>> The Covid-19 pandemic poses immense challenges for medical care systems worldwide. Analogous to the focus of care on the acute course of the disease, international research also tends to concentrate on acute, serious courses. However, most care systems have a staggered care system in which the first point of contact for patients with suspected SARS-CoV-2 infection are general practitioners. Accordingly, research impulses to improve the facts about Covid-19 should not only focus on inpatient and intensive care care, but should also include data from outpatient care in order to provide an authentic picture of the risks for severe courses and the long-term development of the disease, in addition to research into the acute course of the disease draw.
However, a number of factors are hindering the implementation of Covid-19 studies, particularly in the outpatient sector:
• High workload of the medical staff in the practices; Free valences for research are missing because patient care is the priority;
• Comparatively weaker research infrastructure than in the stationary sector, even if strong research impulses can be found;
• a sometimes precipitous increase in cases, which makes orderly recruitment difficult;
• Infectiousness in the acute phase, which means isolation in the outpatient setting and makes physical examination, laboratory diagnosis and written informed consent considerably more difficult;
• Changing the treatment provider or the care provider during the transition from outpatient to inpatient usually means drop-out in the study context.
The Covid-19 disease has only been known since the end of 2019, so it is understandable that questions are still developing. It is all the more obvious to include patients with Covid-19 in registers in order to be able to answer retrospective questions later on a good data basis. This also opens a “window of opportunity” to be able to provide historical comparison groups for future research approaches.
Despite the obstacles described at the beginning, there is significant research activity in Germany, which is reflected in the development of registers and the implementation of register studies. It is worth taking a look at this research landscape.
The German Register of Clinical Studies (DRKS)1 is the primary register for Germany recognized by the WHO. It is responsible for the registration of all patient-oriented clinical studies carried out in Germany and offers the opportunity to search for information on ongoing and completed clinical studies in Germany or to make your own studies accessible to others via registration. The DRKS now contains well over 10,000 studies. Currently around 1,500 studies are added every year.
Studies were searched for in this study database on February 25, 2021 using the search term “Covid-19”. There were 310 hits to which the following filter conditions were applied: Germany as the study location and the research fields of diagnostics, therapy, prognosis, and others. The following were excluded: health economics, health systems research, prevention and screening and supportive care.
Finally, studies were filtered out individually that did not deal with clinical aspects of the Covid-19 disease itself or with its care. This left 153 studies in the hit set.
In 29 of these 153 studies, based on the information provided in the DRKS, there is sufficient certainty that outpatient data will be collected as part of the study. In 44 of the 153 studies it is at least likely that outpatient information will also be recorded. This cannot always be clearly determined, as the entries in the DRKS often do not indicate whether, for example, B. outpatient data can also be collected by a university clinic. In cases where this would fit the question of the study, it was assumed that the collection of outpatient data was part of the respective study.
Of the 153 studies found, 12 claim the label “register” or have a recognizable register structure. Ten of the twelve registry studies also collect outpatient data (Table 1). Four of these ten registry studies have their starting point in hospitals and collect outpatient data retrospectively or carry out outpatient follow-up. The remaining six studies have different orientations: one each has its provenance in pediatrics, nephrology or hematology-oncology. One study is specifically aimed at C1 esterase inhibitors, another is investigating the use of biomarkers in prognostics. One study – the “ABC19 study” – is aimed exclusively at the outpatient care system and is therefore presented in more detail below as an example.
In summary, it can be said that the focus of the registry studies found in the DRKS is in the inpatient area; The focus is on severe courses of Covid-19.
Under the impact of the pandemic, a large number of research initiatives were launched in a very short space of time with the aim of uncovering insights into the threatening and sometimes novel developments in the disease process surrounding the SARS-CoV-2 infection. It is all too understandable that research efforts initially concentrate on hospitalized patients, since controlling severe disease and reducing mortality in the acute situation are in the foreground of clinical and public interest. However, this contradicts the reality of care in which around 80% of Covid-19 patients are treated on an outpatient basis (Beerheide 2020). What is needed here is a methodological orientation that addresses questions about the care and management of SARS-CoV-2 infected people
medical everyday life can be examined. At the same time, it is also the outpatient care sector that decides on the hospitalization of certain patients, which is of great importance in many respects: the timeliness of the decision is likely to be significant in terms of prognosis, but it is certainly the correctness of the decision that has a bearing on capacity issues is relevant because, on the one hand, hospital beds and ventilation places are not fully available and, on the other hand, the outpatient sector performs a buffer function, the quality of which depends equally on the number of avoidable and missed hospital admissions.
Prognostic factors must therefore be evaluated and described as precisely as possible, and practical strategies are required to be able to detect these factors reliably and efficiently. In addition, science is currently still in the early stages of researching the long-term consequences of the SARS-CoV-2 infection. The course of the disease that has been observed so far - keyword “Long Covid” - suggests that such long-term effects will appear primarily in outpatient therapy management and in very different care contexts (Carfi et al. 2020; Mahase 2020; Tenforde et al. 2020; Wu & McGoogan 2020).
There are already indications of typical ones
Long-term consequences have been reported by internal, cardiological, urological and neurological-psychiatric specialists, among others (Covid Symptom Study 2020; Nehme et al. 2020; Townsend et al. 2020). Three out of four patients
Tens are slow to recover from Covid-19, and some could suffer permanent health damage (Huang et al. 2021). Even after a mild course of Covid-19, persistent symptoms can occur. In a cohort study from Switzerland, one in three outpatients still complained of symptoms in the first six weeks after recovering from an acute illness; the most common were fatigue, shortness of breath and a loss of taste or smell (Nehme et al. 2020). Here, health services research has the urgent task of collecting the data from such cases in repositories and providing them for evaluation. With their active, prospective, standardized documentation of observation units on predetermined but expandable questions over time, registries are fundamentally suitable for achieving this by helping to collect and critically analyze the care process and the relevant aspects of population health on a scientific basis (Maier et al . 2014; Stausberg et al. 2020).
Under the name “ABC19 Study – Outpatient Treatment of Covid-19 Infections: Influence of Comorbidities on Hospital Admissions and Other Therapy Decisions” (www.abc19Studie.de), the IGES Institute in collaboration with the Clinical Study Society (CSG), the Faculty of Health Sciences Brandenburg (FGW), the Brandenburg Theodor Fontane Medical School (MHB) and the Central Institute for Statutory Health Insurance (Zi) recently presented a study concept that was approved by the responsible ethics committee and with the participation of specialized Covid-19 practices in the Berlin model region was subjected to a feasibility analysis. The plan is to initially include 1,000 patients in the study through at least 15 practices. A follow-up of the study participants should also record late effects and complications. The data obtained should also enable modeling, for example on avoided hospital stays.
The study concept is designed in such a way that
that an outpatient Covid-19 registry is created with the aim of describing the influence of comorbidities on severe courses and providing practical aids for recording them. The study is based on the relevant specifications for the development, organization and operation of registers, such as those formulated in the “Memorandum Register for Health Services Research” of the German Network for Health Services Research (DNVF eV) (Stausberg et al. 2020). If successful, the necessary foundations will already be created to put a Covid-19 register into operation, with which data from outpatient care can be collected and evaluated.
The knowledge gained with this outpatient Covid-19 register is intended to make hospitalization decisions easier and also support the work of the practices. For this purpose, the registry technology offers patients the opportunity to send clinical data and Patient Reported Outcomes Measures (PROM) electronically to the practices every day while in isolation. Overviews in the registry software alert practitioners to critical clinical developments. This digital management function of the register enables practices to monitor isolated Covid-19 patients, even when there are large numbers of cases.
Conclusion
A look at the German Register of Clinical Studies shows the high level of research intensity that has been devoted to Covid-19 since the beginning of the pandemic. As an instrument of health services research, registries are predestined to map the disease and care process in an area that only takes on contours over time. Some registries can already be found, but the outpatient sector does not receive the attention it deserves. There is currently no national comprehensive register that would include purely outpatient cases and also monitor them prospectively. However, we urgently need more outpatient corona research, as the pandemic will still pose a number of challenges - both in terms of cases and scientific questions. <<
from: Dr. Holger Gothe (1) and Dr. Marc Kurepkat (2)

1 Head of Health Services Research, IGES Institute
2 Managing Director CSG Clinical Studies Society mbH

literature

Beerheide R (2020): Outpatient care: system advantage in the pandemic. Dtsch Ärztebl 117(41):A-1903/B-1621
Carfì A, Bernabei R, Landi F; Gemelli Against COVID-19 Post-Acute Care Study Group (2020): Persistent symptoms in patients after acute COVID-19. JAMA 324:603–605. DOI: 10.1001/jama.2020.126032.
COVID Symptom Study Sweden (2020). URL: https://csss-resultat.shinyapps.io/csss_dashboard. [Accessed on March 1, 2021]
Huang C, Huang L, Wang Y, Li X, Ren L, Gu X, Kang L, Guo L, Liu M, Zhou X, Luo J, Huang Z, Tu S, Zhao Y, Chen L, Xu D, Li Y , Li C, Peng L, Li Y, Xie W, Cui D, Shang L, Fan G, Xu J, Wang G, Wang Y, Zhong J, Wang C, Wang J, Zhang D, Cao B (2021): 6 -month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet 397: 220–32. DOI: 10.1016/ S0140-6736(20)32656-8.
Mahase E (2020): Covid-19: What do we know about “long covid”. BMJ 370:m2815. DOI: 10.1136/bmj.m28154.
Maier B, Gothe H, Kieschke J (2014): Register data. In: Swart E, Ihle P, Gothe H, Matusiewicz D (eds.). Routine healthcare data. Handbook of secondary data analysis: basics, methods and perspectives. 2nd, completely revised and expanded edition. pp. 234–244. Bern: Verlag Hans Huber, 2014.
Nehme M, Braillard O, Alcoba G, Aebischer Perone S, Courvoisier D, Chappuis F, Guessous I, for the COVICARE group (2020): COVID-19 Symptoms: Longitudinal Evolution and Persistence in Outpatient Settings. Ann Intern Med. DOI: 10.7326/M20-5926.
Stausberg J, Maier B, Bestehorn K, Gothe H, Groene O, Jacke C, Jänicke M, Kostuj T, Mathes T, Niemeyer A, Olbrich K, Schmitt J, Neugebauer E (2020): Memorandum Register for Health Care Research: Update 2019 (Long version) Healthcare 82(3):e39–e66. DOI: 10.1055/a-1083-6417.
Tenforde MW, Kim SS, Lindsell CJ, Billig Rose E, Shapiro NI, Files DC, Gibbs KW, Erickson HL, Steingrub JS, Smithline HA, Gong MN, Aboodi MS, Exline MC, Henning DJ, Wilson JG, Khan A, Qadir N, Brown SM, Peltan ID, Rice TW, Hager DN, Ginde AA, Stubblefield WB, Patel MM, Self WH, Feldstein LR; IVY Network Investigators; CDC COVID-19 Response Team (2020): Symptom duration and risk factors for delayed return to usual health among outpatients with COVID-19 in a multistate health care systems network – United States, March–June 2020. Morb Mortal Wkly Rep 69:993 –998. DOI: 10.15585/mmwr.mm6930e13.
Townsend L, Dyer AH, Jones K, DunneI J, Mooney A, Gaffney F, O'Connor L, Leavy D, O'Brien K, Dowds J, Sugrue JA, Hopkins D, Martin-Loeches I, Cheallaigh CN, Nadarajan P , McLaughlin AM, Bourke NM, Bergin C, O'Farrelly C, Bannan C, Conlon N (2020): Persistent fatigue following SARS-CoV-2 infection is common and independent of severity of initial infection. PLoS ONE 15(11). e0240784. DOI: 10.1371/journal.pone.0240784.
Wu Z, McGoogan JM (2020): Characteristics of and important lessons from the Coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72,314 cases from the Chinese Center for Disease Control and Prevention. JAMA 323:1239–1242. DOI: 10.1001/jama.2020.2648.