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Background. An outbreak of coronavirus disease 2019 is becoming a public health emergency. Data are limited on the duration and host factors related to viral shedding.Methods. In this retrospective study, risk factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA shedding were evaluated in a cohort of 113 symptomatic patients from 2 hospitals outside Wuhan.Results. The median (interquartile range) duration of SARS-CoV-2 RNA detection was 17 (13-22) days as measured from illness onset. When comparing patients with early (<15 days) and late (≥15 days after illness onset) viral RNA clearance, prolonged SARS-CoV-2 RNA shedding was associated with male sex (P = .009), old age (P = .033), concomitant hypertension (P = .009), delayed admission to hospital after illness onset (P = .001), severe illness at admission (P = .049), invasive mechanical ventilation (P = .006), and corticosteroid treatment (P = .025). Patients with longer SARS-CoV-2 RNA shedding duration had slower recovery of body temperature (P < .001) and focal absorption on radiograph images (P < .001) than patients with early SARS-CoV-2 RNA clearance. Male sex (OR, 3.24; 95% CI, 1.31-8.02), delayed hospital admission (OR, 1.30; 95% CI, 1.10-1.54), and invasive mechanical ventilation (OR, 9.88; 95% CI,.02) were independent risk factors for prolonged SARS-CoV-2 RNA shedding.Conclusions. Male sex, delayed admission to hospital after illness onset, and invasive mechanical ventilation were associated with prolonged SARS-CoV-2 RNA shedding. Hospital admission and general treatments should be started as soon as possible in symptomatic COVID-19 patients, especially male patients.

Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2 + TMPRSS2 + cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention.

Glucagon supports glucose homeostasis by stimulating hepatic gluconeogenesis, in part by promoting the uptake and conversion of amino acids into gluconeogenic precursors. Genetic disruption or pharmacologic inhibition of glucagon signaling results in elevated plasma amino acids and compensatory glucagon hypersecretion involving expansion of pancreatic α cell mass. Recent findings indicate that hyperaminoacidemia triggers pancreatic α cell proliferation via an mTOR-dependent pathway. We confirm and extend these findings by demonstrating that glucagon pathway blockade selectively increases expression of the sodium-coupled neutral amino acid transporter Slc38a5 in a subset of highly proliferative α cells and that Slc38a5 controls the pancreatic response to glucagon pathway blockade; most notably, mice deficient in Slc38a5 exhibit markedly decreased α cell hyperplasia to glucagon pathway blockade-induced hyperaminoacidemia. These results show that Slc38a5 is a key component of the feedback circuit between glucagon receptor signaling in the liver and amino-acid-dependent regulation of pancreatic α cell mass in mice.

ObjectiveDisease-modifying drugs (DMDs) may alter the immune status and thus increase the susceptibility to coronavirus disease 2019 (COVID-19) in patients with MS or neuromyelitis optica spectrum disorders (NMOSD). However, evidence supporting this notion is currently lacking. In this study, we conducted a survey on the risk of COVID-19 in patients with MS and NMOSD.MethodsThe survey was conducted through the Chinese Medical Network for Neuroinflammation. Patients in 10 MS centers from 8 cities including Wuhan were included. Information about MS and NMOSD disease duration and the usage of DMDs were collected. Data of suspected cases of COVID-19 were obtained from hospital visits, questionnaires, and patient self-reporting. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was confirmed through clinical evaluation by a panel of experts in conjunction with chest CT and viral RNA detection.ResultsEight hundred eighty-two of 1,804 (48.89%) patients with MS and 2,129 of 3,060 (69.58%) patients with NMOSD were receiving DMDs. There were no alterations in the patients' DMD regimen during January 15, 2020, to March 15, 2020, the 3-month period. None of the patients with MS treated with DMDs had COVID-19. However, 2 patients with relapsing NMOSD were diagnosed with COVID-19-related pneumonia. After treatment, both patients recovered from pneumonia and neither patient experienced new attacks due to predisposing SARS-CoV-2 infection in the following 2 months.ConclusionsNo increased risk of COVID-19 infection was observed in patients with MS or NMOSD, irrespective of whether these patients received DMDs. A battery of stringent preventive measures adopted by neurologists to reduce COVID-19 infection in these patients may have contributed to low risk of COVID-19 infection.

The COVID-19 pandemic has brought an unprecedented crisis to the global health sector. When discharging COVID-19 patients in accordance with throat or nasal swab protocols using RT-PCR, the potential risk of reintroducing the infection source to humans and the environment must be resolved. Here, 14 patients including 10 COVID-19 subjects were recruited; exhaled breath condensate (EBC), air samples and surface swabs were collected and analyzed for SARS-CoV-2 using reverse transcription-polymerase chain reaction (RT-PCR) in four hospitals with applied natural ventilation and disinfection practices in Wuhan. Here we discovered that 22.2% of COVID-19 patients (n = 9), who were ready for hospital discharge based on current guidelines, had SARS-CoV-2 in their exhaled breath (~10 5 RNA copies/m 3 ). Although fewer surface swabs (3.1%, n = 318) tested positive, medical equipment such as face shield frequently contacted/used by healthcare workers and the work shift floor were contaminated by SARS-CoV-2 (3–8 viruses/cm 2 ). Three of the air samples (n = 44) including those collected using a robot-assisted sampler were detected positive by a digital PCR with a concentration level of 9–219 viruses/m 3 . RT-PCR diagnosis using throat swab specimens had a failure rate of more than 22% in safely discharging COVID-19 patients who were otherwise still exhaling the SARS-CoV-2 by a rate of estimated ~1400 RNA copies per minute into the air. Direct surface contact might not represent a major transmission route, and lower positive rate of air sample (6.8%) was likely due to natural ventilation (1.6–3.3 m/s) and regular disinfection practices. While there is a critical need for strengthening hospital discharge standards in preventing re-emergence of COVID-19 spread, use of breath sample as a supplement specimen could further guard the hospital discharge to ensure the safety of the public and minimize the pandemic re-emergence risk.

words)Main text (3372 words) AbstractBackground: Respiratory and faecal aerosols play a suspected role in transmitting the SARS-CoV-2 virus. We performed extensive environmental sampling in a dedicated hospital building for Covid-19 patients in both toilet and non-toilet environments, and analysed the associated environmental factors. Methods:We collected data of the Covid-19 patients. 107 surface samples, 46 air samples, two exhaled condensate samples, and two expired air samples were collected were collected within and beyond the four three-bed isolation rooms. We reviewed the environmental design of the building and the cleaning routines. We conducted field measurement of airflow and CO2 concentrations. Findings:The 107 surface samples comprised 37 from toilets, 34 from other surfaces in isolation rooms (ventilated at 30-60 L/s), and 36 from other surfaces outside isolation rooms in the hospital. Four of these samples were positive, namely two ward door-handles, one bathroom toilet-seat cover and one bathroom door-handle; and three were weakly positive, namely one bathroom toilet seat, one bathroom washbasin tap lever and one bathroom ceiling-exhaust louvre. One of the 46 air samples was weakly positive, and this was a corridor air sample. The two exhaled condensate samples and the two expired air samples were negative.Interpretation: The faecal-derived aerosols in patients' toilets contained most of the detected SARS-CoV-2 virus in the hospital, highlighting the importance of surface and hand hygiene for intervention.

Background In early 2020, over 80,000 cases of coronavirus disease (COVID-19) were confirmed in China. Public prevention and control measures, along with efforts from all sectors of society, were undertaken to control and eliminate disease transmission. Objective This paper describes Chinese citizens’ response to the epidemic, the preventive measures they implemented to avoid being infected, and the public strategies that were carried out by the government, health workers, etc. We also discuss the efficacy of these measures in controlling the epidemic in China. Methods Information on the responses and behaviors of Chinese citizens were collected through a cross-sectional, internet-based survey using Dingxiang Doctor’s public account on WeChat. Information on public strategies implemented by all sectors of society to control the epidemic and data on new COVID-19 cases were collected from the internet, mainly from government websites. Standard descriptive statistics and multivariate logistic regression analyses were conducted to analyze the data. Results A total of 10,304 participants responded to the survey, with 10,198 valid responses; 74.1% (n=7557) were female and 25.9% (n=2641) were male. Overall, 98.2% (n=10,013) of participants paid high or very high attention to the epidemic, with WeChat being their main information source (n=9400, 92.2%). Over half the participants (n=5878, 57.7%) were confident that the epidemic could be curbed in China; 92.4% (n=9427) opened windows for ventilation more frequently than usual; 97.9% (n=9986) used masks in public; 95.7% (n=9759) avoided large crowds and stayed at home as much as possible; and 97.9% (n=9988) washed their hands more often than usual. Women were more likely to practice these behaviors than men (P<.001). With a series of strict public control measures, like nationwide health education campaigns, holiday extensions, the Examine and Approve Policy on the resumption of work, close management of working and living quarters, a health QR (Quick Response) code system, community screening, and social distancing policies, the number of new cases have decreased dramatically since February 12, 2020. Conclusions The methods employed by Chinese citizens and authorities have effectively curtailed the spread of COVID-19, demonstrating that this pandemic can be brought under control as long as the right measures are taken.