Hypercytokinemia is a critically fatal factor in COVID-19. However, underlying pathogenic mechanisms are unknown. Here we show that brinogen and leukotriene-A4 hydrolase (LTA4H), two of the most potent in ammatory contributors, are elevated by 67.7 and astonishing 227.7% in the plasma of patients infected by SARS-CoV-2 and admitted to intensive care unit in comparison with healthy control, respectively. Conversely, transferrin identi ed as a brinogen immobilizer in our recent work and Spink6 are down-regulated by 40.3 and 25.9%, respectively. Furthermore, we identify Spink6 as the rst endogenous inhibitor of LTA4H, a pro-in ammatory enzyme catalyzing nal and rating limited step in biosynthesis of leukotriene-B4 that is an extremely in ammatory mediator and a target to design superior anti-in ammatory drugs. Additionally, virus Spike protein is found to evoke LTA4H and brinogen expression in vivo. Collectively, these ndings identify the imbalance between in ammatory drivers and antagonists, which likely contributes to hypercytokinemia in COVID-19. Spink6 may have superior antiin ammatory function because it speci cally targets epoxide hydrolase of LTA4H to inhibit leukotriene-B4 biosynthesis without effecting LTA4H's aminopeptidase activity.

Background: Since December 2019, acute respiratory disease (ARD) due to 2019 novel coronavirus (2019-nCoV) emerged in Wuhan city and rapidly spread throughout China. We sought to delineate the clinical characteristics of these cases. Methods:We extracted the data on 1,099 patients with laboratory-confirmed 2019-nCoV ARD from 552 hospitals in 31 provinces/provincial municipalities through January 29 th , 2020. Results:The median age was 47.0 years, and 41.90% were females. Only 1.18% of patients had a direct contact with wildlife, whereas 31.30% had been to Wuhan and 71.80% had contacted with people from Wuhan. Fever (87.9%) and cough (67.7%) were the most common symptoms. Diarrhea is uncommon. The median incubation period was 3.0 days (range, 0 to 24.0 days). On admission, ground-glass opacity was the typical radiological finding on chest computed tomography (50.00%).Significantly more severe cases were diagnosed by symptoms plus reverse-transcriptase polymerase-chain-reaction without abnormal radiological findings than non-severe cases (23.87% vs. 5.20%, P<0.001). Lymphopenia was observed in 82.1% of patients. 55 patients (5.00%) were . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10. 1101 /2020 admitted to intensive care unit and 15 (1.36%) succumbed. Severe pneumonia was independently associated with either the admission to intensive care unit, mechanical ventilation, or death in multivariate competing-risk model (sub-distribution hazards ratio, 9.80; 95% confidence interval, 4.06 to 23.67). Conclusions:The 2019-nCoV epidemic spreads rapidly by human-to-human transmission. Normal radiologic findings are present among some patients with 2019-nCoV infection. The disease severity (including oxygen saturation, respiratory rate, blood leukocyte/lymphocyte count and chest X-ray/CT manifestations) predict poor clinical outcomes. Abstract: 249 words; main text: 2677 words : medRxiv preprint Clinical outcomesThe percentages of patients being admitted to the ICU, requiring invasive ventilation and death were 5.00%, 2.18% and 1.36%, respectively. This corresponded to 67 (6.10%) of patients having reached to the composite endpoint ( Table 3).Results of the univariate competing risk model are shown in Table E1 in Supplementary Appendix. Severe pneumonia cases (SDHR, 9.803; 95%CI, 4.06 to 23.67), leukocyte count greater than 4,000/mm 3 (SDHR, 4.01; 95%CI, 1.53 to 10.55) and interstitial abnormality on chest X-ray (SDHR, 4.31; 95%CI, 1.73 to 10.75) were associated with the composite endpoint (Fig. 2, see Table E2 in Supplementary Appendix). Sensitivity analyses are shown in Figure E2 in Supplementary Appendix. DiscussionThis study has shown that fever occurred in only 43.8% of patients with 2019-nCoV ARD on presentation but developed in 87.9% following hospitalization. Severe pneumonia occurred in 15.7% of cases. No radiolo...

Disease 2019 (COVID-19) as a pandemic. As of 22 April, more than 2.4 million cases have been confirmed worldwide 1 . In light of the widely documented lung injuries related with COVID-19 2-3 , concerns are raised regarding the assessment of the lung injury for discharged patients. A recent report portrayed that discharged patients with COVID-19 pneumonia are still having residual abnormalities in chest CT scans, with ground-glass opacity as the most common pattern 4 . Persistent impairment of pulmonary function and exercise capacity have been known to last for months or even years [5][6][7][8] in the recovered survivors with other coronavirus pneumonia (severe acute respiratory syndrome/SARS and middle east respiratory syndrome/MERS). However, until now, there is no report in regard to pulmonary function in discharged COVID-19 survivors. Our manuscript aims to describe the characteristics of pulmonary function in these subjects.We recruited laboratory confirmed non-critical COVID-19 cases, from February 5th to March 17th from admitted patients. According to the WHO interim guidance 9 and the guidance from china 10 , disease severity were categorized as mild illness(mild symptoms without radiographic appearance of pneumonia), pneumonia(having symptoms and the radiographic evidence of pneumonia, with no requirement for supplemental oxygen), severe pneumonia(having pneumonia, including one of the following: respiratory rate > 30 breaths/minute; severe respiratory distress; or SpO2 ≤ 93% on room air at rest), and critical cases (e.g. respiratory failure requiring mechanical ventilation, Septic shock, other organ failure occurrence or admission into the ICU). Critical cases were excluded from our study.Spirometry and pulmonary diffusion capacity test (Cosmed PFT Quark, Rome, Italy) were performed following the ATS-ERS guidelines on the day of or one day before discharge. To minimize cross infections, carbon monoxide diffusion capacity (DLCO) was measured by the single-breath method. Written informed consent was obtained from all patients, and the study was approved by the ethics committee of The Guangzhou Eighth People's Hospital.One-hundred and ten discharged cases were recruited, which included 24 cases of mild illness, 67 cases of pneumonia and 19 cases of severe pneumonia (Table 1). The mean age of these cases was 49.1 years and fifty-five of them were females. Forty-four (40%) patients had at least one underlying comorbidity, of which 23.6% had hypertension and 8.2% had diabetes. Only 3 patients (2.7%) were reported having chronic respiratory diseases (one patient with asthma, one with chronic bronchitis and one with bronchiectasis). No significant differences were found among the three groups of cases, in the relation to gender, smoking status, underlying disease and the BMI value. The duration from onset of disease to pulmonary function test was 20±6 days in cases with mild illness, 29±8 days in cases with pneumonia and 34±7 days in cases that presented severe pneumonia. On the day of discharge, the SpO2% on ro...