COVID-19-associated anorexia
For COVID-19 frequently asked outpatient questions, click here
For COVID-19 frequently asked inpatient questions, click here
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 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 and 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.
Historical Perspective
- COVID-19 was first discovered in Wuhan, China. 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.[1]
- Nanopore sequencing and bioinformatic analyses indicated that the virus had features typical of the coronavirus family and belonged to the Betacoronavirus 2B lineage.[1]
- COVID-19 was primarily known as a respiratory disease. In the initial reports from WHO, the mode of transmission of COVID-19 was droplets and fomites during close unprotected contact between an infector and the infectee. Airborne transmission was not reported initially.
- Fecal shedding was reported to be demonstrated from some patients, with viable virus identified in a limited number of case reports. However, fecal-oral route did not appear to drive COVID-19 transmission.[1][2]
- 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.[3]
- 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.[3]
- On March 11th, 2020, WHO declared the COVID-19 outbreak a pandemic.[4]
- 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.
Classification
There is no established system for the classification of anorexia in COVID-19.
Pathophysiology
- 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 alongwith the prevalence of gustatory system dysfunction in mild-moderate COVID-19 cases partly explains anorexia in COVID-19. In addition, olfactory dysfunction also contributes to loss of appetite.[5]
- 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 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.[6][7] 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.[8] A relationship of cytokines and COVID-19 infection has been established.[9]
- 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.[10]
- 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.[11]
Causes
Anorexia among patients hospitalized due to COVID-19 may be due to:
- COVID-19-associated hepatic injury
- Underlying conditions such as cancer
- Medication administered to treat the COVID-19 infection such as Remdesivir[12]
- COVID-19 associated pancreatitis[13]
- Superimposed bacterial infections
- Anxiety associated with the infection itself
Differentiating COVID-19 associated anorexia from other Diseases
- For further information regarding the differential diagnosis, click here.
- To view the differential diagnosis of COVID-19, click here
Epidemiology and Demographics
- 48.5% of COVID-19 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 recent studies anorexia is the most common (40-84%) digestive symptoms associated with COVID-19.[15][16]
Race
- China being the major source demographic data on clinical features of COVID-19 and fewer studies on the demographics among other races, enabled the scientists to compare the incidence of anorexia among Chinese population and rest of the world.
- Data demonstrated 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
- 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 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.
- 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.[17]
- Prognosis the odds ratio for severe disease among 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 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.
- Based on a retrospective observational study including 1141 cases of COVID-19 from Wuhan, China anorexia was the most common gastrointestinal symptom of COVID-19.[19]
- The most common accompanying symptoms of COVID-19 besides anorexia were nausea, vomiting, and diarrhea.[18]
- The timing of symptoms and presence of co-morbid conditions helps differentiate the diseases with similar symptoms.
Physical Examination
- Patients with COVID-19 associated anorexia may appear lethargic, fatigued or irritable.
- Signs of dehydration such as sunken eyes and dry mucosa.
- Vital signs:[20][21]
- 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:[22][13]
- Inspection: A patient with COVID-19-associated hepatic injury causing anorexia may have jaundice.
- Auscultation: Accompanying gastrointestinal infection may present as increased bowel sounds due to enteritis.
- Palpation: Based of 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.
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 increased Hb due to hemoconcentration if dehydration accompanies.
- Value of CRP and procalcitonin provide information on the inflammation and superimposed bacterial source of infection.[21]
Electrocardiogram
- There are no ECG findings associated with COVID-19 associated [[anorexia].
- The electrocardiogram findings in COVID-19 can be viewed by clicking here.
X-ray
- In patients with COVID-19 associated GI symptoms with anorexia as one of the symptoms, abdominal Xrays have been reported to be normal in a few studies available.[13][22]
- 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.[23]
- 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.[23]
- 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.
CT scan
- 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.[21]
- The CT scan findings in COVID-19 can be viewed by clicking here.
MRI
- 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.[21]
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 administered 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.[24][25]
Primary Prevention
- Effective measures for the primary prevention of COVID-19 include::[26]
- 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.[27]
- 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.
- There have been rigorous efforts in order to develop a vaccine for novel coronavirus and several vaccines are in the later phases of trials.[28]
Secondary prevention
- 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.[29].
- Screening of fecal microbiota transplant donors for COVID-19 is also recommended.[30]
- Contact tracing helps reduce the spread of the disease.[31]
References
- ↑ 1.0 1.1 1.2 "www.who.int" (PDF).
- ↑ 3.0 3.1 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.
- ↑ "WHO Director-General's opening remarks at the media briefing on COVID-19 - 11 March 2020".
- ↑ 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.
- ↑ 13.0 13.1 13.2 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). - ↑ 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.
- ↑ Luo S, Zhang X, Xu H (June 2020). "Don't Overlook Digestive Symptoms in Patients With 2019 Novel Coronavirus Disease (COVID-19)". Clin. Gastroenterol. Hepatol. 18 (7): 1636–1637. doi:10.1016/j.cgh.2020.03.043. PMC 7154217 Check
|pmc=value (help). PMID 32205220 Check|pmid=value (help). - ↑ Telias, Irene; Katira, Bhushan H.; Brochard, Laurent (2020). "Is the Prone Position Helpful During Spontaneous Breathing in Patients With COVID-19?". JAMA. 323 (22): 2265. doi:10.1001/jama.2020.8539. ISSN 0098-7484.
- ↑ 21.0 21.1 21.2 21.3 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). - ↑ 22.0 22.1 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). - ↑ 23.0 23.1 Cozzi D, Albanesi M, Cavigli E, Moroni C, Bindi A, Luvarà S, Lucarini S, Busoni S, Mazzoni LN, Miele V (August 2020). "Chest X-ray in new Coronavirus Disease 2019 (COVID-19) infection: findings and correlation with clinical outcome". Radiol Med. 125 (8): 730–737. doi:10.1007/s11547-020-01232-9. PMC 7282464 Check
|pmc=value (help). PMID 32519256 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.
- ↑ "How to Protect Yourself & Others | CDC".
- ↑ "NIH clinical trial of investigational vaccine for COVID-19 begins | National Institutes of Health (NIH)".
- ↑ 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). - ↑ "Contact Tracing for COVID-19 | CDC".