Serological Testing for COVID-19 (SARS-CoV-2) in ESKD

In late 2019, a cluster of patients with unexplained pneumonia was linked to a novel
beta-coronavirus, now known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
1. The world health organization subsequently has coined this disease as COVID-19. By the
time the scientific community was alerted, the epidemiological data suggested that the virus
had already spread to other regions of mainland China, as well as foreign cities with close
transport links to the original epicenter 2. The world initially answered by divergent
responses. Two months on, we are experiencing a devastating pandemic with local outbreaks
across all continents.

As more and more patients arrive at the hospitals, our focus is drawn to the acute and the
important issues, treating large numbers of patients in grave condition. The surge in
patients requiring medical care may overwhelm even the most sophisticated healthcare systems
3. The approach adopted by almost all nations is to 'flatten the curve', i.e. to reduce peak
demand of healthcare resources 4. While individual countries follow different paths, the
common denominator is to maximize social distancing. The main goal is to reduce the basic
reproduction number (R0) as much as possible, to ideally less than 1.

An overview of the clinical characteristics of confirmed cases in China alerted the world
that young age does not protect against infection 5. Disease severity, however, varies by age
with more elderly people becoming seriously ill, and by underlying medical condition(s) 6.
The impact on peak medical demand thus will be even greater if we succeed in maximizing
social distancing of the most vulnerable and most frail patients, those who are more likely
to become seriously ill.

This is, however, difficult for dialysis patients who cannot self-isolate and cannot avoid
multiple contacts per week with health care workers and other patients. While isolating
dialysis patients and health care workers with a suspected SARS-CoV-2 infection is important
to limit transmission of the virus, these measures are insufficient to avoid transmission
since it is estimated that asymptomatic or paucisymptomatic people play a major role in the
spread of the virus. So far, epidemiological data in patients on IHD during an SARS-CoV-2
outbreak are limited. A single case-series of cases from China has been reported in
prepublication. 37 out of 230 patients were infected with SARS-CoV-2, of which 6 died (crude
mortality rate 16.2%). The authors suggest that not all of these died directly from the
consequences of COVID-19. However, adjudication of cause of death might differ in future case
series.

The current gold standard for the diagnosis of acute respiratory syndrome due to SARS-CoV-2
(COVID-19) is the detection of viral RNA in respiratory tract samples. The sensitivity of a
negative PCR result is, however, not 100%. False-negatives can occur, especially when using
nasopharyngeal swabs (positivity rate estimated at 54%-74%) due to sampling error and in
patients with low viral loads, especially in patients who present at day 8 or later and mild
cases. While a CT scan can be a valuable tool in patients with a suspicion of COVID-9,
measurement of antibodies against SARS-CoV-2 is the only reliable way to estimate the
prevalence of SARS-CoV-2 infection since patients can be pauci-symptomatic or asymptomatic.

A number questions remain regarding the use of antibodies for epidemiologic studies and to
determine immunity. Can someone have a colonization with SARS-CoV-2 without developing IgG
antibodies? In this case, would this person be protected against reinfection? Doctors of the
University of Bonn recently reported on April 9th (H. Streeck et al.,data not yet published)
that only 15% of a sample of 1.000 inhabitants of the small town Gangelt, a local hotspot in
North Rhine Westphalia tested positive for IgG antibodies. These data suggest that even in
severely affected regions the critical threshold for herd immunity might not have been
reached. This means that there is a significant risk of new outbreaks, particularly after
schools might reopen later (maybe in summer 2020, and in fall 2020).

Given that dialysis patients are at the same time potentially more vulnerable to SARS-CoV-2
infection, and cannot self-isolate, it is important to closely monitor this group of
patients. A second benefit of this population is that it easily accessible for blood
sampling, and close clinical follow-up is ensured.

The aim of this study is to determine the prevalence of patients who were infected with
SARS-CoV-2 by measuring IgG antibodies at different time points.

Trial objectives The aim of the current study is to collect epidemiological data of the
incidence of severe acute respiratory syndrome Corona Virus type 2 (SARS-CoV-2) infections
patients with end-stage kidney disease in a Belgian Hospital setting.

The objective is to compare two means of detection of infection, one symptom-driven
surveillance and a second based on cross-sectional serology.

Primary endpoints Positive serology for SARS-CoV-2 at census date(s)

Secondary endpoints Detection of SARS-CoV-2 infection by symptom-driven surveillance

Trial Design Cross-sectional and longitudinal observational study of prevalent patients with
end-stage kidney disease