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1.
PLoS Comput Biol ; 17(12): e1009629, 2021 12.
Article in English | MEDLINE | ID: covidwho-1581906

ABSTRACT

Identifying order of symptom onset of infectious diseases might aid in differentiating symptomatic infections earlier in a population thereby enabling non-pharmaceutical interventions and reducing disease spread. Previously, we developed a mathematical model predicting the order of symptoms based on data from the initial outbreak of SARS-CoV-2 in China using symptom occurrence at diagnosis and found that the order of COVID-19 symptoms differed from that of other infectious diseases including influenza. Whether this order of COVID-19 symptoms holds in the USA under changing conditions is unclear. Here, we use modeling to predict the order of symptoms using data from both the initial outbreaks in China and in the USA. Whereas patients in China were more likely to have fever before cough and then nausea/vomiting before diarrhea, patients in the USA were more likely to have cough before fever and then diarrhea before nausea/vomiting. Given that the D614G SARS-CoV-2 variant that rapidly spread from Europe to predominate in the USA during the first wave of the outbreak was not present in the initial China outbreak, we hypothesized that this mutation might affect symptom order. Supporting this notion, we found that as SARS-CoV-2 in Japan shifted from the original Wuhan reference strain to the D614G variant, symptom order shifted to the USA pattern. Google Trends analyses supported these findings, while weather, age, and comorbidities did not affect our model's predictions of symptom order. These findings indicate that symptom order can change with mutation in viral disease and raise the possibility that D614G variant is more transmissible because infected people are more likely to cough in public before being incapacitated with fever.


Subject(s)
COVID-19/diagnosis , COVID-19/virology , Models, Biological , SARS-CoV-2 , COVID-19/epidemiology , China/epidemiology , Computational Biology , Cough/etiology , Diarrhea/etiology , Fever/etiology , Humans , Japan/epidemiology , Mutation , Nausea/etiology , Pandemics , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Time Factors , United States/epidemiology , Vomiting/etiology
2.
Dig Dis ; 39(6): 622-625, 2021.
Article in English | MEDLINE | ID: covidwho-1574067

ABSTRACT

BACKGROUND/AIMS: The COVID-19 disease, which was declared epidemic by the WHO, is a global emergency public health problem. Patients with extrapulmonary symptoms are the group of patients who should be considered for person-to-person transmission in the community. In our study, it was aimed to investigate the characteristics of patients with COVID-19-related diarrhea symptoms. MATERIALS AND METHODS: The study was conducted retrospectively in CO-VID-19 rtRT-PCR-positive patients in 5 medical centers. Three or more loose/liquid stools per day or increased number of defecations compared to normal defecation were defined as diarrhea. The patients were analyzed in 2 groups as those with and without diarrhea. RESULTS: One thousand eighty-six patients were included in the study. Seventy-eight (7.2%) of the patients had diarrhea. Diarrhea was watery in 54 (69.2%) patients while with blood and mucus in 18 (23.1%) patients. Diarrhea continued for an average of 5.2 ± 1.6 (2-11) days. The clinical and laboratory findings of patients with diarrhea were more serious than those without diarrhea. Diarrhea is more common in the elderly and people with comorbid disease, and patients with diarrhea had higher CMI score and CRP and higher complaints of fever, cough, shortness of breath, myalgia, and fatigue. CONCLUSIONS: The presence of diarrhea should indicate a suspected COVID-19 infection and suggest testing for early diagnosis of the disease. It should be kept in mind that the course of the disease may be more severe in these patients, and precautions should also be taken in terms of fecal transmission during discharge.


Subject(s)
COVID-19 , Aged , Diarrhea/epidemiology , Diarrhea/etiology , Feces , Humans , Retrospective Studies , SARS-CoV-2
3.
J Korean Med Sci ; 36(48): e336, 2021 Dec 13.
Article in English | MEDLINE | ID: covidwho-1572279

ABSTRACT

In 2020, the novel coronavirus disease 2019 (COVID-19) began to spread worldwide and remains an ongoing medical challenge. This case series reports on the clinical features and characteristics of patients with inflammatory bowel disease (IBD) and confirmed COVID-19 infection. From February 2020 to March 2021, nine patients with IBD had confirmed COVID-19 across four hospitals in Korea. The median age at COVID-19 diagnosis was 42 years. Six patients were male, and seven patients had ulcerative colitis (UC). No patients required oxygen therapy, intensive care unit hospitalizations, or died. The most common symptom was fever, and gastrointestinal (GI) symptoms developed as diarrhea in five patients with UC. Oral steroids were used to combat UC aggravation in two patients. In this case series of nine IBD patients diagnosed with COVID-19 in Korea, the clinical presentation was predominately a mild respiratory tract infection. Most patients with UC developed new GI symptoms including diarrhea.


Subject(s)
COVID-19/diagnosis , Inflammatory Bowel Diseases/pathology , Administration, Oral , Adult , COVID-19/complications , COVID-19/pathology , COVID-19/virology , Colitis, Ulcerative/complications , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/pathology , Diarrhea/etiology , Female , Fever/etiology , Hospitalization , Humans , Inflammatory Bowel Diseases/complications , Intensive Care Units , Male , Middle Aged , Republic of Korea , SARS-CoV-2/isolation & purification , Steroids/therapeutic use , Young Adult
4.
J Korean Med Sci ; 36(44): e301, 2021 Nov 15.
Article in English | MEDLINE | ID: covidwho-1526760

ABSTRACT

We used serial rectal swabs to investigate the amount and duration of virus secretion through the gastrointestinal tract and assessed the association between fecal shedding and gastrointestinal symptoms and to clarify the clinical usefulness testing rectal swabs. We enrolled ten adult patients hospitalized with symptomatic coronavirus disease 2019 (COVID-19). Respiratory and stool specimens were collected by physicians. The presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed using real-time reverse-transcription polymerase chain reaction. All ten patients had respiratory symptoms, six had diarrhea, and seven were positive for SARS-CoV-2 on rectal swabs. The viral loads in the respiratory specimens was higher than those in the rectal specimens, and no rectal specimens were positive after the respiratory specimens became negative. There was no association between gastrointestinal symptoms, pneumonia, severity, and rectal viral load. Rectal swabs may play a role in detecting SARS-CoV-2 in individuals with suspected COVID-19, regardless of gastrointestinal symptoms.


Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19/virology , Rectum/virology , SARS-CoV-2/isolation & purification , Virus Shedding , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/complications , COVID-19/transmission , Diarrhea/etiology , Diarrhea/virology , Feces/virology , Female , Humans , Male , Middle Aged , Nasopharynx/virology , Prospective Studies , Real-Time Polymerase Chain Reaction , Severity of Illness Index , Time Factors , Viral Load
5.
Sci Rep ; 11(1): 21725, 2021 11 05.
Article in English | MEDLINE | ID: covidwho-1504567

ABSTRACT

SARS-CoV-2 enters the intestine by the spike protein binding to angiotensin-converting enzyme 2 (ACE2) receptors in enterocyte apical membranes, leading to diarrhea in some patients. Early treatment of COVID-19-associated diarrhea could relieve symptoms and limit viral spread within the gastrointestinal (GI) tract. Diosmectite, an aluminomagnesium silicate adsorbent clay with antidiarrheal effects, is recommended in some COVID-19 management protocols. In rotavirus models, diosmectite prevents pathogenic effects by binding the virus and its enterotoxin. We tested the trapping and anti-inflammatory properties of diosmectite in a SARS-CoV-2 model. Trapping effects were tested in Caco-2 cells using spike protein receptor-binding domain (RBD) and heat-inactivated SARS-CoV-2 preparations. Trapping was assessed by immunofluorescence, alone or in the presence of cells. The effect of diosmectite on nuclear factor kappa B (NF-kappaB) activation and CXCL10 secretion induced by the spike protein RBD and heat-inactivated SARS-CoV-2 were analyzed by Western blot and ELISA, respectively. Diosmectite bound the spike protein RBD and SARS-CoV-2 preparation, and inhibited interaction of the spike protein RBD with ACE2 receptors on the Caco-2 cell surface. Diosmectite exposure also inhibited NF-kappaB activation and CXCL10 secretion. These data provide direct evidence that diosmectite can bind SARS-CoV-2 components and inhibit downstream inflammation, supporting a mechanistic rationale for consideration of diosmectite as a management option for COVID-19-associated diarrhea.


Subject(s)
COVID-19/drug therapy , Chemokine CXCL10/metabolism , NF-kappa B p50 Subunit/metabolism , SARS-CoV-2 , Silicates/chemistry , Adsorption , Aluminum Compounds/chemistry , Angiotensin-Converting Enzyme 2/metabolism , Anti-Inflammatory Agents , Binding Sites , Caco-2 Cells , Chromatography, Liquid , Clay , Diarrhea/etiology , Diarrhea/therapy , Enterocytes/metabolism , Gastroenterology , Humans , Magnesium Compounds/chemistry , Mass Spectrometry , Molecular Docking Simulation , Molecular Dynamics Simulation , Protein Binding/drug effects , Protein Domains , Rotavirus , Silicates/metabolism
6.
Sci Rep ; 11(1): 19713, 2021 10 05.
Article in English | MEDLINE | ID: covidwho-1454811

ABSTRACT

The novel coronavirus disease 2019 (COVID-19) presents with non-specific clinical features. This may result in misdiagnosis or delayed diagnosis, and lead to further transmission in the community. We aimed to derive early predictors to differentiate COVID-19 from influenza and dengue. The study comprised 126 patients with COVID-19, 171 with influenza and 180 with dengue, who presented within 5 days of symptom onset. All cases were confirmed by reverse transcriptase polymerase chain reaction tests. We used logistic regression models to identify demographics, clinical characteristics and laboratory markers in classifying COVID-19 versus influenza, and COVID-19 versus dengue. The performance of each model was evaluated using receiver operating characteristic (ROC) curves. Shortness of breath was the strongest predictor in the models for differentiating between COVID-19 and influenza, followed by diarrhoea. Higher lymphocyte count was predictive of COVID-19 versus influenza and versus dengue. In the model for differentiating between COVID-19 and dengue, patients with cough and higher platelet count were at increased odds of COVID-19, while headache, joint pain, skin rash and vomiting/nausea were indicative of dengue. The cross-validated area under the ROC curve for all four models was above 0.85. Clinical features and simple laboratory markers for differentiating COVID-19 from influenza and dengue are identified in this study which can be used by primary care physicians in resource limited settings to determine if further investigations or referrals would be required.


Subject(s)
COVID-19/pathology , Dengue/pathology , Influenza, Human/pathology , Adult , Area Under Curve , COVID-19/complications , COVID-19/virology , Cohort Studies , Dengue/complications , Dengue/virology , Diagnosis, Differential , Diarrhea/etiology , Female , Fever/etiology , Humans , Influenza, Human/complications , Influenza, Human/virology , Lymphocyte Count , Male , Middle Aged , Platelet Count , RNA, Viral/analysis , RNA, Viral/metabolism , ROC Curve , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Vomiting/etiology , Young Adult
7.
Trop Biomed ; 38(3): 360-365, 2021 Sep 01.
Article in English | MEDLINE | ID: covidwho-1404405

ABSTRACT

COVID-19, caused by the SARS-CoV-2 virus, can lead to massive inflammation in the gastrointestinal tract causing severe clinical symptoms. SARS-CoV-2 infects lungs after binding its spike proteins with alveolar angiotensin-converting enzyme 2 (ACE2), and it also triggers inflammation in the gastrointestinal tract. SARS-CoV-2 invades the gastrointestinal tract by interacting with Toll-like receptor-4 (TLR4) that induces the expression of ACE2. The influx of ACE2 facilitates cellular binding of more SARS-CoV-2 and causes massive gastrointestinal inflammation leading to diarrhea. Diarrhea prior to COVID-19 infection or COVID-19-induced diarrhea reportedly ends up in a poor prognosis for the patient. Flavonoids are part of traditional remedies for gastrointestinal disorders. Preclinical studies show that flavonoids can prevent infectious diarrhea. Recent studies show flavonoids can inhibit the multiplication of SARS-CoV-2. In combination with vitamin D, flavonoids possibly activate nuclear factor erythroid-derived-2-related factor 2 that downregulates ACE2 expression in cells. We suggest that flavonoids have the potential to prevent SARS-CoV-2 induced diarrhea.


Subject(s)
COVID-19/complications , Diarrhea/prevention & control , Flavonoids/therapeutic use , SARS-CoV-2 , Angiotensin-Converting Enzyme 2/physiology , Diarrhea/etiology , Humans
10.
J R Soc Med ; 114(9): 428-442, 2021 09.
Article in English | MEDLINE | ID: covidwho-1311226

ABSTRACT

Globally, there are now over 160 million confirmed cases of COVID-19 and more than 3 million deaths. While the majority of infected individuals recover, a significant proportion continue to experience symptoms and complications after their acute illness. Patients with 'long COVID' experience a wide range of physical and mental/psychological symptoms. Pooled prevalence data showed the 10 most prevalent reported symptoms were fatigue, shortness of breath, muscle pain, joint pain, headache, cough, chest pain, altered smell, altered taste and diarrhoea. Other common symptoms were cognitive impairment, memory loss, anxiety and sleep disorders. Beyond symptoms and complications, people with long COVID often reported impaired quality of life, mental health and employment issues. These individuals may require multidisciplinary care involving the long-term monitoring of symptoms, to identify potential complications, physical rehabilitation, mental health and social services support. Resilient healthcare systems are needed to ensure efficient and effective responses to future health challenges.


Subject(s)
COVID-19/complications , Quality of Life , COVID-19/therapy , Delivery of Health Care , Diarrhea/etiology , Employment , Fatigue/etiology , Headache/etiology , Humans , Mental Disorders/etiology , Mental Health , Pain/etiology , Respiratory Tract Diseases/etiology , SARS-CoV-2 , Sensation Disorders/etiology
11.
Nutr Hosp ; 38(3): 622-630, 2021 Jun 10.
Article in English | MEDLINE | ID: covidwho-1264738

ABSTRACT

Introduction: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). Compared with adults, children with SARS-CoV-2 infection may have fewer and less severe symptoms. Gastrointestinal symptoms are commonly reported in children, sometimes as the only manifestation of the disease, and most often manifest as anorexia, diarrhea, nausea and vomiting, or abdominal pain. Although most children have asymptomatic or mild disease, 10 % of those infected may experience serious or critical disease, or even death. Multisystem inflammatory syndrome is a rare but serious condition recently reported in children with COVID-19. Studies indicate that children with obesity are at higher risk of developing severe COVID-19, and inflammation associated with obesity could be one of the factors that worsens COVID-19 symptoms due to an increased inflammatory response involving molecules such as interleukin 6, tumor necrosis factor alpha, and monocyte chemoattractant protein. On the other hand, evidence has been reported of a higher protein expression of ACE2 in the visceral adipose tissue of obese and malnourished humans, and this could be associated with complications and severity of COVID-19. Therefore, regulation of the intake of macronutrients or micronutrients could be used as a strategy to reduce the consequences of COVID-19. Diet in general and bioactive compounds could play an important role in the prevention of the inflammatory cascade. The micronutrients with the most evidence suggesting a role in immune support are vitamins C and D, zinc, and polyphenols.


La enfermedad por coronavirus 2019 (COVID-19) está causada por el virus "síndrome respiratorio agudo severo-coronavirus 2" (SARS-CoV-2). En comparación con los adultos, los niños con infección por SARS-CoV-2 pueden tener menos síntomas y estos pueden ser menos graves. Los síntomas gastrointestinales se informan comúnmente en los niños, a veces como única manifestación de la enfermedad. Los más comunes son anorexia, diarrea, náuseas y vómitos, y dolor abdominal. Aunque la mayoría de los niños tienen un cuadro leve o asintomático, el 10 % de los infectados pueden experimentar un cuadro grave o crítico, e incluso la muerte. El síndrome inflamatorio multisistémico es una afección poco común, pero grave, que se documentó recientemente en niños con COVID-19. Los estudios indican que los niños con obesidad tienen mayor riesgo de desarrollar COVID-19 grave, y la inflamación asociada con la obesidad podría ser uno de los factores que empeoran los síntomas de la COVID-19 debido a una respuesta inflamatoria aumentada en donde se ven involucradas moléculas como la interleucina 6, el factor de necrosis tumoral alfa y la proteína quimioatrayente de monocitos. Por otro lado, se ha encontrado evidencia de una mayor expresión proteica de ACE2 en el tejido adiposo visceral de los seres humanos obesos y desnutridos, y esto podría estar asociado a las complicaciones y la severidad de la COVID-19. Por tanto, la regulación de la ingesta de macronutrientes o micronutrientes podría utilizarse como estrategia para reducir las consecuencias de la enfermedad. La dieta en general y los compuestos bioactivos podrían desempeñar un papel importante en la prevención de la cascada inflamatoria. Los micronutrientes con mayor evidencia indicativa de que desempeñan un papel en el apoyo inmunológico son las vitaminas C y D, el zinc y los polifenoles.


Subject(s)
COVID-19/complications , Gastrointestinal Diseases/etiology , Pediatric Obesity/complications , Abdominal Pain/etiology , Angiotensin-Converting Enzyme 2/metabolism , Anorexia/etiology , Ascorbic Acid/administration & dosage , COVID-19/etiology , COVID-19/metabolism , Child , Diarrhea/etiology , Female , Humans , Inflammation/complications , Male , Nausea/etiology , Overweight/complications , Oxidative Stress , Pediatric Obesity/metabolism , Polyphenols/administration & dosage , Systemic Inflammatory Response Syndrome/etiology , Thinness/complications , Thinness/metabolism , Vitamin D/administration & dosage , Vitamins/administration & dosage , Vomiting/etiology , Zinc/administration & dosage , Zinc/deficiency
12.
J Trop Pediatr ; 67(2)2021 05 17.
Article in English | MEDLINE | ID: covidwho-1246757

ABSTRACT

BACKGROUND: Data on the gastrointestinal (GI) manifestations of Pediatric Corona Virus Disease (COVID-19) are conflicting and the relationship between GI involvement and the severity of COVID-19 disease has not been evaluated. The objectives of this systematic review were to determine the GI manifestations of pediatric COVID-19 and to evaluate their role as risk factors for a severe clinical course. METHODS: : A systematic literature search was carried out in PubMed and Scopus for studies published before 31 December 2020 with information about the GI manifestations of pediatric COVID-19. Patients with a severe and nonsevere clinical course were compared using the inverse variance heterogeneity model and odds ratio (OR) as the effect size. A sensitivity analysis was performed if the heterogeneity was high among studies. RESULTS: A total of 811 studies were identified through a systematic search of which 55 studies (4369 patients) were included in this systematic review. The commonest GI symptoms were diarrhea-19.08% [95% confidence interval (CI) 10.6-28.2], nausea/vomiting 19.7% (95% CI 7.8-33.2) and abdominal pain 20.3% (95% CI 3.7-40.4). The presence of diarrhea was significantly associated with a severe clinical course with a pooled OR of 3.97 (95% CI 1.80-8.73; p < 0.01). Abdominal pain and nausea/vomiting were not associated with disease severity. CONCLUSIONS: Diarrhea, nausea/vomiting or abdominal pain are present in nearly one-fifth of all children with COVID-19. The presence of diarrhea portends a severe clinical course.


Subject(s)
COVID-19 , Gastrointestinal Diseases , Child , Diarrhea/epidemiology , Diarrhea/etiology , Gastrointestinal Diseases/epidemiology , Gastrointestinal Diseases/etiology , Humans , SARS-CoV-2 , Vomiting/epidemiology , Vomiting/etiology
13.
J Pediatr Gastroenterol Nutr ; 72(4): 511-513, 2021 04 01.
Article in English | MEDLINE | ID: covidwho-1132657

ABSTRACT

OBJECTIVES: Novel coronavirus 2019 (corona virus disease 2019 [COVID-19]) binds angiotensin-converting enzyme-2 (ACE-2) receptors to enter the cell. These receptors are widely expressed in the intestine, and COVID-19 may cause gastrointestinal symptoms via these receptors during the course of the disease. Helicobacter pylori is known to increase the expression of ACE-2 receptors in the gastrointestinal tract. The aim of this study was to investigate the effects of H pylori on the presentation and clinical course of COVID-19 infections. METHODS: This study was carried out from June 1 to July 20, 2020. Patients diagnosed with COVID-19 infections by PCR tests were included in the study. Antigen screening tests were performed on stool samples to determine the presence of H pylori. All patients were evaluated for manifestations of COVID-19 infection, severity of the course, hospitalized days because of the virus and outcome of the disease process. RESULTS: Of 108 COVID-19 positive patients evaluated, 31 with a mean age of 49.54 ±â€Š17.94 years were H pylori-positive (8 girls [25.8%]) and 77 with a mean age of 47.85 ±â€Š20.51 years; (31 girls [40.3%]) were H pylori-negative. Abdominal pain (19.4% vs 2.6%) and diarrhea (32.3% vs 9.1%) were significantly higher in patients with H pylori than those without (P = 0.007 and P = 0.006, respectively). There was no statistically significant difference between H pylori positivity and the number of hospitalized days, the severity of the course of COVID-19 infection, or the outcome of the disease (P > 0.05). CONCLUSION: Our results revealed that the findings of abdominal pain and diarrhea strongly correlated with the presence of H pylori in COVID-19 patients.


Subject(s)
Abdominal Pain/etiology , COVID-19/complications , Diarrhea/etiology , Helicobacter Infections/complications , Helicobacter pylori , Abdominal Pain/microbiology , Adult , Aged , Angiotensin-Converting Enzyme 2/metabolism , Diarrhea/microbiology , Female , Helicobacter Infections/microbiology , Hospitalization , Humans , Male , Middle Aged , SARS-CoV-2 , Severity of Illness Index
14.
Chest ; 159(3): e159-e162, 2021 03.
Article in English | MEDLINE | ID: covidwho-1108124

ABSTRACT

CASE PRESENTATION: A 78-year-old woman was admitted to the ED with a 10-day history of diarrhea and recent onset of dry cough, fever, and asthenia. She had a medical history of obesity (BMI 32) and arterial hypertension treated with irbesartan. In the context of a large-scale lockdown in France during the COVID-19 pandemic, she only had physical contact with her husband, who did not report any symptoms. She required mechanical ventilation because of severe hypoxemia within 1 hour after admission to the ED.


Subject(s)
COVID-19 Testing/methods , COVID-19 , Lung/diagnostic imaging , Respiration, Artificial/methods , Respiratory Insufficiency , SARS-CoV-2/isolation & purification , Tomography, X-Ray Computed/methods , Aged , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/physiopathology , COVID-19/therapy , Comorbidity , Diagnosis, Differential , Diarrhea/diagnosis , Diarrhea/etiology , Female , Humans , Obesity/diagnosis , Obesity/epidemiology , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy , Treatment Outcome
15.
Clin Nutr ESPEN ; 43: 495-500, 2021 06.
Article in English | MEDLINE | ID: covidwho-1095915

ABSTRACT

BACKGROUND: There is a lack of evidence about the tolerance of enteral nutrition (EN) in COVID-19 critically ill patients. However, several gastrointestinal manifestations related to COVID-19 have been described. The aims of this study were to analyze the incidence of gastrointestinal intolerance (GI) associated to EN (diarrhea, vomiting, gastroparesis and constipation) and to describe energy/protein provision along with biochemical alterations during the first week of EN. METHODS: A retrospective cohort of COVID-19 critically ill patients under mechanical ventilation. We reported daily enteral nutrition infusion and gastrointestinal manifestations within the first week of intubation and enteral nutrition initiation. RESULTS: Fifty-two patients were included; 40.3% were overweight and 46.2% were obese. During the first 7 days of EN, manifestations of GI intolerance such as vomiting, diarrhea and gastroparesis were present in 18 patients (32.4%). Hypernatremia (39%) was the most frequent electrolyte abnormality. Only Acute Kidney Injury (AKI) diagnosis was associated with a higher energy deficit on day 7. No associations between drug prescription and GI intolerance were observed. On day 4, 94.5% of patients were receiving more than 80% of energy requirements and 94.2% of protein requirements. Accumulated energy and protein deficits at day 3 were 2171.2 ± 945 kcal and 114.9 ± 49.2 g, respectively; and 2586.4 ± 1151 kcal, 133.3 ± 60.4 g at day 7. CONCLUSION: Enteral nutrition is feasible and well-tolerated in COVID-19 patients with mechanical ventilation within the first week of enteral nutrition initiation. More studies are needed to elucidate the impact of nutritional therapy on infection course and outcomes.


Subject(s)
COVID-19 , Critical Illness/therapy , Energy Intake , Enteral Nutrition/adverse effects , Gastrointestinal Diseases/etiology , Nutritional Requirements , Respiration, Artificial , Acute Kidney Injury/etiology , Adult , Aged , Aged, 80 and over , COVID-19/complications , COVID-19/therapy , Constipation/etiology , Diarrhea/etiology , Female , Gastroparesis/etiology , Humans , Hypernatremia/etiology , Intensive Care Units , Male , Middle Aged , Nutritional Status , Retrospective Studies , SARS-CoV-2 , Vomiting/etiology
16.
Cochrane Database Syst Rev ; 2: CD013665, 2021 02 23.
Article in English | MEDLINE | ID: covidwho-1095222

ABSTRACT

BACKGROUND: The clinical implications of SARS-CoV-2 infection are highly variable. Some people with SARS-CoV-2 infection remain asymptomatic, whilst the infection can cause mild to moderate COVID-19 and COVID-19 pneumonia in others. This can lead to some people requiring intensive care support and, in some cases, to death, especially in older adults. Symptoms such as fever, cough, or loss of smell or taste, and signs such as oxygen saturation are the first and most readily available diagnostic information. Such information could be used to either rule out COVID-19, or select patients for further testing. This is an update of this review, the first version of which published in July 2020. OBJECTIVES: To assess the diagnostic accuracy of signs and symptoms to determine if a person presenting in primary care or to hospital outpatient settings, such as the emergency department or dedicated COVID-19 clinics, has COVID-19. SEARCH METHODS: For this review iteration we undertook electronic searches up to 15 July 2020 in the Cochrane COVID-19 Study Register and the University of Bern living search database. In addition, we checked repositories of COVID-19 publications. We did not apply any language restrictions. SELECTION CRITERIA: Studies were eligible if they included patients with clinically suspected COVID-19, or if they recruited known cases with COVID-19 and controls without COVID-19. Studies were eligible when they recruited patients presenting to primary care or hospital outpatient settings. Studies in hospitalised patients were only included if symptoms and signs were recorded on admission or at presentation. Studies including patients who contracted SARS-CoV-2 infection while admitted to hospital were not eligible. The minimum eligible sample size of studies was 10 participants. All signs and symptoms were eligible for this review, including individual signs and symptoms or combinations. We accepted a range of reference standards. DATA COLLECTION AND ANALYSIS: Pairs of review authors independently selected all studies, at both title and abstract stage and full-text stage. They resolved any disagreements by discussion with a third review author. Two review authors independently extracted data and resolved disagreements by discussion with a third review author. Two review authors independently assessed risk of bias using the Quality Assessment tool for Diagnostic Accuracy Studies (QUADAS-2) checklist. We presented sensitivity and specificity in paired forest plots, in receiver operating characteristic space and in dumbbell plots. We estimated summary parameters using a bivariate random-effects meta-analysis whenever five or more primary studies were available, and whenever heterogeneity across studies was deemed acceptable. MAIN RESULTS: We identified 44 studies including 26,884 participants in total. Prevalence of COVID-19 varied from 3% to 71% with a median of 21%. There were three studies from primary care settings (1824 participants), nine studies from outpatient testing centres (10,717 participants), 12 studies performed in hospital outpatient wards (5061 participants), seven studies in hospitalised patients (1048 participants), 10 studies in the emergency department (3173 participants), and three studies in which the setting was not specified (5061 participants). The studies did not clearly distinguish mild from severe COVID-19, so we present the results for all disease severities together. Fifteen studies had a high risk of bias for selection of participants because inclusion in the studies depended on the applicable testing and referral protocols, which included many of the signs and symptoms under study in this review. This may have especially influenced the sensitivity of those features used in referral protocols, such as fever and cough. Five studies only included participants with pneumonia on imaging, suggesting that this is a highly selected population. In an additional 12 studies, we were unable to assess the risk for selection bias. This makes it very difficult to judge the validity of the diagnostic accuracy of the signs and symptoms from these included studies. The applicability of the results of this review update improved in comparison with the original review. A greater proportion of studies included participants who presented to outpatient settings, which is where the majority of clinical assessments for COVID-19 take place. However, still none of the studies presented any data on children separately, and only one focused specifically on older adults. We found data on 84 signs and symptoms. Results were highly variable across studies. Most had very low sensitivity and high specificity. Only cough (25 studies) and fever (7 studies) had a pooled sensitivity of at least 50% but specificities were moderate to low. Cough had a sensitivity of 67.4% (95% confidence interval (CI) 59.8% to 74.1%) and specificity of 35.0% (95% CI 28.7% to 41.9%). Fever had a sensitivity of 53.8% (95% CI 35.0% to 71.7%) and a specificity of 67.4% (95% CI 53.3% to 78.9%). The pooled positive likelihood ratio of cough was only 1.04 (95% CI 0.97 to 1.11) and that of fever 1.65 (95% CI 1.41 to 1.93). Anosmia alone (11 studies), ageusia alone (6 studies), and anosmia or ageusia (6 studies) had sensitivities below 50% but specificities over 90%. Anosmia had a pooled sensitivity of 28.0% (95% CI 17.7% to 41.3%) and a specificity of 93.4% (95% CI 88.3% to 96.4%). Ageusia had a pooled sensitivity of 24.8% (95% CI 12.4% to 43.5%) and a specificity of 91.4% (95% CI 81.3% to 96.3%). Anosmia or ageusia had a pooled sensitivity of 41.0% (95% CI 27.0% to 56.6%) and a specificity of 90.5% (95% CI 81.2% to 95.4%). The pooled positive likelihood ratios of anosmia alone and anosmia or ageusia were 4.25 (95% CI 3.17 to 5.71) and 4.31 (95% CI 3.00 to 6.18) respectively, which is just below our arbitrary definition of a 'red flag', that is, a positive likelihood ratio of at least 5. The pooled positive likelihood ratio of ageusia alone was only 2.88 (95% CI 2.02 to 4.09). Only two studies assessed combinations of different signs and symptoms, mostly combining fever and cough with other symptoms. These combinations had a specificity above 80%, but at the cost of very low sensitivity (< 30%). AUTHORS' CONCLUSIONS: The majority of individual signs and symptoms included in this review appear to have very poor diagnostic accuracy, although this should be interpreted in the context of selection bias and heterogeneity between studies. Based on currently available data, neither absence nor presence of signs or symptoms are accurate enough to rule in or rule out COVID-19. The presence of anosmia or ageusia may be useful as a red flag for COVID-19. The presence of fever or cough, given their high sensitivities, may also be useful to identify people for further testing. Prospective studies in an unselected population presenting to primary care or hospital outpatient settings, examining combinations of signs and symptoms to evaluate the syndromic presentation of COVID-19, are still urgently needed. Results from such studies could inform subsequent management decisions.


Subject(s)
Ambulatory Care , COVID-19/diagnosis , Primary Health Care , SARS-CoV-2 , Symptom Assessment , Ageusia/diagnosis , Ageusia/etiology , Anosmia/diagnosis , Anosmia/etiology , Arthralgia/diagnosis , Arthralgia/etiology , Bias , COVID-19/complications , COVID-19/epidemiology , Cough/diagnosis , Cough/etiology , Diarrhea/diagnosis , Diarrhea/etiology , Dyspnea/diagnosis , Dyspnea/etiology , Fatigue/diagnosis , Fatigue/etiology , Fever/diagnosis , Fever/etiology , Headache/diagnosis , Headache/etiology , Humans , Myalgia/diagnosis , Myalgia/etiology , Outpatient Clinics, Hospital/statistics & numerical data , Pandemics , Physical Examination , Selection Bias , Symptom Assessment/classification , Symptom Assessment/statistics & numerical data
18.
Cold Spring Harb Mol Case Stud ; 7(2)2021 04.
Article in English | MEDLINE | ID: covidwho-1087882

ABSTRACT

Coronavirus disease 2019 (COVID-19), which is caused by infection with SARS-CoV-2, presents with a broad constellation of both respiratory and nonrespiratory symptoms, although it is primarily considered a respiratory disease. Gastrointestinal symptoms-including nausea, abdominal pain, vomiting, and diarrhea-rank chief among these. When coupled with the presence of viral RNA in fecal samples, the presence of gastrointestinal symptoms raises relevant questions regarding whether SARS-CoV-2 can productively infect the upper or lower gastrointestinal tract. Despite the well-documented prevalence of gastrointestinal symptoms and the high rate of SARS-CoV-2 fecal RNA shedding, the biological, clinical, and epidemiological relevance of these findings is unclear. Furthermore, the isolation of replication-competent virus from fecal samples has not been reproducibly and rigorously demonstrated. Although SARS-CoV-2 shedding likely occurs in a high proportion of patients, gastrointestinal symptoms affect only a subset of individuals. Herein, we summarize what is known about gastrointestinal symptoms and fecal viral shedding in COVID-19, explore the role of the gut microbiome in other respiratory diseases, speculate on the role of the gut microbiota in COVID-19, and discuss potential future directions. Taking these concepts together, we propose that studying gut microbiota perturbations in COVID-19 will enhance our understanding of the symptomology and pathophysiology of this novel devastating disease.


Subject(s)
Abdominal Pain/etiology , COVID-19/complications , Diarrhea/etiology , Gastrointestinal Microbiome , Nausea/etiology , Vomiting/etiology , Abdominal Pain/diagnosis , Abdominal Pain/microbiology , Abdominal Pain/pathology , Animals , COVID-19/diagnosis , COVID-19/microbiology , COVID-19/pathology , Diarrhea/diagnosis , Diarrhea/microbiology , Diarrhea/pathology , Feces/microbiology , Feces/virology , Humans , Nausea/diagnosis , Nausea/microbiology , Nausea/pathology , SARS-CoV-2/isolation & purification , Vomiting/diagnosis , Vomiting/microbiology , Vomiting/pathology
19.
Neurogastroenterol Motil ; 33(3): e14104, 2021 03.
Article in English | MEDLINE | ID: covidwho-1085279

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with gastrointestinal and hepatic manifestation in up to one fifth of patients. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of COVID-19, infects gastrointestinal epithelial cells expressing angiotensin-converting enzyme 2 (ACE2) receptors triggering a cascade of events leading to mucosal and systemic inflammation. Symptomatic patients display changes in gut microbiota composition and function which may contribute to intestinal barrier dysfunction and immune activation. Evidence suggests that SARS-CoV-2 infection and related mucosal inflammation impact on the function of the enteric nervous system and the activation of sensory fibers conveying information to the central nervous system, which, may at least in part, contribute symptom generation such as vomiting and diarrhea described in COVID-19. Liver and pancreas dysfunctions have also been described as non-respiratory complications of COVID-19 and add further emphasis to the common view of SARS-CoV-2 infection as a systemic disease with multiorgan involvement. PURPOSE: The aim of this review was to highlight the current knowledge on the pathophysiology of gastrointestinal SARS-CoV-2 infection, including the crosstalk with the gut microbiota, the fecal-oral route of virus transmission, and the potential interaction of the virus with the enteric nervous system. We also review the current available data on gastrointestinal and liver manifestations, management, and outcomes of patients with COVID-19.


Subject(s)
COVID-19/complications , COVID-19/physiopathology , Gastrointestinal Diseases/etiology , Gastrointestinal Diseases/physiopathology , Gastrointestinal Microbiome/physiology , Gastrointestinal Tract/physiopathology , Animals , Diarrhea/etiology , Diarrhea/physiopathology , Diarrhea/virology , Dysbiosis/etiology , Dysbiosis/physiopathology , Dysbiosis/virology , Enteric Nervous System/physiopathology , Enteric Nervous System/virology , Gastrointestinal Diseases/virology , Gastrointestinal Tract/virology , Humans , Liver Diseases/etiology , Liver Diseases/physiopathology , Liver Diseases/virology , Pancreatic Diseases/etiology , Pancreatic Diseases/physiopathology , Pancreatic Diseases/virology
20.
Twin Res Hum Genet ; 23(6): 316-321, 2020 12.
Article in English | MEDLINE | ID: covidwho-1072088

ABSTRACT

Susceptibility to infection such as SARS-CoV-2 may be influenced by host genotype. TwinsUK volunteers (n = 3261) completing the C-19 COVID-19 symptom tracker app allowed classical twin studies of COVID-19 symptoms, including predicted COVID-19, a symptom-based algorithm to predict true infection, derived from app users tested for SARS-CoV-2. We found heritability of 49% (32-64%) for delirium; 34% (20-47%) for diarrhea; 31% (8-52%) for fatigue; 19% (0-38%) for anosmia; 46% (31-60%) for skipped meals and 31% (11-48%) for predicted COVID-19. Heritability estimates were not affected by cohabiting or by social deprivation. The results suggest the importance of host genetics in the risk of clinical manifestations of COVID-19 and provide grounds for planning genome-wide association studies to establish specific genes involved in viral infectivity and the host immune response.


Subject(s)
COVID-19/etiology , COVID-19/epidemiology , COVID-19/genetics , Diarrhea/etiology , Diarrhea/genetics , Diarrhea/virology , Diseases in Twins , Fatigue/etiology , Fatigue/genetics , Fatigue/virology , Humans , Mobile Applications , Prevalence , Self Report , Twins, Dizygotic , Twins, Monozygotic
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