Risk factors for severity on admission and the disease progression during hospitalization in a large cohort of COVID-19 patients in Japan

ObjectivesTo investigate the risk factors contributing to severity on admission. Additionally, risk factors on worst severity and fatality were studied. Moreover, factors were compared based on three points: early severity, worst severity, and fatality. DesignA observational cohort study utilizing data entered in a Japan nationwide COVID-19 inpatient registry, COVIREGI-JP. SettingAs of August 31, 2020, 7,546 cases from 780 facilities have been registered. Participating facilities cover a wide range of hospitals where COVID-19 patients are admitted in Japan. ParticipantsParticipants who had a positive test result on any applicable SARS-CoV-2 diagnostic tests, and were admitted to participating healthcare facilities. A total of 3,829 cases were identified from January 16 to May 31, 2020, of which 3,376 cases were included in this study. Primary and secondary outcoe measuresPrimary outcome was severe or non-severe on admission, determined by the requirement of mechanical ventilation or oxygen therapy, SpO2, or respiratory rate. Secondary outcome was the worst severity during hospitalization, judged by the requirement of oxygen and/or IMV/ECMO. ResultsRisk factors for severity on admission were older age, male, cardiovascular disease, chronic respiratory disease, diabetes, obesity, and hypertension. Cerebrovascular disease, liver disease, renal disease or dialysis, solid tumor, and hyperlipidemia did not influence severity on admission; however it influenced worst severity. Fatality rates for obesity, hypertension, and hyperlipidemia were relatively lower. ConclusionsThis study segregated the comorbidities driving severity and death. It is possible that risk factors for severity on admission, worst severity, and fatality are not consistent and may be propelled by different factors. Specifically, while hypertension, hyperlipidemia, and obesity had major effect on worst severity, their impact was mild on fatality in the Japanese population. Some studies contradict our results; therefore, detailed analyses, considering in-hospital treatments, are needed for validation. Trial registrationUMIN000039873. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000045453 Strengths and limitations of this studyO_LIIn this article, we studied the disease progression of COVID-19, by comparing the risk factors on three points: early severity, worst severity, and fatality. C_LIO_LIOur results are useful from a public health perspective, as we provide risk factors for predicting the severity on admission and disease progression from patients background factors. C_LIO_LIThis study pointed out the possibility that risk factors of the severity on admission, worst severity, and fatality are not consistent and may be propelled by different factors. C_LIO_LIOur data were collected from hundreds of healthcare facilities; thus data accuracy may be questionable. C_LIO_LIAlso, treatment type, dosage, duration, and combination varied immensely across the facilities and we did not consider treatments prior to and during hospitalization in the analysis. C_LI

Efficacy of remdesivir in Japanese patients hospitalised with COVID-19: A large observational study using the COVID-19 Registry Japan

ObjectivesAlthough several randomised controlled trials have compared the efficacy of remdesivir with that of placebo, there is limited evidence regarding its effect in the early stage of nonsevere COVID-19 cases. MethodsWe evaluated the efficacy of remdesivir on the early stage of nonsevere COVID-19 using the COVID-19 Registry Japan, a nationwide registry of hospitalised COVID-19 patients in Japan. Two regimens (start remdesivir therapy within 4 days from admission vs. no remdesivir during hospitalisation) among patients without the need for supplementary oxygen therapy were compared by a three-step processing (cloning, censoring, and weighting) method. The primary outcome was supplementary oxygen requirement during hospitalisation. Secondary outcomes were 30-day fatality risk and risk of invasive mechanical ventilation or extracorporeal membrane oxygenation (IMV/ECMO). ResultsThe data of 12,657 cases met our inclusion criteria. The start remdesivir regimen showed a lower risk of supplementary oxygen requirement (hazard ratio: 0.861, p < 0.001). Both 30-day fatality risk and risk of IMV/ECMO introduction were not significantly different between the two regimens (hazard ratios: 1.05 and 0.886, p values: 0.070 and 0.440, respectively). ConclusionsRemdesivir might reduce the risk of oxygen requirement during hospitalisation in the early stage of COVID-19; however, it had no positive effect on the clinical outcome and reduction of IMV/ECMO requirement.

<b>Information: Recommendations for developing postmarketing surveys and clinical investigations using SS-MIX standardized storage </b> / 薬剤疫学

The Standardized Structured Medical record Information eXchange (SS-MIX) was started in 2006 as the project supported by the Ministry of Health, Labour and Welfare (MHLW) for promoting the exchange of the standardized medical information. Free soft wares developed in the project allow the storage of medical information to receive HL7 messages for prescription, laboratory test results, diagnoses and patient demographics in the hospital information system (HIS). We encourage the use of the SS-MIX standardized storage for postmarketing surveys and clinical studies. The recommendations consist of the following 7 parts. [1] In surveys and clinical studies, the information of drugs and laboratory test results in the SS-MIX standardized storage can be directly transferred to the electronic questionnaire and the investigators may obtain the information with high accuracy and granularity. [2] The SS-MIX standardized storage works as the backup system for the HIS because it can provide the minimum information essential in patient care even under the disastrous condition like earthquake or unexpected network failure. [3] The SS-MIX standardized storage may be useful to conduct a good pharmacoepidemiology study not only because it provides the information in the storage efficiently but also it can be used to identify “new users” who started the drug after some period of non-use.The “new user” design is often essential to have the unbiased results. [4] When the drug company conducts postmarketing surveys according to the current regulation, the use of the SS-MIX standardized storage will facilitate the fast and efficient collection of data to develop the timely measure to minimize the drug-related risk. With the SS-MIX standardized storage, it is also expected that many types of study design can be employed and the quality of data is improved in the survey. [5] The SS-MIX standardized storage maybe also useful to evaluate the risk minimization action plan by comparing the prescription pattern or incidence of the targeted adverse event between two periods before and after the implementation of the action plan. [6] In planning clinical trials, the SS-MIX standardized storage may be used to estimate the size of eligible patients. The storage may also allow conducting cross-sectional studies to know characteristics of diseases or drug treatment. In addition, cohorts of those who had coronary artery angiography, new users of a drug and those with a rare disease may be readily identified. Using such cohorts, investigators can initiate a case-control study nested within the cohort, pharmacogenomic studies and comparative effectiveness researches. [7] The SS-MIX standardized storage may be used as the formal data source in clinical trials in the future when some conditions are satisfied. For instance, the formal agreement should be reached between industry, government and academia on the use of standards of data structure in Clinical Data Interchange Standards Consortium (CDISC) and on the operation of computerized system validation (CSV) in the clinical trials.

<b>Expectations and Challenges Regarding the Use of the SS-MIX in a Clinical Trial </b> / 薬剤疫学

While there is an advantage to be able to directly utilize some research database of medical information must solve several problems. It also includes support for international standardization, led by computerized system validation, and CDISC. We should countermeasures with epidemiological studies using SS-MIX standardized storage, in anticipation of its application to clinical trials in the near future in Japan. (Jpn J Pharmacoepidemiol 2013；18(1)：35-39)