key: cord-0926449-v88vdim4
authors: Sosa, Regina; Garcia, Pablo; Cipriano, Ever O.; Hernández, Agualuz; Hernández, Elmer E.; Chavez, Paola I.; Manchinelli, Angélica; Morales, Oscar A.; Flores, Lourdes E.; Romero, Hair J.; Raquec, Yulany; Sapón, Byron F.; Soch, Kevin E.; Anand, Shuchi; Sánchez-Polo, Vicente
title: Coronavirus Disease 2019 in Patients with End-Stage Kidney Disease on Hemodialysis in Guatemala
date: 2021-01-29
journal: Kidney Int Rep
DOI: 10.1016/j.ekir.2021.01.028
sha: 257dd707bdbb2a73f1ada59fb1d7aecba8b2f453
doc_id: 926449
cord_uid: v88vdim4

INTRODUCTION: COVID-19 is public health concern across the world. Data on the epidemiology among patients on hemodialysis in Latin America and low and middle-income countries is limited. METHODS: Using electronic medical records from the second largest dialysis network in Guatemala, we performed a retrospective analysis of all adult patients on hemodialysis with the diagnosis of COVID-19 to estimate incidence of infection, and describe the demographics, comorbidities, and outcomes. We stratified incidence rate by region. We reviewed data from May 1 to July 31, 2020, with outcome data ascertained up to August 28, 2020. RESULTS: Of 3201 patients undergoing hemodialysis, 325 patients were diagnosed with COVID-19 (incidence rate: 102 per 1,000 patients on hemodialysis, compared with 3 per 1,000 in the general population). Incidence was higher in the Central region (207 per 1,000) and lowest in the Southeast region with 33 per 1,000, and unlike in the general population, incidence was lower in Guatemalan city. Mean age of the COVID-19 diagnosed patients was 51.1 (SD 14.8) years, and 84 (25.8%) were female. The median length of hospital stay was 12 days [IQR 10-16]. 229 (69.8%) of the patients recovered, 90 patients died (27.7%), and 6 (1.8%) patients were still in the hospital at the time of last follow-up. CONCLUSION: In summary, incidence of diagnosed COVID-19 in Guatemalan patients on hemodialysis was much higher than reported in the general population, with outcomes similar to those described in high income countries. Rural regions had higher incidence rates than the major metropolitan area.

Coronavirus Disease 2019 infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first recognized in December 2019 in Wuhan, China. 1 Since then, SARS-CoV-2 has affected more than 200 countries across the world causing more than 1,800,000 deaths globally, more than 400,000 deaths of which have occurred in Latin America. 2 On March 13, 2020, the Guatemalan Ministry of Health (MoH) reported the first case of COVID-19 in Guatemala City. This was followed by several interventions to mitigate the effect of the outbreak. However, as of December 31, 2020, there have been more than 125,000 cases, 4 ,500 deaths and an overall excess in mortality attributed to COVID-19. [2] [3] [4] Patients on in-center hemodialysis face extreme threats to their health during the COVID-19 pandemic: not only do their comorbidities (older age, diabetes) place them at higher risk for severe illness, but by the nature of their illness, they cannot shelter in place, and instead require routine interactions with healthcare personnel and other patients in a shared space. In low-and middle-income countries these threats are further compounded by: 1. protective equipment shortages for patients and staff, 2. Public transport required to arrive at a central unit from far flung areas, 5 and 3. Decreased access to immediate testing to prevent further infection among healthcare staff or household members. 6 Data from patients on dialysis in Europe, China and the United States indicate that incidence of infection ranges in between 11 to 19.3% and estimates for mortality range between 6.5 to 52% [7] [8] [9] [10] [11] [12] [13] , far exceeding estimates in the general population. In the U.S., odds of death among hospitalized patients on dialysis are 40% higher than in the general population 14 . Little is known J o u r n a l P r e -p r o o f about incidence and outcomes of COVID-19 in patients on dialysis in Latin America, and lowmiddle-and middle-income countries around the world.

To address this knowledge gap, we conducted a retrospective review of all patients diagnosed with COVID-19 at the Guatemalan Social Security Institute (IGSS) in the second largest healthcare system and dialysis provider in Guatemala. We determined the incidence rate of symptomatic COVID-19 infection among patients on hemodialysis, described the infection control practices, and delineated the demographics, comorbidities, and outcomes of the affected patients.

We enrolled all adults with diagnosis of COVID-19 and ESKD on hemodialysis admitted or treated at any of the six hospitals or 15 dialysis centers supported by IGSS. This study was approved by IGSS Institutional Review Board.

Guatemala is an upper-middle-income country with 16.4 million people located in Central America. 15 In Guatemala, there are three healthcare systems (public, private and employer-based health insurance). Approximately 8% of the Guatemalan population has access to private health insurance and private health care. 16 However, most Guatemalans are unable to cover the costs of dialysis in the private sector. 17 As a result, clinical care for kidney diseases in Guatemala is primarily delivered in the public-sector institutions, which includes the Ministry of Health National Center for Chronic Renal Disease (UNAERC) and IGSS. UNAERC is the only J o u r n a l P r e -p r o o f freestanding dialysis network for those uninsured or without access to an employer-based health insurance in Guatemala. Approximately 64% of those patients with access to kidney replacement therapy are being dialyzed by UNAERC. 18 IGSS is an employer-based health insurance system available to 18% of the overall population. IGSS provides dialytic care to approximately 34% of those with access to ESKD care in Guatemala. 16, 17 There is a predominance of men affiliated with the social security system (66.2%). As of July 31, 2020, there were 3201 patients with ESKD on hemodialysis and 551 on peritoneal dialysis receiving care at IGSS. 17 Those patients with ESKD on hemodialysis at IGSS get dialytic treatment three times a week in one of the 15 dialysis centers located across the country. Initially, all the patients diagnosed with COVID-19 infection were admitted to any of the six social security hospitals in Guatemala appointed for the care of patients infected with COVID-19. As of July 20, 2020, the patients without symptoms or indications for hospitalization were clinically managed as an outpatient.

For those patients managed outside the hospital, we developed a protocol to provide uninterrupted dialysis care. In our dialysis units, we usually have two shifts per day. We established a third shift in the evenings only for those patients diagnosed with COVID-19. After the last shift, our staff dedicates time to clean and disinfect the dialysis center, including machines, beds, and chairs.

We included all the adult patients (≥18 years of age) with ESKD on hemodialysis with the diagnosis of COVID-19 at the IGSS dialysis centers from May 1, 2020 to July 31, 2020. We considered COVID-19 disease diagnosis if the patients had a nasopharyngeal swab positive for J o u r n a l P r e -p r o o f SARS-CoV-2 using reverse transcriptase-polymerase chain reaction (RT-PCR) or SARS-CoV-2 rapid antigen test positive. We initially tested only those patients with symptoms suggesting COVID-19. Later, we developed a proactive testing protocol to prevent COVID-19 transmission in our dialysis units. In our testing protocol, we included those patients in close contact with another patient with a diagnosis of COVID-19. We excluded those patients who were started on dialysis due to COVID-19 infection related complications.

Study investigators at each social security hospital or dialysis center collected epidemiological, clinical, and outcomes data by manually reviewing electronic medical records and used a case report form to enter data into a secure database.

We followed patients until hospital discharge, death, or August 28, 2020.

Patient-level data included baseline information on demographics, comorbidities, symptoms, underlying cause of chronic kidney disease and vascular access. The nephrologists defined chronic kidney disease of nontraditional etiology among those younger than 50 years, without history of diabetes, hypertension, glomerulopathies, or other known causes of kidney disease. 19 We collected data on dialysis center location based on six geographical regions Metropolitan, North, Northeast, Southeast, Central and Southwest.

To describe baseline characteristics, and outcomes, we express continuous variables as means (SD) for normally distributed continues measures, and medians (interquartile range). Categorical variables as number (percentage). We described proportion of death associated with COVID-19 infection during the follow up period. We described overall incidence of SARS-CoV-2 infection, 

We identified a total of 325 patients on hemodialysis with diagnosis of COVID-19 infection at IGSS. Mean age in the cohort was 51.1 (SD 14.8) years, and 84 (25.8%) of the patients were female ( Table 1 ). The most common comorbidity and CKD etiology was diabetes (39.4%).

All patients received three hemodialysis sessions per week in an outpatient clinic. (Table 1) . We identified a dialysis unit located in Sacatepéquez with 30% incidence of SARS-CoV-2 infection ( Figure 3 ).

The first case of COVID-19 in a patient on hemodialysis in Guatemala was reported on May 13, 2020 ( Figure 2 ). The majority of the patients presented at least one symptom and the most common symptom was fever (71.1%) followed by cough (53.2%). There were no differences in symptom presentation by sex ( Figure 1 ). Those patients who died were more prone to shortness of breath (44.4%) when compared with those who recovered ( Figure 2 ). Death rate amongst those patients 45 years old or younger was 15% and significantly higher in those older than 60 years. Death rate amongst those with diabetes was significantly higher at 45% (Figure 4 ).

J o u r n a l P r e -p r o o f

The overall incidence of COVID-19 among patients on hemodialysis was 102 per 1,000 people (325 out of 3201). Incidence rate was higher in the Central region (207 per 1,000 people) and the region with the lowest incidence was the Southeast region with 33 per 1,000. The incidence in the Metropolitan region, where Guatemala City is located, was 86 per 1,000 (Figure 3 ). In the general population, the overall incidence was 3 per 1,000 over the same time period. We observed an outbreak in one of the dialysis units located in the central region, with an incidence of 300 per 1000 people in a single dialysis unit (Figure 3 ).

In this retrospective analysis of patients undergoing hemodialysis in Guatemala, we find that 1 in 10 patients had symptomatic disease. Despite their young age compared with other described cohorts of patients on dialysis, 14,21,22 more than 1 in 4 succumbed to the disease. While detection bias likely exists, compared to the general population, incidence rates were 10-fold higher. In the context of the severity of illness of a majority of patients on dialysis affected-more than half required oxygen support-the diagnosed cases likely reflect clinically significant disease. We noted a comparatively lower incidence of SARS-CoV-2 infection in Guatemala city, an unexpected finding since densely populated areas are anticipated to have higher SARS-CoV-2 infection incidence, and this could imply risk amplification by the requirement of transportation from far flung areas to a single dialysis unit in the rural areas. 23 Compared to the rest of the regions in Guatemala with incidences between 33 to 103 per 1,000 people, we noticed a markedly increased incidence of infection in the Central region (207 per 1,000 people). There was an outbreak in one of the dialysis units located in the Central region, J o u r n a l P r e -p r o o f perhaps caused by contact with healthcare workers or acquired in the community while traveling to the dialysis unit. We favor the latter because it is known that patients in Guatemala travel long distances to have access to dialytic therapy. A study in the pediatric population in Guatemala found that travel time to the dialysis center was 2.5 hours on average, with 17% using a combination of public transportation types. 24 Furthermore, a study including adult patients on hemodialysis in Guatemala reported a traveling distance to a dialysis center in between 2 to 200 miles. 25 Thus, we recommend our colleagues in low, lower-middle or upper-middle income countries such as Guatemala to arrange transportation for each individual on dialysis at least in regions with a high incidence of infection to prevent infections while traveling on public transportation. With the possible arrival of the COVID-19 vaccine to Guatemala. We recommend that the Guatemalan MoH or IGSS prioritize patients on dialysis for two main reasons: 1) those patients on dialysis are more susceptible to infection than the general population, 2) due to the increased death rate when compared to the general population.

Initially, when a patient was positive for SARS-CoV-2 infection, our protocols recommended hospitalizing them for clinical management and monitorization. Therefore, the higher proportion of patients being hospitalized in our cohort compared to other reports from dialysis centers across the world. 10, 21, 22, 26 Our cohort was significantly younger (Mean 51.1 years old) than European and American cohorts (66 to 69 years). 14, 21, 22 In general, the population in Guatemala is younger than the American and European countries. 20 In our cohort, most patients were men (74.2%), which is explained by the predominance of men affiliated to the social security system (66.2%). 27 There is also a growing body of evidence indicating sex differences in the clinical J o u r n a l P r e -p r o o f outcomes of COVID-19. 10, [28] [29] [30] However, whether immune responses towards SARS-CoV-2 are different between sexes is currently unknown.

The most common clinical presentation was fever (71.1%), followed by cough and myalgia.

Similar to our study, in a recent report from the Spanish Society of Nephrology Registry, including only patients with end-stage kidney disease (ESKD), the most common symptom was fever (75%) and only 50% shortness of breath. 22 A study on critically ill adult patients in the United States reported cough as the most common symptom, followed by dyspnea (74.9%).

Since volume overload and shortness of breath is very common among patients on dialysis, 31 it may be more challenging to differentiate baseline shortness of breath from the additional symptoms caused by COVID-19, thus the difference in clinical symptoms at presentation between those with and those without ESKD.

Although the incidence we report in our patient population in much higher than in the general population in Guatemala, it is similar to prior reports from Europe among patients receiving dialysis. A study by the Brescia Renal COVID Task Force in Italy found that among 643 hemodialysis patients, SARS-CoV-2 RNA positivity was detected in 94 (150 per 1000 patients). 13 One of the largest cohorts from France reported an incidence of COVID-19 from less than 10 to 100 per 1000 people between regions and an overall incidence of 330 per 1000 patients. 21 Interestingly, a study addressing the seroprevalence of SARS-CoV-2 antibodies in a hemodialysis population in the United Kingdom found that around 36.2% of the patients tested positive for COVID-19 and almost half were asymptomatic. 32

Most of the patients recovered (70%) and 28% died. This death rate is consistent with the death rate reported in other studies from Europe, China, and the United States (20 to 31.2%). 13, 33, 34 A recent study including 151 Guatemalan patients on dialysis cared at the public health system found a death rate relatively higher (37.7%) than the death rate reported in our study. This contrast in death rate may be explained by differences in access to care between the public health system and the IGSS system. These differences in care are mainly derived from an overwhelmed public health system. 18, 35 However, further studies are needed to better explain the reasons for this difference in death rate. In the present study, we identified some factors potentially associated with better outcomes: 1) patients were younger in our cohort, 2) most of the patients were admitted to the hospital with closer follow and monitorization. The healthcare workers were able to act promptly if the patient presented a complication associated with the disease, 3) IGSS hospitals and dialysis units are part of a single healthcare system, therefore facilitating implementation of protocols at the dialysis units to expedite referrals. This study has some limitations. There are two main dialysis providers in Guatemala: the Guatemalan MoH and IGSS. We only captured those patients affiliated with IGSS, which represent around 34% of the population with access to renal replacement therapy. 17 We didn't include those patients on peritoneal dialysis in our cohort. We mainly diagnosed the patients based on symptoms, and we might have missed a significant proportion of those patients with asymptomatic infection. Whenever a patient had symptoms suspicious of COVID-19, the medical staff at each dialysis unit referred them to the Social Security reference hospital to confirm the diagnosis of COVID-19 by RT-PCR or SARS-CoV-2 antigen test. We found that among patients on hemodialysis with COVID-19 in Guatemala the lethality rate was similar to other regions across the world.

There was a regional variation in the incidence of COVID-19 in Guatemala.

None of the authors have any relevant financial disclosures related to this paper FUNDING This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. 

Supplementary information is available at KI Report's website FIGURES FIGURE 1. Symptoms by gender. Most of the patients presented with fever. Males were more prone to present with fever than females. 

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