An epidemic of respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in China and has spread to other countries. 1 Real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) of nasopharyngeal swabs typically has been used to confirm the clinical diagnosis. 2 However, whether the virus can be detected in specimens from other sites, and therefore potentially transmitted in other ways than by respiratory droplets, is unknown.Methods | We investigated the biodistribution of SARS-CoV-2 among different tissues of inpatients with coronavirus disease 2019 (COVID-19) diagnosed based on symptoms and radiology and confirmed by SARS-CoV-2 detection. This study was approved by the ethics commissions of the participating hospitals, with a waiver of informed consent.Patients with specimens collected based on clinical indications from 3 hospitals in the Hubei and Shandong provinces and Beijing, China, from January 1 through February 17, 2020, were included. Pharyngeal swabs were collected from most patients 1 to 3 days after hospital admission. Blood, sputum, feces, urine, and nasal samples were collected throughout the illness. Bronchoalveolar lavage fluid and fibrobronchoscope brush biopsy were sampled from patients with severe illness or undergoing mechanical ventilation. RNA was extracted from clinical specimens and determined by rRT-PCR targeting the open reading frame 1ab gene of SARS-CoV-2 as previously described. 2 The cycle threshold values of rRT-PCR were used as indicators of the copy number of SARS-CoV-2 RNA in specimens with lower cycle threshold values corresponding to higher viral copy numbers. A cycle threshold value less than 40 is interpreted as positive for SARS-CoV-2 RNA. Four SARS-CoV-2 positive fecal specimens with high copy numbers were cultured, and then electron microscopy was performed to detect live virus. Patterns in a subgroup of patients with multiple specimens collected during hospitalization were explored.

Journal Pre-proof J o u r n a l P r e -p r o o f Journal Pre-proof J o u r n a l P r e -p r o o f 3 Abstract Factors associated with negative conversion of SARS-CoV-2 RNA in hospitalized patients have not yet been systematically determined. We conducted a retrospective cohort study of COVID-19 patients in Qingdao, China. Both univariate and multivariate analysis were performed to identify independent factors for time to viral RNA negative conversion. Data on patients with re-detectable viral RNA after showing negative on RT-PCR test (intermittent negative status) were also analyzed. A total of 59 patients confirmed with COVID-19 were included in this study, with a median duration of 1 (interquartile range, IQR: 0-2) day from symptom onset to hospital admission. Median communicable period (from first day of positive nucleic acid test to first day of consecutive negative results) was 14 (IQR: 10-18) days, and 7 (IQR: 6-10) days for 10 patients with intermittent negative results. Age older than 45 years (hazard ratio, HR: 0.378; 95% confidence interval, CI: 0.205-0.698) and chest tightness (HR: 0.290; 95%CI: 0.091-0.919) were factors indepently affecting negative conversion of SARS-CoV-2 RNA. Headache (odds ratio: 7.553; 95%CI: 1.011-28.253)was significantly associated with intermittent negative status, with a predicted probability of 60%. Older age and chest tightness were independently associated with delayed clearance of SARS-CoV-2 RNA in hospitalized patients. These predictors would provide a new perspective on early identification of patients with prolonged viral shedding and facilitate optimal isolation protocols and treatment strategies.

The outbreak of COVID-19 has become a worldwide pandemic. The pathogenesis of this infectious disease and how it differs from other drivers of pneumonia is unclear. Here we analyze urine samples from COVID-19 infection cases, healthy donors and non-COVID-19 pneumonia cases using quantitative proteomics. The molecular changes suggest that immunosuppression and tight junction impairment occur in the early stage of COVID-19 infection. Further subgrouping of COVID-19 patients into moderate and severe types shows that an activated immune response emerges in severely affected patients. We propose a two-stage mechanism of pathogenesis for this unusual viral infection. Our data advance our understanding of the clinical features of COVID-19 infections and provide a resource for future mechanistic and therapeutics studies.

SummaryBackgroundThe age-specific association between blood pressure and vascular disease has been studied mostly in high-income countries, and before the widespread use of brain imaging for diagnosis of the main stroke types (ischaemic stroke and intracerebral haemorrhage). We aimed to investigate this relationship among adults in China.Methods512 891 adults (59% women) aged 30–79 years were recruited into a prospective study from ten areas of China between June 25, 2004, and July 15, 2008. Participants attended assessment centres where they were interviewed about demographic and lifestyle characteristics, and their blood pressure, height, and weight were measured. Incident disease was identified through linkage to local mortality records, chronic disease registries, and claims to the national health insurance system. We used Cox regression analysis to produce adjusted hazard ratios (HRs) relating systolic blood pressure to disease incidence. HRs were corrected for regression dilution to estimate associations with long-term average (usual) systolic blood pressure.FindingsDuring a median follow-up of 9 years (IQR 8–10), there were 88 105 incident vascular and non-vascular chronic disease events (about 90% of strokes events were diagnosed using brain imaging). At ages 40–79 years (mean age at event 64 years [SD 9]), usual systolic blood pressure was continuously and positively associated with incident major vascular disease throughout the range 120–180 mm Hg: each 10 mm Hg higher usual systolic blood pressure was associated with an approximately 30% higher risk of ischaemic heart disease (HR 1·31 [95% CI 1·28–1·34]) and ischaemic stroke (1·30 [1·29–1·31]), but the association with intracerebral haemorrhage was about twice as steep (1·68 [1·65–1·71]). HRs for vascular disease were twice as steep at ages 40–49 years than at ages 70–79 years. Usual systolic blood pressure was also positively associated with incident chronic kidney disease (1·40 [1·35–1·44]) and diabetes (1·14 [1·12–1·15]). About half of all vascular deaths in China were attributable to elevated blood pressure (ie, systolic blood pressure >120 mm Hg), accounting for approximately 1 million deaths (<80 years of age) annually.InterpretationAmong adults in China, systolic blood pressure was continuously related to major vascular disease with no evidence of a threshold down to 120 mm Hg. Unlike previous studies in high-income countries, blood pressure was more strongly associated with intracerebral haemorrhage than with ischaemic stroke. Even small reductions in mean blood pressure at a population level could be expected to have a major impact on vascular morbidity and mortality.FundingUK Wellcome Trust, UK Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, Chinese Ministry of Science and Technology, and the National Science Foundation of China.

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