This is the first national study of hemodialysis patients with COVID-19 in Lebanon. Our results confirm the high mortality rate of this vulnerable population, as described in several previous reports from other countries [14,17,19,20,22,23,26]. Our patients' death rate was estimated at 23.8%, very close to the 25% reported by the ERACODA study of 26 European and North Mediterranean countries including 768 dialysis patients [24]. To our knowledge, this is the first study that evaluates the number of comorbidities or multimorbidities as a risk factor for death in hemodialysis patients with COVID-19. The nine comorbidities included in our analysis were diabetes, hypertension, obesity, heart failure, coronary artery disease, history of stroke, lung disease, dementia and cancer. When analyzed one by one, only heart failure, coronary artery disease, history of stroke and dementia were found significant risk factors for increased mortality. However, when they were added, every increase in one comorbidity on a scale of 1 to 9, was associated with a 59% more death. Other studies identified one or two of these poor prognostic factors. For instance, in the ERACODA study, obesity was found a risk factor but not diabetes, nor lung disease, nor coronary artery disease [24]. Diabetes had a trend to increase mortality in the French study but did not reach significance [14].
Importantly, in all dialysis and general population's COVID-19 studies, the most consistent demographic risk factor for death was age. Our study confirmed the significant association of older age and death, which is also aligned with the findings of the European ERACODA study [24]. Age was also identified as a risk factor for higher mortality in studies from the UK Renal Registry, from Japan and Spain [16,15,22]. On top of age, the ERA-EDTA study that included 3285 patients found male patients at higher risk for death [25]. In our population, only male patients who were admitted to the hospital showed a non-significant trend to higher mortality compared to females.
Regarding dialysis-related factors, dialysis vintage was not associated with higher death in our series although it was demonstrated to be a risk factor in the 2385 patients from the UK Renal Registry [16]. On the other hand, hypotension during dialysis was a poor prognostic factor in our patients consistent with the results of a study of 108 patients from London [27]. Interestingly our study showed a CRP cutoff above 100 mg/L as a poor prognostic marker. This is aligned with the French study from the Paris region that found an association between a CRP >175 mg/L and higher mortality [14]. This also concurs well with two studies one from Wuhan, China, and a second one from Turkey that identified a high CRP as predictor for higher mortality [28, 29]. These studies found as well the low neutrophil/lymphocyte ratio as a predictor for death [28]; this was not confirmed in our patients.
In our infected hemodialysis population, 90% of patients were symptomatic. The symptomatology described is consistent with several worldwide reports. Fever is the most frequent symptom, followed by dry cough, dyspnea and to a lesser degree diarrhea [30,28,23,31]. The first reports of COVID-19 in dialysis emphasized the frequency of diarrhea [3] but it was not confirmed in larger samples. In a Spanish case-series, 77% of patients had fever (33% pneumonia), these results are similar in our population [30]. However, in one Turkish and one Chinese series, fever was found in 30% and 51.9% of 42 and 131 cases respectively [28, 13]. Surprisingly, the Turkish patients had more cough and dyspnea than other populations although they had no difference in demographic factors. In series that found higher rate of asymptomatic patients, dialysis units were screened regularly [32]. Screening of dialysis units was performed in our dialysis population only in centers where number of infected patients was high, thus we may have missed several asymptomatic cases.
The 50% rate of admission of our patients was lower than other countries. In the Dutch-speaking Belgian Renal Society patients, 138 out of 228 patients (60%) were admitted [18]. In the French series, 41 out of 44 patients (93%) were admitted although only thirty-three needed oxygen therapy [14]. Despite the difference in admission rates, the death rate was similar. In fact, our results showed that managing these patients on an outpatient basis is possible and safe as long as the patient does not need oxygen therapy.
The decision to end isolation was based on different criteria across the 41 units that took part in this study. A high percentage of our patients needed repeated PCR testing before it became negative. This is in agreement with several previous reports confirming the prolonged shedding of SARS-CoV-2 in hemodialysis patients that can reach sometimes 74 days [23]. Therefore, many are convinced of the importance of repeating PCR testing before ending isolation [33]. However, despite this prolonged shedding, 28 out of the 176 patients that survived were removed from isolation after 14 days without PCR testing. Only one of these 28 patients presented relapsing fatigue leading to a further third-week isolation. The remaining 27 patients did not show any symptoms. Although several reports in the literature recommended not to end isolation without two consecutive negative PCRs, the Center for Disease Control and Prevention (CDC) states that isolation could be ended in asymptomatic patients without confirmation with a negative PCR [10]. This was shown to be uneventful in our population.
Finally, the treatment used in the first diagnosed patients was hydroxychloroquine and did not cause an increase in death as opposed to the study published by the Spanish kidney registry in March 2020 [22]. Hydroxychloroquine was also found safe in a French series of 21 hemodialysis patients [34]. In our extremely ill patients admitted to the ICU, antiviral treatment did not show any benefit regarding mortality but we cannot make further conclusions because it was prescribed in severe cases, which is considered as a bias of indication.
Our study has some limitations. First, data were collected retrospectively leading to some information biases especially regarding symptoms that would have not been documented in medical charts like loss of smell or taste. Second, missing data on neutrophil/lymphocyte ratio for a large number of patients may have underestimated the importance of this possible risk factor. Third, the lack of information about the dose of hydroxychloroquine used cannot lead to definite conclusions regarding the safety of this drug in dialysis patients.
Despite these imitations, the major strength of our study is the representative sample that included almost all hemodialysis patients infected with SARS-CoV-2 in Lebanon during a seven-month period. Although a few centers did not share their data but this study still included 95% of all reported patients. This study highlights the importance of comorbidities as risk factors for mortality in hemodialysis patients with COVID-19.