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.

Serotonin Syndrome After Treatment of Nausea and Vomiting in Pregnancy.

BACKGROUND: Nausea and vomiting in pregnancy often require pharmacotherapy for symptom management. Serotonin syndrome is a rare clinical entity that can be precipitated by the medications used to treat nausea and vomiting in pregnancy. CASE: A 35-year-old pregnant individual with a history of hyperemesis gravidarum in an earlier pregnancy requiring prolonged hospitalization presented with nausea and vomiting at 7 weeks of gestation. She was incidentally found to have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection when she was universally screened at the time of admission. She required pharmacotherapy, including prochlorperazine and ondansetron for treatment of nausea as well as sumatriptan for migraine. She developed acute spasticity, autonomic dysfunction, and temperature rise, precipitated by antiemetic therapy, consistent with serotonin syndrome. The syndrome resolved with supportive care and benzodiazepines. CONCLUSION: Serotonin syndrome is a serious clinical entity that can be provoked by the pharmacotherapy given to treat nausea and vomiting in pregnancy. This medical emergency requires early recognition and prompt management.

Are gastrointestinal symptoms associated with higher risk of Mortality in COVID-19 patients? A systematic review and meta-analysis.

BACKGROUND: Gastrointestinal symptoms have been reported in patients with COVID-19. Several clinical investigations suggested that gastrointestinal symptoms were associated with disease severity of COVID-19. However, the relevance of gastrointestinal symptoms and mortality of COVID-19 remains largely unknown. We aim to investigate the relationship between gastrointestinal symptoms and COVID-19 mortality. METHODS: We searched the PubMed, Embase, Web of science and Cochrane for studies published between Dec 1, 2019 and May 1, 2021, that had data on gastrointestinal symptoms in COVID-19 patients. Additional literatures were obtained by screening the citations of included studies and recent reviews. Only studies that reported the mortality of COVID-19 patients with/without gastrointestinal symptoms were included. Raw data were pooled to calculate OR (Odds Ratio). The mortality was compared between patients with and without gastrointestinal symptoms, as well as between patients with and without individual symptoms (diarrhea, nausea/vomiting, abdominal pain). RESULTS: Fifty-three literatures with 55,245 COVID-19 patients (4955 non-survivors and 50,290 survivors) were included. The presence of GI symptoms was not associated with the mortality of COVID-19 patients (OR=0.88; 95% CI 0.71-1.09; P=0.23). As for individual symptoms, diarrhea (OR=1.01; 95% CI 0.72-1.41; P=0.96), nausea/vomiting (OR=1.16; 95% CI 0.78-1.71; P=0.46) and abdominal pain (OR=1.55; 95% CI 0.68-3.54; P=0.3) also showed non-relevance with the death of COVID-19 patients. CONCLUSIONS: Gastrointestinal symptoms are not associated with higher mortality of COVID-19 patients. The prognostic value of gastrointestinal symptoms in COVID-19 requires further investigation.

Correlation of Gastrointestinal Symptoms at Initial Presentation with Clinical Outcomes in Hospitalized COVID-19 Patients: Results from a Large Health System in the Southern USA.

BACKGROUND: We aimed to understand the association of gastrointestinal (GI) symptoms at initial presentation with clinical outcomes during COVID-19 hospitalization. METHODS: This retrospective, multicenter cohort study included consecutive hospitalized COVID-19 patients from a single, large health system. The presence of GI symptoms was assessed at initial presentation and included one or more of the following: nausea, vomiting, diarrhea and abdominal pain. Patients were divided into three cohorts: Only GI symptoms, GI and non-GI symptoms and only non-GI symptoms. The primary outcome was association of GI symptoms with mortality. Secondary outcomes included prevalence of GI symptoms and survival analysis. RESULTS: A total of 1672 COVID-19 patients were hospitalized (mean age: 63 ± 15.8 years, females: 50.4%) in our system during the study period. 40.7% patients had at least one GI symptom (diarrhea in 28.3%, nausea/vomiting in 23%, and abdominal pain in 8.8% patients), and 2.6% patients had only GI symptoms at initial presentation. Patients presenting with GI symptoms (with or without non-GI symptoms) had a lower mortality rate compared to patients presenting with only non-GI symptoms (20% vs. 26%; p < 0.05). The time from hospitalization to being discharged was less for patients presenting with only GI symptoms (7.4 days vs. > 9 days, p < 0.0014). After adjusting for other factors, the presence of GI symptoms was not associated with mortality (p > 0.05). CONCLUSION: Among a hospitalized COVID-19 positive Southern US population, 41% patients presented with either diarrhea, nausea, vomiting or abdominal pain initially. The presence of GI symptoms has no association with in-hospital all-cause mortality.

Modeling the onset of symptoms of COVID-19: Effects of SARS-CoV-2 variant.

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.

Gastrointestinal Disease and COVID-19: A Review of Current Evidence.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had an unprecedented and catastrophic impact on humanity and continues to progress. In addition to typical respiratory symptoms such as fever, cough, and dyspnea, a large percentage of COVID-19 patients experience gastrointestinal (GI) complaints, with the most common symptoms being diarrhea, nausea, vomiting, and abdominal discomfort. SUMMARY: We comprehensively summarize the latest knowledge of the adverse effects of COVID-19 and therapeutic drugs on the GI system, as well as related disease pathogenesis, and then provide a discussion focusing on the management and vaccination of patients who have inflammatory bowel disease (IBD) and GI cancer. The virus can affect the digestive system via binding to ACE2 receptors and subsequent gut microbiome dysbiosis. Through a variety of molecular pathways and mechanisms, numerous drugs for the treatment of COVID-19 could interfere with GI function and lead to multiple clinical manifestations, which may further intensify the risk and severity of GI symptoms of COVID-19 infection, such as nausea, vomiting, gastroparesis, and gastric ulcers. KEY MESSAGES: We should monitor GI manifestations closely while managing COVID-19 patients and take timely measures to reduce the incidence of SARS-CoV-2 infections in GI cancer patients. IBD patients should receive vaccination timely, but corticosteroid use should be minimized when they are vaccinated. Simultaneously, for persons with IBD who have known or suspected COVID-19, immunosuppressive agents, especially thiopurines, should be avoided/minimized if possible.

Efficacy of Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules in treatment of COVID-19: A randomized controlled trial.

BACKGROUND: With the global epidemic of coronavirus disease (COVID-19), China has made progress in the prevention and control of the epidemic, and traditional Chinese medicine (TCM) has played a key role in dealing with the disease's effects on the respiratory system. This randomized controlled clinical trial evaluated the clinical efficacy and prognosis of Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules in patients with COVID-19. METHODS: A total of 283 patients participated in this clinical trial, and participants were randomly assigned to receive either 1) Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules or 2) Linahua granules, both combined with western medicine, or 3) western medicine alone for 14 days. At the end of the trial, the improvement and resolution rates of clinical symptoms and the rate of patients who progressed to severe disease status were evaluated. RESULTS: After 14 days of treatment, there was no significant difference in the improvement rate of clinical symptoms among the three groups (P > 0.05). Huoxiang Zhengqi dropping pills combined with Lianhua Qingwen granules has advantages in the treatment of nausea, vomiting and limb soreness. During treatment, all participants were treated with western medicine, and there was a significant difference in the use of macrolides among the three groups (P < 0.05). Specifically, the utilization rate of antibiotics in the western medicine group was significantly greater than that of the other two groups. Among the 182 diagnosed patients who completed this clinical trial, 13 patients progressed to severe disease, including one case in the Huoxiang + Lianhua group (1.6 %), five cases in the Lianhua group (8.6 %), and seven cases in the western medicine group (11.1 %). There was no statistical differences in this rate among the three groups (P > 0.05). However, the proportion of patients who progressed to severe disease in the Huoxiang + Lianhua group was the lowest, suggesting that the combination of TCM with western medicine has a potential advantage in improving the prognosis of patients with COVID-19. CONCLUSION: The use of Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules combined with western medicine may have clinical advantages for COVID-19 patients in improving clinical symptoms, reducing utilization rate of anti-infective drugs, and improving patient prognosis, which could pave the way for the use of complementary medicine in treating this infection.

Hipótesis sobre las conexiones entre COVID-19 severo en niños y nutrición: una revisión narrativa.

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.

INTRODUCCIÓN: 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.

The gut microbiome: a missing link in understanding the gastrointestinal manifestations of COVID-19?

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.

Clinical Characteristics of Hospitalized Patients with COVID-19 in Sofia, Bulgaria.

Introduction: SARS-CoV-2 infection is spreading around the world, including countries from Southeastern Europe. The purpose of the study was to present the clinical manifestations of COVID-19 patients admitted to the Military Medical Academy, Sofia, Bulgaria. Materials and Methods: A retrospective study was conducted for a period of 3 months from March 2020 to June 2020 on this infection in our hospital. All participants were laboratory confirmed cases of COVID-19. RT-PCR was performed for etiological diagnosis. The hospitalized patients were divided into two groups on admission, that is, nonsevere and severe. Results: One hundred thirty-eight COVID-19 patients were hospitalized and analyzed during the study period. The mean age was 52.9 years. Male was the dominant sex (sex ratio: male/female = 1/0.6). The leading clinical signs were fever, fatigue, cough, and headache. On comparative analysis of both groups (nonsevere and severe) was measured significant elevation of white blood cells (odds ratio [OR] = 1.238; p value = 0.006), C-reactive protein (OR = 1.021; p < 0.001), creatinine (OR = 1.037; p < 0.001), aspartate aminotransferase (OR = 1.014; p = 0.040), lactate dehydrogenase (OR = 1.004; p < 0.001), ferritin (OR = 1.002; p < 0.001), fibrinogen (OR = 2.028; p < 0.001), and d-dimer (OR = 2.162; p = 0.002) in severe group than in nonsevere group. Interleukin 6 was tested in 17.4% of patients and high value was found-38.6 pg/mL (95% confidence interval: 16.5-60.7). Conclusion: The first Bulgarian retrospective study of COVID-19 hospitalized patients was presented. Older age, male sex, comorbidity, and signs of dyspnea and nausea were estimated as higher risk factors for severe form. Abnormality in inflammatory markers was associated with poor progression of the illness.

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.