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Abstract Background Since December 2019, 2019 novel coronavirus pneumonia emerged in Wuhan city and rapidly spread throughout China and even the world. We sought to analyse the clinical characteristics and laboratory findings of some cases with 2019 novel coronavirus pneumonia . Methods In this retrospective study, we extracted the data on 95 patients with laboratory-confirmed 2019 novel coronavirus pneumonia in Wuhan Xinzhou District People’s Hospital from January 16th to February 25th, 2020. Cases were confirmed by real-time RT-PCR and abnormal radiologic findings. Outcomes were followed up until March 2th, 2020. Results Higher temperature, blood leukocyte count, neutrophil count, neutrophil percentage, C-reactive protein level, D-dimer level, alanine aminotransferase activity, aspartate aminotransferase activity, α - hydroxybutyrate dehydrogenase activity, lactate dehydrogenase activity and creatine kinase activity were related to severe 2019 novel coronavirus pneumonia and composite endpoint, and so were lower lymphocyte count, lymphocyte percentage and total protein level. Age below 40 or above 60 years old, male, higher Creatinine level, and lower platelet count also seemed related to severe 2019 novel coronavirus pneumonia and composite endpoint, however the P values were greater than 0.05, which mean under the same condition studies of larger samples are needed in the future. Conclusion Multiple factors were related to severe 2019 novel coronavirus pneumonia and composite endpoint, and more related studies are needed in the future.
Randomized clinical trials provide the highest-quality evidence for identifying therapies to help people attain longer and healthier lives. As of March 2020, ClinicalTrials.gov listed 262 366 ongoing randomized clinical trials, including 146 420 trials studying drug or biologic interventions, 85 045 trials of behavioral interventions, and 61 351 trials of surgical or device interventions.1 Suddenly, and quite dramatically, the coronavirus pandemic threatens the integrity of these clinical trials. The National Institutes of Health has advised investigators to consult with their institutional review boards and institutions about potential measures to protect participants and research staff. Responses from academic medical center and other research groups have varied from mandatory suspension of research involving human participants (except when this increases risk to participants) to relying on principal investigator discretion.
Coronavirus mitigation efforts include self-isolation and avoiding health care centers where symptomatic patients congregate for medical care and where randomized trials are typically conducted. Mitigation efforts interfere with all aspects of a successful clinical trial: efficient accrual and randomization, intervention adherence and delivery, and outcome collection. Those most susceptible to severe consequences of coronavirus, older individuals and those with chronic disease, are commonly included in randomized trials designed to improve health in these vulnerable populations.
When considering the risks and benefits of continuing clinical trials during the pandemic, one approach is to discontinue randomized trials that do not provide an immediate clear benefit to enrolled participants. However, benefits of therapeutic interventions in randomized trials are unknown until the trial is completed. Ongoing trials have potential to benefit millions of people with debilitating chronic diseases long after the coronavirus pandemic has ended. Furthermore, discontinuing ongoing trials wastes previously invested resources and squanders the time and effort of participants who may have already completed the trial. In contrast, sustaining ongoing trials could help millions of people realize substantial, durable health benefits that will be important once the coronavirus pandemic ends. Therefore, efforts and resources should be dedicated to support continuing randomized trials using creative and thoughtful methods and proactive planning. Adapting protocols to facilitate continued intervention adherence, outcome measurement, and some aspects of recruitment for trials already underway is likely to have the greatest benefit for the most people.
The following solutions may minimize disruption and preserve integrity of ongoing randomized clinical trials, while ensuring participant health and safety. These recommendations consider that the coronavirus pandemic has confined many staff and most participants to their homes, unable to visit a medical center for clinical trial activities. Each trial is unique, and the suggestions below will not be applicable to all trials. For example, risks of clinical trial participation during the coronavirus pandemic are different for a patient with end-stage cancer, for whom the clinical trial provides the only hope of survival, than for a patient with peripheral artery disease enrolled in a trial of a novel exercise intervention. For all clinical trials, however, research staff should keep participants informed about the effects of the coronavirus pandemic on their trial participation. Participants should be informed of necessary changes in protocol and how this may affect the risk associated with study participation. For many randomized trials, communication from research staff is likely to help protect against dropout or nonadherence by reassuring participants that their trial involvement remains important, even during the pandemic.
Collection of outcome data requires thoughtful consideration. First, outcomes should be prioritized. The primary outcome has highest priority, whereas outcomes that are exploratory or not prespecified are more appropriate to eliminate temporarily. Second, alternative methods for measuring primary outcomes that cannot be collected in-person should be prepared and protocols modified to facilitate collection of alternative self-reported or medical record data that can be adjudicated as a surrogate for the primary outcome. Once the trial resumes, collection of both the original outcome and the surrogate “remote” data allows better understanding of how the self-reported or medical record data can best be used to impute an objective measure that temporarily was not attainable. For example, self-report and medical record data from participants could be used to impute a 400-m walk outcome.2
Third, outcomes that can be collected remotely (ie, self-administered outcomes or outcomes collected by telephone or online) should be continued. Fourth, questionnaires previously collected in person can be converted to telephone administration. Self-administered questionnaires previously collected at an in-person visit can be mailed. Fifth, when feasible and when safe, objective outcomes could be collected at home. Sixth, when a high-priority outcome cannot be obtained at home, such as a 6-minute walk test, which requires a 100-foot hallway, consideration can be given to outcome collection off-site, away from the medical center, where exposure to potentially infectious individuals is minimized. However, collecting data off-site depends on local mandates and will not be feasible when all individuals are advised to stay home.
Delivery of intervention requires thoughtful consideration, emphasizing safety and feasibility under coronavirus restrictions. Interventions that can be safely adhered to without leaving home should be continued. In addition, when safe to do so, it may be appropriate to continue interventions, such as medications, beyond the originally intended stop date. For example, a 6-month drug or behavioral intervention could be extended by an additional 2 or 3 months, so that follow-up testing can be carried out while the participant is still receiving the intervention once isolation restrictions are lifted. If it becomes necessary to temporarily discontinue the intervention when necessary monitoring cannot take place, the intervention could potentially be resumed once restrictions are removed, to preserve originally planned intervention duration and outcome measure timing as much as possible. Moreover, some interventions may require modification to accommodate the inability of participants to attend behavioral interventions requiring group visits or exercise sessions at a gym. A supervised exercise session could be temporarily converted to a home-based session with remote monitoring—for example, by telephone, telecommunication tools such as Skype, or the internet—if feasible and safe. Virtual interventions are additional alternatives.
Another consideration is how the intervention might interact with coronavirus infection and whether the study drug should be continued if a participant becomes ill with symptoms of coronavirus. Conceivably, some interventions could improve outcomes. For example, a trial testing efficacy of a therapy such as a statin might mitigate the cardiovascular consequences of an acute inflammatory state. If continuing the intervention becomes untenable, intention-to-treat methods are essential for understanding risks and protective factors for infection, illness, or recovery.
Additional considerations follow. First, while baseline in-person visits will not be possible during the pandemic, self-isolation facilitates telephone eligibility screening by staff working from home, who may have few other study activities they can carry out. Potentially eligible participants who are identified should be encouraged to attend study visits later. Second, alternate contact information, including cell phone and email addresses for family members and friends (at least 3) should be requested in the event that contact is lost with the participant. Third, when study visits are essential, investigators may help participants avoid public transportation, or shared ride services, where risk of disease exposure may be greater. Instead, participants could travel in their own car or obtain a ride from a friend or study staff member. Fourth, when in-person visits are continued, participants should be advised of the potential risk of leaving their home and offered the opportunity to decline. These participants may be willing to resume participation after the pandemic.
Fifth, experienced staff conducting randomized trials may be at risk for lost wages, especially if they were temporary workers whose primary duties were in-person data collection or if they have childcare needs that prevent them from working. Providing work-from-home opportunities, such as making additional retention telephone calls, will help retain this valuable workforce. Sixth, the US Food and Drug Administration has released guidance with additional suggestions for continuing randomized trials during the coronavirus pandemic, emphasizing participant safety and the importance of maintaining clinical trial integrity as much as possible.3 Seventh, the clinical trial community should consider scaling back or placing selected trials on hold, if doing so does not substantially harm the trials, so that investigators and research personnel can shift from their own ongoing trials to work on urgent trials of interventions to address the coronavirus pandemic, such as trials of therapeutic interventions for coronavirus.
Clinical trials require years to design, fund, conduct, and complete but are essential for improving health and preventing disability. The effects of the coronavirus pandemic on randomized trials hopefully will be short-lived, relative to the long-term benefits of these trials to millions of people who will continue to live with debilitating medical diseases after the crisis ends. To maximize public health benefits, creativity and persistence are required, especially during these unprecedented and uncertain times.
Abstract Background Coronavirus can cross the species barrier and infect humans with a severe respiratory syndrome. SARS-CoV-2 with potential origin of bat is still circulating in China. In this study, a prediction model is proposed to evaluate the infection risk of non-human-origin coronavirus for early warning. Methods The spike protein sequences of 2666 coronaviruses were collected from 2019 Novel Coronavirus Resource (2019nCoVR) Database of China National Genomics Data Center on Jan 29, 2020. A total of 507 human-origin viruses were regarded as positive samples, whereas 2159 non-human-origin viruses were regarded as negative. To capture the key information of the spike protein, three feature encoding algorithms (amino acid composition, AAC; parallel correlation-based pseudo-amino-acid composition, PC-PseAAC and G-gap dipeptide composition, GGAP) were used to train 41 random forest models. The optimal feature with the best performance was identified by the multidimensional scaling method, which was used to explore the pattern of human coronavirus. Results The 10-fold cross-validation results showed that well performance was achieved with the use of the GGAP (g = 3) feature. The predictive model achieved the maximum ACC of 98.18% coupled with the Matthews correlation coefficient (MCC) of 0.9638. Seven clusters for human coronaviruses (229E, NL63, OC43, HKU1, MERS-CoV, SARS-CoV, and SARS-CoV-2) were found. The cluster for SARS-CoV-2 was very close to that for SARS-CoV, which suggests that both of viruses have the same human receptor (angiotensin converting enzyme II). The big gap in the distance curve suggests that the origin of SARS-CoV-2 is not clear and further surveillance in the field should be made continuously. The smooth distance curve for SARS-CoV suggests that its close relatives still exist in nature and public health is challenged as usual. Conclusions The optimal feature (GGAP, g = 3) performed well in terms of predicting infection risk and could be used to explore the evolutionary dynamic in a simple, fast and large-scale manner. The study may be beneficial for the surveillance of the genome mutation of coronavirus in the field.
Although a great deal of attention has been given to the coronavirus disease 2019 (COVID-19) epidemic, it is most severe in one area of China and appears to have limited clinical ramifications outside of that region. Lost in the discussion about COVID-19 is the fact that the US is experiencing a severe influenza season that has already resulted in more than 16 000 deaths. This JAMA Infographic compares prevalence and number of deaths for the 2 diseases.
Sources: CDC weekly US influenza surveillance report. https://www.cdc.gov/flu/weekly/index.htm
2019-2020 US flu season: preliminary burden estimates.
Coronavirus COVID-19 global cases by Johns Hopkins CSSE. https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6
Coronavirus Disease 2019 (COVID-19) in the US.
JAMA Network coronavirus disease 2019 (COVID-19) resource center. https://jamanetwork.com/journals/jama/pages/coronavirus-alert
Image source: C. Goldsmith and D. Rollin/Centers for Disease Control and Prevention