There is an increasing number of reports on the clinical course of Coronavirus disease
2019 (COVID-19) in hemodialysis patients [1–4].
On this background, we would like to report data on a large multicenter cohort of
hemodialysis patients with COVID-19 in Germany, which demonstrates an inverse distribution
of mild and severe courses compared to the general population. Through the analysis
of the impact of underlying renal disease and cardiovascular comorbidities on adverse
outcome, we could identify cardiorenal syndrome as an outstanding risk factor for
death.
Since the first cases of pneumonia of unknown origin were reported in December 2019
in Wuhan, knowledge on SARS-CoV-2 and COVID-19 is rapidly expanding. Preexisting cardiovascular
disease, diabetes, hypertension, and chronic kidney disease were identified as risk
factors for severe disease and mortality [5–7]. Thus, the hemodialysis population
may be at outstanding risk for a severe course of COVID-19. Moreover, hemodialysis
centers are prone to SARS-CoV-2 transmission. Patients have to refer to the outpatient
facility three times per week to undergo dialysis and are thereby limited in their
ability to social distance. As expected, mortality rates were substantially higher
than in the general population, ranging from 18.9 (Wuhan) to 52% (Lombardy) [1, 2].
Interestingly, the causes of death were frequently not directly related to pneumonia
but to cardiovascular or cerebrovascular disease [1]. Although there was a shift to
more critical courses of COVID-19, the spectrum of severity of COVID-19 was similar
to the general population including several asymptomatic patients. It remains elusive
which hemodialysis patients are at increased risk for adverse outcome. We would therefore
like to add to the present knowledge by reporting on the clinical characterization
of COVID-19 in hemodialysis patients in Germany and identifying risk factors for adverse
outcome.
Five hemodialysis outpatient centers in Germany were contacted in April 2020 and asked
to participate in the analysis. All of them agreed and provided clinical data of their
hemodialysis patients with COVID-19 from February to April 2020. Data collection was
performed by nephrologists from the outpatient centers and included both outpatient
data and in-hospital data; analysis was centralized at a University Hospital (Ruhr-University
Bochum). Data comprised course of the disease, stratified as "mild", "severe", "critical",
or "fatal". The disease was considered as "mild" if it was successfully managed in
an outpatient setting, "severe" if it needed hospitalization, "critical" in case of
transfer to an intensive care unit, and "fatal" in case of death. Intensive care medicine
was offered to all patients with a medical indication. Information on the following
symptoms was retrieved: fever, cough, dyspnea, dysgeusia, anosmia, diarrhea. Information
on cause of end-stage kidney disease (ESRD), preexisting comorbidities and immunosuppression
was also obtained. Associations of underlying renal diseases and comorbidities with
mortality were analyzed by Chi-squared tests and univariate analyses providing odds
ratios (OR) and 95% confidence intervals (CI).
Fifty-six patients tested positive for SARS-CoV-2 by RT-PCR (SARS-CoV-2 RT-PCR Kit
1.0 from Altona Diagnostics, Hamburg) in either nasopharyngeal swab test or bronchoalveolar
lavage. The overall number of patients on chronic hemodialysis in the five centers
was 755 with a median age of 67 years, yielding an incidence of 7.4%. At that point
of the pandemic RT-PCR tests were routinely performed in symptomatic patients, whereas
asymptomatic cases were tested only in case of contact with a person with COVID-19.
Median age of the infected subjects was 76.0 years (IQR 69.0–82.8); 23 (41.1%) were
female, 33 (58.9%) were male. Mean dialysis vintage was 37.5 months (IQR 18.3–93.0)
with diabetic nephropathy being the most frequent cause of ESRD followed by nephrosclerosis,
glomerulonephritis, and cardiorenal syndrome. 76.8%/ Seventy-six point eight%??? Jaya-depending
on journal policy for beginning sentences with numbers? of the COVID-19 population
was hypertensive, 37.5% suffered from coronary artery disease, and 44.6% were diabetic.
The renal diseases and comorbidities are summarized in Table 1.
Table 1
Renal diseases and comorbidities of the study population and their association with
mortality
Patients positive for COVID 19
Deceased patients vs. survivors (chi-squared test)
Association with mortality in univariate analysis
Deceased (n = 15)
Survivors (n = 41)
p
OR (95% CI)
95% CI
Cause of ESRD
Diabetic nephropathy
15 (26.8%)
2
13
0.17
0.331
0.065–1.687
Hypertension/nephrosclerosis
11 (19.6%)
4
7
0.42
1.766
0.434–7.191
Glomerulonephritis
7 (12.5%)
0
7
0.09
0.829
0.722–0.953
Cystic kidney disease
4 (7.1%)
2
2
0.28
3.000
0.083–23.491
Cardiorenal syndrome
6 (10.7%)
5
1
0.001
20.000
2.095–190.913
Others
13 (23.2%)
2
11
0.29
0.420
0.081–2.166
Comorbidities
Hypertension
43 (76.8%)
9
34
0.07
0.309
0.083–1.150
Diabetes
25 (44.6%)
7
18
0.85
1.118
0.341–3.665
Coronary artery disease
21 (37.5%)
5
16
0.70
0.781
0.225–2.709
Need for immunosuppression
5 (8.9%)
3
2
0.48
1.949
0.292–12.987
Value in bold is significant (p < 0.05)
The overall hemodialysis population of the five centers comprised 755 patients yielding
a COVID-19 incidence of 7.4% in the observation period
ESRD End stage renal disease, OR odds ratio, CI confidence interval
The most frequent symptom of COVID-19 was fever (n = 31, 55.4%), followed by cough
(n = 26, 46.4%). Data on diarrhea and anosmia/dysgeusia were not available for the
overall study population. Among those with available data, diarrhea occurred in 19.6%
and anosmia/dysgeusia in 13.5%. In 13 patients (23.2%), the disease was successfully
managed in an outpatient setting (mild course). Hospitalization was necessary in 43
patients (76.8%). Of these hospitalized patients, 16 (28.6%) were transferred to the
intensive care unit. 15/Fifteen—Jaya—depending on journal policy for beginning sentences
with numbers? patients died from COVID-19. Thus, 23.2% showed a mild, 35.7% a severe,
14.3% a critical, and 26.8% a fatal course (Fig. 1).
Fig. 1
Clinical course of COVID-19 in the population of hemodialysis patients
Patients who died after infection with SARS-CoV-2 had a median age of 77 years (IQR
72–85) and were predominantly male (n = 11, 73.3%). Cardiorenal syndrome was associated
with a significantly increased risk of mortality in a univariate analysis (OR 20,
95% CI 2.095–190.913), whereas glomerulonephritis was associated with a slightly decreased
risk (OR 0.829, 0.722–0.953). Due to the low number of deceased patients, confidence
intervals were large. Among the six patients with cardiorenal syndrome, five died.
None of the comorbidities including hypertension, diabetes, coronary artery disease,
or need for immunosuppression showed a significant association with mortality. Hypertension,
however, tended to be inversely associated with death (p = 0.07). Accordingly, mortality
was lower in those subjects with (20.9%) than without hypertension (46.1%).
In this multicenter cohort of hemodialysis patients with COVID-19, severe courses
and mortality were substantially increased compared to the general population affected
by COVID-19 in Germany. Whereas in this country the course was mild in > 80% of the
general population [8], almost 80% of our hemodialysis population showed a severe
to fatal course, with an “inverse distribution” of COVID-19 severity in the present
hemodialysis patients as compared to the general population. Beyond ESRD itself, age
and comorbidities are likely to contribute to this finding. Among hemodialysis patients
in our series, those with cardiorenal syndrome displayed the highest risk for death
due to COVID-19.
While the small number of cases requires further confirmation, it may be mentioned
that our patients suffered from cardiorenal syndrome type 2; these patients overall
have an extremely poor prognosis and suffer from resistance to diuretics. One-year
mortality of patients with cardiorenal syndrome and moderate to severe kidney function
impairment is approximately 50% [9]. Due to the limited cardiac reserve, blood pressure
frequently turns from hyper- to hypotension, and this phenomenon may explain the finding
of an inverse association of hypertension with fatal outcome.
The present analysis confirms that also in Germany, a country initially spared by
the COVID-19 epidemic, the clinical course of COVID-19 is substantially more severe
in hemodialysis patients than in the general population, and only 23% of the dialysis
patients have a mild course of the disease. Among this high risk group, patients with
cardiorenal syndrome and decreased blood pressure have the highest risk of death.
Nephrologists should be aware of these findings in order to guarantee extended testing
and early hospitalization in case of symptoms of COVID-19 pneumonia.