Abstract
Background
The clinical manifestations of maintenance haemodialysis (MHD) outpatients diagnosed with coronavirus disease 2019 (COVID-19) are highly heterogeneous. They are prone to progress to severe conditions, and they often require hospitalization. To better guide the management of MHD outpatients, this retrospective observational study assessed risk factors for hospitalization of MHD patients after a diagnosis of COVID-19.
Methods
The demographic data, comorbidities, laboratory indicators and imaging data of 128 MHD outpatients at our haemodialysis centre with confirmed COVID-19 infection from December 2022 to January 2023 were collected. The relationships between these factors and hospitalization of patients were analyzed.
Results
Among the 128 patients, 25 (19.53%) were hospitalized. One of the 25 inpatients was mechanically ventilated, and two of them died. Multivariate logistic regression analysis showed that the hospitalization rate was correlated with age, comorbid diabetes and peripheral blood lymphocyte count.
Conclusion
Older age, comorbid diabetes and lower lymphocyte count are important risk factors for hospitalization of MHD outpatients after a diagnosis of COVID-19. Focusing on these factors may help in early identification of patients who may need to be admitted due to potential disease progression.
1. Introduction
Since December 2022, the number of coronavirus disease 2019 (COVID-19) cases in Chengdu, China, has risen sharply. The current strain of the virus is Omicron BA.5.2. Haemodialysis (HD) patients have a high COVID-19 infection rate, have low immunity, have a worse nutritional status than the general population, often have multiple underlying diseases and are at high risk of progressing to severe or critical conditions after the diagnosis of COVID-19. Several studies have reported the clinical course and prognosis of maintenance haemodialysis (MHD) patients diagnosed with COVID-19 and found that the clinical manifestations of COVID-19 infection in HD patients vary widely, from no symptoms to bilateral pneumonia, systemic muscle damage and even multiple-organ failure. Severe and critically ill patients account for up to 41% of MHD patients diagnosed with COVID-19, and the mortality rate of those with worsening disease can be as high as 61.1% [Citation1,Citation2]. With the Omicron strain becoming the dominant COVID-19 virus, the virulence has decreased, but the virus still poses a great threat to HD patients. In a report on the clinical data of 102 MHD patients diagnosed with COVID-19 during the Omicron outbreak in Shanghai in April 2022, 45.1% of the patients were complicated with pneumonia, 11.8% of the patients died and multivariate regression analysis showed that all-cause mortality was correlated with lymphocyte count, B-type natriuretic peptide, C-reactive protein (CRP) and D-dimer levels [Citation3].
Given the prevalence of Omicron strains in China, the COVID-19 infection rate among MHD patients in our centre has been high, as is the proportion of patients progressing to severe conditions and needing hospitalization. To identify patients who are likely to progress to severe conditions early, this retrospective observational study was conducted to assess the risk factors for hospitalization of MHD outpatients after a diagnosis of COVID-19, aiming to guide the care strategies for MHD outpatients during the COVID-19 pandemic.
2. Subjects and methods
2.1. Research subjects
This study included 128 MHD outpatients with confirmed COVID-19 infection (the polymerase chain reaction (PCR) test was used as the nucleic acid amplification tests (NAATs), and reagents were from DaAn Gene Co., Ltd, China. Both ORF1ab gene and N gene were detected, and ≤40 CT indicates a positive COVID-19 test.) in the HD centre of the General Hospital of Western Theater Command of the Chinese People’s Liberation Army (PLA) from December 2022 to January 2023 (MHD time ≥3 months, all patients receiving conventional bicarbonate HD three times a week for 4 h each time, with a blood flow rate of 200–300 ml/min and a dialysate flow rate of 500 ml/min).
The exclusion criteria were as follows: (1) patients with no history of chronic kidney disease who received blood purification treatment for acute kidney injury; (2) patients with incomplete clinical data and (3) patients receiving hormone or immunosuppressive therapy. This retrospective study was approved by the Ethics Committee of the General Hospital of Western Theater Command (2023EC3-ky016), and all of the patients provided written informed consent.
2.2. Methods
The sex, age, dialysis duration, body mass index and comorbidities (including diabetes, hypertension, tumour, autoimmune disease (AID) and coronary heart disease (CHD)) of the patients were collected. The clinical symptoms and blood pressure during dialysis after COVID-19 infection were recorded. Laboratory data (haemoglobin, platelet count, lymphocyte count, albumin, CRP, potassium, total bilirubin, lactate dehydrogenase, creatine kinase, myoglobin) and chest computed tomography (CT) results within 1 week of COVID-19 infection were recorded. The hospitalizations of HD patients within 2 weeks after the diagnosis of COVID-19 were recorded.
2.3. Statistical methods
IBM SPSS statistics 26.0 was used for statistical analysis. The Shapiro–Wilk test was used to test for a normal distribution of measurement variables. The normally distributed measurement variables are presented as mean ± standard deviation (SD), the non-normally distributed measurement variables are presented as median (P25, P75), and the count variables are described by frequency and percentage. The two-independent-samples t test was run to compare the means of normally distributed measurement variables between the two groups, the Mann–Whitney U test was used to compare the medians of non-normally distributed measurement variables, and the Pearson χ2 test or Fisher’s exact test compared the count variables. The influencing factors that differed between the two groups (hospitalized and non-hospitalized patients) in the univariate analysis were included in the multivariate logistic regression model. Stepwise regression was used to screen for independent risk factors for the hospitalization of HD patients, and their odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. p < .05 was statistically significant.
3. Results
3.1. Infection symptoms
A total of 128 patients were included in this study, and they were all from the HD centre of our hospital. Eighty-five patients (66.41%) had clinical symptoms. Cough and expectoration (43.75%), hypotension during dialysis (25.00%) and fever (21.88%) were the most common symptoms. The main symptoms after the diagnosis of COVID-19 are listed in .
Table 1. The symptoms after infected with COVID-19.
3.2. Univariate analysis
Among the 128 patients, 25 (19.53%) were hospitalized. Univariate correlation analysis showed that hospitalization was correlated with age, diabetes, hypertension, coronary heart disease, CRP, albumin, myoglobin and lymphocyte count ().
Table 2. Comparison of indicators between the admission group and non-admission group.
No correlation between vaccination and hospitalization among HD patients diagnosed with COVID-19 was found, but the percentage of HD patients vaccinated against SARS-COV-2 was only 18.75% (The vaccines were all inactivated. Nine patients had received three doses, 10 patients had received two doses, and five patients had only received the first dose.).
3.3. Multivariate analysis
Multivariate binary logistic regression analysis showed that by adjusting for sex, dialysis duration, CRP and other factors, age (OR = 4.857), diabetes (OR = 4.608) and lymphocyte count (OR = 0.110) were revealed as important risk factors for the hospitalization of MHD patients diagnosed with COVID-19 ().
Table 3. Multivariate regression analysis of relationship between admission rate and clinical parameters.
3.4. Laboratory results and outcomes of admitted HD patients
In this study, 128 patients were observed, of which 25 patients were admitted to the hospital. The levels of lactate, IL-6 and D-dimer in these HD inpatients at the time of admission are shown in . Nine of them had hypoxaemia (partial pressure of oxygen (PO2) ≤80 mmHg), and three of them showed subclinical hypoxaemia. One of the 25 inpatients was mechanically ventilated, and two of them died.
Table 4. The situation of patient admissions.
4. Discussion
Since the HD outpatients are at high risk of COVID-19, several measures were taken to prevent the transmission of COVID-19 in our centre. Pre-screening and triage were based on temperature, presence of respiratory or gastrointestinal symptoms and epidemiological investigation. Separate access was set for HD outpatients. HD was performed in different zones and time slots according to the risk areas classified by the local Centre for Disease Control and Prevention (CDC) and daily epidemiological survey results. Confirmed COVID-19 patients were isolated during HD (single-room isolation and treatment under personal protection). When the epidemic was severe, patients were required to enter the corresponding department with a negative COVID-19 NAAT result within 24 h. With these measures, the COVID-19 infection rate in our centre was low, but when SARS-CoV-2 broke out in Chengdu in December 2022, the infection rate among HD outpatients increased rapidly, which may be related to outpatients travelling on public transport and cross infection by family members. Ibernon et al. [Citation4] reported that the structural and organizational changes adopted early on played an important role in minimizing the spread of COVID-19, which worth learning from.
This study retrospectively investigated the clinical features and laboratory indicators of 128 MHD patients diagnosed with COVID-19 and analyzed their predictive value for hospitalization within 14 days after a diagnosis of COVID-19. Multivariate logistic regression analysis showed that the risk factors for the hospitalization of patients diagnosed with COVID-19 were age over 60 years, comorbid diabetes and peripheral blood lymphocyte count. Ageing itself is a major risk factor for severe disease and death. Data from Italy, France, the United States and other countries show that the severe case ratio and case fatality ratio after diagnosis of COVID-19 increase with age [Citation5–10]. This study also found that the older the MHD patient diagnosed with COVID-19, the higher the hospitalization rate. The hospitalization rate of patients over 60 years old was 4.857 times that of patients under 60, which may be related to the fact that patients with end-stage renal disease at an advanced age are often immunocompromised and have multiple comorbidities.
As MHD patients often have multiple comorbidities, a HD centre from Wuhan, China reported that the main cause of death of MHD patients after diagnosis of COVID-19 is cardiovascular events [Citation11]. This study analyzed the comorbidities diabetes, hypertension, tumours, autoimmune diseases and coronary heart disease in the included patients, and the results showed that 19.53% of the patients had diabetes, 65.63% had hypertension, 2.34% had tumours, 7.03% had autoimmune diseases (including four cases of anti-neutrophil cytoplasmic antibody-associated vasculitis, two cases of rheumatoid arthritis and three cases of systemic lupus erythematosus, none of them being treated with hormone or immunosuppressive therapy) and 11.72% had coronary heart disease. Multivariate analysis found that comorbid diabetes was a high-risk factor for the hospitalization of MHD patients within 2 weeks after a diagnosis of COVID-19. The severity and mortality of COVID-19 are significantly increased in patients with diabetes, especially those with poor glycaemic control [Citation12-17], which may be related to postinfection stress hyperglycaemia, exacerbated insulin resistance, immune disorders or β-cell damage induced by COVID-19 [Citation12]. There were only three cases of comorbid tumours in this study, which may have limited the strength of the analysis of the hospitalization of COVID-19 patients with tumours. All patients in this study underwent laboratory tests, such as routine blood, liver and kidney function, CRP and myoglobin tests, within 1 week after the diagnosis of COVID-19, and the results showed that the peripheral blood lymphocyte count was particularly important in predicting hospitalization. Among MHD patients diagnosed with COVID-19, those with lower lymphocyte counts have a greater risk of death [Citation1,Citation18,Citation19Citation], and a lymphocyte count below 0.61 × 109/L has predicted a higher risk of death in HD patients diagnosed with COVID-19 [Citation2]. Lymphopenia and a high neutrophil/lymphocyte ratio (NLR) are predictors of COVID-19 death [Citation20–23]. The increase in neutrophils may reflect the acute inflammatory response associated with cytokine storms, and the decrease in lymphocytes may reflect the depletion of CD4+ and CD8+ T lymphocytes caused by cellular immunity in the early stage of COVID-19 [Citation20].
Effective and safe COVID-19 vaccination is a good strategy to stop the spread of the virus and control the pandemic, and T lymphocytes are the key cells for adaptive immune protection and vaccination. HD patients often have low immunity and insufficient immune response to the vaccine, and only 18.75% of the patients in this study were vaccinated.
The low vaccination rate in the HD outpatients in this study may be related to the fact that patients were not sufficiently aware of the importance of vaccines, the overconcern of risks of vaccinating with underlying diseases, and the vaccination education by our centre did not cover every patient. All patients in our centre received inactivated vaccines, and only nine patients received all three doses. No correlation was found between vaccination and hospitalization due to COVID-19 infection in HD outpatients, which may be related to the small sample size and low vaccination rate. There is still a need to boost vaccination in HD patients and to develop vaccines or vaccination methods that are more suitable for these immunocompromised patients.
A study found that in critically ill patients diagnosed with COVID-19, the levels of markers of myocardial injury were elevated, and the increase in myoglobin level was the most significant [Citation24]. The univariate analysis of this study also found significantly different myoglobin levels between hospitalized and non-hospitalized patients. The myoglobin level was higher in HD patients who were hospitalized, and these patients often had significant myalgia, fatigue and even severe hyperkalaemia, which might be due to a hypercatabolic state resulting from the acute infection phase. In these patients the dialysis interval may need to be shortened, the frequency of dialysis may need to be increased, or ordinary dialysis may need to be switched to continuous renal replacement therapy. However, the multivariate binary logistic regression analysis in this study showed that there was no significant correlation between the myoglobin level and the hospitalization rate, which may be related to the small sample size.
The D-dimer test was routinely performed on inpatients, and no cerebrovascular events or vascular access dysfunction were detected. Therefore, vascular ultrasound, brain magnetic resonance imaging (MRI) and thoracic contrast-enhanced CT were not routinely performed, and the incidence of thrombotic events cannot be evaluated. Previous studies have suggested that the incidence of thrombotic events after COVID-19 is high and correlated with prognosis [Citation25,Citation26]; therefore, routine prophylactic low molecular weight heparin (LMWH) was given to inpatients with COVID-19.
There are some limitations to this study. First, it was a single-centre, retrospective study with a small sample. Second, due to the rapid infection rate of HD patients in this epidemic, there were not enough COVID-19-negative patients as controls, and a very few patients may not have undergone timely laboratory tests because they died out of hospital due to rapid disease progression, which could have lowered the observed risk of hospitalization in this study. Third, in this study, 25 patients were admitted to the hospital, of which one patient was mechanically ventilated. Since the sample size was too small and the use of mechanical ventilation might be affected by the relative shortage of ventilators during the COVID-19 pandemic, this study did not conduct further analyses of influencing factors of mechanical ventilation.
In conclusion, this retrospective analysis of 128 MHD patients diagnosed with COVID-19 showed that age older than 60 years, comorbid diabetes and low lymphocyte count were the main risk factors leading to hospitalization shortly after diagnosis of COVID-19. Paying attention to these factors may help with the early detection of MHD outpatients who are likely to progress to severe or critical COVID-19 and to formulate better treatment strategies for them.
Authors contributions
Professor Yue Cheng and Professor Fan Zhang contributed to the conception of the study and designed the work. Doctor Yanlin Zhu and Doctor Jie He performed the data analyses and wrote the manuscript. Professor Yunming Li and Doctor Mingyuan Cao contributed significantly to the analysis and manuscript preparation. Doctor Guchuan Yang played an important role in the data collection. All authors agree to be accountable for all aspects of the work.
Disclosure statement
The authors declare no conflicts of interest.
Data availability
Data are available on request due to privacy/ethical restrictions.
Additional information
Funding
References
- Marian G, Luis ASC, Nicola M, et al. COVID-19: clinical course and outcomes of 36 hemodialysis patients in Spain. Kidney Int. 2020;98:1–6.
- Gabriel S, Ana MM, Iuliana A, et al. Clinical features and outcome of maintenance hemodialysis patients with COVID-19 from a tertiary nephrology care center in Romania. Renal Failure. 2021;43:49–57.
- Wen JB, Shun KF, Hua Z, et al. Clinical characteristics and short-term mortality of 102 hospitalized hemodialysis patients infected with SARS-COV-2 omicron BA.2.2.1 variant in shanghai, China. New Microbe New Infect. 2022;49:101058.
- Ibernon M, Bueno I, Rodríguez-Farré N, et al. The impact of COVID-19 in hemodialysis patients: experience in a hospital dialysis unit. Hemodial Int. 2021;25(2):205–213. doi: 10.1111/hdi.12905.
- Chen Y, Klein SL, Garibaldi BT, et al. Aging in COVID-19: vulnerability, immunity and intervention. Ageing Res Rev. 2021;65:101205. doi: 10.1016/j.arr.2020.101205.
- Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese center for disease control and prevention. JAMA. 2020;323(13):1239–1242. doi: 10.1001/jama.2020.2648.
- Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382(8):727–733. doi: 10.1056/NEJMoa2001017.
- Onder G, Rezza G, Brusaferro S. Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy. JAMA. 2020;323(18):1775–1776. doi: 10.1001/jama.2020.4683.
- Salje H, Tran Kiem C, Lefrancq N, et al. Estimating the burden of SARS-CoV-2 in France. Science. 2020;369(6500):208–211. doi: 10.1126/science.abc3517.
- Richardson S, Hirsch JS, Narasimhan M, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York city area. JAMA. 2020;323(20):2052–2059. doi: 10.1001/jama.2020.6775.
- Ma Y, Diao B, Xifeng LV, et al. Novel coronavirus disease in hemodialysis (HD) patients: report from one HD center in Wuhan, China. 2019; medRxivpre print. Available at: doi: 10.1101/2020.02.24.20027201.Accessed February 27, 2020.
- Singh AK, Khunti K. COVID-19 and diabetes. Annu Rev Med. 2022;73(1):129–147. doi: 10.1146/annurev-med-042220-011857.
- Cariou B, Hadjadj S, Wargny M, et al. Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study. Diabetologia. 2020;63(8):1500–1515. doi: 10.1007/s00125-020-05180-x.
- Shi Q, Zhang X, Jiang F, et al. Clinical characteristics and risk factors for mortality of COVID-19 patients with diabetes in Wuhan, China: a two-center, retrospective study. Diabetes Care. 2020;43(7):1382–1391. doi: 10.2337/dc20-0598.
- Seiglie J, Platt J, Cromer SJ, et al. Diabetes as a risk factor for poor early outcomes in patients hospitalized with COVID-19. Diabetes Care. 2020;43(12):2938–2944. doi: 10.2337/dc20-1506.
- Agarwal S, Schechter C, Southern W, et al. Preadmission diabetes-specific risk factors for mortality in hospitalized patients with diabetes and coronavirus disease 2019. Diabetes Care. 2020;43(10):2339–2344. doi: 10.2337/dc20-1543.
- Singh AK, Gillies CL, Singh R, et al. Prevalence of co-morbidities and their association with mortality in patients with COVID-19: a systematic review and meta-analysis. Diabetes Obes Metab. 2020;22(10):1915–1924. doi: 10.1111/dom.14124.
- Kular D, Chis Ster I, Sarnowski A, et al. The characteristics, dynamics, and the risk of death in COVID-19 positive dialysis patients in London, UK. Kidney360. 2020;1(11):1226–1243. doi: 10.34067/KID.0004502020.
- Fisher M, Yunes M, Mokrzycki MH, et al. Chronic hemodialysis patients hospitalized with COVID-19: short-term outcomes in the Bronx, New York. Kidney360. 2020;1(8):755–762. doi: 10.34067/KID.0003672020.
- Wang F, Nie J, Wang H, et al. Characteristics of peripheral lymphocyte subset alteration in COVID-19 pneumonia. J Infect Dis. 2020;221(11):1762–1769. doi: 10.1093/infdis/jiaa150.
- Chen R, Sang L, Jiang M, et al. Longitudinal hematologic and immunologic variations associated with the progression of COVID-19 patients in China. J Allergy Clin Immunol. 2020;146(1):89–100. doi: 10.1016/j.jaci.2020.05.003.
- Qin C, Zhou L, Hu Z, et al. Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis. 2020;71(15):762–768. doi: 10.1093/cid/ciaa248.
- Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054–1062. doi: 10.1016/S0140-6736(20)30566-3.
- Du Y, Lu Z, Jin J, et al. Hematological characteristics of patients with novel coronavirus pneumonia in intensive care unit. Int Immunopharmacol. 2021;97:107697. doi: 10.1016/j.intimp.2021.107697.
- Vacchi C, Meschiari M, Milic J, et al. COVID-19-associated vasculitis and thrombotic complications: from pathological findings to multidisciplinary discussion. Rheumatology (Oxford). 2020;59(12):e147–e150. doi: 10.1093/rheumatology/keaa581.
- Zhang L, Feng X, Zhang D, et al. Deep vein thrombosis in hospitalized patients with COVID-19 in Wuhan, China: prevalence, risk factors, and outcome. Circulation. 2020;142(2):114–128. doi: 10.1161/CIRCULATIONAHA.120.046702.