The COVID-19 Registry in Rhineland-Palatinate in the context of international registry activities documenting COVID-19 outcomes.

Rationale of COVID-19 registries

The global spread of Coronavirus SARS-CoV‑2 (SARS-CoV-2) was declared a pandemic by the World Health Organization (WHO) on March 11, 2020 and is currently posing major challenges for health care systems around the world . Besides the planning of intensive care resources, the lack of evidence-based therapy options is a particular problem for the treating physicians. General statements on the typical course of SARS-CoV‑2 infection cannot be made reliably at present. Disease patterns are unspecific, diverse, and vary widely, from asymptomatic courses to severe complications, such as pneumonia with lung failure, cardiovascular and cerebral manifestations, and ultimately death. Symptoms include fever, cough, and shortness of breath as well as neurological and cardiac manifestations [1]. Risk groups are mainly older people (with a steadily increasing risk of severe courses from above 50–60 years of age), smokers, and patients with certain pre-existing conditions (e.g., cardiovascular diseases, lung diseases, diabetes mellitus, cancer, and weakened immune system [2, 3]). Therefore, standardized and coordinated data collection on a large scale is of pivotal importance to learn about the natural course of the disease, to accelerate knowledge on the role of pre-existing comorbidities in the COVID-19 pandemic, and to identify factors associated with outcomes.

Planned and already enrolling COVID-19 registry activities in Germany and Europe

There are a plethora of planned and ongoing activities documenting the COVID-19 disease patterns using chart reviews or collecting prospective data. In Germany, many professional medical societies are currently planning or setting up registries for COVID-19 patients with different focuses on disease patterns and specific pre-existing conditions in their scientific fields, e.g., in patients with rheumatic diseases (DGRh—Deutsche Gesellschaft für Rheumatologie e. V.) or in patients with renal diseases (DGfN—Deutsche Gesellschaft für Nephrologie). In addition, large private hospital groups such as HELIOS announced data collection and analysis of COVID-19 patients in their hospitals. Most of these activities are in a planning stage and little information is available in the public domain to date.

Currently, three large-scale prospective data collections are already ongoing: the international LEOSS registry (Lean European Open Survey on SARS-CoV‑2 Infected Patients), the CAPACITY-COVID registry (registry of patients with COVID-19 including cardiovascular risk and complications), and the German COVID-19-RLP-Registry. Both LEOSS and CAPACITY-COVID have received support by national and international professional organizations; the CAPACITY-COVID registry was started in The Netherlands and recently endorsed by the European Society of Cardiology (ESC) for international enrolment. Study designs, objectives, and planned outcome analyses are summarized in Table 1. The expert committees of COVID-19-RLP, LEOSS, and CAPACITY-COVID have exchanged their codebooks to ensure consistency and comparability of data collection. Data collection of the ongoing activities is an extension of the Case Record Form (CRF) that was released by the ISARIC (International Severe Acute Respiratory and Emerging Infection Consortium) and the WHO for data collection in the COVID-19 pandemic, ensuring comparability of data but focusing on specific aspects of the disease. Due to the prospective design of COVID-19-RLP and CAPACITY-COVID with patients’ informed consent both registries have planned short- and mid-term follow-ups of the enrolled patients (Table 1).

Table 1

Current initiatives enrolling hospitalized COVID-19 patients

Registry	COVID-19-RLP	LEOSS	CAPACITY-COVID [4]
Initiated/Run by	IHF, Germany	DZIF, Germany	UMC Utrecht, Netherlands
Involved specialties	Cardiology/Internal Medicine Neurology/Psychosomatic Medicine	Infectious Diseases (inviting all other specialties for participation in LEOSS.deep)	Cardiology
Participating countries	Germany	EU countries	EU countries
Study type	Observational disease registry (cross-sectional/longitudinal)	Observational disease registry/survey (cross-sectional)	Observational disease registry (cross-sectional/longitudinal)
Inclusion criteria	Inpatients with confirmed SARS-CoV‑2 infection	Inpatients with confirmed SARS-CoV‑2 infection	Inpatients with highly suspected/confirmed with SARS-CoV-2-infection; ≥18 years
Status	Recruiting	Recruiting	Recruiting
Outcome measures	In-hospital outcome with specific focus on cardiovascular, neurological complications	In-hospital outcome	In-hospital outcome with specific focus on cardiovascular complications
Follow-up	Planned at 30 days and 3 months with specific focus on cardiovascular, neurological, mental health, and psychosocial complications	None	Planned at 7 and 30 days with specific focus on cardiovascular complications

IHF Institut für Herzinfarktforschung Ludwigshafen, DZIF Deutsches Zentrum für Infektionsforschung, UMC University Medical Center Utrecht

COVID-19-RLP

The aim of COVID-19-RLP is to document all consecutive patients undergoing in-hospital treatment in Rhineland-Palatinate hospitals for a SARS-CoV‑2 infection. Target variables are the clinical status at admission, pre-existing conditions, laboratory parameters, therapeutic strategies, and the course of the disease. The primary objectives are (a) to characterize patients with SARS-CoV‑2 infection requiring in-hospital treatment in Rhineland-Palatinate, (b) to describe the current therapeutic strategies, (c) to document the complications (with a special focus on cardiovascular and cerebrovascular events) and mortality of SARS-CoV‑2 infection, and (d) to develop a risk stratification for severe disease progression, which could potentially contribute to a prediction of the need for ventilation and thus to better planning of resources. The study is supported by the Ministry of Social Affairs, Labor, Health, and Demography of Rhineland-Palatinate and conducted in accordance with the World Medical Association—Declaration of Helsinki—Ethical Principles for Medical Research Involving Human Subjects and approved by the ethics committee of the Landesärztekammer Rheinland-Pfalz. The study is registered at ClincialTrials.gov (NCT04335188). Eligible for enrolment are all patients with confirmed SARS-CoV‑2 infection undergoing in-hospital treatment. A total of 84 hospitals in Rhineland-Palatinate in Germany treating patients with SARS-CoV‑2 infection are eligible for participation and have started enrolment on April 6, 2020. All data collected are web-based using the software solution EBogen©. During documentation, plausibility and completeness checks are generated immediately. All data are transferred with SSL encryption standard and stored on a server of the Institut für Herzinfarktforschung Ludwigshafen (IHF). Descriptive statistics on the registry population, the applied therapeutic measures, and the clinical course will be generated. Subgroup analyses for risk stratification are planned and defined in a detailed statistical analysis plan.

Perspective

Despite the current additional significant workload of clinically active physicians involved in the care of patients of the COVID-19 pandemic, different groups have put a lot of effort into the initiation of a number of prospective planned registry studies to better understand the natural course of this new infectious disease. Scientific collaborations are already planned and should be continued to ensure data consistency and comparability. We look forward to obtaining additional data on the short- and mid-term course of the disease with prospective follow-ups of hospital survivors in the COVID-19-RLP as well as in the CAPACITY-COVID registries with specific focus on cardiovascular and neurological outcomes. COVID-19-RLP in addition will also collect data on the yet-unknown consequences for mental health and the psychosocial outcomes of survivors of COVID-19.