Neurological Manifestations in COVID-19 Infection: A Systematic Review and Meta-Analysis.

BACKGROUND: Growing evidence showed that coronavirus disease 2019 (COVID-19) infection may present with neurological manifestations. This review aimed to determine the neurological manifestations and complications in COVID-19. METHODS: We conducted a systematic review and meta-analysis that included cohort and case series/reports involving a population of patients confirmed with COVID-19 infection and their neurologic manifestations. We searched the following electronic databases until April 18, 2020: PubMed, Embase, Scopus, and World Health Organization database (PROSPERO registration number: CRD42020180658). RESULTS: From 403 articles identified, 49 studies involving a total of 6,335 confirmed COVID-19 cases were included. The random-effects modeling analysis for each neurological symptom showed the following proportional point estimates with 95% confidence intervals: "headache" (0.12; 0.10-0.14; I2 = 77%), "dizziness" (0.08; 0.05-0.12; I2 = 82%), "headache and dizziness" (0.09; 0.06-0.13; I2 = 0%), "nausea" (0.07; 0.04-0.11; I2 = 79%), "vomiting" (0.05; 0.03-0.08; I2 = 74%), "nausea and vomiting" (0.06; 0.03-0.11; I2 = 83%), "confusion" (0.05; 0.02-0.14; I2 = 86%), and "myalgia" (0.21; 0.18-0.25; I2 = 85%). The most common neurological complication associated with COVID-19 infection was vascular disorders (n = 23); other associated conditions were encephalopathy (n = 3), encephalitis (n = 1), oculomotor nerve palsy (n = 1), isolated sudden-onset anosmia (n = 1), Guillain-Barré syndrome (n = 1), and Miller-Fisher syndrome (n = 2). Most patients with neurological complications survived (n = 14); a considerable number of patients died (n = 7); and the rest had unclear outcomes (n = 12). CONCLUSION: This review revealed that neurologic involvement may manifest in COVID-19 infection. What has initially been thought of as a primarily respiratory illness has evolved into a wide-ranging multi-organ disease.

Gastrointestinal manifestations of COVID-19: results from a European centre.

BACKGROUND: Infection due to severe acute respiratory syndrome coronavirus 2 is typically associated with a respiratory syndrome, but gastrointestinal symptoms have been described in early reports from China. However, data from European centres are scarce. OBJECTIVES: We aimed to characterise the gastrointestinal manifestations of patients with coronavirus disease 2019 (COVID-19) and their disease course. METHODS: Patients admitted at our centre between March and April 2020 with diagnosis of COVID-19 were included. Asymptomatic patients or those without symptom information were excluded. Clinical features, laboratory data and disease severity (mechanical ventilation, intensive care admission or death) were analysed. RESULTS: Two-hundred one patients were included (median age 71 years; 56.2% male). Digestive symptoms were reported by 60 (29.9%) patients during the disease course, being part of the disease presentation in 34 (16.9%). The most frequent were diarrhoea in 36 patients (17.9%). Patients with gastrointestinal symptoms were younger (P = 0.032), had higher haemoglobin levels (P = 0.002) and lower C-reactive protein (P = 0.045) and potassium levels (P = 0.004). Patients with digestive symptoms had less severe disease (28.3 vs. 44.0%; P = 0.038). Regarding liver damage, aspartate aminotransferase (AST) was elevated in 65.2% of patients and alanine aminotransferase (ALT) in 62.7%, but these patients did not present a more severe disease (elevated AST P = 0.062; elevated ALT P = 0.276). CONCLUSION: A significant portion of COVID-19 patients have digestive symptoms, mostly at presentation. This should be taken into account in order to keep a high level of suspicion to reach an early diagnosis and setup infection control measures to control the transmission rate. This subgroup of patients appears to have a less severe disease course.

Distinguishing active pediatric COVID-19 pneumonia from MIS-C.

IMPORTANCE: Active pediatric COVID-19 pneumonia and MIS-C are two disease processes requiring rapid diagnosis and different treatment protocols. OBJECTIVE: To distinguish active pediatric COVID-19 pneumonia and MIS-C using presenting signs and symptoms, patient characteristics, and laboratory values. DESIGN: Patients diagnosed and hospitalized with active COVID-19 pneumonia or MIS-C at Children's of Alabama Hospital in Birmingham, AL from April 1 through September 1, 2020 were identified retrospectively. Active COVID-19 and MIS-C cases were defined using diagnostic codes and verified for accuracy using current US Centers for Disease Control case definitions. All clinical notes were reviewed for documentation of COVID-19 pneumonia or MIS-C, and clinical notes and electronic medical records were reviewed for patient demographics, presenting signs and symptoms, prior exposure to or testing for the SARS-CoV-2 virus, laboratory data, imaging, treatment modalities and response to treatment. FINDINGS: 111 patients were identified, with 74 classified as mild COVID-19, 8 patients as moderate COVID-19, 8 patients as severe COVID-19, 10 as mild MIS-C and 11 as severe MIS-C. All groups had a male predominance, with Black and Hispanic patients overrepresented as compared to the demographics of Alabama. Most MIS-C patients were healthy at baseline, with most COVID-19 patients having at least one underlying illness. Fever, rash, conjunctivitis, and gastrointestinal symptoms were predominant in the MIS-C population whereas COVID-19 patients presented with predominantly respiratory symptoms. The two groups were similar in duration of symptomatic prodrome and exposure history to the SARS-CoV-2 virus, but MIS-C patients had a longer duration between presentation and exposure history. COVID-19 patients were more likely to have a positive SAR-CoV-2 PCR and to require respiratory support on admission. MIS-C patients had lower sodium levels, higher levels of C-reactive protein, erythrocyte sedimentation rate, d-dimer and procalcitonin. COVID-19 patients had higher lactate dehydrogenase levels on admission. MIS-C patients had coronary artery changes on echocardiography more often than COVID-19 patients. CONCLUSIONS AND RELEVANCE: This study is one of the first to directly compare COVID-19 and MIS-C in the pediatric population. The significant differences found between symptoms at presentation, demographics, and laboratory findings will aide health-care providers in distinguishing the two disease entities.

Potential intestinal infection and faecal-oral transmission of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to more than 200 countries and regions globally. SARS-CoV-2 is thought to spread mainly through respiratory droplets and close contact. However, reports have shown that a notable proportion of patients with coronavirus disease 2019 (COVID-19) develop gastrointestinal symptoms and nearly half of patients confirmed to have COVID-19 have shown detectable SARS-CoV-2 RNA in their faecal samples. Moreover, SARS-CoV-2 infection reportedly alters intestinal microbiota, which correlated with the expression of inflammatory factors. Furthermore, multiple in vitro and in vivo animal studies have provided direct evidence of intestinal infection by SARS-CoV-2. These lines of evidence highlight the nature of SARS-CoV-2 gastrointestinal infection and its potential faecal-oral transmission. Here, we summarize the current findings on the gastrointestinal manifestations of COVID-19 and its possible mechanisms. We also discuss how SARS-CoV-2 gastrointestinal infection might occur and the current evidence and future studies needed to establish the occurrence of faecal-oral transmission.

Clinical characteristics of hospitalized and home isolated COVID-19 patients with type 1 diabetes.

BACKGROUND AND AIMS: To elucidate the clinical features of COVID-19 patients with type 1 diabetes (T1D) under hospitalization and home isolation conditions. METHOD: This retrospective study was conducted among 32 patients with COVID-19 and T1D, who sought treatment at the Prince Sultan Military Medical City, Riyadh, Saudi Arabia between May 01, 2020 and July 30, 2020. Patients data were extracted from electronic medical records. RESULTS: Of the total of 32 COVID-19 patients with T1D, 21.9% required hospitalization, while 78.1% underwent home isolation. Among the study population, 9.4% (3/32) were reported to have hypertension, 21.9% (7/32) had chronic pulmonary disease (CPD), 18.8% (6/32) had thyroid disorders, and 18.8% (6/32) had the celiac disease. Of the 32 studied patients, 68.8% (22/32) of them were reported as normal, while 28.1% (9/32) had chronic kidney disease (CKD) II and 3.1% (1/32) had end-stage renal failure. The most common symptoms observed among the hospitalized patients were nausea and vomiting (71.4%; 5/7), followed by fever (57.1%; 4/7), cough (42.8%; 3/7), sore throat (42.8%; 3/7), abdominal pain (42.8%; 3/7) and dyspnea (42.%; 3/7). The most common reasons for hospitalization were diabetic ketoacidosis (71.4%; 5/7) followed by bacterial pneumonia (14.3%; 1/7), fever (14.3%; 1/7), sore throat (14.3%; 1/7), severe hyperglycemia (14.3%; 1/7) and COVID-19 pneumonia (14.3%; 1/7). Except the severity of COVID-19 (p = 0.0001), none of the demographic and clinical parameters indicated statistically significant differences between patients requiring hospitalization and home isolation. CONCLUSION: Majority of the COVID-19 patients with T1D recovered with conservative treatment at home. Diabetic ketoacidosis was the most common reason for hospitalization.

Value of chest imaging in the newborn with suspected COVID-19.

OBJECTIVE: This paper presents a newborn (G2P2, gestational age of 39+6 weeks, birth weight of 3,200 g, with normal fetal amniotic fluid) with suspected coronavirus disease 2019 (COVID-19) admitted to our hospital on February 10, 2020, at the birth age of 16 hours and 34 minutes. The Apgar scores at 1 and 5 min were 9 and 10 points, respectively. PATIENTS AND METHODS: The mother of the newborn was exposed to a patient with COVID-19 five days before delivery. The newborn had nausea and vomiting after birth, with feeding intolerance, and full enteral feeding was given on the 6th day after birth. The newborn was in good general condition during the period of hospitalization. RESULTS: The two 2019-nCoV nucleic acid tests of the newborn were negative on the 5th and 7th days after birth. On the 1st and 8th days after birth, typical pulmonary lesions were detected in the newborn by chest CT. Our study supports that chest imaging examination should be actively performed in the newborn even with a negative 2019-nCoV nucleic acid test in cases where a pregnant woman is exposed to a patient with COVID-19 or is confirmed with 2019-nCoV infection. CONCLUSIONS: For newborns with typical pulmonary lesions, strict quarantine measures are suggested if the possibility of COVID-19 cannot be excluded.

Clinical Characteristics of COVID-19 Patients With Gastrointestinal Symptoms in Northern Italy: A Single-Center Cohort Study.

INTRODUCTION: The most typical presentation of COVID-19 is an acute respiratory syndrome whose most common symptoms include fever, cough, and dyspnea. However, gastrointestinal symptoms, such as diarrhea and nausea/vomiting, are increasingly reported in patients affected by COVID-19. This study aimed to describe the prevalence and time of onset of gastrointestinal symptoms in patients affected by COVID-19 and to find potential associations between gastrointestinal symptoms and clinical outcomes. METHODS: We performed a prospective single-center cohort study, enrolling patients who received diagnosis of COVID-19 at our institution between March 23, 2020, and April 5, 2020. We collected patient demographics and medical history, laboratory data, and clinical outcomes. Furthermore, we used a specifically designed questionnaire, administered to patients at time of diagnosis, to obtain data on the presence and time of onset of fever, typical respiratory symptoms, gastrointestinal symptoms, and other symptoms (fatigue, headache, myalgia/arthralgia, anosmia, ageusia/dysgeusia, sore throat, and ocular symptoms). RESULTS: In our cohort, 138 (69%) of 190 patients showed at least 1 gastrointestinal symptom at diagnosis; if excluding hyporexia/anorexia, 93 patients (48.9%) showed at least 1 gastrointestinal symptom. Gastrointestinal symptoms, in particular diarrhea, were associated with a lower mortality. At multivariate analysis, diarrhea was confirmed as independent predictive factor of lower mortality. DISCUSSION: Gastrointestinal symptoms are very frequent in patients with COVID-19 and may be associated with a better prognosis. These data suggest that, in some patients, the gastrointestinal tract may be more involved than the respiratory system in severe acute respiratory syndrome coronavirus 2 infection, and this could account for the less severe course of disease.

Focus on uncommon symptoms of COVID-19: Potential reason for spread of infection.

Focus on uncommon symptoms of COVID-19: Potential reason for spread of infection.

Clinical characteristics of coronavirus disease (COVID-19) patients with gastrointestinal symptoms: A report of 164 cases.

Objective: To explore the clinical characteristics of Coronavirus Disease (COVID-19) patients with gastrointestinal symptoms. Methods: The clinical data of 164 COVID-19 patients with gastrointestinal symptoms were extracted and analysed retrospectively. Results: In total, 505 COVID-19 patients were divided into two groups: those with gastrointestinal symptoms (G group) and those without gastrointestinal symptoms (NG group). Common gastrointestinal symptoms included inappetence, diarrhoea, nausea, abdominal pain, and vomiting. Significantly higher proportions of patients with fever, dizziness, myalgia, and fatigue were noted in group G than in group NG. Compared with patients without fever, there was a significant difference between G group and NG group in moderate fever or above, while there was no significant difference between the two groups in low fever. The laboratory results showed that patients in the G group had significantly higher C-reactive protein, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase levels than those in the NG group. Moreover, the proportion of patients with severe pneumonia was significantly higher in the G group than in the NG group. Conclusion: In Wuhan, the proportion of COVID-19 patients who experience gastrointestinal symptoms is relatively high. Patients who experience gastrointestinal symptoms are more likely to suffer from severe pneumonia, which may help clinicians identify patients at high risk of COVID-19 and thus reduce the incidence of this condition.

Where are we with understanding of COVID-19?

Coronavirus disease 2019 caused by SARS-CoV-2 originated from China and spread across every corner of the world. The scientific interest on COVID-19 increased after WHO declared it a pandemic in the early February of 2020. In fact, this pandemic has had a worldwide impact on economy, health, and lifestyle like no other in the last 100 years. SARS-CoV-2 belongs to Coronaviridae family and causes the deadliest clinical manifestations when compared to other viruses in the family. COVID-19 is an emerging zoonotic disease that has resulted in over 383,000 deaths around the world. Scientists are scrambling for ideas to develop treatment and prevention strategies to thwart the disease condition. In this review, we have attempted to summarize the latest information on the virus, disease, prevention, and treatment strategies. The future looks promising.

Atypical manifestations of COVID-19 in general practice: a case of gastrointestinal symptoms.

During the previous months, we have seen the rapid pandemic spread of SARS-CoV-2. Despite being considered a respiratory virus, it has become clear that other clinical presentations are possible and some of these are quite frequent. In this paper, a case of a man in his late 70s showing atypical symptoms in general practice is presented. Apart from fever, the patient complained of diarrhoea, borborygmus, loss of appetite and nausea. He developed no respiratory symptoms during his disease. Due to his symptoms, malignant disease was suspected, and he was referred for further testing which revealed typical COVID-19 findings on a chest CT scan. The occurrence of atypical symptoms is discussed, including the importance of recognising these in an ongoing pandemic.

Heart transplant recipient patient with COVID-19 treated with tocilizumab.

A heart transplant 62-year-old patient referred for coronavirus-19 disease (COVID-19) pneumonia. At admission, he was febrile, tachypnoeic, and mild hypoxic with dry cough; during hospitalization, a diffuse morbilliform skin rash appeared. He was treated with tocilizumab with symptoms improvement, without a complete pulmonary function recovery. Skin rash, highly suggestive for COVID-19 cutaneous involvement, persisted for ten days despite tocilizumab administration.

Clinical Insights into the Gastrointestinal Manifestations of COVID-19.

The month of December 2019 became a critical part of the time of humanity when the first case of coronavirus disease 2019 (COVID-19) was reported in the Wuhan, Hubei Province in China. As of April 13th, 2020, there have been approximately 1.9 million cases and 199,000 deaths across the world, which were associated with COVID-19. The COVID-19 is the seventh coronavirus to be identified to infect humans. In the past, Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome were the two coronaviruses that infected humans with a high fatality, particularly among the elderly. Fatalities due to COVID-19 are higher in patients older than 50 years of age or those with multimorbid conditions. The COVID-19 is mainly transmitted through respiratory droplets, with the most common symptoms being high fever, cough, myalgia, atypical symptoms included sputum production, headache, hemoptysis and diarrhea. However, the incubation period can range from 2 to 14 days without any symptoms. It is particularly true with gastrointestinal (GI) symptoms in which patients can still shed the virus even after pulmonary symptoms have resolved. Given the high percentage of COVID-19 patients that present with GI symptoms (e.g., nausea and diarrhea), screening patients for GI symptoms remain essential. Recently, cases of fecal-oral transmission of COVID-19 have been confirmed in the USA and China, indicating that the virus can replicate in both the respiratory and digestive tract. Moreover, the epidemiology, clinical characteristics, diagnostic procedures, treatments and prevention of the gastrointestinal manifestations of COVID-19 remain to be elucidated.

The emergence of a novel coronavirus (SARS-CoV-2) disease and their neuroinvasive propensity may affect in COVID-19 patients.

An outbreak of a novel coronavirus (SARS-CoV-2) infection has recently emerged and rapidly spreading in humans causing a significant threat to international health and the economy. Rapid assessment and warning are crucial for an outbreak analysis in response to serious public health. SARS-CoV-2 shares highly homological sequences with SARS-CoVs causing highly lethal pneumonia with respiratory distress and clinical symptoms similar to those reported for SARS-CoV and MERS-CoV infections. Notably, some COVID-19 patients also expressed neurologic signs like nausea, headache, and vomiting. Several studies have reported that coronaviruses are not only causing respiratory illness but also invade the central nervous system through a synapse-connected route. SARS-CoV infections are reported in both patients and experimental animals' brains. Interestingly, some COVID-19 patients have shown the presence of SARS-CoV-2 virus in their cerebrospinal fluid. Considering the similarities between SARS-CoV and SARS-CoV-2 in various aspects, it remains to clarify whether the potent invasion of SARS-CoV-2 may affect in COVID-19 patients. All these indicate that more detailed criteria are needed for the treatment and the prevention of SARS-CoV-2 infected patients. In the absence of potential interventions for COVID-19, there is an urgent need for an alternative strategy to control the spread of this disease.

The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients.

Following the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), another highly pathogenic coronavirus named SARS-CoV-2 (previously known as 2019-nCoV) emerged in December 2019 in Wuhan, China, and rapidly spreads around the world. This virus shares highly homological sequence with SARS-CoV, and causes acute, highly lethal pneumonia coronavirus disease 2019 (COVID-19) with clinical symptoms similar to those reported for SARS-CoV and MERS-CoV. The most characteristic symptom of patients with COVID-19 is respiratory distress, and most of the patients admitted to the intensive care could not breathe spontaneously. Additionally, some patients with COVID-19 also showed neurologic signs, such as headache, nausea, and vomiting. Increasing evidence shows that coronaviruses are not always confined to the respiratory tract and that they may also invade the central nervous system inducing neurological diseases. The infection of SARS-CoV has been reported in the brains from both patients and experimental animals, where the brainstem was heavily infected. Furthermore, some coronaviruses have been demonstrated able to spread via a synapse-connected route to the medullary cardiorespiratory center from the mechanoreceptors and chemoreceptors in the lung and lower respiratory airways. Considering the high similarity between SARS-CoV and SARS-CoV2, it remains to make clear whether the potential invasion of SARS-CoV2 is partially responsible for the acute respiratory failure of patients with COVID-19. Awareness of this may have a guiding significance for the prevention and treatment of the SARS-CoV-2-induced respiratory failure.