COVID-19-associated anorexia
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Javaria Anwer M.D.[2]
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.
Overview
COVID-19 is primarily known to be a respiratory disease. Anorexia associated with COVID-19 is the most common of the digestive systems in patients with SARS-CoV-2. 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 and it is important to suspect COVID-19 to catch COVI-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. Hygiene practice and social distancing are important primary and contact tracing is an important tool of secondary prevention.
Historical Perspective
- On 30th December 2019, three bronchoalveolar lavage samples 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.[1]
- Initially in reports till Feb 20, 2020, the patients are known to have NCOV were reported to age between 30–69 years.
- In the initial reports from WHO, COVID-19 was shown to be transmitted via droplets and fomites during close unprotected contact between an infector and infectee. Airborne was not reported for COVID-19. Fecal shedding was reported to be demonstrated from some patients, with viable virus identified in a limited number of case reports. However, the fecal-oral route did not appear to be a driver of COVID-19 transmission.[1]
- On March 12, 2020, WHO declared the COVID-19 outbreak a pandemic.
- Initially COVID-19 was primarily known as a respiratory disease. In the initial phase of the pandemic, the screening criteria for COVID‐19 did not include symptoms of abdominal pain.
- On Feb 3rd, 2020, a study published by Wang D et al. first described abdominal pain as one of the less common symptoms of COVID-19.[2]
- With the increasing evidence and ongoing research, anorexia associated with COVID-19 is now reported to be a common symptom in patients with COVID-19, and the viral infection is suspected in a patient presenting with anorexia along with other gastrointestinal symptoms. Research is underway to develop a better understanding of the etiology, risk factors, and treatment of anorexia associated with COVID-19.
- Anorexia was described as one of the common symptoms at the onset of illness and it was also reported to be more common in ICU patients.[2]
Pathophysiology
- The exact mechanisms through which COVID-19 causes anorexia is yet to be completely unveiled. The described possible mechanism of anorexia, a general response to infection is as follows:
- Gustatory system dysfunction partly explains anorexia in COVID-19 due to its high incidence mild-moderate COVID-19 patients. Olfactory dysfunction in addition contributes to loss of appetite.[3]
- The microbial products during infection set off the development of acute phase proteins such as cytokines (Interleukin and TNF alpha) which are known to cause anorexia. Cytokines 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 involved in the anorexia during infection.[4][5] Studies have reported several pro-inflammatory cytokines and chemokines, particularly CXCL10, CXCL8, CCL2, TNFα and IFNγ to be higher in the plasma of SARS-CoV-2 patients.[6] A relationship of cytokines and COVID-19 infection has been established.[7]
- 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.[8]
- COVID-19-associated hepatic injury can lead to anorexia.[9]
Causes
Anorexia in a patient hospitalized due to COVID-19 may be due to:
- COVID-19-associated hepatic injury
- Underlying conditions such as cancer
- Medication used to treat the COVID-19 infection such as Remdesivir[10]
- COVID-19 associated ppancreatitis[11]
- Superimposed bacterial infections
- Anxiety associated with the infection itself
Differentiating anorexia associated with COVID-19 from other Diseases
- Anorexia associated with COVID-19 must be differentiated from other diseases that cause anorexia such as:[12][13]
- Hepatitis: Acute hepatitis especially autoimmune hepatitis shared common symptoms such as fatigue, abdominal pain, nausea, vomiting, diarrhea, skin rash. Some hepatic infections may involve pleuritis and pleural effusion thus chest pain.
- Crohn's disease: The disease may have remissions and relapses and present with symptoms shared by COVID-19 infection as well specially during a relapse. Other symptoms of Crohn's disease include abdominal pain, diarrhea that may or may not be bloody, fever and rash. A history of Crohn's disease can help the clinician decide on the differential diagnosis but it is equally important to access for possible COVID-19 infection. Patient should be counselled about the similarities in two diseases.
- Ulcerative colitis: A relapse can have symptoms similar to COVID-19 such as: abdominal pain,diarrhea, rash. A history of ulcerative colitis is important it is equally important to access for possible COVID-19 infection. Patient should be counselled about the similarities in two diseases.
- Chronic underlying disease-associated anorexia: Cancer patients have anorexia and are an increased risk of COVID-19 infection itself. High suspicion is required and the patient should be tested for COVID-19 infection if required.
Epidemiology and Demographics
- According to Pan et al, 48.5% of patients presented with digestive symptoms as their chief complaint. With COVID-19 primarily being a respiratory disease, surprisingly around 3% of cases had just the digestive symptoms but no respiratory symptoms.[14]
- According to some studies anorexia is the most common (40-84%) of digestive symptoms associated with SARS-Cov2 infection.[15] Other studies describe the incidence of anorexia associated with COVID-19 ranging from 1.0% to 79%.[16]
Race
- China being the source of most of the demographic data on clinical features of COVID-19 and fewer studies on the demographics in other races, enabled the scientists to compare the incidence of anorexia in Chinese population and rest of the world. Data showed that loss of appetite was similar in both subgroups non-Chinese and Chinese. There is limited data to comment on the racial predilection of the symptom in other races.
Risk Factors
- So far, the risk factor for the development of anorexia associated with COVID-19 is the infection COVID-19 itself. Other risk factors involved in the process have yet to be unveiled.
Natural History, Complications and Prognosis
- The appearance of anorexia has no fixed pattern of appearance in the COVID-19 clinical course but the symptom is usually associated with nausea and vomiting.
- Most SARS-CoV-2 patients develop anorexia associated with COVID-19 during hospitalization. Anorexia as an initial presentation is observed in a minority of patients.[17]
- Prognosis: In a meta-analysis by Mao R. et al. the odds ratio for severe disease in patients with anorexia as one of the gastrointestinal symptoms were 2.83.[18]
- Prolonged anorexia with no supplementation may lead to hypotension, and electrolyte imbalances.
Diagnosis
Diagnostic Study of Choice
- There are no established criteria for the diagnosis of loss of appetite in COVID-19.
- COVID-19 anorexia can be diagnosed based on the history, timing of the symptom, 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 SARS-CoV-2.
History and Symptoms
- Important associated gastrointestinal symptoms with anorexia are nausea or vomiting, diarrhea.[18] The timing of symptoms and presence of comorbid conditions helps differentiate the diseases with similar symptoms. History of contact with person suspected or confirmed to have COVID-19 infection is important.
Physical Examination
- Patients with COVID-19 associated anorexia may appear lethargic, fatigued or irritable.
- Signs of dehydration such as sunken eyes and dry mucosa; low volume pulse and hypotension can be observed in severe cases.
- A COVID-19 positive patient may have pulmonary manifestations depicting pneumonia or ARDS.
- Based of a few case reports generalised abdominal or epigastric tenderness or right iliac fossa tenderness may accompany the symptom mimicking acute appendicitis.[19][11]
Laboratory Findings
- Infectious virions in the GI or respiratory tract can be detected via reverse transcriptase polymerase chain reaction (rRT-PCR).
- Electrolyte disturbances such as hypokalemia especially if diarrhea or vomiting accompanies. Hypovolemic Hyponatremia may occur in severe cases.
- In CBC incraesed Hb due to hemoconcentration if dehydration accompanies.
- Value of CRP and procalcitonin provide information on the inflammation and superimposed bacterial source of infection.[20]
X-ray
- A Chest X-ray may be normal or show consolidation, bilateral perihilar and interstitial opacities opacities with air bronchograms.
- Abdominal Xray has been reported to be normal in a few studies available.[11][19]
Ultrasound
Ultrasound of the abdomen may or may not show any abnormal findings. A case of bowel inflammatory signs (peri-intestinal inflammatory reaction) has been reported in a patient with abdominal pain associated with COVID-19.[20]
CT scan
CT scan abdomen maybe normal or confirm the peri-intestinal inflammatory reaction.[20]
Other Imaging Findings
A study by Poggiali et al. strongly recommends bedside lung ultrasound to detect the signs of respiratory COVID-19 infection even when there are no respiratory symptoms.[20]
Treatment
Medical Therapy
- The mainstay of treatment in COVID-19 infection is antiviral therapy such as lopinavir and ritonavir tablets and supportive therapy.
- Rehydration, IV fluid therapy, are essential if vomiting accompanies anorexia.
- Associated vomiting is treated with antiemetic drugs and diarrhea is treated with antidiarrheal drugs such as loperamide. Loperamide is not given if the patient has C. difficile infection or signs of infection such as fever, 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 becomesCOVID-19 positive or prevent infection.[21][22]
Primary Prevention
- There have been rigorous efforts in order to develop a vaccine for novel coronavirus and several vaccines are in the later phases of trials.[23]
- Effective measures for the primary prevention of COVID-19 include::[24]
- Frequent handwashing with soap and water for at least 20 seconds or using a alcohol based hand sanitizer with at least 60% alcohol
- Staying at least 6 feet (about 2 arms’ length) from other people 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
Secondary prevention
- Contact tracing helps reduce the spread of the disease.[25]
- Effective measures for the secondary prevention of COVID-19 include:
- Use of personal protective equipment (PPE) by the personnel handling the fecal matter.
- Screening of fecal microbiota transplant donors for COVID-19 is also recommended.[26]
References
- ↑ 1.0 1.1 "www.who.int" (PDF).
- ↑ 2.0 2.1 Wang, Dawei; Hu, Bo; Hu, Chang; Zhu, Fangfang; Liu, Xing; Zhang, Jing; Wang, Binbin; Xiang, Hui; Cheng, Zhenshun; Xiong, Yong; Zhao, Yan; Li, Yirong; Wang, Xinghuan; Peng, Zhiyong (2020). "Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China". JAMA. 323 (11): 1061. doi:10.1001/jama.2020.1585. ISSN 0098-7484.
- ↑ Lechien JR, Chiesa-Estomba CM, De Siati DR, Horoi M, Le Bon SD, Rodriguez A, Dequanter D, Blecic S, El Afia F, Distinguin L, Chekkoury-Idrissi Y, Hans S, Delgado IL, Calvo-Henriquez C, Lavigne P, Falanga C, Barillari MR, Cammaroto G, Khalife M, Leich P, Souchay C, Rossi C, Journe F, Hsieh J, Edjlali M, Carlier R, Ris L, Lovato A, De Filippis C, Coppee F, Fakhry N, Ayad T, Saussez S (April 2020). "Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study". Eur Arch Otorhinolaryngol. doi:10.1007/s00405-020-05965-1. PMC 7134551 Check
|pmc=value (help). PMID 32253535 Check|pmid=value (help). - ↑ Kanra GY, Ozen H, Kara A (2006). "Infection and anorexia". Turk. J. Pediatr. 48 (4): 279–87. PMID 17290560.
- ↑ Langhans W, Hrupka B (October 1999). "Interleukins and tumor necrosis factor as inhibitors of food intake". Neuropeptides. 33 (5): 415–24. doi:10.1054/npep.1999.0048. PMID 10657519.
- ↑ Chu H, Chan JF, Wang Y, Yuen TT, Chai Y, Hou Y, Shuai H, Yang D, Hu B, Huang X, Zhang X, Cai JP, Zhou J, Yuan S, Kok KH, To KK, Chan IH, Zhang AJ, Sit KY, Au WK, Yuen KY (April 2020). "Comparative replication and immune activation profiles of SARS-CoV-2 and SARS-CoV in human lungs: an ex vivo study with implications for the pathogenesis of COVID-19". Clin. Infect. Dis. doi:10.1093/cid/ciaa410. PMC 7184390 Check
|pmc=value (help). PMID 32270184 Check|pmid=value (help). - ↑ Coperchini F, Chiovato L, Croce L, Magri F, Rotondi M (June 2020). "The cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system". Cytokine Growth Factor Rev. 53: 25–32. doi:10.1016/j.cytogfr.2020.05.003. PMC 7211650 Check
|pmc=value (help). PMID 32446778 Check|pmid=value (help). - ↑ Zou, Xin; Chen, Ke; Zou, Jiawei; Han, Peiyi; Hao, Jie; Han, Zeguang (2020). "Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection". Frontiers of Medicine. 14 (2): 185–192. doi:10.1007/s11684-020-0754-0. ISSN 2095-0217.
- ↑ Laviano A, Cangiano C, Preziosa I, Riggio O, Conversano L, Cascino A, Ariemma S, Rossi Fanelli F (March 1997). "Plasma tryptophan levels and anorexia in liver cirrhosis". Int J Eat Disord. 21 (2): 181–6. doi:10.1002/(sici)1098-108x(199703)21:2<181::aid-eat9>3.0.co;2-h. PMID 9062842.
- ↑ Wang, Yeming; Zhang, Dingyu; Du, Guanhua; Du, Ronghui; Zhao, Jianping; Jin, Yang; Fu, Shouzhi; Gao, Ling; Cheng, Zhenshun; Lu, Qiaofa; Hu, Yi; Luo, Guangwei; Wang, Ke; Lu, Yang; Li, Huadong; Wang, Shuzhen; Ruan, Shunan; Yang, Chengqing; Mei, Chunlin; Wang, Yi; Ding, Dan; Wu, Feng; Tang, Xin; Ye, Xianzhi; Ye, Yingchun; Liu, Bing; Yang, Jie; Yin, Wen; Wang, Aili; Fan, Guohui; Zhou, Fei; Liu, Zhibo; Gu, Xiaoying; Xu, Jiuyang; Shang, Lianhan; Zhang, Yi; Cao, Lianjun; Guo, Tingting; Wan, Yan; Qin, Hong; Jiang, Yushen; Jaki, Thomas; Hayden, Frederick G; Horby, Peter W; Cao, Bin; Wang, Chen (2020). "Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial". The Lancet. 395 (10236): 1569–1578. doi:10.1016/S0140-6736(20)31022-9. ISSN 0140-6736.
- ↑ 11.0 11.1 11.2 Hadi A, Werge M, Kristiansen KT, Pedersen UG, Karstensen JG, Novovic S, Gluud LL (June 2020). "Coronavirus Disease-19 (COVID-19) associated with severe acute pancreatitis: Case report on three family members". Pancreatology. 20 (4): 665–667. doi:10.1016/j.pan.2020.04.021. PMC 7199002 Check
|pmc=value (help). PMID 32387082 Check|pmid=value (help). - ↑ Occhipinti V, Pastorelli L (May 2020). "Challenges in the Care of IBD Patients During the CoViD-19 Pandemic: Report From a "Red Zone" Area in Northern Italy". Inflamm. Bowel Dis. 26 (6): 793–796. doi:10.1093/ibd/izaa084. PMC 7188155 Check
|pmc=value (help). PMID 32314792 Check|pmid=value (help). - ↑ Ponnurangam Nagarajan V, Palaniyadi A, Sathyamoorthi M, Sasitharan R, Shuba S, Padur Sivaraman R, Scott JX (2012). "Pleural effusion - An unusual cause". Australas Med J. 5 (7): 369–72. doi:10.4066/AMJ.2012.1024. PMC 3413004. PMID 22905065.
- ↑ Pan L, Mu M, Yang P, Sun Y, Wang R, Yan J, Li P, Hu B, Wang J, Hu C, Jin Y, Niu X, Ping R, Du Y, Li T, Xu G, Hu Q, Tu L (May 2020). "Clinical Characteristics of COVID-19 Patients With Digestive Symptoms in Hubei, China: A Descriptive, Cross-Sectional, Multicenter Study". Am. J. Gastroenterol. 115 (5): 766–773. doi:10.14309/ajg.0000000000000620. PMC 7172492 Check
|pmc=value (help). PMID 32287140 Check|pmid=value (help). - ↑ "Management of Patients with Confirmed 2019-nCoV | CDC".
- ↑ Mao R, Qiu Y, He JS, Tan JY, Li XH, Liang J, Shen J, Zhu LR, Chen Y, Iacucci M, Ng SC, Ghosh S, Chen MH (July 2020). "Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-analysis". Lancet Gastroenterol Hepatol. 5 (7): 667–678. doi:10.1016/S2468-1253(20)30126-6. PMC 7217643 Check
|pmc=value (help). PMID 32405603 Check|pmid=value (help). - ↑ Lin L, Jiang X, Zhang Z, Huang S, Zhang Z, Fang Z, Gu Z, Gao L, Shi H, Mai L, Liu Y, Lin X, Lai R, Yan Z, Li X, Shan H (June 2020). "Gastrointestinal symptoms of 95 cases with SARS-CoV-2 infection". Gut. 69 (6): 997–1001. doi:10.1136/gutjnl-2020-321013. PMC 7316116 Check
|pmc=value (help). PMID 32241899 Check|pmid=value (help). - ↑ 18.0 18.1 Mao, Ren; Qiu, Yun; He, Jin-Shen; Tan, Jin-Yu; Li, Xue-Hua; Liang, Jie; Shen, Jun; Zhu, Liang-Ru; Chen, Yan; Iacucci, Marietta; Ng, Siew C; Ghosh, Subrata; Chen, Min-Hu (2020). "Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-analysis". The Lancet Gastroenterology & Hepatology. 5 (7): 667–678. doi:10.1016/S2468-1253(20)30126-6. ISSN 2468-1253.
- ↑ 19.0 19.1 Abdalhadi A, Alkhatib M, Mismar AY, Awouda W, Albarqouni L (2020). "Can COVID 19 present like appendicitis?". IDCases. 21: e00860. doi:10.1016/j.idcr.2020.e00860. PMC 7265835 Check
|pmc=value (help). PMID 32523872 Check|pmid=value (help). - ↑ 20.0 20.1 20.2 20.3 Poggiali E, Ramos PM, Bastoni D, Vercelli A, Magnacavallo A (2020). "Abdominal Pain: A Real Challenge in Novel COVID-19 Infection". Eur J Case Rep Intern Med. 7 (4): 001632. doi:10.12890/2020_001632. PMC 7162568 Check
|pmc=value (help). PMID 32309266 Check|pmid=value (help). - ↑ Queiroz N, Barros LL, Azevedo M, Oba J, Sobrado CW, Carlos AS, Milani LR, Sipahi AM, Damião A (2020). "Management of inflammatory bowel disease patients in the COVID-19 pandemic era: a Brazilian tertiary referral center guidance". Clinics (Sao Paulo). 75: e1909. doi:10.6061/clinics/2020/e1909. PMC 7153358 Check
|pmc=value (help). PMID 32321117 Check|pmid=value (help). Vancouver style error: initials (help) - ↑ Su, Song; Shen, Jun; Zhu, Liangru; Qiu, Yun; He, Jin-Shen; Tan, Jin-Yu; Iacucci, Marietta; Ng, Siew C; Ghosh, Subrata; Mao, Ren; Liang, Jie (2020). "Involvement of digestive system in COVID-19: manifestations, pathology, management and challenges". Therapeutic Advances in Gastroenterology. 13: 175628482093462. doi:10.1177/1756284820934626. ISSN 1756-2848.
- ↑ "NIH clinical trial of investigational vaccine for COVID-19 begins | National Institutes of Health (NIH)".
- ↑ "How to Protect Yourself & Others | CDC".
- ↑ "Contact Tracing for COVID-19 | CDC".
- ↑ Green CA, Quraishi MN, Shabir S, Sharma N, Hansen R, Gaya DR, Hart AL, Loman NJ, Iqbal TH (June 2020). "Screening faecal microbiota transplant donors for SARS-CoV-2 by molecular testing of stool is the safest way forward". Lancet Gastroenterol Hepatol. 5 (6): 531. doi:10.1016/S2468-1253(20)30089-3. PMC 7225406 Check
|pmc=value (help). PMID 32240618 Check|pmid=value (help).
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