Original Article

Risk Factors and Predictors of 1-year Overall Mortality in Patients with COVID-19

10.4274/haseki.galenos.2022.8501

  • Serkan Surme
  • Gulsah Tuncer
  • Osman Faruk Bayramlar
  • Hindirin Takak
  • Betul Copur
  • Meltem Yazla
  • Esra Zerdali
  • Inci Yilmaz Nakir
  • Gonul Sengoz
  • Filiz Pehlivanoglu

Received Date: 25.05.2022 Accepted Date: 05.10.2022 Med Bull Haseki 2022;60(5):439-446

Aim:

To date, limited data exists on 1-year mortality and associated factors in patients with coronavirus diseases-2019 (COVID-19). We determined risk factors and predictors of 1-year mortality.

Methods:

In this retrospective and single-center study, hospitalized patients with COVID-19 were enrolled between March 11 and March 11, 2020. The primary outcome was 1-year all-cause mortality after discharge from the hospital. Secondary outcomes were the risk factors and predictors of 1-year mortality. A comparative analysis was applied to patients who died after recovering from acute COVID-19 and patients who survived.

Results:

A total of 567 patients were analyzed. The 1-year mortality occurred in 18 (3.2%) patients. Older age (p=0.001), chronic obstructive pulmonary disease (p=0.001), chronic artery disease (p=0.001), chronic renal failure (p=0.001), presence of pleural fluid (p=0.001), high levels of leukocyte (p=0.001), neutrophil (p=0.001), monocyte (p=0.026), C-reactive protein (p=0.042), procalcitonin (p=0.004), urea (p=0.001), creatinine (p=0.001), troponin (p=0.001), lactate dehydrogenase (p=0.019), potassium (p=0.003), and a low level of alanine aminotransferase (p=0.001) at the first admission were associated with increased long-term mortality. Additionally, the need for intensive care unit (ICU) admission (p=0.007) and invasive ventilation (p=0.019) during the hospital stay for COVID-19 were associated with increased 1-year mortality.

Conclusion:

This study suggests that age, underlying diseases, pleural fluid, certain laboratory parameters, and ICU care are somewhat associated with 1-year mortality.

Keywords: COVID-19, 1-year mortality, risk factors, predictors

Introduction

The coronavirus disease-2019 (COVID-19) has had a global impact, resulting in over 6 million deaths as of April 2022 (1). Hospitalized patients with COVID-19 frequently have pneumonia, which causes respiratory failure and results in multiorgan dysfunction, the need for invasive ventilation, and death (2,3). While most survivors have a full recovery after discharge from the hospital, some patients need long-term follow-up care due to the complications of COVID-19 and long-COVID symptoms (4,5).

To date, limited data exists on 1-year mortality in patients with COVID-19, although 30-day and 3-6-month outcomes of COVID-19 are well-known (6,7). Therefore, in this study, we aimed to determine the prevalence of 1-year mortality among survivors and to explore the risk factors and predictors of long-term mortality after discharge from the hospital.


Materials and Methods

Compliance with Ethical Standards

All procedures performed in this study were in accordance with the ethical standards of the Declaration of Helsinki. This study was approved by the Ethics Committee of University of Health Sciences Turkey, Istanbul Haseki Training and Research Hospital (approval number: 102-2022, date number: 08.06.2022) and the Advisory Board on Coronavirus Research of the Republic of Turkey Ministry of Health (approval number: 2022-01-26T10_14_12, date: 27.01.2022). Written informed consent was waived because of the retrospective nature of this study.

Study Design

In this single-center study, all hospitalized adult patients (older than 18 years old) with laboratory-confirmed COVID-19 between March 11 and March 11, 2020, were retrospectively enrolled. For laboratory confirmation, positive severe acute respiratory syndromecoronavirus-2 real-time reverse transcriptase polymerase chain reaction testing from oropharyngeal and/or nasopharyngeal swabs was used. We excluded patients with asymptomatic COVID-19 and patients who died during the hospital admission.

Patients’ Evaluation

This study was designed as a continuation of our previous study (8). In the study, demographic and clinical features, laboratory test results, radiological findings, and short-term outcomes were obtained from medical charts and recorded via a follow-up data sheet. The primary outcome was 1-year all-cause mortality after discharge from the hospital. Secondary outcomes were the risk factors and predictors of 1-year mortality. For mortality, the National Death Report Database was used to obtain the 1-year mortality. The patients were divided into two groups: deceased and surviving patients. A comparative analysis was applied to patients who died after recovery from acute COVID-19 and patients who survived.

Statistical Analysis

Categorical parameters were represented as frequencies (n) and percentages (%), whereas quantitative parameters were represented as median and interquartile ranges (IQR). The chi-square test or Fisher’s exact test were used to compare categorical data.The Kolmogorov-Smirnov test was used for normal distribution analysis. The Independent sample t-test was applied for normally distributed variables, while the Mann-Whitney U test was performed for variables without normal distribution. A p value less than 0.05 was considered significant. Odds ratios (OR) with 95% confidence intervals were determined. The analyses were performed using IBM SPSS-21 (Statistical Package for Social Sciences, IL, USA).


Results

A total of 567 patients were enrolled in the study. Of those, 298 (52.6%) were male, and the median (IQR) age was 53 (41-62) years. The 1-year mortality occurred in 18 (3.2%) patients. One-year mortality was found to be higher in older patients (65 years old) than in younger patients (10.9% vs. 1.3%, OR=9.09, p=0.001). The 1-year mortality rate was more frequent in patients with at least one comorbid disease (5.1% vs. 0.8%, OR=6.74, p=0.004), chronic obstructive pulmonary disease (COPD) (25.0% vs. 2.4%, OR=13.69, p=0.001), chronic artery disease (11.5 vs. 2.3%, OR=5.47, p=0.001), and chronic renal failure (29.2% vs. 2.0%, OR=19.9, p=0.001) compared to those with none (Table 1). Figure 1 demonstrates the risk factors for 1-year mortality in patients with COVID-19 in the post-discharge period. However, no significant relationship was detected between the 1-year mortality and the initial symptoms at admission (Table 2).

On chest computed tomography (CT), patients with pleural fluid had a higher 1-year mortality rate than patients without pleural fluid (27.3% vs. 2.3%, OR=16.2, p=0.001) (Table 3).

The median values of leukocyte count (7860/mm3 vs. 5850/mm3, p=0.001), neutrophil count (5690/mm3 vs. 3650/mm3, p=0.001), monocyte count (740/mm3 vs. 510/mm3, p=0.026), C-reactive protein (CRP) (60 mg/L vs. 36 mg/L, p=0.042), procalcitonin (0.13 ng/mL vs. 0.05 ng/mL, p=0.004), urea (44 mmol/L vs. 27 mmol/L, p=0.001), creatinine (1.12 mg/dL vs. 0.73 mg/dL, p=0.001), troponin (59.2 ng/L vs. 3.9 ng/L, p=0.001), lactate dehydrogenase (LDH) (312 UI/L vs. 264 UI/L, p=0.019), and potassium (4.5 mmol/L vs. 4.1 mmol/L, p=0.003) at admission were higher in deceased patients than in surviving patients. Only alanine aminotransferase (ALT) at admission was lower in deceased patients than in surviving patients (16 UI/L vs. 23 UI/L, p=0.001) (Table 4).

The 1-year mortality after discharge from the hospital was higher in patients requiring invasive ventilation (12.0% vs. 2.8%, OR=4.79, p=0.019) and intensive care unit (ICU) admission (11.8% vs. 2.6%, OR=4.94, p=0.007) than those with none (Table 5).


Discussion

In this study, we presented a detailed analysis of the predictors of 1-year mortality in 567 hospitalized patients with COVID-19. The 1-year mortality rate was relatively low (3.2%). Older age, COPD, chronic artery disease, chronic renal failure, presence of pleural fluid on chest CT, high levels of leukocyte, neutrophil, monocyte, CRP, procalcitonin, urea, creatinine, troponin, LDH, potassium, and a low level of ALT were associated with increased long-term mortality. Additionally, the need for ICU admission and ventilatory support, including non-invasive ventilation, during the hospital stay for COVID-19 was associated with about a 5-fold increased 1-year mortality.

Recently, new concerns about increased long-term mortality in patients with certain risk factors have arisen (9). Nevertheless, only a few studies have provided information on risk factors or predictors of 1-year mortality (10-12). The 1-year mortality rate was decisively lower in this study compared to the previous studies on community-acquired pneumonia in Turkey (13,14). This might be partly explained by the difference between COVID-19 and other etiological agents of community-acquired pneumonia in the disease severity and their nature. Most patients with COVID-19 during the first period of the pandemic were admitted to isolated wards according to the national guidelines due to the unknown consequences. Thus, hospitalized patients with COVID-19 were younger and had fewer previous history of comorbid diseases. This also explains the long-term better outcomes of COVID-19 in our study compared to community-acquired pneumonia in previous studies.

The 1-year mortality rates vary between studies and range from 1% to 39% depending on the study population (10-12,15-18). Maestre-Muñiz et al. (10) reported that the 1-year mortality in COVID-19 patients applying to emergency departments but not hospitalized was 3.1% (n=10). Additionally, they revealed that the 1-year mortality rate in patients with COVID-19 after discharge from the hospital was 12.8% (n=34). However, they did not evaluate the risk factors or predictors of 1-year mortality. In their study, the higher mortality rates might be explained by the older age of their study population and the higher comorbidities in hospitalized patients. In the study by Maestre-Muñiz et al. (10), of the hospitalized patients with COVID-19, about 70% were older than 65 years and about 90% had at least one underlying disease. In our study, only 19.4% of the cohort was over 65 years old, and 55.3% of patients had a previous history of any comorbidity.

In the study by Akhtar et al. (15), they demonstrated that a high rate of subsequent 1-year mortality (n=28, 17.6%) was associated with increased poor outcomes. They revealed that older age, diabetes mellitus, and post-COVID electrocardiographic findings were associated with an increased risk of long-term mortality. Akhtar et al. (15) showed that about a quarter of patients with diabetes mellitus and 17% of patients with hypertension died one year after recovery from acute COVID-19. In our study, 25% of patients with COPD, 11.5% of patients with chronic artery disease, and 29.2% of patients with chronic renal failure died after discharge in the long-term period.

Chai et al. (11) reported that 3.5% (n=17) of the discharged patients with COVID-19 (n=488) died within the 1-year follow-up in the cohort, while the 1-year mortality rate was 11.4% (n=15) in patients with cancer who had COVID-19. Interestingly, Ceccato et al. (12) demonstrated a low 1-year mortality rate in ICU admitted patients after discharge (1.3%, n=28). Similarly, in another study with comparable findings to our study in terms of age and comorbidities, the 1-year post-discharge mortality rate was 1.3% in the cohort (n=32) and 1.8% (n=8) in patients with diabetes mellitus (16). The researchers found that fasting blood glucose was associated with a 4-fold increased risk of 1-year mortality in patients with no history of diabetes mellitus and about an 11-fold increased risk of 1-year mortality in patients with diabetes. However, they did not find a relationship between post-discharge long-term mortality and diabetes mellitus. Akhtar et al. (15) found that a high red cell distribution width and low albumin level on discharge were associated with long-term mortality.

In a prospective cohort of chronic renal failure patients who needed hemodialysis, 25% of the survived patients (n=14) died within the first year (17). Similarly, a quarter of the survivors with chronic renal failure died within the first year in this study. The prevalence of 6-month mortality after hospitalization in mechanically ventilated patients was 38.6% (n=335) in a multicenter Spanish study. However, their analysis included patients who died during the hospital stay, since they did not exclude patients who were discharged from the hospital. The researchers revealed age, diabetes mellitus, neutrophil to lymphocyte ratio, and other factors measured during the ICU stay as predictors of 6-month survival. Chojnicki et al. (18) analyzed patients over 60 years of age and showed that 13.2% (n=30) of surviving patients (n=227) died during the 6-month post-discharge period. They demonstrated that age, cognitive functions, functional capacity, hemoglobin level, and urea were associated with mortality. As a result, various rates of mortality have been observed depending on the characteristics of the cohorts. Additionally, different risk factors and predictors from different studies have been determined for 1-year mortality in COVID-19.

Study Limitations

This study had some limitations. First, this study was retrospectively conducted in a single center. Second, our sample size was small and not generalizable to different populations. Third, we used crude all-cause mortality since causes of death were not determined in the study. Some deaths may not be directly attributable to COVID-19. However, the observed increased re-hospitalisation rates and high prevalence of multiorgan dysfunction in patients with COVID-19 compared to the general population prove that there is a certain association between COVID-19 and the 1-year consequences, including death (15). Finally, we did not evaluate long-term persistent symptoms, pulmonary sequelae and other complications or secondary outcomes including readmission, need for ventilation support, respiratory or multiorgan failure, since the only outcome that we measured was the 1-year mortality, due to the primary objective of this study. However, we had several strengths. First, to our knowledge, this is the first comprehensive study to evaluate 1-year mortality and its predictors in hospitalized patients with laboratory confirmed COVID-19 in Turkey. Second, we included all hospitalized patients during the first period of the COVID-19 pandemic. Third, we could include multiple comorbidities and different types of variables in the analysis.


Conclusion

This study proves that surviving patients still have an ongoing mortality risk even after recovery from acute COVID-19. Additionally, our study provides a list of predictors of 1-year mortality in patients with COVID-19 and suggests that age, underlying diseases, pleural fluid, certain laboratory parameters, and ICU care during the first admission are somewhat associated with 1-year mortality. Therefore, clinicians should define a comprehensive follow-up plan for survivors and consider close monitoring of patients with these risk factors after discharge from the hospital.

Ethics

Ethics Committee Approval: This study was approved by the Ethics Committee of University of Health Sciences Turkey, Istanbul Haseki Training and Research Hospital (approval number: 102-2022, date number: 08.06.2022).

Informed Consent: Written informed consent was waived because of the retrospective nature of this study.

Peer-review: Externally and internally peer-reviewed.

Authorship Contributions

Concept: S.S., Design: S.S., O.F.B., Data Collection or Processing: S.S., G.T., O.F.B., H.T., B.C., M.Y., E.Z., I.Y.N., Analysis or Interpretation: S.S., O.F.B., Literature Search: S.S., G.T., O.F.B., G.S., F.P., Writing: S.S.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study received no financial support.


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