COVID-19 in Hemodialysis Patients: Experience from a Western Indian Center

Setting

When the pandemic hit India, the western Indian state of Gujarat was affected early and reported high death rates (about 5% against a national average of 3.27% as of May 1, 2020). In mid-May 2020, the patient numbers continued to spike, and public sector subspecialty hospitals (like our kidney institute) were made COVID-19 hospitals. Adoption of home quarantine policy meant only the sick patients got hospitalized. Our 190-bed COVID-19 facility had 50 intensive care unit beds and 70 beds with oxygen facility. The management was headed by nephrologists and intensivists. Only emergency nephrology and urology services remained functional as per government advisory. Our facility provided bedside dialysis for 100 + beds and created an outpatient dialysis unit for COVID-19 suspected patients, and asymptomatic COVID-19 cases were advised home quarantine. In the first week of July, when the epidemic plateaued, the institute ceased to be a COVID-19 hospital and admitted only patients with COVID-19 and renal disease (primarily post kidney transplant cases).

Case definition and management protocols

A case was defined as a person with real-time reverse transcriptase–polymerase chain reaction (RT-PCR)– confirmed COVID-19 infection, irrespective of signs and symptoms. Cases were labeled as mild when patients had oxygen saturation (SpO₂) above 94%, moderate when SpO₂ was 90% to 94%, and severe when SpO₂ was below 90%.[5] The patients underwent basic investigations and investigations to determine prognosis. Most patients received hydroxychloroquine (HCQ), azithromycin, ascorbic acid, and symptomatic treatment as per the government guidelines.[67] Unfractionated heparin was used as 5,000 units subcutaneously twice a day in high-risk patients and thrice a day in those with severe disease, unless contraindicated. Patients requiring oxygen support were given intravenous methylprednisolone sodium succinate (MPSS, 1 mg/kg in two divided doses). At the end of May 2020, tocilizumab became available and was used based on laboratory features suggesting cytokine storm (given as 400 mg single-dose infusion over 1 hour).[6] Favipiravir became available in the third week of June. It was used as 1,800 mg twice a day on the first day and 800 mg twice a day for the next 6 days. Remdesivir (200 mg on Day 1 and 100 mg daily for 5–10 days) and convalescent plasma were used starting from mid-July. Other agents such as ivermectin and doxycycline were not used.

Records of all the patients admitted with COVID-19 infection were screened. Patients who were known to have chronic kidney disease on hemodialysis (CKD-5D) for at least 1 month before admission were included in the study. COVID-19-suspect patients, those with AKI or AKI superimposed on CKD, and those with incomplete information were excluded. The primary aim was to study the clinical outcomes of such patients. We also attempted to identify the prognostic epidemiological and laboratory markers in our cohort.

Based on the previous studies, we studied age, dialysis vintage, saturation on room air at presentation, absolute neutrophil and lymphocyte counts, D-dimer levels, Serum ferritin, C-reactive protein (CRP), lactate dehydrogenase (LDH), and length of hospital stay as potential prognostic factors in our cohort. Peak levels of D-dimer, ferritin, and CRP levels were also evaluated as markers of prognosis. We divided our cohort into an initial phase (first 25 admissions, over the first 3 weeks) and a later phase (beyond 3 weeks) and studied the mortality in each quartile to understand the change of trends over time.

Statistical methods

The results were expressed as numbers with percentages, mean ± standard deviation or median with range as appropriate. The comparison between survivors and non-survivors was done by Student t test, Mann–Whitney U test, Chi-square test, or Fischer's exact test as justified. The effect of various putative prognostic factors was evaluated by binary logistic regression. A P value of <0.05 was taken as significant. Statistical analysis was performed with SPSS Statistics for Windows, Version 20 (Armonk, NY, IBM Corp.).

Clinical profile

The first report of hemodialysis patients with COVID-19 came from Wuhan. In this study, most cases had mild to moderate disease and 21% were asymptomatic, and symptomatic patients were also less likely to have classic features such as fever, cough, or respiratory symptoms compared with the general population.[91011] Another Chinese study reported that the disease was milder in HD patients, possibly due to their impaired cellular immunity.[4] Two Spanish cohorts also reported the initial presentation to be milder in the HD cohort.[1213] These are in agreement with our findings. Twenty-eight (48.3%) had minimal or no symptoms and one third of patients had severe disease at presentation in our study. A pervious observational study from India reported relatively more asymptomatic cases (35.1%) and a similar number of moderate and severe disease presentations compared to our cohort. However, the details of the treatment or laboratory features have not been provided in this report.[14] A major observation of their cohort was that many patients missed their dialysis as they were turned away by dialysis centers.

Most COVID-19 patients (82%–85%) develop bilateral radiological abnormalities.[410] Seven (12.1%) patients had normal X-rays at admission in our study. Normal chest X-rays have been reported in COVID-19 patients from the hemodialysis as well as the general population.[415]

Treatment

There was initial enthusiasm as well as safety concerns (especially in hemodialysis) around the combination of hydroxychloroquine and azithromycin.[1617] Corticosteroids were successfully used in the management of COVID-19 patients with severe disease.[1819] The RECOVERY trial and, more recently, the METCOVID (Methylprednisolone in the Treatment of Patients With Signs of Severe Acute Respiratory Syndrome in COVID-19) study contrasting results with corticosteroids.[2021] Anticoagulation was also shown to have clinical benefit in COVID-19 patients with severe disease.[2223] Other therapeutic modalities including antivirals (remdesivir and favipiravir), tocilizumab, and convalescent plasma were also found beneficial in small cohorts.[24252627] In our study, the number of patients on each therapy was small, and it was not designed to compare the efficacy of treatment protocols.

We monitored the corrected QT interval (QT_c) in all patients and found the combination of HCQ and azithromycin safe in our cohort. We followed patients with blood counts, CRP, procalcitonin, X-ray chest, and blood culture while they were on steroids or tocilizumab. No attributable worsening was found. The safety of remdesivir is not established in advanced renal failure. We used remdesivir in our patients without any dose modification. We observed no elevation in hepatic transaminases or infusion reactions with remdesivir (n = 4) in our cohort.

Outcomes

As per the World Health Organization data, mortality from COVID-19 is 2.9%.[1] Severe disease has been associated with higher mortality (around 40%).[28] Smaller cohorts from China reported moderately high (16.2%) deaths in hemodialysis patients, all in non-ICU patients. They emphasized the importance of comorbidities in the mortality associated with COVID-19 in HD patients.[29] A subsequent study of hemodialysis patients from Spain observed 30.5% mortality in the whole cohort. The patients who had severe disease had higher death rates (61.1%). These trends are reflected in our cohort almost exactly. The Indian cohort had an identical death rate (37.8%) compared with our study.[14]

Predictors of prognosis

The previous studies have reported age, dialysis vintage, comorbidities, high serum levels of blood urea nitrogen, CRP, LDH, ferritin, high leucocyte counts, and lymphopenia to predict death in COVID-19 patients on dialysis.[3031] However, inconsistency in published evidence does exist. Other studies in hemodialysis patients have found none of the laboratory parameters at admission predict in-hospital mortality.[1232] A French cohort reported LDH over two times the upper normal and CRP more than 175 mg/dL predict mortality.[33] In comparison, Goicoechea et al.[12] reported mean CRP levels as low as 18.7 mg/dL in non-survivors.

We found higher mortality in the initial 3 weeks of functioning as a COVID-19 hospital. The initial high mortality rates may be attributed to delay in diagnosis, limited availability of testing and drugs, fear and misinformation, and poor logistic support. Although resource limitation in health care staffing, testing, and medical management was universal during the pandemic, it was more common in the developing world.

Limitations of our study include a retrospective design and a small sample size. Inclusion was hospital based and does not include data from asymptomatic patients on dialysis because they were not routinely screened with RT-PCR or COVID-19 antigen testing. Patients with normal chest X-rays may have shown abnormal findings in a computed tomography (CT) thorax. However, a CT scan was not done routinely and hence not reported here. Treatment protocols with COVID-19 patients were continuously evolving at the time of the study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.