key: cord-0863732-8jkbvar8 authors: Formisano, Elena; Di Maio, Pasquale; Ivaldi, Cecilia; Sferrazzo, Elsa; Arieta, Lorenzina; Bongiovanni, Silvia; Panizzi, Loredana; Valentino, Elena; Pasta, Andrea; Giudice, Marco; Demontis, Stefania title: Nutritional therapy for COVID-19 patients: practical protocol from a single highly affected center by the outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection date: 2020-11-06 journal: Nutrition DOI: 10.1016/j.nut.2020.111048 sha: 89ec49cf5eaf559a499740ef8195df6bc9dd3f20 doc_id: 863732 cord_uid: 8jkbvar8 INTRODUCTION: : Coronavirus disease 2019 (COVID-19) carries a high risk of malnutrition, due to the state of debilitation that results from acute respiratory failure symptoms. The presented protocol aims to provide an approach to reduce the risk of malnutrition and improve the clinical outcomes. METHODS: : Short age-adjusted Nutritional Risk Screening was performed for all 94 non-ICU patients admitted to the Giovanni Borea Civil Hospital in Sanremo. The 49 ICU patients were considered at risk of malnutrition without screening and were fed with EN plus supplemental PN. In non-ICU setting, patients underwent a personalized nutritional protocol, considering their conditions, which consisted of a high-protein and high-calories pureed diet, Oral Nutritional Supplements and/or Artificial Nutrition or other personalized nutritional path. RESULTS: : The nutritional treatment was well tolerated by patients. The 19.1% of non-ICU patients died, they were mainly women, with higher BMI and older in age. On the other hand, the 53.1% of ICU patients died. The non-ICU patients scoring positive on at least one nutritional risk screening item (excluding age) were 72 out of 94. Patients > 70 years old were 68 out of 94. Non-ICU patients who did not meet their energy and protein needs were older (P=0.01) and died more frequently (P <0.001). CONCLUSIONS: : This protocol should not be considered as a guideline, but it is intended to report the clinical experience of a nutrition team in an Italian reference center for the treatment of COVID-19 patients. Nutritional strategies should be implemented to prevent worsening of clinical outcomes. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for coronavirus disease 2019 (COVID- 19) , has been identified for the first time in humans at the end of 2019 in Wuhan, China [1] . Since then, it has gradually spread worldwide, to the point that in March 2020, the World Health Organization (WHO) declared COVID-19 as a global pandemic [2, 3] . COVID-19 patients can develop an interstitial pneumonia with acute respiratory failure symptoms [4] and, in severe cases, sub-intensive or intensive care are requested [5] . Hospitalized patients with COVID-19 are characterized by a hyperinflammatory condition [6] and severe oxidative stress [7] , which is often associated with a polymorbidity status, elderly age [8] and hypoalbuminemia [9] , independently of body mass index (BMI) [10, 11] .This carries a high risk of malnutrition with poor clinical outcomes [12, 13] . In addition, weight loss, low total protein and vitamin D levels [14] are frequently reported, as well as loss of taste and smell, nausea and diarrhea that further worsen nutritional status [15] . The close connection between nutritional status and evolution of COVID-19 is easily appreciated, considering only that pre-albumin is an important marker of malnutrition [16] , and at the same time it seems to be a good predictor of the progression of acute respiratory distress syndrome (ARDS) [17] . The role of nutrition on immune function is well established, in fact, an inadequate intake of Vitamins A, C, D, E, B2, B6, B12, folic acid and the trace elements such as iron, zinc, copper and selenium compromises the immune system and predisposes to infections [18, 19] . Therefore, managing the nutritional status of hospitalized COVID-19 patients is a pivotal point in reducing complications and improving clinical outcomes [20] . The role of nutrition is further enhanced in patients admitted to intensive care unit (ICU) for the severity of respiratory failure. In this population, nutritional intake is often compromised due to the high incidence of swallowing problems after extubation [21] or due to the presence of a temporary tracheostomy leading to dysphagia in 11%-93% of cases [22] . The ESPEN experts' statements for the nutritional management of SARS-CoV-2 positive patients suggest evaluating the nutritional status of all patients (as soon as they are hospitalized) through the Nutrition Risk Screening 2002 (NRS 2002), especially in those at high-risk (such as the elderly patients suffering from chronic or acute disease), to identify their risk of malnutrition early [20] and draw up a personalized diet. This practical protocol aims to provide a management approach to reduce the risk of malnutrition and improve the clinical outcomes of these patients. A short age-adjusted Nutrition Risk Screening was performed ( Figure 1 ) for all new non-ICU patients admitted to the Giovanni Borea Civil Hospital in Sanremo by adapting the NRS-2002 pre-screening tool [23] adding the age question in place of the acute illness question. We used this modified Nutrition Risk Screening to have an immediate management, given the hospital emergency due to COVID-19. Weight and height were estimated or reported by the patients. Non-ICU patients who scored positive in at least one point of the short age-adjusted Nutrition Risk Screening were considered at risk of malnutrition and a nutrition expert physician administered nutritional counseling. ICU patients were considered at risk of malnutrition regardless, without performing the short age-adjusted Nutritional Risk Screening. ICU and non-ICU patients were also valued according to Global Leadership Initiative on Malnutrition (GLIM) malnutrition tool. The latter contemplates the presence of at least one phenotypic criteria, that is low BMI and/or non-volitional weight loss (note that we have considered weight loss in the last week and not in the last 6 months because we observed rapid deterioration in the patients' condition) and one etiological criteria, represented by the inflammatory condition. Energy needs were estimated using the Harris-Benedict equation multiplied by a correction factor of 1.2 or 1.3 for the presence of the acute illness. In addition, the following nutrition-related laboratory parameters were collected: complete blood count, blood glucose, creatinine, C-reactive Protein (PCR), albumin, prealbumin, total proteins, aspartate aminotransferase(AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), total bilirubin, direct bilirubin, Magnesium, Potassium, Chloride, Calcium, Phosphorus, Sodium, 25-OH Vitamin D, Interleukin-6 and fibrinogen. All COVID-19 non-critically ill patients with nasal cannula and simple oxygen face masks (Reservoir Systems or Venturi Oxygen Mask), were subjected to an assessment of the nutritional status and nutritional needs and were subsequently treated with a personalized nutritional protocol, which consisted of a fractionated pureed diet (Basic Diet) (1477 Kcal -percentage of proteins: 19% of total Kcal; percentage of lipids: 45% of total Kcal; percentage of carbohydrates: 36% of total Kcal) with modified-texture food, enriched with commercially available products designed for dysphagia. We decided to use these commercial products due to their peculiar characteristics to improve adherence to the diet. These products take the form of natural pureed single-portion meals, which are ready-to-use, pasteurized and which supply high-protein and high-calories (average calories content: 387 Kcal; average proteins content: 26.6 g). Furthermore, they are isolated from the external environment in order to ensure bacteriological safety without affecting the organoleptic qualities. We also used high-protein soluble powdered supplement for breakfast. The detailed composition of the Basic Diet, pureed meals and high-protein food in soluble powder are described in the Supplementary Material. When patients needed more energy than the Basic Diet alone, they were administered with increased portions of meals and/or high-calorie and high-protein pureed tasteless Oral Nutritional Supplement (ONS) (125 g; 200 Kcal; 12.5 g of proteins) in order to achieve the nutritional targets. The management of the critically ill patients was carried out considering the specific device used for their respiratory support:  Patients in sub-intensive care unit with the "Sub Mask" (a specially modified snorkeling mask to be connected to a ventilator), with an oxygen saturation level that can allow the detachment from the "Sub  Patients after extubation or in weaning from tracheostomy were fed Enteral Nutrition (EN) through nasogastric tube (NGT) and supplemental PN. When they were able to eat, they progressed with a gradual reduction in Artificial Nutrition and the introduction of Basic Diet.  In ICU setting, intubated and tracheostomized patients in mechanical ventilation, both EN, via NGT and PN were administered. EN blends were low in carbohydrates (composition from 29% to 39% of carbohydrates, from 18% to37% of proteins, from 500 Kcal to 750 Kcal, in 500 ml). We evaluated glycemia, arterial blood gas (ABG), lactates every 6 hours, while pre-albumin, PCR, creatine phosphokinase, lactate dehydrogenase, liver and kidney function, electrolytes, procalcitonin every 48-72 hours in all critically ill patients taking EN. Categorical variables were examined with the Fisher's exact test. The nutrition department of Giovanni Borea Civil hospital managed the diet of 143 patients: The classification of non-ICU patients according to the short age-adjusted Nutrition Risk Screening is shown in Table 3 . The percentage of patients scoring positive to at least one of malnutrition screening tool item (excluded age) were 72 out of 94. Patients > 70 years old were 68 out of 94. ICU and non-ICU patients were further classified according to GLIM malnutrition tool (Table 3) . Patients presented at least one phenotypic criterion (between non-volitional weight loss, low BMI, low muscle mass) and one etiological criterion (between reduced food intake, state of inflammation, comorbidity status). Table 4 reported that the non-ICU patients who reached their energy and protein needs with the personalized nutritional management were 56 out of 94 patients. They reached their nutritional needs in a median of 14 days (IQR: 7-27). They were younger than the outstanding subjects who did not reach the protein and energy targets (median, IQR: 75, 64-82 vs 80, 74-87 years, respectively, P = 0.01). Non-ICU patients meeting nutritional targets were more frequently discharged than those not meeting their nutritional targets. In fact, 52 out of 56 patients who met their nutritional targets were discharged from hospital. Instead, 14 out of 38 patients (36.8%) who did not reach their nutritional targets died, conversely only 4 out of 56 patients (7.1%) at target deceased (P < 0.001). The present manuscript aims to provide practical indications for the nutritional management of COVID-19 patients. It is based on the experience of a single hospital, reference center for the SARS-CoV-2 outbreak, in a province, Imperia (Liguria, Italy), with a prevalence of infected of 39.21% on 215800 inhabitants. [24] Nutritional therapy is essential to avoid deterioration of health conditions and worsening of prognosis, even for non-critically ill patients [25] . To date, there is still no guideline for the nutritional management of patients with COVID-19, although the use of the Nutritional Risk Screening reported in our protocol is consistent with ESPEN Expert Recommendation [20] . The Nutritional Risk Screening was integrated with an age question because COVID-19 patients are often elderly and with poor nutritional status [26] . The rationale of our short age-adjusted Nutrition Risk Screening was the early identification of those patients who may benefit from personalized nutritional intervention. Non-ICU patients older than 70 years were 68 out of 94. Using the age adjustment tool, an additional 22 patients were considered at risk of malnutrition because elderly and therefore received nutritional support (Table 3) . Moreover, according to the GLIM criteria for the diagnosis of malnutrition, all COVID-19 patients presented at least one phenotypical and one etiological criteria, and this provides further evidence to validate the importance of nutritional intervention [27] . In the non-ICU group, the dead patients were mainly women; to date the mortality from COVID-19 seems to be higher in the male gender even though sex-related death mechanism are not yet well known [28] . Furthermore, it would be useful to carry out a multivariate analysis to consider the influence of other variables other than sex that, due to the state of emergency, we were unable to collect. Non-ICU death patients also had a higher BMI than discharged patients; in literature it emerges that overweight patients have a higher risk of mortality than normal weight patients [29] [30] [31] and this is in line with our findings. A crucial evidence of our preliminary results was the importance of reaching nutritional targets in non-ICU patients. In fact, patients who did not reach their energy and protein needs died more frequently than outstanding patients who reached their targets. This result is consistent with the literature as shown in recently published reviews that highlighted the pivotal role of nutritional status in influencing the clinical outcomes of patients infected by SARS-CoV-2 [32, 33] . Moreover, as reported in the ESPEN guidelines on clinical nutrition and hydration in geriatrics [12] , even advanced age can influence the achievement of nutritional needs, in fact, in our sample the patients who did not reach their nutritional needs were older than the outstanding subjects. Non-critically ill patients were fed with a fractional pureed diet with high protein and energy content to reduce the duration and the volume of the meal. This Basic Diet with a soft consistency was also chosen with the aim of reducing energy expenditure during meals, in patients already made fatigued and weakened from the respiratory effort associated with ARDS [34] . Critically ill patients treated with NIV were mostly fed by PN to limit gastrointestinal symptoms associated with EN, and to avoid NGT positioning, which can compromise NIV and increase the risk of aspiration [35] . However, liquid ONS (or Basic Diet for patients treated with "Sub Mask") were also administered in order to increase nutrient intake in order to meet energy needs when these could not be satisfied with PN alone, and to preserve intestinal mucosal trophism [36] . We opted for the use of tasteless ONS, as many positive SARS-CoV-2 patients reported dysgeusia and/or anosmia at the time of admission. Subsequently, several studies confirmed this observation; and a recent meta-analysis has estimated that in COVID-19 patients there is a prevalence of dysgeusia of 43.93% (95% CI, 20.46% -68.95%) and olfactory dysfunction of 52.73% (CI 95 %, 29.64% -75.23%) [37] . The extubation and/or weaning phase of the tracheostomy represented an important challenge of nutritional management, due to the almost constant presence in patients of a certain degree of dysphagia. In intubated patients, endotracheal tubes for mechanical ventilation can cause mucosal ulcerations and/or inflammation of the pharyngeal and laryngeal district; moreover, if the endotracheal intubation lasts more than 48 hours, and therefore can be defined as prolonged oral endotracheal intubation, it tends to influence neuromuscular weakness of oropharyngeal structures. All this means that after extubation, patients often have problems with swallowing, from odynophagia to aspiration [20] . In patients with tracheotomy, according to some authors, dysphagia could be explained by a reduction in sensory intake and subglottic air pressure, by the disuse of the laryngeal structure and its consequent slight atrophy; others, however, assert that swallowing impairment is partly due to the limitations that the tracheal tube gives to movement of the hyoid bone and laryngeal excursion [38] . These clinical categories of patients were therefore initially supported with EN via NGT and supplemental PN, then gradually the PN was suspended and the EN was integrated with the resumption of the Basic Diet orally. Finally, in both critically and non-critically ill patients, carbohydrate intake was reduced, as the high carbohydrate content in the diet has been associated with worsening of ARDS due to the increase in CO2 production and the consequent hypercapnia [25] . In addition, ESPEN guidelines on clinical nutrition in ICU suggest using low-carbohydrates formulas to avoid insulin resistance and hyperglycemia that are frequent in critically ill patients. [36] The main limitation of our protocol is that it was not possible to validate it, due to the lack of measurements during hospitalization and at discharge. In fact, in our center, as in many others in Italy, the hospital directives advocated to avoid excessive contact with COVID-19 patients, due to the high risk of contagion of the health personnel. Moreover, it was not possible to collect data from all patients admitted to the ICU due to their critical conditions. Furthermore, as the COVID-19 health emergency is still ongoing in our hospital, we only have partial preliminary data on the patient's adherence to the protocol and its effectiveness. Another important limit of the present study is the lack of the sample size calculation due to the evolving trend of the COVID-19 pandemic that characterized the period of patients' hospitalization; therefore, the essential data for the calculation of the sample size, such as a real and certain data of the infected population and loco-regional outcome data (i.e. mortality), were not available. This protocol should not be considered as guidelines but is intended to report the clinical experience of an Italian hospital heavily affected by the pandemic emergency of COVID-19. The early implementation of appropriate nutritional strategies in these patients could improve the evolution and clinical outcome of the disease. 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