Interim guideline for treatment options on cancer patients during SARS-CoV-2 pandemic

In the current pandemic of SARS-Cov-2 (formally known as novel coronavirus disease 2019, COVID-19), the cancer treatment is particularly a challenge that must be overcome as soon as possible. Currently, the clinical data on the prevalence of SARS-Cov-2 in cancer patients is very limited, alone with constant evolving situations. To obtain existing evidence, we reviewed a wide range of medical literature and relevant websites including the National Health Commission of China. With the actual situation of Hubei Cancer Hospital, we formulated the interim guideline which was developed by all contributors from different disciplines after fully discussion, to provide the reference for treatment options on cancer patients, especially the cancer patients recovered from COVID-19 infection. This guideline highlighted the multidisciplinary team (MDT) diagnostic model, the assessment between risks and benefits prior to treatment, individualized service for patients' medical needs, and the acceptability in ethics and patients' socio-economic conditions.

Impact of the COVID−19 Pandemic on Farm Households’ Vulnerability to Multidimensional Poverty in Rural China

The COVID−19 pandemic has significantly impacted the economy and livelihoods of people worldwide. To analyze the impact of the pandemic on material conditions, income levels, health conditions, industrial development and employment opportunities of farmers in China’s rural areas, especially poor areas and explore whether farmers can achieve stable poverty eradication during the COVID−19 pandemic, we interviewed 2662 farm households in poverty−stricken areas of China and used the multidimensional poverty measurement model, three−step feasible generalized least squares and propensity score matching to analyze data. We achieved the following results. First, the overall level of multidimensional poverty vulnerability index (MPVI) of the surveyed households was low and the MPVI of each dimension varied significantly. The MPVI of households in the treated group was higher than that of the control group. Second, COVID−19 increased farm households’ vulnerability to multidimensional poverty in poverty−stricken regions;MPVI increased by 27.9%. Third, COVID−19′s impact on various dimensions differed: the greatest impact was on the vulnerability to health deprivation, followed by industrial development, employment and income deprivation. However, the pandemic slightly reduced the vulnerability to material deprivation. Finally, we proposed various measures in response to the impact of the pandemic to assist farm households in poverty−stricken areas.

Development and Clinical Evaluation of a Rapid Antibody Lateral Flow Assay for the Diagnosis of SARS-CoV-2 Infection (preprint)

Background: The novel coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has quickly spread worldwide since its outbreak in December 2019. One of the primary measures for controlling the spread of SARS-CoV-2 infection is an accurate assay for its diagnosis. SARS-CoV-2 real-time PCR kits suffer from some limitations, including false-negative results in the clinic. Therefore, there is an urgent need for the development of a rapid antibody test kit for COVID-19 diagnosis.Methods: The nuclear capsid protein (N) and spike protein 1 (S1) fragments of SARS-CoV-2 were expressed in Escherichia coli, and rapid antibody-based tests for the diagnosis of SARS-CoV-2 infection were developed and compared. To evaluate their clinical applications, the serum from COVID-19 patients, suspected COVID-19 patients, recovering COVID-19 patients, patients with general fever or pulmonary infection, doctors and nurses who worked at the fever clinic, and health professionals was analyzed by the rapid antibody test kits. The serum from patients infected with Mycoplasma pneumoniae and patients with respiratory tract infection was further analyzed to test its cross-reactivity with other respiratory pathogens.Results: A 47 kDa N protein and 67 kDa S1 fragment of SARS-CoV-2 were successfully expressed, purified, and renatured. The rapid antibody test with recombinant N protein showed higher sensitivity and specificity than the rapid IgM antibody test with recombinant S1 protein. Clinical evaluation showed that the rapid antibody test kit with recombinant N protein had 88.56% sensitivity and 97.42% specificity for COVID-19 patients, 53.48% positive rate for suspected COVID-19 patients, 57.14% positive rate for recovering COVID-19 patients, and 3.20%-3.27% cross-reactivity with other respiratory pathogens. The sensitivity of the kit did not significantly differ in COVID-19 patients with different disease courses (p < 0.01).Conclusion: The rapid antibody test kit with recombinant N protein has high specificity and sensitivity, and can be used for the diagnosis of SARS-CoV-2 infection combined with RT-PCR.

A Cohort of SARS-CoV-2 Infected Asymptomatic and Pre-Symptomatic Contacts from COVID-19 Contact Tracing in Hubei Province, China: Short-Term Outcomes (preprint)

Background: Contact tracing with quarantine of SARS-CoV-2 positive contacts is required on an unprecedented scale worldwide.Methods: During February 1-March 25, 2020, COVID-19 cases in Hubei province were traced by more than 1800 teams. PCR positive contacts without COVID-19 symptoms with two or more consecutive positive tests for SARS-CoV-2 were categorized as: (a) asymptomatic SARS-CoV-2 if without COVID-19 symptoms throughout the > 14 days of quarantine, (b) pre-symptomatic SARS-CoV-2 if COVID-19 symptoms started during the quarantine, and (c) false positive contacts if two consecutive follow-up qRT-PCRs were negative after an initial positive SARS-CoV-2 test.Findings: 48,944 COVID-19 patients identified 277,066 contacts who were tested for SARS-CoV-2; upon ascertainment, 3,152 contacts without symptoms were SARS-CoV-2 PCR positive without symptoms, and 50 contacts were false positives. After quarantine, 2928 were classified as asymptomatic and 174 were pre-symptomatic SARS-CoV-2 contacts, with a pre-symptomatic case fatality (11/174) of 6.3%. The average interval between the initial SARS-CoV-2 PCR positive and onset of COVID-19 symptoms was 9.7 days, and the average time from onset of symptoms to death for deceased pre-symptomatic cases was 6.3 days (range = 1 - 35 days).Interpretation: Contact tracing of COVID-19 cases required many contact tracing teams, testing all contacts without COVID-19 symptoms, and quarantine of asymptomatic SARS-CoV-2 positive contacts. Countries with limited contact tracing, testing and quarantine of asymptomatic SARS-CoV-2 infected contacts under-estimate the number of infected asymptomatic SARS-CoV-2 contacts, and their contribution to COVID-19 spread.Funding Statement: National Natural Science Foundation of China (82041021), Bill & Melinda Gates Foundation (INV-006371).Declaration of Interests: The authors declare they have no conflict of interest.Ethics Approval Statement: This study was approved by the Medical Research Ethics Review Committee of Sun Yat-sen University School of Public Health (No.: 2020016). Consistent with public health regulations the informed consent was waived because data were collected as part of public health practice associated with the COVID-19 outbreak investigation and response.

Resumption of the Treatment for Non-COVID-19 Gynecologic Patients after Lifting Lock down: Experiences from Wuhan (preprint)

Background: To share our experiences of resumption of the treatment for gynecologic patients after lifting lockdown in a hotspot area of the Corona Virus Disease 2019 (COVID-19)pandemic.Methods: The triage process used to resume the medical activities for gynecologic patients at the Wuhan Union Hospital after a 76-day lockdown of the city is described and its effectiveness to avoid COVID-19 nosocomial transmission is shown.Results:The non-emergency patients are pre-triaged by contact history and body temperature at outpatient clinic and negative COVID-19 screening tests are required for an admissionin the buffering rooms at the gynecologic department. The buffering lastsfor at least three days for symptom monitoring and a second round of COVID-19 tests before they can be transferred to the regular gynecologic wards. For patients who need emergency surgery, the first screening should be completed at the quarantine wards after the surgery, followed by buffering at the gynecologic department. We received 19298 outpatient visits, admitted 326 patients, and performed 223 operations in the first two months after the lockdown was lifted, andno single COVID-19 case occurredin the hospitalized patients while the proportion of potentially high-risk patients with cancer and severe anemia were increased in comparison with the same period in 2019 and the latest two months before the lockdown.Conclusions:We provide an effective triage system with buffering at two levels to guarantee safe and timely treatment for non-COVID-19 gynecologic patients in a post-lockdown phase.

Resumption of the Treatment for Non-COVID-19 Gynecologic Patients after Lifting Lockdown: Experiences from Wuhan (preprint)

Background: To share our experiences of resumption of the treatment for gynecologic patients after lifting lockdown in a hotspot area of the Corona Virus Disease 2019 (COVID-19)pandemic.Methods: The triage process used to resume the medical activities for gynecologic patients at the Wuhan Union Hospital after a 76-day lockdown of the city is described and its effectiveness to avoid COVID-19 nosocomial transmission is shown.Results:The non-emergency patients are pre-triaged by contact history and body temperature at outpatient clinic and negative COVID-19 screening tests are required for an admissionin the buffering rooms at the gynecologic department. The buffering lasts for at least three days for symptom monitoring and a second round of COVID-19 tests before they can be transferred to the regular gynecologic wards. For patients who need emergency surgery, the first screening should be completed at the quarantine wards after the surgery, followed by buffering at the gynecologic department. We received 19298 outpatient visits, admitted 326 patients, and performed 223 operations in the first two months after the lockdown was lifted, and no single COVID-19 case occurred in the hospitalized patients while the proportion of potentially high-risk patients with cancer and severe anemia were increased in comparison with the same period in 2019 and the latest two months before the lockdown.Conclusions:We provide an effective triage system with buffering at two levels to guarantee safe and timely treatment fornon-COVID-19 gynecologic patients in a post-lockdown phase.

Long period dynamics of viral load and antibodies for SARS-CoV-2 infection: an observational cohort study (preprint)

ABSTRACT OBJECTIVE To investigate the dynamics of viral RNA, IgM, and IgG and their relationships in patients with SARS-CoV-2 pneumonia over an 8-week period. DESIGN Retrospective, observational case series. SETTING Wenzhou Sixth Peoples Hospital PARTICIPANTS Thirty-three patients with laboratory confirmed SARS-CoV-2 pneumonia admitted to hospital. Data were collected from January 27 to April 10, 2020. MAIN OUTCOME MEASURES Throat swabs, sputum, stool, and blood samples were collected, and viral load was measured by reverse transcription PCR (RT-PCR). Specific IgM and IgG against spike protein (S), spike protein receptor binding domain (RBD), and nucleocapsid (N) were analyzed. RESULTS At the early stages of symptom onset, SARS-CoV-2 viral load is higher in throat swabs and sputum, but lower in stool. The median (IQR) time of undetectable viral RNA in throat swab, sputum, and stool was 18.5 (13.25-22) days, 22 (18.5-27.5) days, and 17 (11.5-32) days, respectively. In sputum, 17 patients (51.5%) had undetectable viral RNA within 22 days (short persistence), and 16 (48.5%) had persistent viral RNA more than 22 days (long persistence). Three patients (9.1%) had a detectable relapse of viral RNA in sputum within two weeks of their discharge from the hospital. One patient had persistent viral RNA for 59 days or longer. The median (IQR) seroconversion time of anti-S IgM, anti-RBD IgM, and anti-N IgM was 10.5 (7.75-15.5) days, 14 (9-24) days, and 10 (7-14) days, respectively. The median (IQR) seroconversion time of anti-S IgG, anti-RBD IgG, and anti-N IgG was 10 (7.25-16.5) days, 13 (9-17) days, and 10 (7-14) days, respectively. By week 8 after symptom onset, IgM were negative in many of the previously positive patients, and IgG levels remained less than 50% of the peak levels in more than 20% of the patients. In about 40% of the patients, anti-RBD IgG levels were 4-times higher in convalescence than in acute phase. SARS-CoV-2 RNA coexisted with antibodies for more than 50 days. Anti-RBD IgM and IgG levels, including anti-RBD IgM levels at presentation and peak time, were significantly higher in viral RNA short persistence patients than in long persistence patients. CONCLUSION This study adds important new information about the features of viral load and antibody dynamics of SARS-CoV-2. It is clear from these results that the viral RNA persists in sputum and stool specimens for a relatively long time in many patients. Anti-RBD may also serve as a potential protective antibody against SARS-CoV-2 infection, as viral persistence appears to be related to anti-RBD levels. Earlier treatment intervention also appears to be a factor in viral persistence.

Rapid and accurate identification of COVID-19 infection through machine learning based on clinical available blood test results (preprint)

Since the sudden outbreak of coronavirus disease 2019 (COVID-19), it has rapidly evolved into a momentous global health concern. Due to the lack of constructive information on the pathogenesis of COVID-19 and specific treatment, it highlights the importance of early diagnosis and timely treatment. In this study, 11 key blood indices were extracted through random forest algorithm to build the final assistant discrimination tool from 49 clinical available blood test data which were derived by commercial blood test equipments. The method presented robust outcome to accurately identify COVID-19 from a variety of suspected patients with similar CT information or similar symptoms, with accuracy of 0.9795 and 0.9697 for the cross-validation set and test set, respectively. The tool also demonstrated its outstanding performance on an external validation set that was completely independent of the modeling process, with sensitivity, specificity, and overall accuracy of 0.9512, 0.9697, and 0.9595, respectively. Besides, 24 samples from overseas infected patients with COVID-19 were used to make an in-depth clinical assessment with accuracy of 0.9167. After multiple verification, the reliability and repeatability of the tool has been fully evaluated, and it has the potential to develop into an emerging technology to identify COVID-19 and lower the burden of global public health. The proposed tool is well-suited to carry out preliminary assessment of suspected patients and help them to get timely treatment and quarantine suggestion. The assistant tool is now available online at http://lishuyan.lzu.edu.cn/COVID2019_2/.

Aerodynamic Characteristics and RNA Concentration of SARS-CoV-2 Aerosol in Wuhan Hospitals during COVID-19 Outbreak (preprint)

BackgroundThe ongoing outbreak of COVID-19 has spread rapidly and sparked global concern. While the transmission of SARS-CoV-2 through human respiratory droplets and contact with infected persons is clear, the aerosol transmission of SARS-CoV-2 has been little studied. MethodsThirty-five aerosol samples of three different types (total suspended particle, size segregated and deposition aerosol) were collected in Patient Areas (PAA) and Medical Staff Areas (MSA) of Renmin Hospital of Wuhan University (Renmin) and Wuchang Fangcang Field Hospital (Fangcang), and Public Areas (PUA) in Wuhan, China during COVID-19 outbreak. A robust droplet digital polymerase chain reaction (ddPCR) method was employed to quantitate the viral SARS-CoV-2 RNA genome and determine aerosol RNA concentration. ResultsThe ICU, CCU and general patient rooms inside Renmin, patient hall inside Fangcang had undetectable or low airborne SARS-CoV-2 concentration but deposition samples inside ICU and air sample in Fangcang patient toilet tested positive. The airborne SARS-CoV-2 in Fangcang MSA had bimodal distribution with higher concentration than those in Renmin during the outbreak but turned negative after patients number reduced and rigorous sanitization implemented. PUA had undetectable airborne SARS-CoV-2 concentration but obviously increased with accumulating crowd flow. ConclusionsRoom ventilation, open space, proper use and disinfection of toilet can effectively limit aerosol transmission of SARS-CoV-2. Gathering of crowds with asymptomatic carriers is a potential source of airborne SARS-CoV-2. The virus aerosol deposition on protective apparel or floor surface and their subsequent resuspension is a potential transmission pathway and effective sanitization is critical in minimizing aerosol transmission of SARS-CoV-2.