WikiDoc Resources for COVID-19-associated anorexia
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Synonyms and Keywords: COVID-19 associated loss of appetite, COVID-19 and hunger, appetite and COVID-19, loss of appetite in COVID, COVID and hunger, SARS-Cov-2 associated anorexia, SARS-Cov-2 associated loss of appetite, SARS CoV2 and hunger, Coronavirus and hunger, appetite and COVID-19.
COVID-19 is primarily known to be a respiratory disease. Anorexia associated with COVID-19 is the most common digestive symptom among patients with COVID-19. The exact mechanism of loss of appetite associated with the infection is unknown, but the symptom may be due to various causes. Several diseases share loss of appetite symptom, so it is important to suspect COVID-19 and perform RT-PCR to detect the infection or CXR to detect possible lung manifestations. Patients with loss of appetite may present with associated symptoms such as nausea or vomiting and diarrhea. The mainstay of treatment in COVID-19 infection is supportive therapy and antiviral therapy. Hand hygiene and social distancing are important primary prevention tools. Contact tracing is an important tool of secondary prevention.
- COVID-19 was first discovered in Wuhan, China. On 30th December 2019, three bronchoalveolar lavage samples were collected from a patient with pneumonia of unknown etiology – a surveillance definition established following the SARS outbreak of 2002-2003 – in Wuhan Jinyintan Hospital. Real-time PCR (RT-PCR) assays on these samples were positive for pan-Betacoronavirus.
- Nanopore sequencing and bioinformatic analyses indicated that the virus had features typical of the coronavirus family and belonged to the Betacoronavirus 2B lineage.
- COVID-19 was primarily known as a respiratory disease. In the initial reports from the World Health Organization (WHO), the mode of transmission of COVID-19 was reported to spread through droplets and fomites during close unprotected contact between an infector and an infectee. Airborne transmission was not reported initially.
- Fecal shedding was demonstrated from patients, with viable virus identified in a limited number of case reports. However, fecal-oral route did not appear to drive COVID-19 transmission.
- COVID-19 associated anorexia was first described as one of the less common symptoms of COVID-19 in a retrospective, single-center case series by Wang D et al. published on Feb 7th, 2020. The patient data was derived from January 1st-Jan 28th,2020 at Zhongnan Hospital in Wuhan, China.
- COVID-19 associated anorexia was not only described as one of the common symptoms at the illness onset, it was reported to be more common among ICU patients.
- On March 11th, 2020, WHO declared the COVID-19 outbreak a pandemic.
- With the increasing evidence and ongoing research, anorexia associated with COVID-19 is now reported to be a common symptom among patients with COVID-19, and the viral infection is suspected in a patient presenting with anorexia along with other gastrointestinal symptoms.
There is no established system for the classification of anorexia in COVID-19.
- The exact mechanism through which anorexia develops in COVID-19 is yet to be completely understood. The possible mechanism of anorexia in COVID-19, which is also a general response to infection is as follows:
- The relationship of the sense of taste and appetite along with the prevalence of gustatory system dysfunction in mild-moderate COVID-19 cases partly explains anorexia in COVID-19. In addition, olfactory dysfunction contributes to loss of appetite.
- According to another proposed mechanism of development of anorexia in infection, the microbial products set off the development of acute phase proteins such as cytokines (Interleukin and TNF alpha) during an infection. The acute phase proteins are known to cause anorexia. Cytokines that are locally released activate the peripheral sensory fibers causing loss of appetite. The direct effect of cytokines and microbial products on the CNS (the center of appetite) is also involved in the development of anorexia during infection. Studies have reported several pro-inflammatory cytokines and chemokines, particularly CXCL10, CXCL8, CCL2, TNFα and IFNγ to be higher in the plasma of COVID-19 patients. A relationship of cytokines and COVID-19 infection has been established.
- The detection of viral nucleocapsid protein in gastrointestinal epithelial cells and viral RNA in fecal specimens reflects the infectivity and chance of direct cytokine or chemokine response.
- The association between increased brain tryptophan availability in patients with chronic liver disease and anorexia partially explains the mechanism of anorexia in COVID-19-associated hepatic injury.
- COVID-19-associated hepatic injury
- Underlying conditions such as cancer
- Medications administered to treat the COVID-19 infection such as remdesivir, favipiravir and chloroquine or hydroxychloroquine (anorexia is a common side effect for the three drugs mentioned)
- COVID-19 associated pancreatitis
- Superimposed bacterial infections
- Stress associated with the COVID-19 infection itself
- For further information regarding the differential diagnosis, click here.
- To view the differential diagnosis of COVID-19, click here
Epidemiology and Demographics
- The pooled prevalence of COVID-19 associated anorexia is 21% according to a systematic review and meta-analysis based on the studies worldwide published between January 1st, 2020, and April 4th, 2020.
- The pooled prevalence of COVID-19 associated anorexia in Hong Kong is approximately 26.8%. The information is presented in a meta-analysis from the cohort of COVID-19 patients from Hong Kong (N = 59, from February 2 through February 29, 2020). 25% of the patients had GI symptoms associated with COVID-19.
- According to recent reviews and meta-analyses of COVID-19, patients from different parts of the world (China, Hong Kong) anorexia is the most common (40-84%) digestive symptoms associated with COVID-19.
- A retrospective study from Wuhna, China describing 1,141 cases of COVID-19 reported loss of appetite in 98% patients (n=180). Anorexia was the most common presenting symptom among all GI symptoms of COVID-19.
- There is insufficient data to support an age group that is affected to a greater extent from COVID-19 associated anorexia.
- There is no racial predilection for COVID-19 associated anorexia according to a systematic review and meta-analysis of observational studies on 12,797 patients. The meta-analysis compared Chinese race (Chinese group) from all other races (non-Chinese group) as the data from China makes a major part of COVID-19 related literature.
- The most potent risk factor for the development of anorexia associated with COVID-19 is the infection COVID-19 itself.
- Other risk factors involved in the process COVID-19 infected people presenting with anorexia have yet to be understood.
Natural History, Complications and Prognosis
- The majority of COVID-19 patients develop anorexia associated with COVID-19 during hospitalization. Anorexia as an initial presentation is observed among minority of patients.
- In a retrospective, single-center case series, 66.7% (n=24) of the patients treated in the ICU had anorexia versus 30.4% (n=31) who were not treated in the ICU. The data comprised of 138 hospitalized patients with confirmed COVID-19 associated pneumonia in Wuhan, China, from January 1st to January 28, 2020.
- Approximately 3% of COVID-19 cases present with mere digestive symptoms and no respiratory symptoms. The observation is based upon a descriptive cross-sectional multi-center study from China.
- Prognosis is variable and depends upon multiple factors. The odds of having a severe disease among patients with COVID-19 associated anorexia as one of the gastrointestinal symptoms are 2.83. *As a complication, prolonged anorexia with no supplementation may lead to hypotension, and electrolyte imbalances.
Diagnostic Study of Choice
- There are no established criteria to identify the cause of COVID-19 associated loss of appetite/ anorexia. COVID-19 associated anorexia/ loss of appetite is a symptom, not a disease. Anorexia may be a symptom of direct injury of an involved abdominal organ or merely one of the symptoms of COVID-19.
- COVID-19 anorexia can be diagnosed based on the history, timing of the symptoms, associated symptoms and signs such as abdominal pain, nausea or vomiting (2nd and third most common symptoms) and most importantly, a positive reverse transcriptase polymerase chain reaction (rRT-PCR) for COVID-19.
History and Symptoms
- History of contact with a person suspected or confirmed to have COVID-19 infection is important to suspect COVID-19 in a patient.
- Anorexia is itself a symptom. Based on a retrospective observational study including 1,141 cases of COVID-19 from Wuhan, China anorexia was the most common gastrointestinal symptom of COVID-19.
- The most common accompanying symptoms of COVID-19 besides anorexia were nausea, vomiting, and diarrhea.
- The timing of symptoms and presence of co-morbid conditions helps differentiate the diseases with similar symptoms.
- Patients with COVID-19 associated anorexia may appear lethargic, fatigued or irritable. Signs of dehydration include sunken eyes and dry mucosa.
Physical examination may be remarkable for:
- Vital signs:
- Heart rate/Pulse: Tachycardia may be due to fever, pain or shock. A low volume pulse is observed in severe dehydration.
- Blood pressure: Depending upon the cause of anorexia a patient with mild disease may have a normal blood pressure and others may present with shock due to infection and resulting sepsis.
- Respiratory rate: Tachypnea maybe due to high metabolic rate such as in fever and sepsis due to COVID-19 along with inefficient ventilation. Inefficient ventilation can be due to COVID-19 lung infection such as pneumonia or ARDS. Shallow breathing can be due to severe respiratory distress or associated severe abdominal pain.
- Temperature: The patient can be febrile due to COVID-19 infection, hypothermic, or have a normal temperature.
- On Abdominal exam:
- Inspection: A patient with COVID-19-associated hepatic injury causing anorexia may have jaundice. (Jaundice may be observed in DILI associated with COVID-19).
- Auscultation: Accompanying gastrointestinal infection may present as increased bowel sounds due to enteritis.
- Palpation: Based on a few case reports generalized abdominal or epigastric tenderness or right iliac fossa tenderness may accompany the symptom mimicking acute appendicitis.
- Percussion: COVID-19-associated hepatic injury presenting as ascites may show a dull percussion note or shifting dullness.
- Respiratory exam:
- The physical exam findings associated with COVID-19 can be viewed by clicking here.
- There are no specific laboratory findings associated with anorexia among COVID-19 patients.
- Laboratory findings consistent with the presence of infectious virions in the GI or respiratory tract detected via reverse transcriptase-polymerase chain reaction (rRT-PCR) indicate a possible direct viral infectivity of the respective organ.
- Serum electrolytes: Hypokalemia is associated with anorexia, diarrhea and vomiting. Retrospective studies from Italy and China demonstrated an association between hypokalemia, hypomagnesemia and COVID-19 due to degradation of ACE 2 loss, diuretic and corticosteroid use. Hypokalemia may lead to life-threatening arrhythmias. Close monitoring of serum electrolyte levels is essential especially in ICU patients.
- Complete blood count: Provides information regarding the infectious status of the patient via leukocytosis such as in COVID-19 itself. In CBC increased Hb due to hemoconcentration if dehydration accompanies.
- Serum amylase and lipase: Elevated serum levels demonstrate pancreatitis.
- CRP and procalcitonin: The value provides information on the inflammation and superimposed bacterial source of infection. A case of COVID-19 presenting as acute pancreatitis reports elevated procalcitonin.
- Liver function tests: Biochemical markers of liver injury such as bilirubin, CRP, ALT, AST and Gamma GT may be elevated in blood tests depicting liver injury. A meta-analysis found a higher risk of raised ALT and AST among patients with severe COVID-19.
- There are no ECG findings associated with COVID-19 associated anorexia.
- The electrocardiogram findings in COVID-19 can be viewed by clicking here.
- Among patients with COVID-19 associated GI symptoms with anorexia as one of the symptoms, abdominal Xrays have been reported to be normal in the few studies available.
- A Chest X-ray in a COVID-19 patient may be normal or show patchy or diffuse reticular–nodular opacification and consolidation with basal and peripheral predominance bilaterally. Bilateral perihilar and interstitial opacities with air bronchograms have also been reported. These X-ray findings depict pulmonary disease COVID-19.
- The signs are not related to anorexia directly. COVID-19 being primarily a pulmonary disease, the findings may serve as important tools to help strongly suspect COVID-19 even in the absence of RT PCR. A retrospective non-peer reviewed study reports the sensitivity of CXR to be 68% in detecting lung manifestations of COVID-19.
- The x-ray findings in COVID-19 can be viewed by clicking here.
Echocardiography or Ultrasound
- There are no echocardiography/ultrasound findings associated with COVID-19 associated anorexia.
- The echocardiographic findings in COVID-19 can be viewed by clicking here.
- Abdominal CT scan may be helpful in finding the cause of COVID-19 associated anorexia.
- Findings on CT scan suggestive of gastrointestinal symptoms (anorexia one of them) associated with COVID-19 infection include peri-intestinal inflammatory reaction.
- The CT scan findings in COVID-19 can be viewed by clicking here.
- There are no MRI findings associated with COVID-19 associated anorexia.
- The MRI findings in COVID-19 can be viewed by clicking here.
Other Imaging Findings
- Bedside lung ultrasound may be helpful in the diagnosis of COVID-19 infection.
- Other Imaging findings in bedside lung ultrasound to detect the signs of respiratory COVID-19 infection even when there are no respiratory symptoms.
- The mainstay of therapy for COVID-19 associated anorexia is treating the cause. Anorexia may be due to direct injury of an involved abdominal organ or merely one of the symptoms of COVID-19. The recommended medical therapy is based on expert opinion rather than randomized control trials.
- Antiviral therapy for COVID-19 may be administered along with supportive treatment. The antivirals that have been used for the treatment of COVID-19 include remdesivir, lopinavir/ritonavir and darunavir/cobicistat, control and prevent inflammation and symptomatic treatment.
- Treating the cause of anorexia associated with COVID-19 will treat the symptom.
- Rehydration, IV fluid therapy, are essential in dehydration due to respiratory manifestations or if severe vomiting accompanies anorexia.
- Associated vomiting may be treated with antiemetic drugs and diarrhea is treated with antidiarrheal drugs such as loperamide. Thorough literature on the use of antiemetics in COVID-19 was not found.
- Loperamide and narcoticsare not administered if the patient has C. difficile infection or signs of infection such as fever and bloody stools.
- Although the COVID-19 infection and IBDs mimic in some parameters, glucocorticoids such as prednisone treatment should not be abruptly discontinued but tapered to a possible minimum dose.
- A dose above ⩾20 mg/day for prednisone should be tapered to stop if patient becomes COVID-19 positive or prevent infection.
- The medical therapy used for COVID-19 can be viewed by clicking here.
- There are no clear guidelines on the evaluation of response to COVID-19 associated anorexia. A review article on evidence-based management guidelines for the COVID-19 reports a raised CRP and low albumin to be associated with deterioration in patients' condition. Demonstration of viral clearance in two respiratory tract specimens (at least 24 hours apart) may also serve as a monitoring tool.
- There are no available vaccines for the prevention of COVID-19. There have been rigorous efforts in order to develop a vaccine for novel coronavirus and several vaccines are in the later phases of trials.
- Effective measures for the primary prevention of COVID-19 include::
- Frequent hand-washing with soap and water for at least 20 seconds or using a alcohol based hand sanitizer with at least 60% alcohol. Alcohol means ethanol here not methanol/ wood alcohol, as FDA warns against the use of methanol containing hand-wash.
- Staying at least 6 feet (approximately 2 arms’ length) from other individuals who do not live with you.
- Covering your mouth and nose with a cloth face cover when around others and covering sneezes and coughs.
- Cleaning and disinfecting.
- Effective measures for the secondary prevention of COVID-19 include:
- Use of personal protective equipment (PPE) by the personnel handling the fecal matter or visiting the patient. Protective eyewear (such as goggles or a face shield) used by healthcare personnel should cover the front and sides of the face with no gaps between glasses and the face..
- Screening of fecal microbiota transplant donors for COVID-19 is also recommended.
- Contact tracing helps reduce the spread of the disease.
- Oncologists from Wright State University OH, USA suggest fellow oncologists reconsider the routine use of prophylactic dexamethasone as an antiemetic among [cancer patients who are not infected with [COVID-19]]. As reported in several studies, higher lymphocyte level may be associated with better outcomes in COVID-19, avoiding dexamethasone will help avoid inducing lymphopenia.
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