COVID-19-associated anorexia
(Redirected from COVID and hunger)
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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, covid19 associated anorexia.
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, 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.
Historical Perspective
- 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.[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 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.[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 among 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 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.[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 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.[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
COVID-19 associated anorexia may be classified according to the COVID-19 associated entity causing the symptom:
- COVID-19-associated hepatic injury[11]
- Underlying conditions such as cancer[12]
- Medications administered to treat the COVID-19 infection such as remdesivir[13], favipiravir and chloroquine or hydroxychloroquine (anorexia is a common side effect for the three drugs mentioned)[14]
- COVID-19 associated pancreatitis[15]
- Superimposed bacterial infections[6][7]
- Stress associated with the COVID-19 infection itself[16][17]
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
- According to WHO the prevalence of anorexia associated with COVID-19 is 40-84%.[18]
- 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.[19]
- 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.[20]
- 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.[21][19][20]
- 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.[22]
Age
- There is insufficient data to support an age group that is affected to a greater extent from COVID-19 associated anorexia.
Gender
Men more commonly presented with GI symptoms with anorexia being the most common symptom in Wuhan, China according to a retrospective study involving 1,141 cases of COVID-19.[22]
Race
- 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.[23]
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 majority of COVID-19 patients develop anorexia associated with COVID-19 during hospitalization. Anorexia as an initial presentation is observed among minority of patients.[24]
- 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.[3]
- 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.[25]
- 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.[26] *As a complication, 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.
- 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.[22]
- The most common accompanying symptoms of COVID-19 besides anorexia were nausea, vomiting, and diarrhea.[26]
- 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 include sunken eyes and dry mucosa.
Physical examination may be remarkable for:
- Vital signs:[27][28][28][29]
- 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:[30][31][32][15]
- 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.
Laboratory Findings
- 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.[33]
- 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.[34][35]
- 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.[36]
- CRP and procalcitonin: The value provides information on the inflammation and superimposed bacterial source of infection.[28] A case of COVID-19 presenting as acute pancreatitis reports elevated procalcitonin.[37]
- 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.[28] A meta-analysis found a higher risk of raised ALT and AST among patients with severe COVID-19.[19]
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
- 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.[15][32]
- 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.[38]
- 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.[38]
- 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.[28]
- 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.[28]
Treatment
Medical Therapy
- 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.[39][40][41]
- 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.[41]
- 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.[42]
- 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.[43][44]
- 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.[41]
Primary Prevention
- 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.[45]
- Effective measures for the primary prevention of COVID-19 include::[46]
- 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.[47]
- 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.
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.[48].
- Screening of fecal microbiota transplant donors for COVID-19 is also recommended.[49]
- Contact tracing helps reduce the spread of the disease.[50]
- 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.[51]
References
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|pmc=value (help). PMID 32253535 Check|pmid=value (help). - ↑ 6.0 6.1 Kanra GY, Ozen H, Kara A (2006). "Infection and anorexia". Turk. J. Pediatr. 48 (4): 279–87. PMID 17290560.
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|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.
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- ↑ Di Lorenzo G, Di Trolio R, Kozlakidis Z, Busto G, Ingenito C, Buonerba L, Ferrara C, Libroia A, Ragone G, Ioio CD, Savastano B, Polverino M, De Falco F, Iaccarino S, Leo E (August 2020). "COVID 19 therapies and anti-cancer drugs: A systematic review of recent literature". Crit. Rev. Oncol. Hematol. 152: 102991. doi:10.1016/j.critrevonc.2020.102991. PMC 7239789 Check
|pmc=value (help). PMID 32544802 Check|pmid=value (help). - ↑ 15.0 15.1 15.2 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). - ↑ Yau YH, Potenza MN (September 2013). "Stress and eating behaviors". Minerva Endocrinol. 38 (3): 255–67. PMC 4214609. PMID 24126546.
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|pmc=value (help). PMID 32405603 Check|pmid=value (help). - ↑ 20.0 20.1 Cheung KS, Hung I, Chan P, Lung KC, Tso E, Liu R, Ng YY, Chu MY, Chung T, Tam AR, Yip C, Leung KH, Fung AY, Zhang RR, Lin Y, Cheng HM, Zhang A, To K, Chan KH, Yuen KY, Leung WK (April 2020). "Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples From a Hong Kong Cohort: Systematic Review and Meta-analysis". Gastroenterology. doi:10.1053/j.gastro.2020.03.065. PMC 7194936 Check
|pmc=value (help). PMID 32251668 Check|pmid=value (help). Vancouver style error: initials (help) - ↑ "Management of Patients with Confirmed 2019-nCoV | CDC".
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|pmc=value (help). PMID 32205220 Check|pmid=value (help). - ↑ Tariq, Raseen; Saha, Srishti; Furqan, Fateeha; Hassett, Leslie; Pardi, Darrell; Khanna, Sahil (2020). "Prevalence and Mortality of COVID-19 patients with Gastrointestinal Symptoms: A Systematic Review and Meta-analysis". Mayo Clinic Proceedings. doi:10.1016/j.mayocp.2020.06.003. ISSN 0025-6196.
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|pmc=value (help). PMID 32241899 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). - ↑ 26.0 26.1 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.
- ↑ 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.
- ↑ 28.0 28.1 28.2 28.3 28.4 28.5 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). - ↑ Guan, Wei-jie; Ni, Zheng-yi; Hu, Yu; Liang, Wen-hua; Ou, Chun-quan; He, Jian-xing; Liu, Lei; Shan, Hong; Lei, Chun-liang; Hui, David S.C.; Du, Bin; Li, Lan-juan; Zeng, Guang; Yuen, Kwok-Yung; Chen, Ru-chong; Tang, Chun-li; Wang, Tao; Chen, Ping-yan; Xiang, Jie; Li, Shi-yue; Wang, Jin-lin; Liang, Zi-jing; Peng, Yi-xiang; Wei, Li; Liu, Yong; Hu, Ya-hua; Peng, Peng; Wang, Jian-ming; Liu, Ji-yang; Chen, Zhong; Li, Gang; Zheng, Zhi-jian; Qiu, Shao-qin; Luo, Jie; Ye, Chang-jiang; Zhu, Shao-yong; Zhong, Nan-shan (2020). "Clinical Characteristics of Coronavirus Disease 2019 in China". New England Journal of Medicine. 382 (18): 1708–1720. doi:10.1056/NEJMoa2002032. ISSN 0028-4793.
- ↑ Olry A, Meunier L, Délire B, Larrey D, Horsmans Y, Le Louët H (July 2020). "Drug-Induced Liver Injury and COVID-19 Infection: The Rules Remain the Same". Drug Saf. 43 (7): 615–617. doi:10.1007/s40264-020-00954-z. PMC 7279629 Check
|pmc=value (help). PMID 32514859 Check|pmid=value (help). - ↑ Boettler T, Newsome PN, Mondelli MU, Maticic M, Cordero E, Cornberg M, Berg T (June 2020). "Care of patients with liver disease during the COVID-19 pandemic: EASL-ESCMID position paper". JHEP Rep. 2 (3): 100113. doi:10.1016/j.jhepr.2020.100113. PMC 7128473 Check
|pmc=value (help). PMID 32289115 Check|pmid=value (help). - ↑ 32.0 32.1 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). - ↑ "CDC's Diagnostic Test for COVID-19 Only and Supplies | CDC".
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|pmc=value (help). PMID 32525548 Check|pmid=value (help). - ↑ Alfano, Gaetano; Ferrari, Annachiara; Fontana, Francesco; Perrone, Rossella; Mori, Giacomo; Ascione, Elisabetta; Riccardo, Magistroni; Venturi, Giulia; Pederzoli, Simone; Margiotta, Gianluca; Romeo, Marilina; Piccinini, Francesca; Franceschi, Giacomo; Volpi, Sara; Faltoni, Matteo; Ciusa, Giacomo; Bacca, Erica; Tutone, Marco; Raimondi, Alessandro; menozzi, marianna; Franceschini, Erica; Cuomo, Gianluca; Orlando, Gabriella; Santoro, Antonella; Di Gaetano, Margherita; Puzzolante, Cinzia; Carli, Federica; Bedini, Andrea; Milic, Jovana; Meschiari, Marianna; Mussini, Cristina; Cappelli, Gianni; Guaraldi, Giovanni (2020). doi:10.1101/2020.06.14.20131169. Missing or empty
|title=(help) - ↑ Wang, Fan; Wang, Haizhou; Fan, Junli; Zhang, Yongxi; Wang, Hongling; Zhao, Qiu (2020). "Pancreatic Injury Patterns in Patients With Coronavirus Disease 19 Pneumonia". Gastroenterology. 159 (1): 367–370. doi:10.1053/j.gastro.2020.03.055. ISSN 0016-5085.
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|pmc=value (help). PMID 32444169 Check|pmid=value (help). - ↑ 38.0 38.1 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). - ↑ Cao, Bin; Wang, Yeming; Wen, Danning; Liu, Wen; Wang, Jingli; Fan, Guohui; Ruan, Lianguo; Song, Bin; Cai, Yanping; Wei, Ming; Li, Xingwang; Xia, Jiaan; Chen, Nanshan; Xiang, Jie; Yu, Ting; Bai, Tao; Xie, Xuelei; Zhang, Li; Li, Caihong; Yuan, Ye; Chen, Hua; Li, Huadong; Huang, Hanping; Tu, Shengjing; Gong, Fengyun; Liu, Ying; Wei, Yuan; Dong, Chongya; Zhou, Fei; Gu, Xiaoying; Xu, Jiuyang; Liu, Zhibo; Zhang, Yi; Li, Hui; Shang, Lianhan; Wang, Ke; Li, Kunxia; Zhou, Xia; Dong, Xuan; Qu, Zhaohui; Lu, Sixia; Hu, Xujuan; Ruan, Shunan; Luo, Shanshan; Wu, Jing; Peng, Lu; Cheng, Fang; Pan, Lihong; Zou, Jun; Jia, Chunmin; Wang, Juan; Liu, Xia; Wang, Shuzhen; Wu, Xudong; Ge, Qin; He, Jing; Zhan, Haiyan; Qiu, Fang; Guo, Li; Huang, Chaolin; Jaki, Thomas; Hayden, Frederick G.; Horby, Peter W.; Zhang, Dingyu; Wang, Chen (2020). "A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19". New England Journal of Medicine. 382 (19): 1787–1799. doi:10.1056/NEJMoa2001282. ISSN 0028-4793.
- ↑ Lim J, Jeon S, Shin HY, Kim MJ, Seong YM, Lee WJ, Choe KW, Kang YM, Lee B, Park SJ (February 2020). "Case of the Index Patient Who Caused Tertiary Transmission of COVID-19 Infection in Korea: the Application of Lopinavir/Ritonavir for the Treatment of COVID-19 Infected Pneumonia Monitored by Quantitative RT-PCR". J. Korean Med. Sci. 35 (6): e79. doi:10.3346/jkms.2020.35.e79. PMC 7025910 Check
|pmc=value (help). PMID 32056407 Check|pmid=value (help). - ↑ 41.0 41.1 41.2 Nicola M, O'Neill N, Sohrabi C, Khan M, Agha M, Agha R (May 2020). "Evidence based management guideline for the COVID-19 pandemic - Review article". Int J Surg. 77: 206–216. doi:10.1016/j.ijsu.2020.04.001. PMC 7151371 Check
|pmc=value (help). PMID 32289472 Check|pmid=value (help). - ↑ Khanna S, Pardi DS (November 2012). "Clostridium difficile infection: new insights into management". Mayo Clin. Proc. 87 (11): 1106–17. doi:10.1016/j.mayocp.2012.07.016. PMC 3541870. PMID 23127735.
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|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.
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- ↑ 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".
- ↑ Marinella MA (June 2020). "Routine antiemetic prophylaxis with dexamethasone during COVID-19: Should oncologists reconsider?". J Oncol Pharm Pract: 1078155220931921. doi:10.1177/1078155220931921. PMID 32507102 Check
|pmid=value (help).