Evaluating clinical characteristics studies produced early in the Covid-19 pandemic: A systematic review.

OBJECTIVES: Clinical characterisation studies have been essential in helping inform research, diagnosis and clinical management efforts, particularly early in a pandemic. This systematic review summarises the early literature on clinical characteristics of patients admitted to hospital, and evaluates the quality of evidence produced during the initial stages of the pandemic. METHODS: MEDLINE, EMBASE and Global Health databases were searched for studies published from January 1st 2020 to April 28th 2020. Studies which reported on at least 100 hospitalised patients with Covid-19 of any age were included. Data on clinical characteristics were independently extracted by two review authors. Study design specific critical appraisal tools were used to evaluate included studies: the Newcastle Ottawa scale for cohort and cross sectional studies, Joanna Briggs Institute checklist for case series and the Cochrane collaboration tool for assessing risk of bias in randomised trials. RESULTS: The search yielded 78 studies presenting data on 77,443 people. Most studies (82%) were conducted in China. No studies included patients from low- and middle-income countries. The overall quality of included studies was low to moderate, and the majority of studies did not include a control group. Fever and cough were the most commonly reported symptoms early in the pandemic. Laboratory and imaging findings were diverse with lymphocytopenia and ground glass opacities the most common findings respectively. Clinical data in children and vulnerable populations were limited. CONCLUSIONS: The early Covid-19 literature had moderate to high risk of bias and presented several methodological issues. Early clinical characterisation studies should aim to include different at-risk populations, including patients in non-hospital settings. Pandemic preparedness requires collection tools to ensure observational studies are methodologically robust and will help produce high-quality data early on in the pandemic to guide clinical practice and public health policy. REVIEW REGISTRATION: Available at https://osf.io/mpafn.

Addressing challenges for clinical research responses to emerging epidemics and pandemics: a scoping review.

BACKGROUND: Major infectious disease outbreaks are a constant threat to human health. Clinical research responses to outbreaks generate evidence to improve outcomes and outbreak control. Experiences from previous epidemics have identified multiple challenges to undertaking timely clinical research responses. This scoping review is a systematic appraisal of political, economic, administrative, regulatory, logistical, ethical and social (PEARLES) challenges to clinical research responses to emergency epidemics and solutions identified to address these. METHODS: A scoping review. We searched six databases (MEDLINE, Embase, Global Health, PsycINFO, Scopus and Epistemonikos) for articles published from 2008 to July 2018. We included publications reporting PEARLES challenges to clinical research responses to emerging epidemics and pandemics and solutions identified to address these. Two reviewers screened articles for inclusion, extracted and analysed the data. RESULTS: Of 2678 articles screened, 76 were included. Most presented data relating to the 2014-2016 Ebola virus outbreak or the H1N1 outbreak in 2009. The articles related to clinical research responses in Africa (n = 37), Europe (n = 8), North America (n = 5), Latin America and the Caribbean (n = 3) and Asia (n = 1) and/or globally (n = 22). A wide range of solutions to PEARLES challenges was presented, including a need to strengthen global collaborations and coordination at all levels and develop pre-approved protocols and equitable frameworks, protocols and standards for emergencies. Clinical trial networks and expedited funding and approvals were some solutions implemented. National ownership and community engagement from the outset were a key enabler for delivery. Despite the wide range of recommended solutions, none had been formally evaluated. CONCLUSIONS: To strengthen global preparedness and response to the COVID-19 pandemic and future epidemics, identified solutions for rapid clinical research deployment, delivery, and dissemination must be implemented. Improvements are urgently needed to strengthen collaborations, funding mechanisms, global and national research capacity and capability, targeting regions vulnerable to epidemics and pandemics. Solutions need to be flexible to allow timely adaptations to context, and research led by governments of affected regions. Research communities globally need to evaluate their activities and incorporate lessons learnt to refine and rehearse collaborative outbreak response plans in between epidemics.