-dimensional (3D)-printed biosensing platform. This platform consists of a micropillar array electrode fabricated via 3D printing of aerosolized gold nanoparticles and coated with nanoflakes of graphene and specific SARS-CoV-2 antigens, including spike S1, S1 receptor-binding domain (RBD) and nucleocapsid (N). The sensor works on the principle of electrochemical transduction, where the change of sensor impedance is realized by the interactions between the viral proteins attached to the sensor electrode surface and the antibodies. The three sensors were used to test samples from 17 COVID-19 patients and 3 patients without COVID-19. Unlike other serological tests, the 3D sensors quantitatively detected antibodies at a concentration as low as picomole within 10-12 s in human plasma samples. We found that the studied COVID-19 patients had higher concentrations of antibodies to spike proteins (RBD and S1) than to the N protein. These results demonstrate the enormous potential of the rapid antibody test platform for understanding patients' immunity, disease epidemiology and vaccine efficacy, and facilitating the control and prevention of infectious epidemics.

[Overview of Meta-analysis of Lianhua Qingwen preparations in treatment of viral diseases].

This study aims to obtain higher-level evidence by overviewing the Meta-analysis of Lianhua Qingwen preparations in the treatment of viral diseases including influenza, coronavirus disease 2019(COVID-19), and hand, foot and mouth disease(HFMD). CNKI, Wanfang, VIP, China Clinical Trial Registry(ChiCTR), PubMed, EMbase, Web of Science, and Cochrane Library were searched for the Meta-analysis about the treatment of viral diseases with Lianhua Qingwen preparations from the database establishment to April 1, 2022. After literature screening and data extraction, AMSTAR2 and the grading of recommendations assessment, development and evaluations(GRADE) system were used to assess the methodological quality and evidence quality, respectively, and then the efficacy and safety outcomes of Lianhua Qingwen preparations in the treatment of viral diseases were summarized. Thirteen Meta-analysis were finally included, three of which were rated as low grade by AMSTAR2 and ten as very low grade. A total of 75 outcome indicators were obtained, involving influenza, COVID-19, and HFMD. According to the GRADE scoring results, the 75 outcome indicators included 5(6.7%) high-level indicators, 18(24.0%) mediate-level indicators, 25(33.3%) low-level evidence indicators, and 27(36.0%) very low-level indicators.(1)In the treatment of influenza, Lianhua Qingwen preparations exhibited better clinical efficacy than other Chinese patent medicines and Ribavirin and had similar clinical efficacy compared with Oseltamivir. Lianhua Qingwen preparations were superior to other Chinese patent medicines, Oseltamivir, and Ribavirin in alleviating clinical symptoms. They showed no significant differences from Oseltamivir or conventional anti-influenza treatment in terms of the time to and rate of negative result of viral nucleic acid test.(2)In the treatment of COVID-19, Lianhua Qingwen preparation alone or combined with conventional treatment was superior to conventional treatment in terms of total effective rate, main symptom subsidence rate and time, fever clearance rate, duration of fever, time to fever clearance, cough subsidence rate, time to cough subsidence, fatigue subsidence rate, time to fatigue subsidence, myalgia subsidence rate, expectoration subsidence rate, chest tightness subsidence rate, etc. Lianhua Qingwen preparations no difference from conventional treatment in terms of subsiding sore throat, nausea, diarrhea, loss of appetite, headache, and dyspnea. In terms of chest CT improvement rate, rate of progression to severe case, cure time, and hospitalization time, Lianhua Qingwen alone or in combination with conventional treatment was superior to conventional treatment.(3)In the treatment of HFMD, Lianhua Qingwen Granules was superior to conventional treatment in terms of total effective rate, average fever clearance time, time to herpes subsidence, and time to negative result of viral nucleic acid test.(4)In terms of safety, Lianhua Qingwen preparations led to low incidence of adverse reactions, all of which were mild and disappeared after drug withdrawal. The available evidence suggests that in the treatment of influenza, COVID-19, and HFMD, Lianhua Qingwen preparations can relieve the clinical symptoms, shorten the hospitalization time, and improve the chest CT. They have therapeutic effect and good safety in the treatment of viral diseases. However, due to the low quality of available studies, more high-quality clinical trials are needed to support the above conclusions.

N protein-based ultrasensitive SARS-CoV-2 antibody detection in seconds via 3D nanoprinted, microarchitected array electrodes.

Rapid detection of antibodies to SARS-CoV-2 is critical for COVID-19 diagnostics, epidemiological research, and studies related to vaccine evaluation. It is known that the nucleocapsid (N) is the most abundant protein of SARS-CoV-2 and can serve as an excellent biomarker due to its strong immunogenicity. This paper reports a rapid and ultrasensitive 3D biosensor for quantification of COVID-19 antibodies in seconds via electrochemical transduction. This sensor consists of an array of three-dimensional micro-length-scale electrode architecture that is fabricated by aerosol jet 3D printing, which is an additive manufacturing technique. The micropillar array is coated with N proteins via an intermediate layer of nano-graphene and is integrated into a microfluidic channel to complete an electrochemical cell that uses antibody-antigen interaction to detect the antibodies to the N protein. Due to the structural innovation in the electrode geometry, the sensing is achieved in seconds, and the sensor shows an excellent limit of detection of 13 fm and an optimal detection range of 100 fm to 1 nm. Furthermore, the sensor can be regenerated at least 10 times, which reduces the cost per test. This work provides a powerful platform for rapid screening of antibodies to SARS-CoV-2 after infection or vaccination.

Anti-Inflammatory Azaphilones from the Edible Alga-Derived Fungus Penicillium sclerotiorum.

To discover the new medical entity from edible marine algae, our continuously natural product investigation focused on endophytes from marine macroalgae Grateloupia sp. Two new azaphilones, 8a-epi-hypocrellone A (1), 8a-epi-eupenicilazaphilone C (2), together with five known azaphilones, hypocrellone A (3), eupenicilazaphilone C (4), ((1E,3E)-3,5-dimethylhepta-1,3-dien-1-yl)-2,4-dihydroxy-3-methylbenzaldehyde (5), sclerotiorin (6), and isochromophilone IV (7) were isolated from the alga-derived fungus Penicillium sclerotiorum. The structures of isolated azaphilones (1-7) were elucidated by spectrometric identification, especially HRESIMS, CD, and NMR data analyses. Concerning bioactivity, cytotoxic, anti-inflammatory, and anti-fibrosis activities of those isolates were evaluated. As a result, compound 1 showed selective toxicity toward neuroblastoma cell line SH-SY5Y among seven cancer and one fibroblast cell lines. 20 µM of compounds 1, 3, and 7 inhibited the TNF-α-induced NFκB phosphorylation but did not change the NFκB activity. Compounds 2 and 6 respectively promoted and inhibited SMAD-mediated transcriptional activities stimulated by TGF-ß.

An observation approach in evaluation of ozone production to precursor changes during the COVID-19 lockdown.

The increase of surface ozone during the Corona Virus Disease 2019 (COVID-19) lockdown in China has aroused great concern. In this study, we combine 1.5 years of measurements for ozone, volatile organic compounds (VOCs), and nitrogen oxide (NOX) at four sites to investigate the effect of COVID-19 lockdown on surface ozone in Dongguan, an industrial city in southern China. We show that the average concentrations of NOX and VOCs decreased by 70%-77% and 54%-68% during the lockdown compared to pre-lockdown, respectively. Based on the source apportionment of VOCs, the contribution of industrial solvent use reduced significantly (86%-94%) during the lockdown, and climbed back slowly along with the re-opening of the industry after lockdown. A slight increase in mean ozone concentration (3%-14%) was observed during the lockdown. The rise of ozone was the combined effect of substantial increase at night (58%-91%) and small reduction in the daytime (1%-17%). These conflicting observations in ozone response between day and night to emission change call for a more detailed approach to diagnostic ozone production response with precursor changes, rather than directly comparing absolute concentrations. We propose that the ratio of daily Ox (i.e. ozone + NO2) enhancement to solar radiation can provide a diagnostic parameter for ozone production response during the lockdown period. Smaller ratio of daily OX (ozone + NO2) enhancement to solar radiation during the lockdown were observed from the long-term measurements in Dongguan, suggesting significantly weakened photochemistry during the lockdown successfully reduces local ozone production. Our proposed approach can provide an evaluation of ozone production response to precursor changes from restrictions of social activities during COVID-19 epidemic and also other regional air quality abatement measures (e.g. public mega-events) around the globe.

Antibody Tests: Sensing of COVID-19 Antibodies in Seconds via Aerosol Jet Nanoprinted Reduced-Graphene-Oxide-Coated 3D Electrodes (Adv. Mater. 7/2021)

In article number 2006647, Rahul Panat and co-workers report the development of a 10-second COVID-19 antibody test that represents the fastest detection of this pathogen biomarker. The test uses an electrochemical cell consisting of aerosol jet nanoprinted 3D micropillar electrodes coated with reduced graphene oxide and viral antigens. This generic platform could be a game-changer in controlling the spread of infectious diseases during pandemics.

Structural Basis of SARS-CoV-2 Polymerase Inhibition by Favipiravir.

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed into an unprecedented global pandemic. Nucleoside analogs, such as Remdesivir and Favipiravir, can serve as the first-line broad-spectrum antiviral drugs by targeting the viral polymerases. However, the underlying mechanisms for the antiviral efficacies of these drugs are far from well understood. Here, we reveal that Favipiravir, as a pyrazine derivative, could be incorporated into the viral RNA products by mimicking both adenine and guanine nucleotides. This drug thus inhibits viral replication mainly by inducing mutations in progeny RNAs, different from Remdesivir or other RNA-terminating nucleoside analogs that impair the elongation of RNA products. We further determined the cryo-EM structure of Favipiravir bound to the replicating polymerase complex of SARS-CoV-2 in the pre-catalytic state. This structure provides a missing snapshot for visualizing the catalysis dynamics of coronavirus polymerase, and reveals an unexpected base-pairing pattern between Favipiravir and pyrimidine residues that may explain its capacity for mimicking both adenine and guanine nucleotides. These findings shed light on the mechanism of coronavirus polymerase catalysis and provide a rational basis for developing antiviral drugs to combat the SARS-CoV-2 pandemic.

Sensing of COVID-19 Antibodies in Seconds via Aerosol Jet Nanoprinted Reduced-Graphene-Oxide-Coated 3D Electrodes.

Rapid diagnosis is critical for the treatment and prevention of diseases. An advanced nanomaterial-based biosensing platform that detects COVID-19 antibodies within seconds is reported. The biosensing platform is created by 3D nanoprinting of three-dimensional electrodes, coating the electrodes by nanoflakes of reduced-graphene-oxide (rGO), and immobilizing specific viral antigens on the rGO nanoflakes. The electrode is then integrated with a microfluidic device and used in a standard electrochemical cell. When antibodies are introduced on the electrode surface, they selectively bind with the antigens, changing the impedance of the electrical circuit which is detected via impedance spectroscopy. Antibodies to SARS-CoV-2 spike S1 protein and its receptor-binding-domain (RBD) are detected at a limit-of-detection of 2.8 × 10-15 and 16.9 × 10-15 m, respectively, and read by a smartphone-based user interface. The sensor can be regenerated within a minute by introducing a low-pH chemistry that elutes the antibodies from the antigens, allowing successive sensing of test samples using the same sensor. Sensing of S1 and RBD antibodies is specific, which cross-reacts neither with other antibodies such as RBD, S1, and nucleocapsid antibody nor with proteins such as interleukin-6. The proposed sensing platform could also be useful to detect biomarkers for other infectious agents such as Ebola, HIV, and Zika.

Update on recommendations for the diagnosis and treatment of SARS-CoV-2 infection in children.

Since the outbreak of novel coronavirus infection pneumonia in Wuhan City, China, in late 2019, such cases have been gradually reported in other parts of China and abroad. Children have become susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) because of their immature immune function. As the outbreak has progressed, more cases of novel coronavirus infection/pneumonia in children have been reported. Compared with adults, the impact of SARS-CoV-2 infection in children is less severe, with a lower incidence and susceptibility in children, which results in fewer children being tested, thereby underestimating the actual number of infections. Therefore, strengthening the diagnosis of the disease is particularly important for children, and early and clear diagnosis can determine treatment strategies and reduce the harm caused by the disease to children. According to the Novel Coronavirus Infection Pneumonia Diagnosis and Treatment Standards (trial version 7) issued by National Health Committee and the latest diagnosis and treatment strategies for novel coronavirus infection pneumonia in children, this review summarizes current strategies on diagnosis and treatment of SARS-CoV-2 infection in children.

Structural and Biochemical Characterization of the nsp12-nsp7-nsp8 Core Polymerase Complex from SARS-CoV-2.

The ongoing global pandemic of coronavirus disease 2019 (COVID-19) has caused a huge number of human deaths. Currently, there are no specific drugs or vaccines available for this virus (SARS-CoV-2). The viral polymerase is a promising antiviral target. Here, we describe the near-atomic-resolution structure of the SARS-CoV-2 polymerase complex consisting of the nsp12 catalytic subunit and nsp7-nsp8 cofactors. This structure highly resembles the counterpart of SARS-CoV with conserved motifs for all viral RNA-dependent RNA polymerases and suggests a mechanism of activation by cofactors. Biochemical studies reveal reduced activity of the core polymerase complex and lower thermostability of individual subunits of SARS-CoV-2 compared with SARS-CoV. These findings provide important insights into RNA synthesis by coronavirus polymerase and indicate adaptation of SARS-CoV-2 toward humans with a relatively lower body temperature than the natural bat hosts.