Engineering Immunosuppressive Drug Resistant Armored (IDRA) SARS-CoV-2 T cells for cell therapy (preprint)

Solid organ transplant (SOT) recipients receive immunosuppressive drugs (ISDs) and are susceptible to develop severe COVID-19. Here, we analyzed the Spike-specific T cell response after 3 doses of mRNA vaccine in a group of SOT patients (n=136) treated with different ISDs. We demonstrated that combination of calcineurin inhibitor (CNI), mycophenolate mofetil (MMF), and prednisone (Pred) treatment regimen displayed strong suppression of mRNA vaccine-induced Spike-specific cellular response. Such defects have clinical consequences since the magnitude of vaccine-induced Spike-specific T cells was directly proportional to the ability of SOT patients to rapidly clear SARS-CoV-2 after breakthrough infection. To then compensate the T cell defects induced by immunosuppressive treatment and to develop an alternative therapeutic strategy for SOT patients, we describe the production of 6 distinct SARS-CoV-2 epitope-specific ISD-resistant T Cell Receptor (TCR)-T cells engineered using mRNA electroporation method with reactivity minimally affected by mutations occurring in Beta, Delta, Gamma, and Omicron variants. This strategy with transient expression characteristics marks an improvement in the immunotherapeutic field and provides an attractive and novel therapeutic possibility for immunosuppressed COVID-19 patients.

The relationship between oxygen therapy, drug therapy, and COVID-19 mortality.

Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19). We conducted a retrospective study of COVID-19 inpatients in Wuhan Pulmonary Hospital (Wuhan, China) from January 1 to February 29, 2020. The subjects were divided into four groups due to different treatment regimes. We used the Kaplan-Meier method to determine the cumulative rates of in-hospital death and the Cox proportional hazard model to calculate the risk factors and corresponding hazard ratios. A total of 185 patients were included in this study. The median age of the patients was 62 years, including 94 men and 91 women. Kaplan-Meier analysis demonstrated that mortality was higher in older patients, higher in men, and lower in the low-flow oxygen therapy group. Body mass index (BMI) had no influence on mortality, as well as high flow oxygen therapy, Lopinavir-ritonavir (LPV/r) therapy, and the interferon-alpha add LPV/r therapy. Cox proportional hazard regression confirmed that the low flow oxygen therapy was independent protective factor for in-hospital death after adjusting for age, gender, and BMI. In conclusion, the mortality was higher in older patients, higher in men, and lower in the low-flow oxygen therapy group. BMI had no influence on mortality, as well as high flow oxygen therapy, LPV/r therapy, and interferon-alpha add LPV/r therapy.

Genetic characterization of SARS-CoV-2 from cross-border trucks and containers in Kashgar Prefecture, Xinjiang Uygur Autonomous Region, China

Kashgar is a prefecture in Xinjiang Uygur Autonomous Region. China. Kashgar Prefecture (KP) is a land-cargo port connecting China with central Asian countries and Europe. Frequent transportation of cargo has increased the risk of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) introduction into China, which has increased the pressure on coronavirus disease-2019 (COVID-19) prevention and control. In November 2020, an imported virus-induced COVID-19 outbreak occurred in KP. To investigate the genetic characterization of SARS-CoV-2 that contaminated the trucks and containers, and the potential of border rapid logistics system to serve as carriers for SARS-CoV-2 transmission, thirty-five SARS-CoV-2-positive nucleic-acid samples collected from KP cross-border trucks and containers from 6-10 November 2020 were subjected into SARS-CoV-2 genomic sequencing and comparative analyses. The results showed that the median (minimum to maximum) Ct value of ORF1ab was 37.64 (28.91-39.81) . and that of the N gene was 36.50 (26.35-39.30), and the median (minimum to maximum) of the reads mapping ratio to SARS-CoV-2 was 51.95% (0.86%-99.31%), which indicated low viral loads in these environmental samples. Eighteen of 35 samples had genomic coverage >70%. According to the Pango nomenclature, 18 SARS-CoV-2 sequences belonged to six lineages (B.1, B.I.1, B.1.9. B.1.1.220, B.1.153 and B.1.465), three of which (B.I. B.1.1 and 8.1.153) were found in case samples from the same period of four China-neighboring countries. Analyses of nucleotide mutations and phylogenetic trees showed that the genome sequences of SARS-CoV-2 collected from the same location were similar. Four of 18 sequences were in a sub-lineage with the representative strain of COVID-19 outbreak in KP, one of which had 1 or 2 differences in nucleotide mutation sites with the strain that caused the COVID-19 outbreak in KP, which indicated high homology in the viral genome. We showed that cross-border trucks and containers were contaminated by various genotypes of SARS-CoV-2 from other countries during the outbreak in KP. and in which contained the parental virus of the KP cases. These trucks and containers served as carriers for SARS-CoV-2 introduction from other countries to cause local transmission. Our results provide important references for COVID-19 prevention-and-control strategies in border ports and tracing of outbreak sources in China.

Effect of Noninvasive Respiratory Strategies on Intubation or Mortality Among Patients With Acute Hypoxemic Respiratory Failure and COVID-19: The RECOVERY-RS Randomized Clinical Trial.

Importance: Continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO) have been recommended for acute hypoxemic respiratory failure in patients with COVID-19. Uncertainty exists regarding the effectiveness and safety of these noninvasive respiratory strategies. Objective: To determine whether either CPAP or HFNO, compared with conventional oxygen therapy, improves clinical outcomes in hospitalized patients with COVID-19-related acute hypoxemic respiratory failure. Design, Setting, and Participants: A parallel group, adaptive, randomized clinical trial of 1273 hospitalized adults with COVID-19-related acute hypoxemic respiratory failure. The trial was conducted between April 6, 2020, and May 3, 2021, across 48 acute care hospitals in the UK and Jersey. Final follow-up occurred on June 20, 2021. Interventions: Adult patients were randomized to receive CPAP (n = 380), HFNO (n = 418), or conventional oxygen therapy (n = 475). Main Outcomes and Measures: The primary outcome was a composite of tracheal intubation or mortality within 30 days. Results: The trial was stopped prematurely due to declining COVID-19 case numbers in the UK and the end of the funded recruitment period. Of the 1273 randomized patients (mean age, 57.4 [95% CI, 56.7 to 58.1] years; 66% male; 65% White race), primary outcome data were available for 1260. Crossover between interventions occurred in 17.1% of participants (15.3% in the CPAP group, 11.5% in the HFNO group, and 23.6% in the conventional oxygen therapy group). The requirement for tracheal intubation or mortality within 30 days was significantly lower with CPAP (36.3%; 137 of 377 participants) vs conventional oxygen therapy (44.4%; 158 of 356 participants) (absolute difference, -8% [95% CI, -15% to -1%], P = .03), but was not significantly different with HFNO (44.3%; 184 of 415 participants) vs conventional oxygen therapy (45.1%; 166 of 368 participants) (absolute difference, -1% [95% CI, -8% to 6%], P = .83). Adverse events occurred in 34.2% (130/380) of participants in the CPAP group, 20.6% (86/418) in the HFNO group, and 13.9% (66/475) in the conventional oxygen therapy group. Conclusions and Relevance: Among patients with acute hypoxemic respiratory failure due to COVID-19, an initial strategy of CPAP significantly reduced the risk of tracheal intubation or mortality compared with conventional oxygen therapy, but there was no significant difference between an initial strategy of HFNO compared with conventional oxygen therapy. The study may have been underpowered for the comparison of HFNO vs conventional oxygen therapy, and early study termination and crossover among the groups should be considered when interpreting the findings. Trial Registration: isrctn.org Identifier: ISRCTN16912075.

SARS-CoV-2 environmental contamination from hospitalised patients with COVID-19 receiving aerosol-generating procedures.

BACKGROUND: Continuous positive airways pressure (CPAP) and high-flow nasal oxygen (HFNO) are considered 'aerosol-generating procedures' in the treatment of COVID-19. OBJECTIVE: To measure air and surface environmental contamination with SARS-CoV-2 virus when CPAP and HFNO are used, compared with supplemental oxygen, to investigate the potential risks of viral transmission to healthcare workers and patients. METHODS: 30 hospitalised patients with COVID-19 requiring supplemental oxygen, with a fraction of inspired oxygen ≥0.4 to maintain oxygen saturation ≥94%, were prospectively enrolled into an observational environmental sampling study. Participants received either supplemental oxygen, CPAP or HFNO (n=10 in each group). A nasopharyngeal swab, three air and three surface samples were collected from each participant and the clinical environment. Real-time quantitative polymerase chain reaction analyses were performed for viral and human RNA, and positive/suspected-positive samples were cultured for the presence of biologically viable virus. RESULTS: Overall 21/30 (70%) participants tested positive for SARS-CoV-2 RNA in the nasopharynx. In contrast, only 4/90 (4%) and 6/90 (7%) of all air and surface samples tested positive (positive for E and ORF1a) for viral RNA respectively, although there were an additional 10 suspected-positive samples in both air and surfaces samples (positive for E or ORF1a). CPAP/HFNO use or coughing was not associated with significantly more environmental contamination than supplemental oxygen use. Only one nasopharyngeal sample was culture positive. CONCLUSIONS: The use of CPAP and HFNO to treat moderate/severe COVID-19 did not appear to be associated with substantially higher levels of air or surface viral contamination in the immediate care environment, compared with the use of supplemental oxygen.

Pig farmers' willingness to recover their production under COVID-19 pandemic shock in China - empirical evidence from a farm survey. (Special Focus: Impacts of COVID-19 on agriculture and rural poverty in China.)

Pig farmers' willingness to recover production under the COVID-19 pandemic shock is significant to recover live pigs' supply in China in 2020. Increasing farmers' willingness to recover pig production contributes to enhance pig supply, stabilize the pig and pork market, and to improve pig farmers' income. This research studies the determinants of pig farmers' willingness to recover production under COVID-19 pandemic shock by applying survey data of 201 farmers in Huai'an City and Lin'an City and a logit regression model. The estimation results show that a farmer's risk perception, the duration time of a farmer's feed supply under COVID-19 pandemic shock, whether or not being a cooperative member, and a farmer's knowledge on government's policy designed to encourage pig production, a farmer's education level and production experience are the key determinants to a farmer's willingness to recover pig production. Thus, it's important for policymakers to solve the problems for farmers to get access to feed during the pandemic, to encourage the development of cooperatives, as well as to issue and advocate policies to encourage pig production. The study contributes to the scant literature by providing fresh empirical evidences on determinants of farmers' willingness to recover pig production. It has significance to farmers and governments to enhance farmers' willingness to recover production, which contributes to secure pig supply in China after the COVID-19 pandemic.

Rehabilitation Exercise and psycholoGical support After covid-19 InfectioN' (REGAIN): a structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The primary objective is to determine which of two interventions: 1) an eight week, online, home-based, supervised, group rehabilitation programme (REGAIN); or 2) a single online session of advice (best-practice usual care); is the most clinically and cost-effective treatment for people with ongoing COVID-19 sequelae more than three months after hospital discharge. TRIAL DESIGN: Multi-centre, 2-arm (1:1 ratio) parallel group, randomised controlled trial with embedded process evaluation and health economic evaluation. PARTICIPANTS: Adults with ongoing COVID-19 sequelae more than three months after hospital discharge Inclusion criteria: 1) Adults ≥18 years; 2) ≥ 3 months after any hospital discharge related to COVID-19 infection, regardless of need for critical care or ventilatory support; 3) substantial (as defined by the participant) COVID-19 related physical and/or mental health problems; 4) access to, and able/supported to use email and internet audio/video; 4) able to provide informed consent; 5) able to understand spoken and written English, Bengali, Gujarati, Urdu, Punjabi or Mandarin, themselves or supported by family/friends. EXCLUSION CRITERIA: 1) exercise contraindicated; 2) severe mental health problems preventing engagement; 3) previous randomisation in the present study; 4) already engaged in, or planning to engage in an alternative NHS rehabilitation programme in the next 12 weeks; 5) a member of the same household previously randomised in the present study. INTERVENTION AND COMPARATOR: Intervention 1: The Rehabilitation Exercise and psycholoGical support After covid-19 InfectioN (REGAIN) programme: an eight week, online, home-based, supervised, group rehabilitation programme. Intervention 2: A thirty-minute, on-line, one-to-one consultation with a REGAIN practitioner (best-practice usual care). MAIN OUTCOMES: The primary outcome is health-related quality of life (HRQoL) - PROMIS® 29+2 Profile v2.1 (PROPr) - measured at three months post-randomisation. Secondary outcomes include dyspnoea, cognitive function, health utility, physical activity participation, post-traumatic stress disorder (PTSD) symptom severity, depressive and anxiety symptoms, work status, health and social care resource use, death - measured at three, six and 12 months post-randomisation. RANDOMISATION: Participants will be randomised to best practice usual care or the REGAIN programme on a 1:1.03 basis using a computer-generated randomisation sequence, performed by minimisation and stratified by age, level of hospital care, and case level mental health symptomatology. Once consent and baseline questionnaires have been completed by the participant online at home, randomisation will be performed automatically by a bespoke web-based system. BLINDING (MASKING): To ensure allocation concealment from both participant and REGAIN practitioner at baseline, randomisation will be performed only after the baseline questionnaires have been completed online at home by the participant. After randomisation has been performed, participants and REGAIN practitioners cannot be blind to group allocation. Follow-up outcome assessments will be completed by participants online at home. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 535 participants will be randomised: 263 to the best-practice usual care arm, and 272 participants to the REGAIN programme arm. TRIAL STATUS: Current protocol: Version 3.0 (27th October 2020) Recruitment will begin in December 2020 and is anticipated to complete by September 2021. TRIAL REGISTRATION: ISRCTN:11466448 , 23rd November 2020 FULL PROTOCOL: The full protocol Version 3.0 (27th October 2020) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interests of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines.

Identification of COVID-19 Clinical Phenotypes by Principal Component Analysis-Based Cluster Analysis.

Background: COVID-19 has been quickly spreading, making it a serious public health threat. It is important to identify phenotypes to predict the severity of disease and design an individualized treatment. Methods: We collected data from 213 COVID-19 patients in Wuhan Pulmonary Hospital from January 1 to March 30, 2020. Principal component analysis (PCA) and cluster analysis were used to classify patients. Results: We identified three distinct subgroups of COVID-19. Cluster 1 was the largest group (52.6%) and characterized by oldest age, lowest cellular immune function, and albumin levels. 38.5% of subjects were grouped into Cluster 2. Most of the lab results in Cluster 2 fell between those of Clusters 1 and 3. Cluster 3 was the smallest cluster (8.9%), characterized by youngest age and highest cellular immune function. The incidence of respiratory failure, acute respiratory distress syndrome (ARDS), heart failure, and usage of non-invasive mechanical ventilation in Cluster 1 was significantly higher than others (P < 0.05). Cluster 1 had the highest death rate of 30.4% (P = 0.005). Although there were significant differences in age between Clusters 2 and 3 (P < 0.001), we found that there was no difference in demand for medical resources. Conclusions: We identified three distinct clusters of the COVID-19 patients. The results show that age alone could not be used to assess a patient's condition. Specifically, management of albumin, and immune function are important in reducing the severity of disease.

Reshaping Cell Line Development and CMC Strategy for Fast Responses to Pandemic Outbreak (preprint)

The global pandemic outbreak, SARS-COV-2, which causes COVID-19, has coerced numerous pharmaceutical companies to sprint for the vaccine and therapeutic biologics development. Most of the therapeutic biologics are common human IgG antibodies, which were identified by next-generation sequencing with the B cells from the convalescent patients in less than one-month post-infection. While the global public health emergency calls for medications urgently, it saves lives to expedite the clinical trials of biologics as much as possible, hence the biologics development strategies are unprecedentedly challenged. Since the advent of therapeutic biologics, transfection, and selection strategy has been continuously improving for developing more robust cell lines with greater productivity and efficiency. Next-generation sequencing (NGS) has also been implemented into cell bank testing for acceleration. These recent advances enable us to rethink and reshape the chemistry, manufacturing and controls (CMC) strategy against the pandemic outbreaks, to start supplying cGMP materials for the life-saving clinical trials as soon as possible. We elucidated an accelerated CMC workflow for biologics against pandemics, including using cGMP-compliant pool materials for Phase I clinical trials, selecting the final clone with similar product quality as Phase I materials for late-stage development and commercial production and matching product quality among different manufacturing stages.

Clinical Management of Gynecological Cancer Patients During COVID-19 Epidemic

During the epidemic of COVID-19, the routine clinical treatment for gynecological cancer patients has been disturbed due to the redistribution of medical resource. Due to the systemic immunosuppression caused by the malignancy and anticancer treatments, gynecological cancer patients are more susceptible to COVID-19. With the improvement of the epidemic, the treatment needs of gynecological cancer patients are extremely strong. During this special period, it should carefully identify fever and respiratory symptoms of gynecological cancer patients receiving chemotherapy, immunotherapy and operations. Therefore, it is quite necessary to carry out comprehensive clinical management. We introduce a clinical management of gynecological cancer patients in three aspects of outpatient, in-hospital and out-of-hospital management during this period, in order to maximize the treatment of tumors and effectively prevent COVID-19.

COVID-19 Societal Response Captured by Seismic Noise in China and Italy

Seismic noise with frequencies above 1 Hz is often called "cultural noise" and is generally correlated quite well with human activities. Recently, cities in mainland China and Italy imposed restrictions on travel and day-to-day activity in response to COVID-19, which gave us an unprecedented opportunity to study the relationship between seismic noise above 1 Hz and human activities. Using seismic records from stations in China and Italy, we show that seismic noise above 1 Hz was primarily generated by the local transportation systems. The lockdown of the cities and the imposition of travel restrictions led to an similar to 4-12 dB decrease in seismic noise power in mainland China. Data also show that different Chinese cities experienced distinct periods of diminished cultural noise, related to differences in local response to the epidemic. In contrast, there was only similar to 1-6 dB decrease of seismic noise power in Italy, after the country was put under a lockdown. The noise data indicate that traffic flow did not decrease as much in Italy and show how different cities reacted distinctly to the lockdown conditions.

RECOVERY- Respiratory Support: Respiratory Strategies for patients with suspected or proven COVID-19 respiratory failure; Continuous Positive Airway Pressure, High-flow Nasal Oxygen, and standard care: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVE: The trial objective is to determine if Continuous Positive Airway Pressure (CPAP) or High-Flow Nasal Oxygen (HFNO) is clinically effective compared to standard oxygen therapy in patients with confirmed or suspected COVID-19. TRIAL DESIGN: Adaptive (group-sequential), parallel group, pragmatic, superiority randomised controlled, open-label, multi-centre, effectiveness trial. PARTICIPANTS: The trial is being conducted across approximately 60 hospitals across England, Wales, Scotland, and Northern Ireland. Inpatients at participating hospitals are eligible to participate if they have respiratory failure with suspected or proven COVID-19, and meet all of the inclusion criteria and none of the exclusion criteria. INCLUSION CRITERIA: 1) Adults ≥ 18 years; 2) Admitted to hospital with suspected or proven COVID-19; 3) Receiving oxygen with fraction of inspired oxygen (FiO2) ≥0.4 and peripheral oxygen saturation (SpO2) ≤94%; and 4) Plan for escalation to tracheal intubation if needed. EXCLUSION CRITERIA: 1) Planned tracheal intubation and mechanical ventilation imminent within 1 hour; 2) Known or clinically apparent pregnancy; 3) Any absolute contraindication to CPAP or HFNO; 4) Decision not to intubate due to ceiling of treatment or withdrawal of treatment anticipated; and 5) Equipment for both CPAP and HFNO not available. INTERVENTION AND COMPARATOR: Intervention one: Continuous positive airway pressure delivered by any device. Set-up and therapy titration is not protocolised and is delivered in accordance with clinical discretion. Intervention two: High-flow nasal oxygen delivered by any device. Set-up and therapy titration is not protocolised and is delivered in accordance with clinical discretion. Comparator group: Standard care- oxygen delivered by face mask or nasal cannula (excluding the use of continuous positive airway pressure or high-flow nasal oxygen). Set-up and therapy titration is not protocolised and is delivered in accordance with clinical discretion. Intervention delivery continues up to the point of death, tracheal intubation, or clinical determination that there is no ongoing need (palliation or improvement). MAIN OUTCOMES: The primary outcome is a composite outcome comprising tracheal intubation or mortality within 30 days following randomisation. Secondary outcomes include tracheal intubation rate, time to tracheal intubation, duration of invasive ventilation, mortality rate, time to mortality, length of hospital stay, and length of critical care stay. RANDOMISATION: Participants are randomised in a 1:1:1 ratio to receive either continuous positive airway pressure, high-flow nasal oxygen or standard care. Due to the challenging environment of study delivery, a specific intervention may not always be available at the hospital site. The study uses two integrated randomisation systems to allow, where required, the site to randomise between all three interventions, between CPAP and standard care, and between HFNO and standard care. System integration ensures maintenance of balance between interventions. Randomisation is performed using a telephone-based interactive voice response system to maintain allocation concealment. The randomisation sequence was computer-generated using the minimisation method. Participant randomisation is stratified by site, gender (M/F), and age (<50, >=50 years). BLINDING (MASKING): The nature of the trial interventions precludes blinding of the researcher, patient and clinical team. Primary and secondary outcomes are all objective outcomes, thereby minimising the risk of detection bias. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 4002 participants (1334 to be randomized to each of the three study arms) TRIAL STATUS: Current protocol: Version 4.0, 29th May 2020. Recruitment began on April 6, 2020 and is anticipated to be complete by April 5, 2021. The trial has been awarded Urgent Public Health status by the National Institute of Health Research on 13th April 2020. TRIAL REGISTRATION: ISRCTN, ISRCTN16912075. Registered 6th April 2020, http://www.isrctn.com/ISRCTN16912075 FULL PROTOCOL: The full protocol (version 4.0, 29th May 2020) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Dynamic changes of D-dimer and neutrophil-lymphocyte count ratio as prognostic biomarkers in COVID-19.

BACKGROUND: Since December 2019, the outbreak of COVID-19 caused a large number of hospital admissions in China. Many patients with COVID-19 have symptoms of acute respiratory distress syndrome, even are in danger of death. This is the first study to evaluate dynamic changes of D-Dimer and Neutrophil-Lymphocyte Count Ratio (NLR) as a prognostic utility in patients with COVID-19 for clinical use. METHODS: In a retrospective study, we collected data from 349 hospitalized patients who diagnosed as the infection of the COVID-19 in Wuhan Pulmonary Hospital. We used ROC curves and Cox regression analysis to explore critical value (optimal cut-off point associated with Youden index) and prognostic role of dynamic changes of D-Dimer and NLR. RESULTS: Three hundred forty-nine participants were enrolled in this study and the mortality rate of the patients with laboratory diagnosed COVID-19 was 14.9%. The initial and peak value of D-Dimer and NLR in deceased patients were higher statistically compared with survivors (P < 0.001). There was a more significant upward trend of D-Dimer and NLR during hospitalization in the deceased patients, initial D-Dimer and NLR were lower than the peak tests (MD) -25.23, 95% CI: - 31.81- -18.64, P < 0.001; (MD) -43.73, 95% CI:-59.28- -31.17, P < 0.001. The test showed a stronger correlation between hospitalization days, PCT and peak D-Dimer than initial D-Dimer. The areas under the ROC curves of peak D-Dimer and peak NLR tests were higher than the initial tests (0.94(95%CI: 0.90-0.98) vs. 0.80 (95% CI: 0.73-0.87); 0.93 (95%CI:0.90-0.96) vs. 0.86 (95%CI:0.82-0.91). The critical value of initial D-Dimer, peak D-Dimer, initial NLR and peak NLR was 0.73 mg/L, 3.78 mg/L,7.13 and 14.31 respectively. 35 (10.03%) patients were intubated. In the intubated patients, initial and peak D-Dimer and NLR were much higher than non-intubated patients (P < 0.001). The critical value of initial D-Dimer, peak D-Dimer, initial NLR and peak NLR in prognosticate of intubation was 0.73 mg/L, 12.75 mg/L,7.28 and 27.55. The multivariable Cox regression analysis showed that age (HR 1.04, 95% CI 1.00-1.07, P = 0.01), the peak D-Dimer (HR 1.03, 95% CI 1.01-1.04, P < 0.001) were prognostic factors for COVID-19 patients' death. CONCLUSIONS: To dynamically observe the ratio of D-Dimer and NLR was more valuable during the prognosis of COVID-19. The rising trend in D-Dimer and NLR, or the test results higher than the critical values may indicate a risk of death for participants with COVID-19.

Mining the Characteristics of COVID-19 Patients in China: Analysis of Social Media Posts.

BACKGROUND: In December 2019, pneumonia cases of unknown origin were reported in Wuhan City, Hubei Province, China. Identified as the coronavirus disease (COVID-19), the number of cases grew rapidly by human-to-human transmission in Wuhan. Social media, especially Sina Weibo (a major Chinese microblogging social media site), has become an important platform for the public to obtain information and seek help. OBJECTIVE: This study aims to analyze the characteristics of suspected or laboratory-confirmed COVID-19 patients who asked for help on Sina Weibo. METHODS: We conducted data mining on Sina Weibo and extracted the data of 485 patients who presented with clinical symptoms and imaging descriptions of suspected or laboratory-confirmed cases of COVID-19. In total, 9878 posts seeking help on Sina Weibo from February 3 to 20, 2020 were analyzed. We used a descriptive research methodology to describe the distribution and other epidemiological characteristics of patients with suspected or laboratory-confirmed SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection. The distance between patients' home and the nearest designated hospital was calculated using the geographic information system ArcGIS. RESULTS: All patients included in this study who sought help on Sina Weibo lived in Wuhan, with a median age of 63.0 years (IQR 55.0-71.0). Fever (408/485, 84.12%) was the most common symptom. Ground-glass opacity (237/314, 75.48%) was the most common pattern on chest computed tomography; 39.67% (167/421) of families had suspected and/or laboratory-confirmed family members; 36.58% (154/421) of families had 1 or 2 suspected and/or laboratory-confirmed members; and 70.52% (232/329) of patients needed to rely on their relatives for help. The median time from illness onset to real-time reverse transcription-polymerase chain reaction (RT-PCR) testing was 8 days (IQR 5.0-10.0), and the median time from illness onset to online help was 10 days (IQR 6.0-12.0). Of 481 patients, 32.22% (n=155) lived more than 3 kilometers away from the nearest designated hospital. CONCLUSIONS: Our findings show that patients seeking help on Sina Weibo lived in Wuhan and most were elderly. Most patients had fever symptoms, and ground-glass opacities were noted in chest computed tomography. The onset of the disease was characterized by family clustering and most families lived far from the designated hospital. Therefore, we recommend the following: (1) the most stringent centralized medical observation measures should be taken to avoid transmission in family clusters; and (2) social media can help these patients get early attention during Wuhan's lockdown. These findings can help the government and the health department identify high-risk patients and accelerate emergency responses following public demands for help.

Cancer is associated with the severity and mortality of patients with COVID-19: a systematic review and meta-analysis (preprint)

Background: Cancer patients are considered a highly vulnerable population in the COVID-19 epidemic, but the relationship between cancer and the severity and mortality of patients with COVID-19 remains unclear. This study aimed to explore the prevalence of cancer in patients with COVID-19 and to examine whether cancer patients with COVID-19 may be at an increased risk of severe illness and mortality. Methods: A comprehensive electronic search in seven databases was performed, to identified studies reporting the prevalence of cancer in COVID-19 patients, or providing data of cancer between patients with severe or non-severe illness or between non-survivors and survivors. Meta-analyses were performed to estimate the pooled prevalence and odds risk (OR) using the inverse variance method with the random-effects model. Results: Thirty-four studies with 8080 patients were included. The pooled prevalence of cancer in patients with COVID-19 was 2.0% (95% CI: 2.0% to 3.0%). The prevalence in Italy (5.0%), France (6.0%), and Korea (4.0%) were higher than that in China (2.0%). Cancer was associated with a 2.84-fold significantly increased risk of severe illness (OR = 2.84, 95%CI: 1.75 to 4.62, P < 0.001) and a 2.60-fold increased risk of death (OR = 2.60, 95%CI: 1.28 to 5.26, P = 0.008) in patients with COVID-19. Sensitivity analyses showed that the results were stable after excluding studies with a sample size of less than 100. Conclusions: Cancer patients have an increased risk of COVID-19 and cancer was associated with a significantly increased risk of severity and mortality of patients with COVID-19.