Enhance antibiotic resistance and human health risks in aerosols during the COVID-19 pandemic.

Aerosols are an important route for the transmission of antibiotic resistance genes (ARGs). Since the 2019 (COVID-19) pandemic, the large-scale use of disinfectants has effectively prevented the spread of environmental microorganisms, but studies regarding the antibiotic resistance of airborne bacteria remain limited. This study focused on four functional urban areas (commercial areas, educational areas, residential areas and wastewater treatment plant) to study the variations in ARG abundances, bacterial community structures and risks to human health during the COVID-19 pandemic in aerosol. The results indicated the abundance of ARGs during the COVID-19 period were up to approximately 13-fold greater than before the COVID-19 period. Large-scale disinfection resulted in a decrease in total bacterial abundance. However, chlorine-resistant bacteria tended to be survived. Among the four functional areas, the diversity and abundance of aerosol bacteria were highest in commercial aera. Antibiotic susceptibility assays suggested elevated resistance of isolated bacteria to several tested antibiotics due to disinfection exposure. The potential exposure risks of ARGs to human health were 2 times higher than before the COVID-19 pandemic, and respiratory intake was the main exposure route. The results highlighted the elevated antibiotic resistance of bacteria in aerosols that were exposed to disinfectants after the COVID-19 pandemic. This study provides theoretical guidance for the rational use of disinfectants and control of antimicrobial resistance.

A Review and Perspective of Environmental Disinfection Technology Based on Microwave Irradiation.

Purpose of Review: In the context of COVID-19 sweeping the world, the development of microbial disinfection methods in gas, liquid, and solid media has received widespread attention from researchers. As a disinfection technology that can adapt to different environmental media, microwave-assisted disinfection has the advantages of strong permeability, no secondary pollution, etc. The purpose of this review is to put forward new development requirements for future microwave disinfection strategies by summarizing current microwave disinfection methods and effects. From the perspective of the interaction mechanism of microwave and microorganisms, this review provides a development direction for more accurate and microscopic disinfection mechanism research. Recent Findings: Compared to other traditional environmental disinfection techniques, microwave-assisted disinfection means have the advantages of being more destructive, free of secondary contamination, and thorough. Currently, researchers generally agree that the efficiency of microwave disinfection is the result of a combination of thermal and non-thermal effects. However, the performance of microwave disinfection shows the differences in the face of different environmental media as well as different types of microorganisms. Summary: This review highlights the inactivation mechanism of microwave-assisted disinfection techniques used in different scenarios. Suggestions for promoting the efficiency and overcoming the limitations of low energy utilization, complex reactor design, and inaccurate monitoring methods are proposed.

Release of microplastics and nanoplastics in water from disposable surgical masks after disinfection.

During the COVID-19 pandemic, disposable surgical masks were generally disinfected and reused due to mask shortages. Herein, the role of disinfected masks as a source of microplastics (MPs) and nanoplastics (NPs) was investigated. The amount of MPs and NPs released from masks disinfected by UV ranged from 1054 ± 106 to 2472 ± 70 and from 2.55 ± 0.22 × 109 to 6.72 ± 0.27 × 109 particles/piece, respectively, comparable to that of the undisinfected masks, and the MPs were changed to small-sized particles. The amount of MPs and NPs released after alcohol and steam treatment were respectively lower and higher than those from undisinfected masks, and MPs were shifted to small-sized particles. The amount of MPs and NPs released in water after autoclaving was lower than for undisinfected masks. In all, the amount of fibers released after disinfection decreased greatly, and certain disinfection processes were found to increase the amount of small-sized NPs released from masks into aqueous environments.

A Novel, Reverse Transcription, Droplet Digital PCR Assay for the Combined, Sensitive Detection of Severe Acute Respiratory Syndrome Coronavirus 2 with Swine Acute Diarrhea Syndrome Coronavirus.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread over the world since its emergence. Although the dominant route of SARS-CoV-2 infection is respiratory, a number of studies revealed infection risk from contaminated surfaces and products, including porcine-derived food and other products. The SARS-CoV-2 outbreak has been severely threatening public health, and disrupting porcine products trade and the pig industry. Swine acute diarrhea syndrome coronavirus (SADS-CoV), which was responsible for large-scale, fatal disease in piglets, emerged in 2017 and has caused enormous economic losses in the pig industry. Currently, reverse transcription real-time PCR (RT-rPCR) is the gold standard method for SARS-CoV-2 diagnosis and is most commonly used for SADS-CoV detection. However, inaccurate detection of the SARS-CoV-2 infection obtained by RT-rPCR is increasingly reported, especially in specimens with low viral load. OBJECTIVE: This study aimed to develop an accurate reverse transcription droplet digital PCR (RT-ddPCR) assay for the detection of SARS-CoV-2 and SADS-CoV simultaneously. METHODS: Two pairs of primers and one double-quenched probe targeting the RNA-dependent RNA polymerase (RDRP) region of the open reading frame 1ab (ORF1ab) gene of SARS-CoV-2 and the corresponding ORF1ab region of SADS-CoV were designed to develop the RT-ddPCR assay. The sensitivity, specificity, repeatability, and reproducibility were tested using complementary RNAs (cRNAs) and clinical specimens. RESULTS: The detection limits of RT-ddPCR were 1.48 ± 0.18 and 1.38 ± 0.17 copies in a 20 µL reaction for SARS-CoV-2 and SADS-CoV cRNAs, respectively (n = 8), showing approximately 4- and 10-fold greater sensitivity than the RT-rPCR assay. This assay also exhibited good specificity, repeatability, and reproducibility. CONCLUSION: The established RT-ddPCR assay was shown to be a highly effective, accurate, and reliable method for the sensitive detection of SARS-CoV-2 and SADS-CoV. HIGHLIGHTS: This RT-ddPCR assay could be used to detect both SARS-CoV-2 and SADS-CoV in a sample with one double-quenched probe, and is also the first reported RT-ddPCR assay for SADS-CoV detection.

Mechanical ventilation strategy for pulmonary rehabilitation based on patient-ventilator interaction.

Mechanical ventilation is an effective medical means in the treatment of patients with critically ill, COVID-19 and other pulmonary diseases. During the mechanical ventilation and the weaning process, the conduct of pulmonary rehabilitation is essential for the patients to improve the spontaneous breathing ability and to avoid the weakness of respiratory muscles and other pulmonary functional trauma. However, inappropriate mechanical ventilation strategies for pulmonary rehabilitation often result in weaning difficulties and other ventilator complications. In this article, the mechanical ventilation strategies for pulmonary rehabilitation are studied based on the analysis of patient-ventilator interaction. A pneumatic model of the mechanical ventilation system is established to determine the mathematical relationship among the pressure, the volumetric flow, and the tidal volume. Each ventilation cycle is divided into four phases according to the different respiratory characteristics of patients, namely, the triggering phase, the inhalation phase, the switching phase, and the exhalation phase. The control parameters of the ventilator are adjusted by analyzing the interaction between the patient and the ventilator at different phases. A novel fuzzy control method of the ventilator support pressure is proposed in the pressure support ventilation mode. According to the fuzzy rules in this research, the plateau pressure can be obtained by the trigger sensitivity and the patient's inspiratory effort. An experiment prototype of the ventilator is established to verify the accuracy of the pneumatic model and the validity of the mechanical ventilation strategies proposed in this article. In addition, through the discussion of the patient-ventilator asynchrony, the strategies for mechanical ventilation can be adjusted accordingly. The results of this research are meaningful for the clinical operation of mechanical ventilation. Besides, these results provide a theoretical basis for the future research on the intelligent control of ventilator and the automation of weaning process.

Wound care during the COVID-19 pandemic: improving outcomes through the integration of telemedicine.

COVID-19 is highly contagious and its rapid spread burdens the healthcare system. As the number of confirmed cases goes up, the shortage of medical resources has become a challenge. To avoid the collapse of the healthcare system during the fight with COVID-19, all healthcare workers, including wound care practitioners, should adapt to new roles and use any appropriate methods available to slow the spread of the virus. Integrating telemedicine into wound care during the outbreak helps maintain social distancing, preserve personal protective equipment and medical resources, and eliminate unnecessary exposure for both vulnerable patients and high-risk healthcare workers.

Dynamics of Blood Viral Load Is Strongly Associated with Clinical Outcomes in Coronavirus Disease 2019 (COVID-19) Patients: A Prospective Cohort Study.

The prevalence and clinical relevance of viremia in patients with coronavirus disease 2019 (COVID-19) have not been well studied. A prospective cohort study was designed to investigate blood viral load and clearance kinetics in 52 patients (median age, 62 years; 31 [59.6%] male) and explore their association with clinical features and outcomes based on a novel one-step RT droplet digital PCR (RT-ddPCR). By using one-step RT-ddPCR, 92.3% (48 of 52) of this cohort was quantitatively detected with viremia. The concordance between the blood and oropharyngeal swab tests was 60.92% (53 of 87). One-step RT-ddPCR was tested with a 3.03% false-positive rate and lower 50% confidence interval of detection at 54.026 copies/mL plasma. There was no reduction in the blood viral load in all critical patients, whereas the general and severe patients exhibited a similar ability to clear the viral load. The viral loads in critical patients were significantly higher than those in their general and severe counterparts. Among the 52 study patients, 30 (58%) were discharged from the hospital. Among half of the 30 discharged patients, blood viral load remained positive, of which 76.9% (10 of 13) completely cleared their blood viral load at follow-up. Meanwhile, none of their close contacts had evidence of infection. Quantitative determination of the blood viral test is of great clinical significance in the management of patients with coronavirus disease 2019.

Mutation profile of over 4500 SARS-CoV-2 isolations reveals prevalent cytosine-to-uridine deamination on viral RNAs.

Aim: The inference of coronavirus evolution is largely based on mutations in SARS-CoV-2 genome. Misinterpretation of these mutations would mislead people about the evolution of SARS-CoV-2. Materials & methods: With 4521 lines of SARS-CoV-2, we obtained 3169 unique point mutation sites. We counted the numbers and calculated the minor allele frequency (MAF) of each mutation type. Results: Nearly half of the point mutations are C-T mismatches and 20% are A-G mismatches. The MAF of C-T and A-G mismatches is significantly higher than MAF of other mutation types. Conclusion: The excessive C-T mismatches do not resemble the random mutation profile. They are likely to be caused by the cytosine-to-uridine deamination system in hosts.

Porcine deltacoronavirus nucleocapsid protein species-specifically suppressed IRF7-induced type I interferon production via ubiquitin-proteasomal degradation pathway.

Coronaviruses (CoVs) is showing obvious interspecies transmission, such as the SARS-CoV, MERS-CoV and SARS-CoV-2. Here, the emerging porcine deltacoronavirus (PDCoV) strain, isolated from Shanghai, China, broadly infects porcine, human and chicken cells in vitro. Previously studies by our group and others have confirmed that PDCoV nucleocapsid (N) protein performs an important role in antagonizing retinoic acid-induced gene I-like receptor (RLR) activation. However, the mechanism of PDCoV N protein suppressing porcine type I IFN production remains unclear, especially the downstream of porcine RLR signaling pathway. In the present study, porcine IRF7 (poIRF7) was identified as the interaction protein of PDCoV N protein through LC-MS/MS. The poIRF7 (268-487aa) was the key region of binding PDCoV N protein. Although IRF7 is a conserved functional protein in species, the PDCoV N protein has been confirmed to interact with only poIRF7 and significantly decrease poIRF7-induced type I IFN production, but not human or chicken IRF7. Furthermore, PDCoV N protein can promote poIRF7 degradation via the ubiquitin-proteasome pathway, which directly increased the K6, K11, and K29-linked polyubiquitination of poIRF7. Lysine 359 of poIRF7 was a key site in PDCoV N protein inducing poIRF7 degradation. Taken together, our results reveal a novel mechanism that PDCoV N protein could species-specifically interact with poIRF7 and then promote its degradation to suppress porcine type I IFN production. The novel findings provide a new insight into PDCoV and other zoonotic coronavirus evading the innate immune response of different species.

Cohort profile: protocol and baseline survey for the Shanghai Suburban Adult Cohort and Biobank (SSACB) study

PURPOSE: The Shanghai Suburban Adult Cohort and Biobank (SSACB) was established to identify environmental, lifestyle and genetic risk factors for non-communicable chronic diseases (NCDs) in adults (20-74 years old) living in a suburban area of Shanghai with rapid urbanisation. PARTICIPANTS: Two of eight suburban district were purposely selected according to participant willingness, health service facilities, population, geographic region and electronic medical record system. From these suburban districts, four communities were selected based on economic level and population size. At stage three, one-third of the committees/villages were randomly selected from each community. All residents aged 20-74 years old were invited as study participants. FINDINGS TO DATE: The baseline data on demographics, lifestyle and physical health-related factors were collected using a face-to-face questionnaire interview. All participants completed physical examinations and had blood and urine tests. Blood and urine samples from these tests were stored in a biobank. From 6 April 2016 through 31 October 2017, we conducted face-to-face interviews and clinical examinations in 44 887 participants: 35 727 from Songjiang District and 9160 from Jiading District. The average age of participants was 56.4±11.2 years in Songjiang and 56.6±10.5 years in Jiading. The prevalence of hypertension, diabetes and dyslipidaemia was 34.0%, 8.2% and 11.1%, respectively. FUTURE PLANS: In-person surveys will be conducted every 5 years. For annual tracking, baseline data was linked to the local health information system, which was composed of an electronic medical record system, a chronic disease management system, a cancer registry system, an infectious disease report system and a death registry system. The data of the SSACB cohort is located in the School of Public Health, Fudan University. International and domestic collaborative research projects are encouraged and inherent in the project.

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: An evidence-based clinical practice guideline (updated version).

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.

GC usage of SARS-CoV-2 genes might adapt to the environment of human lung expressed genes.

Understanding how SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) efficiently reproduces itself by taking resources from the human host could facilitate the development of drugs against the virus. SARS-CoV-2 translates its own proteins by using the host tRNAs, so that its GC or codon usage should fit that of the host cells. It is necessary to study both the virus and human genomes in the light of evolution and adaptation. The SARS-CoV-2 virus has significantly lower GC content and GC3 as compared to human. However, when we selected a set of human genes that have similar GC properties to SARS-CoV-2, we found that these genes were enriched in particular pathways. Moreover, these human genes have the codon composition perfectly correlated with the SARS-CoV-2, and were extraordinarily highly expressed in human lung tissues, demonstrating that the SARS-CoV-2 genes have similar GC usage as compared to the lung expressed human genes. RSCU (relative synonymous codon usage) and CAI (codon adaptation index) profiles further support the matching between SARS-CoV-2 and lungs. Our study indicates that SARS-CoV-2 might have adapted to the human lung environment by observing the high correlation between GC usage of SARS-CoV-2 and human lung genes, which suggests the GC content of SARS-CoV-2 is optimized to take advantage of human lung tissues.

No evidence for vertical transmission of SARS-CoV-2 in two neonates with mothers infected in the second trimester.

BACKGROUND: COVID-19 reported in pregnant women has occured in late pregnancy, while there are no reports of infection in the first and second trimester. We report two neonates born to mothers with COVID-19 during the second trimester. CASE PRESENTATION: Two pregnant women had symptomatic COVID-19 in the second trimester. Throat swabs at delivery for SARS-COV-2 RNA were negative for both women and their newborns. The first woman had positive serum IgM and IgG antibodies to SARS-COV-2 before delivery. Her newborn had negative IgM antibody to SARS-COV-2 but IgG was positive on the 7th day after birth. The second woman had negative serum IgM antibody to SARS-COV-2 but IgG was positive before delivery. Her newborn had negative serum IgM antibody to SARS-COV-2 but IgG was positive at 48 h after birth. None of the neonates developed clinical symptoms of COVID-19. CONCLUSION: SARS-COV-2 is unlikely to be vertically transmitted in utero as evidenced by the specific antibodies in the serum of the two women and their newborns. The two women with SARS-COV-2 infection in the second trimester did not develop serious complications at delivery and outcomes of the neonates were good.

Clinical Characteristics of COVID-19 Patients With Gastrointestinal Symptoms: An Analysis of Seven Patients in China.

Objectives: Patients with novel coronavirus disease 2019 (COVID-19) can present with gastrointestinal symptoms as their initial symptoms or as the main manifestations during disease progression, but the clinical characteristics of these patients are still unknown. Methods: We identified COVID-19 patients who admitted to Xiangyang No. 1 People's Hospital and presented with gastrointestinal symptoms as their initial or main symptoms. Their medical records were reviewed by two independent clinical scientists. The epidemiological and clinical characteristics as well as the clinical outcomes were analyzed. Results: Among 142 confirmed COVID-19 cases, 7 (4.9%) of them presented with gastrointestinal symptoms. Three patients had gastrointestinal symptoms as the initial symptoms and chief complaints, and 4 patients as the main symptoms during disease progression. Six patients had symptoms of diarrhea (3-16 days), 7 with anorexia (7-22 days), 6 with upper abdominal discomfort (1-7 days), and 4 with nausea (1-7 days), 1 with heartburn lasting 2 days, and 2 with vomiting symptoms (1 day). The chest CT scan showed typical COVID-19 imaging features, and associated with the progression of the disease. During treatment, 2 patients died due to organ failure. Discussion: COVID-19 patients with gastrointestinal symptoms are relatively rare and might be misdiagnosed. The clinical features include watery stools, anorexia, and upper abdominal discomfort. These patients may have severe disease and be associated with a poor prognosis. The underlying mechanisms of SARS-CoV-2 related gastrointestinal symptoms need to clarify in future studies.

Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): A multicenter, single-blind, randomized controlled trial.

BACKGROUND: Accumulating evidence proposed Janus-associated kinase (JAK) inhibitors as therapeutic targets warranting rapid investigation. OBJECTIVE: This study evaluated the efficacy and safety of ruxolitinib, a JAK1/2 inhibitor, for coronavirus disease 2019. METHODS: We conducted a prospective, multicenter, single-blind, randomized controlled phase II trial involving patients with severe coronavirus disease 2019. RESULTS: Forty-three patients were randomly assigned (1:1) to receive ruxolitinib plus standard-of-care treatment (22 patients) or placebo based on standard-of-care treatment (21 patients). After exclusion of 2 patients (1 ineligible, 1 consent withdrawn) from the ruxolitinib group, 20 patients in the intervention group and 21 patients in the control group were included in the study. Treatment with ruxolitinib plus standard-of-care was not associated with significantly accelerated clinical improvement in severe patients with coronavirus disease 2019, although ruxolitinib recipients had a numerically faster clinical improvement. Eighteen (90%) patients from the ruxolitinib group showed computed tomography improvement at day 14 compared with 13 (61.9%) patients from the control group (P = .0495). Three patients in the control group died of respiratory failure, with 14.3% overall mortality at day 28; no patients died in the ruxolitinib group. Ruxolitinib was well tolerated with low toxicities and no new safety signals. Levels of 7 cytokines were significantly decreased in the ruxolitinib group in comparison to the control group. CONCLUSIONS: Although no statistical difference was observed, ruxolitinib recipients had a numerically faster clinical improvement. Significant chest computed tomography improvement, a faster recovery from lymphopenia, and favorable side-effect profile in the ruxolitinib group were encouraging and informative to future trials to test efficacy of ruxolitinib in a larger population.