DOI: https://doi.org/10.21203/rs.3.rs-1565933/v1
This study investigated the effects of nutritional status at the time of admission on clinical outcomes in patients with Coronavirus disease 2019 (COVID-19).
A retrospective analysis was performed on 54 patients diagnosed with COVID-19. Clinical data of admitted patients, albumin and pre-serum albumin levels, gastrointestinal intolerance, and general information were collected and analyzed. The primary clinical outcomes were length of hospital stay and hospitalization costs.
The results showed that albumin and pre-serum albumin levels of patients at admission were negatively associated with the length of hospital stay and hospitalization costs (P < 0.001). Patients with poor appetite had longer hospital stays (P < 0.001) and higher hospital costs (P = 0.022).
These results indicated that the nutritional status at admission can directly influence the clinical outcomes of COVID-19.
The novel coronavirus disease 2019 (COVID-19) pneumonia rapidly lead to a global pandemic due to its highly contagious nature and transmission via direct contact or through the respiratory route. As of December 2, 2021, the transmission of COVID-19 has been reported in 215 countries and territories around the world, with 264 million cumulative confirmed cases and more than 5.2 million reported deaths[1]. In effect, COVID-19 has been declared a major global public health emergency.
COVID-19 is a systemic disease characterized by lung damage[2], accompanied by comprehensive organ and immune impairment. Patients commonly present with upper respiratory symptoms such as cough, hacking, shortness of breath, fatigue, and other clinical manifestations such as fever, diarrhea, poor appetite, and drowsiness. The infected person can be asymptomatic but can also have rapid disease progression. This condition may evoke dyspnea, a systemic inflammatory response, and may ultimately cause multiple organ failure and/or death[3-5]. In conclusion, COVID-19 is a serious and life-threatening condition for all human beings.
Currently, COVID-19 remains to have no specific treatment. It is mainly managed by general supportive care, symptom management, and improving immune resistance. Most patients with severe symptoms exhibit a significant decrease in appetite during their illness. In addition, COVID-19 is a consumptive disease. Reduced food intake and hypermetabolism during acute infection are prone to the development of acute malnutrition[6]. The impact of nutritional status on infection and immunity is highly complex, but some evidence suggests that acutely decreased food intake and nutritional deficiency are responsible for the decline in immune function[7, 8]. Some studies indicate that active nutrition interventions have shown positive outcomes in critically ill COVID-19 patients [9, 10]. However, objective studies on the impact of the nutritional status of patients at admission on clinical outcomes have not been sufficiently evaluated.
Our medical team was the first to provide medical care for severe and critical COVID-19 patients in the intensive care unit (ICU) in February 2020. In this study, early in-hospital data were used to explore the correlation between patients' nutritional status and clinical outcomes, and consequently provide an appropriate basis for formulating nutritional intervention plans[11].
Participants
A total of 54 patients (25 men and 29 women) who met the inclusion criteria were hospitalized and evaluated in the E2-1 ward of the Optics Valley ward of Tongji Hospital of Huazhong University of Science and Technology. Data collected were then handed over to the Third Affiliated Hospital of Sun Yat-sen University. The study protocol was approved by the Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University (The Third Affiliated Hospital of Sun Yat-sen University [2020]02-248-01), and was performed in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki) for experiments involving humans.The study was registered on Chinese Clinical Trial Registry (http://www.chictr.org.cn/, No.ChiCTR2100043788) .
Inclusion criteria: Inpatients diagnosed with COVID-19 and ages ranging from 18 to 90 years old.
Exclusion criteria: Primary data were missing; only demographic data were available.
Design and assessment
This study was a retrospective analysis of clinical data during inpatient hospitalizations. The data collected from medical records and nursing records included the following: 1. Demographic information including sex, age, date of onset, duration of disease, main diagnosis, outcome, days of hospitalization, and hospitalization costs.2. Observation indicators collected within 3 days after admission: serum albumin level, serum pre-albumin level, and gastrointestinal intolerance (including nausea, vomiting, poor appetite, abdominal distension, constipation, diarrhea).
Statistical analysis
SPSS 24 was used for statistical analysis, and measurement data were expressed as mean ± standard deviation (SD). The Pearson correlation coefficient was used to compare albumin and pre-serum albumin levels with length of hospital stay and total hospitalization costs. For the clinical outcome measure (the presence or absence of poor appetite), the two-sample independent t-test was used. Statistical significance was set at P < 0.05.
The 54 patients included in this study had varying levels of severity, with 10 moderate cases, 41 severe cases, and 3 critical cases. Eight patients showed clinical improvement and 46 recovered; no fatalities were reported. The duration of hospitalization was 26.59 ± 10.64 days (range, 5–44 days). Hospitalization charges were USD 9735 ± 13444 (range, USD 1006–90164).
The mean serum albumin (g/L) level was 37.6 ± 5.0 (range, 26.9–46.1 g/L). In addition, 30% of cases had values below Normal lower limit (35 g/L). The mean serum pre-albumin value was 220.9 ± 69.2 mg/L, ranging from 86–370 mg/L, with 35% below the lower limit of normal (200 mg/L). In 22 of 54 patients (40.7%), a lack of appetite was observed. None of the patients experienced symptoms of abdominal distension, abdominal pain, nausea, vomiting, or reflux during hospitalization. Only 1 patient had diarrhea during mid-period hospitalization.
As shown in Fig. 1, serum albumin levels showed an inverse relationship with hospital stay (r=-0.684, P < 0.001) and hospitalization costs (r=-0.761, P < 0.001). Similarly, serum prealbumin levels were negatively correlated with hospital days (r=-0.487, P < 0.001) and hospitalization costs (r=-486, P < 0.001).
The hospitalization duration was longer (30.7 ± 8.6 vs. 20.5 ± 12.0 days, P < 0.001, Fig. 2A) and hospital costs was higher (USD 13382 ± 18182 vs. USD 5457 ± 457, t = 2.368, p = 0.022, Fig. 2B) in the group of poor appetite.
This study aimed to assess the effects of nutritional status at admission on the clinical outcomes of 54 COVID-19 patients. The results showed that serum levels of albumin and pre-albumin and poor appetite of patients at admission were negatively correlated with length of hospital stay and hospitalization costs.
Nutritional status, which strongly correlated with clinical outcomes such as length of hospital stay, is affected by numerous conditions such as age, nutritional support, and food intake of patients[12]. Albumin synthesized by the liver is the most abundant protein in human plasma. As early as 1979, Seltzer et al.[13] listed it as a nutritional parameter. Similar to albumin, pre-albumin has been shown to be a good blood marker for malnutrition[14]. Serum proteins, such as albumin and pre-albumin, are now used by a wider community of clinicians and researchers to accurately determine a patient's nutritional status. Although there is an argument that besides nutritional status, serum proteins are also influenced by many external factors[15], studies have demonstrated that albumin and pre-albumin are indeed effective indicators of malnutrition, even in the presence of chronic inflammation[16]. Poor nutritional status is associated with delayed discharge from hospital in COVID-19 patients, which helps to predict the likelihood of longer hospital stays[17]. Therefore, specific attention is needed for lower albumin and pre-albumin levels, which may be associated with adverse outcomes such as in-hospital deaths[15, 18, 19], to help early identification of high-risk populations.
Malnutrition is prevalent among COVID-19 pneumonia patients. Moreover, poor pre-admission nutrition status would further exacerbate malnutrition after onset, leading to longer hospitalization stays and higher hospital costs. In this study, 35% of the patients had lower serum albumin and pre-albumin levels than normal, and 40.7% showed loss of appetite. With the organism in a hypercatabolic state, patients were more likely to expend additional energy, and nutritional supplementation was urgently needed. On the other hand, accompanied by varying degrees of dyspnea, insomnia, and other conditions, COVID-19 contributes to a loss of appetite, which results in a decrease of food intake[20, 21], and in effect, further aggravating nutritional deficiency. Moreover, as another risk factor leading to malnutrition, the use of antibiotics and other drugs for secondary pneumonia also affects patients’ digestive function. The prevalence of undernutrition among COVID-19 inpatients was found to be as high as 42.1%[6]. In addition, other studies that specifically targeted the elderly group (65 years and older) found a higher prevalence of malnutrition (up to 52.7%)[22, 23].
The nutritional status of COVID-19 patients on early admission was investigated in this study, and we found that it affected the clinical outcomes. In relation to this, systematic nutritional support in combination with medication during late treatment could attenuate metabolic stress, prevent oxidative damage to cells, and regulate the immune response to the body, to actively improve the prognosis of COVID-19 patients. Therefore, it is of great importance to enhance immune function, shorten the course of the disease, reduce complications, and mortality. The correction of the potentially adverse effects of malnutrition, however, may result in greater costs.
Nutritional deficiency is prevalent among all ages, as revealed by previous studies[24, 25]. Indeed, patients who were malnourished during the early stages of hospitalization already presented with malnutrition or risk. In particular, individuals in the East consciously control their diet in pursuit of a slim figure. Inadequate dietary composition and lower calorie diets result in nutrient deficiencies. During the coronavirus pandemic, targeting specific supplementation according to a relevant nutritional strategy is a safe, low-cost, and effective way to enhance immunity, which has implications for the control and recovery of infection. Therefore, the implementation of nutritional strategies not only has an impact on individuals, but it can also contribute to anti-epidemics in a global scale.
This study has some limitations. First, our small sample size included patients from the same ward, possibly presenting a risk of selection bias. Second, the absence of some nutritional data (hemoglobin, transferrin, arm circumference, grip strength, etc.) might have influenced the validity of the results. In addition, potential confounders such as age of onset, sex, and underlying chronic diseases were not assessed.
In conclusion, the nutritional status of COVID-19 patients on admission was correlated with the length and cost of hospital stay, suggesting that active daily nutritional support strategies could help fight against COVID-19 during the pandemic.
Acknowledgement
The study was supported by the National Natural Science Foundation of China (grants no. 81401872) .
Data availability statement:The data that support the findings of this study are available from the corresponding author upon reasonable request.
Funding statement: This work was supported by the Guangzhou Key Field Research and Development Plan (202007030001) and National Natural Science Foundation of China (grants no. 81401872) .
Conflict of interest disclosure: The authors confirm that this article contains no conflict of interest.
Ethics approval statement: The study protocol was approved by the Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University ([2020]02-248-01) and registered on Chinese Clinical Trial Registry (http://www.chictr.org.cn/, No.ChiCTR2100043788)
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