Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of chloroquine for the treatment of COVID-19 (preprint)

Background Effective therapies are urgently needed for the SARS-CoV-2 pandemic. Chloroquine has been proved to have antiviral effect against coronavirus in vitro. In this study, we aimed to assess the efficacy and safety of chloroquine with different doses in COVID-19. Method In this multicenter prospective observational study, we enrolled patients older than 18 years old with confirmed SARS-CoV-2 infection excluding critical cases from 12 hospitals in Guangdong and Hubei Provinces. Eligible patients received chloroquine phosphate 500mg, orally, once (half dose) or twice (full dose) daily. Patients treated with non-chloroquine therapy were included as historical controls. The primary endpoint is the time to undetectable viral RNA. Secondary outcomes include the proportion of patients with undetectable viral RNA by day 10 and 14, hospitalization time, duration of fever, and adverse events. Results A total of 197 patients completed chloroquine treatment, and 176 patients were included as historical controls. The median time to achieve an undetectable viral RNA was shorter in chloroquine than in non-chloroquine (absolute difference in medians -6.0 days; 95% CI -6.0 to -4.0). The duration of fever is shorter in chloroquine (geometric mean ratio 0.6; 95% CI 0.5 to 0.8). No serious adverse events were observed in the chloroquine group. Patients treated with half dose experienced lower rate of adverse events than with full dose. Conclusions Although randomised trials are needed for further evaluation, this study provides evidence for safety and efficacy of chloroquine in COVID-19 and suggests that chloroquine can be a cost-effective therapy for combating the COVID-19 pandemic.

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.

Survey of Anxiety and Depression in Patients with Suspected and Confirmed Cases of COVID-19 During Hospitalization and Isolation (preprint)

Objective: To observe the anxiety and depression experienced by patients with suspected and confirmed COVID-19 during hospitalization and isolation.Methods: A cross-sectional survey was performed with 66 patients with suspected and confirmed COVID-19 who were admitted to the Fifth Affiliated Hospital of Sun Yat-sen University from February 9, 2020, to February 22, 2020. The data collected including sex, age, education level, and nucleic acid test results. Anxiety, depression, and sleep disorders were evaluated using the Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS) and Pittsburgh Sleep Quality Index Scale (PSQI), respectively. Statistical analysis: SPSS 23.0 software was used for data processing, and multifactor logistic regression analysis was used to identify the independent risk factors. Spearman correlation analysis was used to study the correlations among the observed indicators; P <0.05 was considered statistically significant.Results: The incidences of anxiety, depression, and sleep disorders in the suspected case group were 18.2%, 18.2%, and 39.4%; the incidences of anxiety, depression, and sleep disorders in the diagnosed group were 42.4%, 57.6%, and 69.7%. The incidence of sleep disorders was higher than the domestic norm, and the difference was statistically significant (P <0.05). Logistic regression analysis adjusted for multiple factors showed that the main factor affecting anxiety was age; the main factors affecting depression were age and a positive nucleic acid test; and the main factor affecting sleep disorders was age. The anxiety, depression and sleep disorder scores were significantly positively correlated (P <0.05).Conclusion: Patients with suspected and confirmed COVID-19, especially people aged 50 years and over, have significant anxiety, depression and sleep disorders. Anxiety, depression and sleep disorders in patients with confirmed cases are more serious than those in patients with suspected cases. It is necessary to focus on the psychological state of such patients, actively conduct psychological counseling, and reduce their anxiety and depression.

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.

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.