Establishment of a clinical nomogram model to predict the progression of COVID-19 to severe disease (preprint)

Background Coronavirus disease 2019 (COVID-19) is a worldwide public health pandemic with a high mortality rate, among severe cases. The disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. It is important to ensure early detection of the virus to curb disease progression to severe COVID-19. This study aimed to establish a clinical-nomogram model to predict the progression to severe COVID-19 in a timely, efficient manner.Methods This retrospective study included 202 patients with COVID-19 who were admitted to the Fifth Affiliated Hospital of Sun Yat-sen University and Shiyan Taihe Hospital from January 17 to April 30, 2020. The patients were randomly assigned to the training dataset (n = 163, with 43 progressing to severe COVID-19) or the validation dataset (n = 39, with 10 progressing to severe COVID-19) at a ratio of 8:2. The optimal subset algorithm was applied to filter for the clinical factors most relevant to the disease progression. Based on these factors, the logistic regression model was fit to distinguish severe (including severe and critical cases) from non-severe (including mild and moderate cases) COVID-19. Sensitivity, specificity, and area under the curve (AUC) were calculated using the R software package to evaluate prediction performance. A clinical nomogram was established and performance assessed with the discrimination curve.Results Risk factors, including demographics data, symptoms, laboratory and image findings were recorded for the 202 patients. Eight of the 52 variables that were entered into the selection process were selected via the best subset algorithm to establish the predictive model; they included gender, age, BMI, CRP, D-dimer, TP, ALB, and involved-lobe. Sensitivity, specificity and AUC were 0.91, 0.84 and 0.86 for the training dataset, and 0.87, 0.66, and 0.80 for the validation dataset.Conclusions We established an efficient and reliable clinical nomogram model which showed that gender, age, and initial indexes including BMI, CRP, D-dimer, involved-lobe, TP, and ALB could predict the risk of progression to severe COVID-19.

Triple Therapy With Budesonide/glycopyrrolate/formoterol Fumarate Used in Asthmatic Coexisting With Covid-19 (preprint)

Background: Awareness of the association between coronavirus disease 2019 (COVID-19) and airway diseases can effectively help in the treatment during the coronavirus pandemic. Case presentation: Herein, we present a COVID-19 case who confirmed to coexist with asthma. BGF was used as sequential medicine to systemic glucocorticoidsfor his persisted symptoms related to bronchospasms.Conclusion: Our case suggests patients with long-term airway diseases like asthma probably attribute to COVID-19 instead of primary diseases, which make it more difficult in the treatment.BGF is able to be an effective and convenient choiceas sequential medicine to systemic glucocorticoidsin some refractoryasthmatic patients complicated with COVID-19.

Key to successful treatment of COVID-19: accurate identification of severe risks and early intervention of disease progression (preprint)

Abstract Background COVID-19 is a new and highly contagious respiratory disease that has caused global spread, high case fatality rate in severe patients, and a huge medical burden due to invasive mechanical ventilation. The current diagnosis and treatment guidelines are still need to be improved, and more excellent clinical experience is needed to provide reference. Methods We analyzed and summarized clinical data of 97 confirmed COVID-19 adult patients (including 26 severe cases) admitted to the Fifth Affiliated Hospital of Sun Yat-sen University from January 17, 2020 to March 10, 2020,included laboratory examination results, imaging findings, treatment effect, prognosis , etc, in order to put forward prediction index of severe COVID-19 patients, principles of early intervention and methylprednisolone usages in COVID-19 patients. Results 1.Hypoxemia, hyperlactic acid, hypoproteinemia, and hypokalemia were prevalent in COVID-19 patients.The significant low lymphocyte count, hypoproteinemia, hypokalemia, the persistent or worsen high CRP, high D-dimer, and high BNP, and the occurrence of hemoptysis and novel coronavirus (SARS-CoV-2) viremia were important indicators for early diagnosis and prediction of severe disease progression. 2.Characteristic images of lung CT had a clear change in COVID - 19, Ground-glass opacity (GGO) and high-density linear combinations may indicate different pathological changes. Rapid lobular progression of GGO suggests the possibility of severe disease. 3.Basic principles of early intervention treatment of COVID-19: on the premise of no effective antiviral drugs, treatment is based on supportive and symptomatic therapy (albumin supplementation, supplement of potassium, supplement blood plasma, etc.) in order to maintain the stability of the intracellular environment and adequately reactivate body immunity to clean up SARS-CoV-2 . 4. According to severity, oxygenation index, body weight, age, underlying diseases, appropriate amount methylprednisolone application on severe/critical COVID-19 patients on demand, improved blood oxygen and reduced the utilization rate of invasive mechanical ventilation, case fatality rate and medical burden significantly. The most common indications for invasive mechanical ventilation should be strictly control in critical COVID-19 patients. Conclusions: 1.Accurate and timely identification of clinical features in severe risks, and early and appropriate intervention can block disease progression. 2.Appropriate dose of methylprednisolone can effectively avoid invasive mechanical ventilation and reduce case fatality rate in critical COVID-19 patients.

A high-efficiency hospital emergency-response mode is key to successful treatment of COVID-19 patients in Zhuhai (preprint)

Background: In December 2019, coronavirus disease 2019 (COVID-19) emerged in Wuhan and has since rapidly spread throughout China. The mortality rates of novel coronavirus pneumonia (NCP) in severe and critical cases are very high. In this public-health emergency, a high-efficiency administrative emergency-response mode in designated hospitals is needed. Method: As an affiliated hospital of Sun Yat-sen University, ours, the Fifth Affiliated Hospital, is the only one designated for the diagnosis and treatment of COVID-19 in Zhuhai, a mid-sized city. The NCP department, for which the president of the hospital is also the direct administrative lead, was established at an early stage of the epidemic at our hospital. This department includes core members of the pulmonary and critical-care medicine (PCCM) specialist and multidisciplinary team. Rather than adhering to national guidelines on NCP, we have focused on individualized treatment, timely adjustment thereof and management strategies in working with COVID-19 patients based on the professional opinions of a professor of respiratory medicine and an expert group. Results: (1) High working efficiency: As of March 2, 2020, we have completed 2974 citywide consultations and treatment of 366 inpatients, including 101 who were diagnosed with COVID-19. (2) Excellent therapeutic effect: Of the 101 patients hospitalized with confirmed COVID-19, only 1 has died, and the rest were all cured and discharged. No secondary hospital infection, pipeline infection or pressure sores were found in any patient. (3) Finding and confirming person-to-person transmission characteristic of COVID-19 prior to the official press conference: Strengthened protection is key to zero infection among the healthcare providers and medical faculty, as well as to a lower rate of second-generation infectious patients. (4) Timely adjustment of management and treatment strategy prior to guideline updates: The first evidence of digestive-tract involvement in COVID-19 has been found, and the earliest clinical trial of chloroquine in the treatment of the disease was carried out at our hospital. Conclusions: At our hospital, establishment of an NCP department, which is directly administered by the hospital president and specialized operation guided by a professor of respiratory medicine, has been key to our success in managing and treating COVID-19 patients. Our hospital’s emergency-response mode could provide a reference for other hospitals and cities in this epidemic situation.

A high efficient hospital emergency responsive mode is the key of successful treatment of 100 COVID-19 patients in Zhuhai (preprint)

Background: Since December 2019, Coronavirus Disease 2019 (COVID-19) emerged in Wuhan city and rapidly spread throughout China. The mortality of novel coronavirus pneumonia (NCP) in severe and critical cases is very high. Facing this kind of public health emergency, high efficient administrative emergency responsive mode in designated hospital is needed. Method: As an affiliated hospital of Sun Yat-sen University, our hospital is the only designated one for diagnosis and treatment of COVID-19 in Zhuhai, a medium-sized city. Novel coronavirus pneumonia department, which is administrative led by the president of hospital directly, has been established at early stage of epidemic crisis in my hospital. In NCP department, there are core members of Pulmonary and Critical Care Medicine (PCCM) specialist and multidisciplinary team. Don't stick to national guidelines of NCP, based on professional opinion by respiratory professor and expert group, we focused on individualized treatment and timely adjustment of treatment and management strategies in working about COVID-19 patients. Results: 1. High working efficiency: By Mar 02, 2020, we have completed 2974 citywide consultations and treatment of 366 inpatients, including 101 patients diagnosed with COVID-19. 2. Excellent therapeutic effectAmong 101 hospitalized patients with confirmed COVID-19, all were cured and discharged, except for one death. No secondary hospital infection, no pipeline infection and no pressure sore were found in all patients. 3. Finding and confirming person-to-person transmission characteristic of COVID-19 prior to official release conference: Strengthened protection is key point to zero infection in healthcare group and medical faculty and lower rate of second generation infectious patients. 4. Timely adjustment management and treatment strategy prior to guideline update: The first evidence of digestive tract involvement in COVID-19 has been found, and the earliest clinical trial of chloroquine in the treatment of COVID-19 has been carried out in our hospital. Conclusions: In our hospital, establishment of NCP department, which is administratively led by the president of hospital directly and specialized conduct by respiratory professor, is the key to success in management and treatment of COVID-19 patients. This hospital emergency responsive mode could provide reference for other hospitals and cities in epidemic situation.

Establishment of a clinical nomogram model to predict the progress to severe COVID-19 (preprint)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is the leading cause of a public health emergency in the world, accompanying with high mortality in severe corona virus disease 2019(COVID-19 ), thereby early detection and stopping the progress to severe COVID-19 is important. Our aim is to establish a clinical nomogram model to calculate and predict the progress to severe COVID-19 timely and efficiently.Methods: In this study, 65 patients with COVID-19 had been included retrospectively in the Fifth Affiliated Hospital of Sun Yat-sen University from January 17, to February 11, 2020. Patients were randomly assigned to train dataset (n=51 with 15 progressing to severe COVID-19) and test dataset (n=14 with 4 progressing to severe COVID-19). Lasso algorithm was applied to filter the most classification relevant clinical factors. Based on selected factors, logistic regression model was fit to predict the severe from mild/common. Meanwhile in nomogram sensitivity, specificity, AUC (Area under Curve), and calibration curve were depicted and calculated by R language, to evaluate the prediction performance to severe COVID-19.Results:High ratio of sever COVID-19 patients (26.5%) had been found in our retrospective study, and 84% of these cases progress to severe or critical after 5 days from their first clinical examination. In these 65 patients with COVID-19, 77 clinical characteristics in first examination were collected and analyzed, and 37 ones had been found different between non-severe and severe COVID-19. But when all these factors were analyzed in establishment of prediction model, six factors are crucial for predicting progress of severe COVID-19 via Lasso algorithm. Based on these six factors, including increased fibrinogen, hyponatremia, decreased PaO2,multiple lung lobes involved, down-regulated CD3（+）T-lymphocyte and fever, a logistic regression model was fit to discriminate severe and common COVID-19 patients. The sensitivity, specificity and AUC were 0.93, 0.86, 0.96 in the train dataset and 0.9, 1.0, 1.0 in test dataset respectively. Nomogram-predicted probability was more consistent with actual probability by R language.Conclusions:In summary, an efficient and reliable clinical nomogram model had been established, which indicate increased fibrinogen, hyponatremia, decreased PaO2, multiple lung lobes involved, down-regulated CD3（+）T-lymphocyte and fever at the first clinical examination, could predict progress of patients to severe COVID-19.

Evidence for gastrointestinal infection of SARS-CoV-2 (preprint)

The new coronavirus (SARS-CoV-2) outbreak originating from Wuhan, China, poses a threat to global health. While it's evident that the virus invades respiratory tract and transmits from human to human through airway, other viral tropisms and transmission routes remain unknown. We tested viral RNA in stool from 73 SARS-CoV-2-infected hospitalized patients using rRT-PCR. 53.42% of the patients tested positive in stool. 23.29% of the patients remained positive in feces even after the viral RNA decreased to undetectable level in respiratory tract. The viral RNA was also detected in gastrointestinal tissues. Furthermore, gastric, duodenal and rectal epithelia showed positive immunofluorescent staining of viral host receptor ACE2 and viral nucleocapsid protein in a case of SARS-CoV-2 infection. Our results provide evidence for gastrointestinal infection of SARS-CoV-2, highlighting its potential fecal-oral transmission route.