COVID-19 Updates: Study Shows That COVID-19 Is Associated With Clinically Significant Weight Loss And Malnutrition, Independent Of Hospitalization

COVID-19 Updates:  A new study by Italian researchers from the School of Medicine, Vita-Salute San Raffaele University-Milan has shown that COVID-19 is associated with clinically significant weight loss and also an increased risk of malnutrition, independent of hospitalization.


 
The study findings were published in the peer reviewed medical journal: Clinical Nutrition. https://www.clinicalnutritionjournal.com/article/S0261-5614(20)30589-6/fulltext?rss=yes
 
The research study was undertaken to investigate the incidence of unintentional weight loss and malnutrition in COVID-19 survivors. A post-hoc analysis of a prospective observational cohort study was designed to include all adult (age ≥ 18 years) individuals with a confirmed diagnosis of COVID-19 who had been discharged home from either a medical ward or the Emergency Department of San Raffaele University Hospital and was re-assessed after remission at the Outpatient COVID-19 Follow-Up Clinic of the same Institution from April 7, 2020, to May 11, 2020.

The study team prospectively obtained demographic, anthropometric, clinical, and biochemical parameters upon admission.
A total of 213 patients were included in the analysis (33% females, median age 59.0 [49.5 – 67.9] years, 70% overweight/obese upon initial assessment, 73% hospitalized). Sixty-one patients (29% of the total, and 31% of hospitalized patients vs. 21% of patients managed at home, p=0.14) had lost >5% of initial body weight (median weight loss 6.5 [5.0 – 9.0] kg, or 8.1 [6.1 – 10.9]%). Patients who lost weight had greater systemic inflammation (C-reactive protein 62.9 [29.0 – 129.5] vs.48.7 [16.1 – 96.3] mg/dL; p=0.02), impaired renal function (23.7% vs. 8.7% of patients; p=0.003) and longer disease duration (32 [27 – 41] vs. 24 [21 – 30] days; p=0.047) as compared with those who did not lose weight. At multivariate logistic regression analysis, only disease duration independently predicted weight loss (OR 1.05 [1.01-1.10] p=0.022).
 
The study findings revealed that COVID-19 might negatively affect body weight and nutritional status. The results suggest that nutritional evaluation, counseling, and treatment should be implemented at initial assessment, throughout the course of the disease, and after clinical remission in COVID-19 patients.
Even patients with mild COVID-19 managed at home might also suffer from malnutrition. Alterations of smell and taste, as well as fatigue and lack of appetite, are reported as very prevalent symptoms in COVID-19 patients that could affect food intake. Confinement at home and COVID-19 symptoms may limit the amount of physical activity, leading to loss of lean mass. These factors, on top of a systemic inflammatory response, might result in malnutrition even in non-hospitalized patients.

Several mechanisms may contribute to weight loss and malnutrition in COVID-19 patients. When comparing patients with or without weight loss, the team found that those who lost weight had greater systemic inflammation (baseline CRP and, in hospitalized patients, peak CRP values), worse renal function (proportion of patients with an eGFR < 60 mL/m in/1.73m2 ), and longer disease duration. Acute systemic inflammation deeply affects several metabolic and hypothalamic pathways contributing to anorexia and decreased food intake as well as elevation of resting energy expenditure and increased muscle catabolism.
 
Of note, acute inflammatory events can trigger persistent neuroinflammatory responses in vulnerable individuals, which may perpetuate inflammation and wasting even after the acute phase. Impaired renal function is an important risk factor for malnutrition, the prevalence of protein-energy wasting increasing with declining eGFR. At multivariate analyses only disease duration and - in hospitalized patients-length of stay were significant independent predictors of weight loss, reflecting the importance of disease severity and inflammation to weight loss. In our cohort of COVID-19 patients, weight loss occurred in a relatively short time (median disease duration: 32 (27-41) days). This is consistent with previous studies showing that even short periods of bed rest induce marked reductions in muscle protein synthesis resulting in loss of skeletal muscle mass, both in middle-aged and elderly individuals.
 
Furthermore, malnutrition is strongly associated with loss of muscle mass and strength in both community-dwelling and hospitalized individuals. Although the study team did not measure body composition, it is likely that the weight loss observed in the cohort of COVID-19 patients was, at least in part, due to loss of lean body mass caused by bed rest or muscle disuse, both in hospitalized and non-hospitalized patients. This could negatively impact time to full recovery and patients’ health status. It has been reported that patients with ARDS exhibit an important weight loss at hospital discharge, approximately 18% of their baseline body weight, mainly due to lean body mass loss. Regain of body weight in the following year is mainly due to an increase in fat mass, which may bear negative implications for cardiovascular risk and functional status. These might be particularly relevant to COVID-19 patients, given the high prevalence of overweight and obesity reported here and in other studies.
 
The study findings support an association between obesity and risk of hospital admission but challenge the association between BMI and critical illness, consistent with recent data on patients hospitalized with COVID19 in New York City.
 
Previous studies demonstrated that obesity is associated with increased risk of ARDS, but lower risk of mortality. This “obesity paradox” has also been observed in patients with obesity hospitalized for pneumonia in a non-ICU setting. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0163677
https://pubmed.ncbi.nlm.nih.gov/27864622/
 
Pre-conditioning induced by the low-grade chronic inflammation associated with obesity has been postulated as a Journal Pre-proof protective mechanism against further insults to the lungs. Increased availability of nutritional reserves protecting obese subjects against hypercatabolism is another possible explanation. This hypothesis is supported by the observation that early enteral nutrition in the ICU minimizes or even abolishes the survival disadvantage for under- and normal-weight patients as compared with those in higher BMI categories and by the finding that recent weight loss has a negative impact on mortality even in non-critically ill overweight and obese inpatients. This suggests that weight loss should not be allowed in the hospital setting, even in patients with obesity. The fact that patients with overweight/obesity lost a significant amount of weight and developed or were at risk for malnutrition supports the ESPEN recommendation that individuals with obesity should be screened for malnutrition and receive nutritional counselling, as malnutrition is defined not only by low body mass but also by unhealthy body composition and skeletal muscle mass. Sarcopenic obesity, i.e. the coexistence of excess fat mass and sarcopenia, is a prevalent and often under recognized complication of obesity that may associate with worse clinical outcomes.
 
In conclusion, the study team report a very high incidence of weight loss and risk of malnutrition among COVID-19 survivors, independent of hospitalization. The association of unintentional weight loss with worse clinical outcomes has long been recognized. Implementing nutritional management strategies is crucial for hospitalized patients, particularly those in the ICU or with older age and polymorbidity. However, the findings support the notion that even individuals managing or recovering from COVID-19 symptoms at home should receive counseling on how to maintain an adequate intake of calories, protein, and fluids. Strategies such as using remote nutritional screening tools recently developed for primary practice should be implemented to improve the nutritional management of patients managed at home.
 
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