The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has highlighted the potential exacerbation of gastrointestinal symptoms in patients with disorders of gut-brain interaction (DGBIs). However, the distinct symptom trajectories and psychological burden in patients with post-COVID-19 DGBIs compared with patients with pre-existing irritable bowel syndrome (IBS)/functional dyspepsia (FD) and non-DGBI controls remain poorly understood.

To examine the long-term gastrointestinal symptom progression and psychological comorbidities in patients with post-COVID-19 DGBI, patients with pre-existing IBS/FD and non-DGBI controls.

This post hoc analysis of a prospective multicenter cohort study reviewed patient charts for demographic data and medical history. Participants completed the Gastrointestinal Symptom Rating Scale at four time points: baseline, 1, 6, and 12 months, and the Hospital Anxiety and Depression Scale at 6 and 12 months. The cohort was divided into three groups: (1) post-COVID-19 DGBIs (2) non-DGBI, and (3) pre-existing IBS/FD, with the post-COVID-19 DGBIs group compared to the latter two control groups.

Among 599 eligible patients, 27 (4.5%) were identified as post-COVID-19 DGBI. This group experienced worsening abdominal pain, hunger pain, heartburn, and acid regurgitation, unlike symptom improvement or stability in non-DGBI controls (p < 0.001 for all symptoms, except hunger pain, p = 0.001). While patients with pre-existing IBS/FD improved in most gastrointestinal symptoms but worsened in constipation and incomplete evacuation, patients with post-COVID-19 DGBI exhibited consistent symptom deterioration across multiple gastrointestinal domains. Anxiety and depression remained unchanged in patients with post-COVID-19 DGBI, contrasting with significant reductions in controls (non-DGBI: p = 0.003 and p = 0.057; pre-existing IBS/FD: p = 0.019 and p = 0.007, respectively).

COVID-19 infection is associated with the development of newly diagnosed DGBIs and distinct symptom trajectories when compared with patients with pre-existing IBS/FD. Patients with post-COVID-19 DGBI experience progressive gastrointestinal symptom deterioration and persistent psychological distress, underscoring the need for tailored management strategies for this unique subgroup.

Several Ephedra Herb-containing Kampo medicines are common initial treatments for various infections; however, the ephedrine alkaloids in Ephedra Herb can cause side effects by stimulating adrenergic receptors. Accordingly, an ephedrine alkaloids-free Ephedra Herb Extract (EFE) has been developed. This study aimed to evaluate whether EFE can be used effectively and safely in patients with mild coronavirus disease 2019 (COVID-19). We randomized patients with mild COVID-19 to receive EFE equivalent to 6 g of Ephedra Herb per day or a placebo for 14 days. The primary efficacy endpoint was the non-aggravation rate up to Day 15. We allocated 41 and 40 patients to the EFE and placebo groups, respectively. All participants were included in the mITT and safety analysis populations [male ratio, mean age: 31.7%, 42.0 years (EFE); 17.5%, 43.2 years (placebo)]. The non-aggravation rate up to Day 15 for the primary endpoint was 100.0% and 94.6% in the EFE and placebo group, respectively, with no between-group difference. The number of days to the improvement in nausea symptoms was significantly shorter in the EFE group. One patient in the placebo group discontinued the trial due to a side effect. Although EFE demonstrated safety in patients with mild COVID-19, it did not show superior efficacy compared to placebo for symptoms other than nausea.

This study aims to assess the feasibility of evaluating the COVID-19 epidemic trend through monitoring the positive percentage of SARS-CoV-19 RNA in wastewater.

The study collected data from January to August 2023, including the number of reported cases, the positive ratio of nucleic acid samples in sentinel hospitals, the incidence rate of influenza-like symptoms in students, and the positive ratio of wastewater samples in different counties and districts in Shangrao City. Wastewater samples were obtained through grabbing and laboratory testing was completed within 24 h. The data were then normalized using Z-score normalization and analyzed for lag time and correlation using the xcorr function and Spearman correlation coefficient.

A total of 2797 wastewater samples were collected. The wastewater monitoring study, based on sampling point distribution, was divided into two phases. Wuyuan County consistently showed high levels of positive ratio in wastewater samples in both phases, reaching peak values of 91.67% and 100% respectively. The lag time analysis results indicated that the peak positive ratio in all wastewater samples in Shangrao City appeared around 2 weeks later compared to the other three indicators. The correlation analysis revealed a strong linear correlation across all four types of data, with Spearman correlation coefficients ranging from 0.783 to 0.977, all of which were statistically significant.

The positive ratio of all wastewater samples in Shangrao City accurately reflected the COVID-19 epidemic trend from January to August 2023. This study confirmed the lag effect of wastewater percent positive and its strong correlation with the reported incidence rate and the positive ratio of nucleic acid samples in sentinel hospitals, supporting the use of wastewater percent positive monitoring as a supplementary tool for infectious disease surveillance in the regions with limited resources.

Cancer patients are particularly vulnerable to the psychological sequels of COVID-19 due to their immunocompromised state and the disruptions to their regular oncological care. There is limited research comparing the effects of SARS-CoV-2 on cancer patients and their co-living individuals. This study aims to explore the similarities and differences in physical and psychological outcomes between these two groups, with a 1-year follow-up to assess long-term effects.

This retrospective observational study was conducted between January and February 2023. A total of 107 participants were included: 72 cancer patients and 35 co-living individuals, all diagnosed with COVID-19. Clinical and laboratory data were collected. Depression, anxiety, and fatigue were assessed at two timepoints: shortly after COVID-19 diagnosis and 1 year later.

Cancer patients exhibited higher rates of gastrointestinal symptoms, such as diarrhea (20.83% vs. 5.71%, p = 0.045), which were associated with increased anxiety and depression (p < 0.05). Advanced-stage cancer (p < 0.01) and lack of vaccination (p < 0.01) correlated with worse psychological outcomes. Female cancer patients reported higher depression scores (p < 0.05). Laboratory findings indicated higher neutrophil percentages (p < 0.001), fibrinogen (p < 0.001), and D-dimer levels (p = 0.015) in cancer patients, signaling a higher risk of inflammation and thrombosis. Both groups showed improvements in depression and fatigue over the 1-year follow-up, but cancer patients continued to report greater psychological distress (p < 0.001) and fatigue (p = 0.024).

Cancer patients infected with COVID-19 experienced more severe physical and psychological symptoms compared to their co-living individuals, with persistent differences 1 year after infection.

ChiCTR2300067577.

Background: Post-COVID-19 irritable bowel syndrome (PCIBS) is a frequent finding and is frequently associated with enteral dysbiosis. This pilot study compared the effects of extracts from curcuma and boswellia on PCIBS and irritable bowel syndrome (IBS) in individuals who had never had a COVID-19 infection (controls). Methods: A total of 16 subjects with PCIBS and 28 controls with evidence of IBS gastrointestinal symptoms and with enteral dysbiosis were recruited and supplemented for 30 days with sunflower-lecithin-based formulations of extracts of Curcuma longa (500 mg) and Boswellia serrata (150 mg) b.i.d. and with low-FODMAP diet. Abdominal bloating, abdominal pain, enteral dysbiosis (as increased urinary indican), and the global assessment of efficacy (GAE) were evaluated at the end of the study. Results: In both cohorts, intra-cohort changes revealed a statistically significant (p < 0.05) reduction in bloating and abdominal pain. The GAE showed similar and relevant satisfactory rates in both groups. On the contrary, urinary indican values showed a significant decrease only in the IBS group. Conclusions: Supplementation with Curcuma and Boswellia has favorable effects on abdominal bloating and abdominal pain of subjects with PCIBS and with IBS, while enteral dysbiosis is significantly decreased only in patients with IBS. Additional studies are needed to confirm these preliminary findings and to clarify the reasons for the persistence of dysbiosis in PCIBS.

Intra-host viral variability is related to pathogenicity, persistence, drug resistance, and the emergence of new clades. This work reviews the large amount of data on SARS-CoV-2 intra-host variability accumulated to date, addressing known and potential implications in COVID-19 and the emergence of VOCs and lineage-defining mutations. Topics covered include the distribution of intra-host polymorphisms across the genome, the corresponding mutational signatures, their patterns of emergence and extinction throughout infection, and the processes governing their abundance, frequency, and type (synonymous, nonsynonymous, indels, nonsense). Besides, evidence is reviewed that the virus can replicate and mutate in isolation at different anatomical compartments, which may imply that what we have learned from respiratory samples could be part of a broader picture.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is common in children, and clinical manifestations can vary depending on age, underlying disease, and vaccination status. Most children will have asymptomatic or mild infection, but certain baseline characteristics can increase the risk of moderate to severe disease. The following article will provide an overview of the clinical manifestations of coronavirus disease 2019 in children, including the post-infectious phenomenon called multisystem inflammatory syndrome in children. Currently available treatment and prophylaxis strategies will be outlined, with the caveat that new therapeutics and clinical efficacy data are constantly on the horizon.

The widespread impact of the coronavirus disease 2019 (COVID-19) epidemic on human health causes sudden lifestyle changes, through social distancing and isolation at home, with social and economic consequences. This qualitative study aimed to identify the lived experiences of recovered adult patients from COVID-19 in Iran.

This qualitative research was conducted using a national phenomenological approach. The participants were patients who recovered from COVID-19 through their treatment period in the hospital or at home. Semi-structured in-depth interviews were applied for 45 participants who were invited using purposeful sampling and continued to achieve data saturation. The five-stage inductive process to analyze the structure of lived experience (IPSE) approach was used to analyze the data using MAXQDA 2020 software.

According to the statements of the participants in the study, five types of experiences extracted during the period of suffering from the disease: nutritional problems, physical problems, the psychological burden caused by the disease, the supporting role of others in the disease tolerance, and the unpleasant and better experiences of the disease.

Patients with COVID-19 disease experience many physical and psychosocial consequences which affect their quality of life. Therefore, sociopsychological support provided by psychologists and family members can have ameliorating effects in reducing disease consequences. Further interventional studies were needed to capture these aspects of diseases.

The coronavirus disease 2019 (COVID-19) pandemic has affected millions of people worldwide, and although it is primarily a respiratory illness, gastrointestinal symptoms have been reported in a significant proportion of patients.

Prevalence of gastrointestinal symptoms after recovery from COVID-19.

A community-based cross-sectional study was conducted in the Aseer region of Saudi Arabia. The study population included individuals aged 18 years or older with COVID-19 and living in the Aseer region. The data were collected through a pretested, structured online questionnaire preceded by consent and were used to maintain the confidentiality of the data. The questionnaire covered participants' data, COVID-19 infection status, and gastrointestinal tract symptoms during and after recovery from the infection.

A total of 409 participants in the Aseer region completed the study survey. The participants' ages ranged from 18 to more than 50 years, with a mean age of 34.5 ± 11.9 years. A total of 205 (50.1%) participants were females. A total of 263 (64.3%) of the study participants experienced gastrointestinal tract symptoms during COVID-19 infection. Additionally, 203 (49.6%) of the study participants had gastrointestinal tract symptoms after recovering from COVID-19 infection. The most commonly reported symptoms were diarrhea (13.2%), nausea (13.2%), anorexia (12.7%), abdominal pain (11%), and constipation. Male sex who suffered form severe COVID-19 infection, and gastrointestinal tract symptoms during acute infection were significantly associated with post-COVID-19 gastrointestinal tract symptoms (p < 0.05).

In conclusion, the current study showed that nearly two-thirds of active COVID-19 patients experienced gastrointestinal tract symptoms. Additionally, approximately half of the COVID-19 patients who recovered had gastrointestinal tract-related symptoms, but few of those patients had gastrointestinal tract-related symptoms within 1 week.

Measuring virus in biofluids is complicated by confounding biomolecules coisolated with viral nucleic acids. To address this, we developed an affinity-based microfluidic device for specific capture of intact severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our approach used an engineered angiotensin-converting enzyme 2 to capture intact virus from plasma and other complex biofluids. Our device leverages a staggered herringbone pattern, nanoparticle surface coating, and processing conditions to achieve detection of as few as 3 viral copies per milliliter. We further validated our microfluidic assay on 103 plasma, 36 saliva, and 29 stool samples collected from unique patients with COVID-19, showing SARS-CoV-2 detection in 72% of plasma samples. Longitudinal monitoring in the plasma revealed our device's capacity for ultrasensitive detection of active viral infections over time. Our technology can be adapted to target other viruses using relevant cell entry molecules for affinity capture. This versatility underscores the potential for widespread application in viral load monitoring and disease management.

The mucosal immune system, as the most extensive peripheral immune network, serves as the frontline defense against a myriad of microbial and dietary antigens. It is crucial in preventing pathogen invasion and establishing immune tolerance. A comprehensive understanding of mucosal immunity is essential for developing treatments that can effectively target diseases at their entry points, thereby minimizing the overall impact on the body. Despite its importance, our knowledge of mucosal immunity remains incomplete, necessitating further research. The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has underscored the critical role of mucosal immunity in disease prevention and treatment. This systematic review focuses on the dynamic interactions between mucosa-associated lymphoid structures and related diseases. We delve into the basic structures and functions of these lymphoid tissues during disease processes and explore the intricate regulatory networks and mechanisms involved. Additionally, we summarize novel therapies and clinical research advances in the prevention of mucosal immunity-related diseases. The review also addresses the challenges in developing mucosal vaccines, which aim to induce specific immune responses while maintaining tolerance to non-pathogenic microbes. Innovative therapies, such as nanoparticle vaccines and inhalable antibodies, show promise in enhancing mucosal immunity and offer potential for improved disease prevention and treatment.

Coronavirus disease 2019 (COVID-19) is a global pandemic with high mortality, and the treatment options for the severe patients remain limited. Previous studies reported the altered gut microbiota in severe COVID-19. But there are no comprehensive data on the role of microbial metabolites in COVID-19 patients.

We identified 153 serum microbial metabolites and assessed the changes in 72 COVID-19 patients upon admission and one-month after their discharge, comparing these changes to those in 133 healthy control individuals from the outpatient department during the same period.

Our study revealed that microbial metabolites varied across different stages and severity of COVID-19 patients. These altered microbial metabolites included tryptophan, bile acids, fatty acids, amino acids, vitamins and those containing benzene. A total of 13 distinct microbial metabolites were identified in COVID-19 patients compared to healthy controls. Notably, correlations were found among these disrupted metabolites and organ injury and inflammatory responses related to COVID-19. Furthermore, these metabolites did not restore to the normal levels one month after discharge. Importantly, two microbial metabolites were the core microbial metabolites related to the severity of COVID-19 patients.

The microbial metabolites were altered in the acute and recovery stage, correlating with disease severity of COVID-19. These results indicated the important role of gut microbiota in the progression of COVID-19, and facilitated the potential therapeutic microbial target for severe COVID-19 patients.

Post-acute coronavirus disease 2019 (COVID-19) syndrome (PACS) is the persistence of sequel of acute SARS-COV-2 infection. Persistent/acquired gastrointestinal symptoms (GI-PACS) include loss of appetite, nausea, weight loss, abdominal pain, heartburn, dysphagia, altered bowel motility, dyspepsia, and irritable bowel syndrome. The study aimed to assess the short- and long-term GI-PACS syndrome on the GSRS scale.

A cross-sectional, retrospective record analysis and telephonic questionnaire-based survey were conducted at a tertiary referral center in northern India. The data incorporated patients treated from April 2021 to March 2023. Exclusion criteria were neurological disorders, dementia, inability to understand Hindi/English languages, and psychiatric problems. All patients who met the inclusion criteria were telephonically called from November 2023 to January 2024.

The study population was 350 recovered patients from SARS-COVID-19 illness. Forty-three responses were removed during data cleaning and removal of duplication. The data analysis of 307 participants (ICU admissions=92, non-ICU admissions=123, and outdoor treatment =92) was done. The proportion of patients not having any GI symptoms, having at least one GI symptom, and having more than one GI symptom before SARS-COV-2 illness was 3%(3/307), 4.9% (15/307), and 3.6% (11/307), respectively. The four major GI symptoms analyzed in the study were vomiting, pain in the abdomen, diarrhea, and constipation. Overall, 13% (40/307) of the study population did not have any major GI symptoms before SARS-COV-2 diseases. During acute SARS-COV-2 illness, 86.97% (267/307) of patients develop new GI symptoms. Post SARS-COV-2 illness, the overall mean GSRS score for 15 items was 2.14 ± 0.829. The acquired GI-PACS was abdominal pain syndrome (mean score 2.5190 ± SD 0.86650), constipation syndrome (mean score 2.3844 ± 0.83840), reflux syndrome (mean score 2.2866 ± 1.31889), indigestion syndrome (mean score 1.8591 ± 0.93076), and diarrhea syndrome (mean score 1.8122 ± 0.90899). Overall, fever (95.1%, P = 0.007), anosmia (45.0%, P = 0.042), cough (80.1%, P = 0.032), and hospitalization (30.0%, P = 0.003) had a more significant association with one of the major four GI symptoms during the acute phase of SARS-COV-2 illness. Home-isolated patients having loss of appetite (95.4%, P = 0.0001) had a significant association with one of the major four GI symptoms during the acute phase of SARS-COV-2 illness. Hospitalized patients having fever (80.7%, P = 0.031), breathlessness (83.8%, P = 0.003), loss of smell (97.0%, P = 0.001), and cough (82.7%, P = 0.048) had a more significant association with one of the major four GI symptoms during the acute SARS-COV-2 illness. Abdominal pain, reflux, and constipation were considered severe GI symptoms (symptom GSRS score greater than total mean GSRS score). Diarrhea and indigestion were considered mild symptoms (symptom GSRS score was less than the total mean GSRS score). The GI symptoms during acute SARS-COV-2 illness recovered in 66.1% (203/307) patients within 3 months. The respondents taking medicines for more than 1 year following SARS-COV-2 illness were 19.2%. 12.0% (37/307) of respondents suffered from persistent GI symptoms on a mean follow-up of 20.1 ± 0.82 months.

Long-term COVID-19 syndrome frequently manifested as GI symptoms, whereas most symptoms subsided with time.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered an unprecedented public health crisis known as the coronavirus disease 2019 (COVID-19) pandemic. Gastrointestinal (GI) symptoms develop in patients during acute infection and persist after recovery from airway distress in a chronic form of the disease (long COVID). A high incidence of irritable bowel syndrome (IBS) manifested by severe abdominal pain and defecation pattern changes is reported in COVID patients. Although COVID is primarily considered a respiratory disease, fecal shedding of SARS-CoV-2 antigens positively correlates with bowel symptoms. Active viral infection in the GI tract was identified by human intestinal organoid studies showing SARS-CoV-2 replication in gut epithelial cells. In this review, we highlight the key findings in post-COVID bowel symptoms and explore possible mechanisms underlying the pathophysiology of the illness. These mechanisms include mucosal inflammation, gut barrier dysfunction, and microbiota dysbiosis during viral infection. Viral shedding through the GI route may be the primary factor causing the alteration of the microbiome ecosystem, particularly the virome. Recent evidence in experimental models suggested that microbiome dysbiosis could be further aggravated by epithelial barrier damage and immune activation. Moreover, altered microbiota composition has been associated with dysregulated serotonin pathways, resulting in intestinal nerve hypersensitivity. These mechanisms may explain the development of post-infectious IBS-like symptoms in long COVID. Understanding how coronavirus infection affects gut pathophysiology, including microbiome changes, would benefit the therapeutic advancement for managing post-infectious bowel symptoms.

Post-Acute Sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID, represents a significant and complex health challenge with a wide range of symptoms affecting multiple organ systems. This review examines the emerging evidence suggesting a critical role of the gut and gut-brain axis in the pathophysiology of Long COVID. It explores how changes in the gut microbiome, disruption of gut barrier integrity, and the persistence of SARS-CoV-2 antigens within the gastrointestinal tract may contribute to the prolonged and varied symptoms seen in Long COVID, including chronic inflammation and neuropsychiatric disturbances. The review also summarizes key insights gained about Long COVID, highlighting its multifactorial nature, which involves immune dysregulation, microvascular damage, and autonomic nervous system dysfunction, with the gut playing a central role in these processes. While progress has been made in understanding these mechanisms, current evidence remains inconclusive. The challenges of establishing causality, standardizing research methodologies, and addressing individual variations in the microbiome are discussed, emphasizing the need for further longitudinal studies and more comprehensive approaches to enhance our understanding of these complex interactions. This review underscores the importance of personalized approaches in developing effective diagnostic and therapeutic strategies for Long COVID, while also acknowledging the significant gaps in our current understanding. Future research should aim to further unravel the complex interplay between the gut and Long COVID, ultimately improving outcomes for those affected by this condition.

The association and interaction between SARS-CoV-2 (COVID-19) infection and irritable bowel syndrome (IBS) has not been adequately explored. We sought to determine whether a mechanistic relationship exists and whether vaccination against COVID-19 plays a role in this relationship.

Using the Veterans Affairs (VA) electronic healthcare database, we obtained a random sample of veterans in October 2022 for this cross-sectional study. Demographic characteristics of the participants (e.g., age, sex, race), prior COVID infection, COVID vaccination status, and IBS diagnosis were extracted from the VA medical records. Univariate and multivariate logistic regression analyses were performed to determine potential associations between the listed factors and IBS diagnosis.

A total of 9,112 veterans were analyzed. In univariate analysis, race, COVID infection, and vaccination were significantly associated with IBS. In multivariate regression analysis, only the effects of COVID infection and vaccination were statistically significant. The odds ratios for development of IBS among veterans with COVID infection versus those without was 1.94 (95% CI: 1.53-2.45), and for vaccinated versus unvaccinated, was 1.49 (95% CI: 1.18-1.89). Further analysis showed that vaccinated veterans who did not contract COVID infection had a lower risk of developing IBS compared to unvaccinated veterans who contracted COVID.

The results of this study suggest that veterans with COVID infection are almost twice as likely to develop IBS compared to those who have never had COVID infection. Vaccinated veterans have a lower risk of contracting COVID and subsequently, a diminished chance of developing IBS. Overall, vaccination of veterans with protection against COVID diminishes the risk of IBS development.

Purpose: The study was to evaluate the physical condition and mental health of Chinese college student COVID-19 survivors, and to perform severity clustering of physical symptoms. Participants: The study finally included 1912 Chinese college students. Methods: A total of 33 symptoms including general physical symptoms, cardiopulmonary system, digestive system, neurological system, mental health and other symptoms were investigated three months after recovery from COVID-19, and these symptoms are identified using latent class analysis. Results: Three clusters were identified through latent class analysis: 13.2% with severe impairment (cluster 1), 27.2% with mild physical symptoms (cluster 2), and 59.5% with no or mild symptoms (cluster 3). The students who smoked, drank alcohol, did not exercise, or had a history of underlying medical conditions were more likely to have moderate to severe symptoms. Conclusions: Young COVID-19 survivors with a history of underlying diseases and unhealthy habits are more likely to have moderate to severe COVID-19 sequelae. Varying degrees of symptoms should be treated with different rehabilitation plans.

Long Covid is defined by a wide range of symptoms that persist after the acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Commonly reported symptoms include fatigue, weakness, postexertional malaise, and cognitive dysfunction, with many other symptoms reported. Symptom range, duration, and severity are highly variable and partially overlap with symptoms of myalgic encephalomyelitis/chronic fatigue syndrome and other post-acute infectious syndromes, highlighting opportunities to define shared mechanisms of pathogenesis. Potential mechanisms of Long Covid are diverse, including persistence of viral reservoirs, dysregulated immune responses, direct viral damage of tissues targeted by SARS-CoV-2, inflammation driven by reactivation of latent viral infections, vascular endothelium activation or dysfunction, and subsequent thromboinflammation, autoimmunity, metabolic derangements, microglial activation, and microbiota dysbiosis. The heterogeneity of symptoms and baseline characteristics of people with Long Covid, as well as the varying states of immunity and therapies given at the time of acute infection, have made etiologies of Long Covid difficult to determine. Here, we examine progress on preclinical models for Long Covid and review progress being made in clinical trials, highlighting the need for large human studies and further development of models to better understand Long Covid. Such studies will inform clinical trials that will define treatments to benefit those living with this condition.

Wastewater-based epidemiological surveillance has proven to be a useful and cost-effective tool for detecting COVID-19 outbreaks. Here, our objective was to evaluate its potential as an early warning system in Venezuela by detecting SARS-CoV-2 RNA in wastewater and its correlation with reported cases of COVID-19. Viral RNA was concentrated from wastewater collected at various sites in Caracas (northern Venezuela), from September 2021 to July 2023, using the polyethylene glycol (PEG) precipitation method. Viral quantification was performed by RT-qPCR targeting the N1 and ORF1ab genes. A significant association (p < 0.05) was found between viral load in wastewater and reported cases of COVID-19 up to six days after sampling. During the whole study, two populated areas of the city were persistent hotspots of viral infection. The L452R mutation, suggestive of the presence of the Delta variant, was identified in the only sample where a complete genomic sequence could be obtained. Significant differences (p < 0.05) between the physicochemical conditions of the wastewater samples positive and negative for the virus were found. Our results support proof of concept that wastewater surveillance can serve as an early warning system for SARS-CoV-2 outbreaks, complementing public health surveillance in those regions where COVID-19 is currently underreported.

Increasing evidence suggests bats are the ancestral hosts of the majority of coronaviruses. In general, coronaviruses primarily target the gastrointestinal system, while some strains, especially Betacoronaviruses with the most relevant representatives SARS-CoV, MERS-CoV, and SARS-CoV-2, also cause severe respiratory disease in humans and other mammals. We previously reported the susceptibility of Rousettus aegyptiacus (Egyptian fruit bats) to intranasal SARS-CoV-2 infection. Here, we compared their permissiveness to an oral infection versus respiratory challenge (intranasal or orotracheal) by assessing virus shedding, host immune responses, tissue-specific pathology, and physiological parameters. While respiratory challenge with a moderate infection dose of 1 × 104 TCID50 caused a systemic infection with oral and nasal shedding of replication-competent virus, the oral challenge only induced nasal shedding of low levels of viral RNA. Even after a challenge with a higher infection dose of 1 × 106 TCID50, no replication-competent virus was detectable in any of the samples of the orally challenged bats. We postulate that SARS-CoV-2 is inactivated by HCl and digested by pepsin in the stomach of R. aegyptiacus, thereby decreasing the efficiency of an oral infection. Therefore, fecal shedding of RNA seems to depend on systemic dissemination upon respiratory infection. These findings may influence our general understanding of the pathophysiology of coronavirus infections in bats.

Phenotypes are important for patient classification, disease prognostication, and treatment customization. We aimed to identify distinct clinical phenotypes of children and adolescents hospitalized with SARS-CoV-2 infection, and to evaluate their prognostic differences.

The German Society of Pediatric Infectious Diseases (DGPI) registry is a nationwide, prospective registry for children and adolescents hospitalized with a SARS-CoV-2 infection in Germany. We applied hierarchical clustering for phenotype identification with variables including sex, SARS-CoV-2-related symptoms on admission, pre-existing comorbidities, clinically relevant coinfection, and SARS-CoV-2 risk factors. Outcomes of this study were: discharge status and ICU admission. Discharge status was categorized as: full recovery, residual symptoms, and unfavorable prognosis (including consequential damage that has already been identified as potentially irreversible at the time of discharge and SARS-CoV-2-related death). After acquiring the phenotypes, we evaluated their correlation with discharge status by multinomial logistic regression model, and correlation with ICU admission by binary logistic regression model. We conducted an analogous subgroup analysis for those aged < 1 year (infants) and those aged ⩾ 1 year (non-infants).

The DGPI registry enrolled 6983 patients, through which we identified six distinct phenotypes for children and adolescents with SARS-CoV-2 which can be characterized by their symptom pattern: phenotype A had a range of symptoms, while predominant symptoms of patients with other phenotypes were gastrointestinal (95.9%, B), asymptomatic (95.9%, C), lower respiratory tract (49.8%, D), lower respiratory tract and ear, nose and throat (86.2% and 41.7%, E), and neurological (99.2%, F). Regarding discharge status, patients with D and E phenotype had the highest odds of having residual symptoms (OR: 1.33 [1.11, 1.59] and 1.91 [1.65, 2.21], respectively) and patients with phenotype D were significantly more likely (OR: 4.00 [1.95, 8.19]) to have an unfavorable prognosis. Regarding ICU, patients with phenotype D had higher possibility of ICU admission than staying in normal ward (OR: 4.26 [3.06, 5.98]), compared to patients with phenotype A. The outcomes observed in the infants and non-infants closely resembled those of the entire registered population, except infants did not exhibit typical neurological/neuromuscular phenotypes.

Phenotypes enable pediatric patient stratification by risk and thus assist in personalized patient care. Our findings in SARS-CoV-2-infected population might also be transferable to other infectious diseases.

This study focused on the gastrointestinal (GI) symptoms in the omicron variant infection and the related factors based on digestive health.

A cross-sectional study was conducted on individuals infected with the omicron variant. A structured questionnaire was developed to gather their demographic characteristics, preexisting digestive problems (diseases & symptoms), and clinical manifestations during the infection.

11,484 questionnaires were received from online platforms. 7,929 infected participants were selected based on inclusion and exclusion criteria. Among them, 4,225 (53.3%) were females, and the mean age was 36.0±8.8 years old. In general, the proportion of GI symptoms in the omicron variant infection was 31.4% (62.6% and 25.0% in participants with pre-existing digestive problems and those without, respectively). The participants with pre-existing digestive problems exhibited more severe clinical manifestations during infection compared to those without. Notably, participants with gastrointestinal symptoms during the infection had more severe clinical manifestations, regardless of basic digestive health. Upper, rather than lower GI symptoms were more closely associated with the severity of the clinical manifestations. NSAIDs may increase the occurrence of GI symptoms in participants with a healthy digestive system but not in those with preexisting digestive problems.

Patients infected with the omicron variant may experience more severe clinical symptoms if they have gastrointestinal issues. Digestive health strongly influences the occurrence of gastrointestinal symptoms and the severity of clinical manifestations.

SARS-CoV-2 infects via the respiratory tract, but COVID-19 includes an array of non-respiratory symptoms, among them gastrointestinal (GI) manifestations such as vomiting and diarrhea. Here we investigated the GI pathology of SARS-CoV-2 infections in rhesus macaques and humans. Macaques experienced mild infection with USA-WA1/2020 and shed viral RNA in the respiratory tract and stool, including subgenomic RNA indicative of replication in the GI tract. Intestinal immune cell populations were disturbed, with significantly fewer proliferating (Ki67+) jejunal B cells in SARS-CoV-2-infected macaques than uninfected ones. Modest translocation of bacteria/bacterial antigen was observed across the colonic epithelium, with a corresponding significant increase in plasma soluble CD14 (sCD14) that may be induced by LPS. Human plasma demonstrated significant decreases in interleukin (IL)-6 and sCD14 upon recovery from COVID-19, suggesting resolution of inflammation and response to translocated bacteria. sCD14 significantly positively correlated with zonulin, an indicator of gut barrier integrity, and IL-6. These results demonstrate that GI perturbations such as microbial translocation can occur in even mild SARS-CoV-2 infections and may contribute to the COVID-19 inflammatory state.IMPORTANCEThis study investigates gastrointestinal (GI) barrier disruption in SARS-CoV-2 infections and how it may contribute to disease. We observed bacteria or bacterial products crossing from the colon interior (the lumen) to the lamina propria during SARS-CoV-2 infection in macaques. Bacteria/bacterial products are tolerated in the lumen but may induce immune responses if they translocate to the lamina propria. We also observed a significant increase in soluble CD14, which is associated with an immune response to bacterial products. In addition, we observed that humans recovering from COVID-19 experienced a significant decrease in soluble CD14, as well as the inflammatory marker interleukin (IL)-6. IL-6 and sCD14 correlated significantly across macaque and human samples. These findings suggest that SARS-CoV-2 infection results in GI barrier disruption that permits microbial translocation and a corresponding immune response. These findings could aid in developing interventions to improve COVID-19 patient outcomes.

Many studies report the importance of using feces as source sample for detecting SARS-CoV-2 in patients with COVID-19 symptoms but who are negative to oropharyngeal/ nasopharyngeal tests. Here, we report the case of an asymptomatic child whose family members had negative results with the rapid antigen nasopharyngeal swab tests. The 21-month-old child presented with fever, diarrhea, bilateral conjunctivitis, and conspicuous lacrimation. In this study, analysis for the presence of SARS-CoV-2 in fecal samples by using Luminex technology allowed accurate detection of the presence of the viral RNA in the feces of the child and of all her relatives, which thus resulted to be positive but asymptomatic. It is the first time that SARS-CoV-2- is observed inside the bacteria of the human gut microbiome and outside a matrix resembling extracellular bacterial lysates, in agreement with a bacteriophage mechanism with the images obtained by transmission electron microscopy (TEM), post-embedding immunogold, and by fluorescence microscope. In addition to the typical observations of respiratory symptoms, accurate evaluation of clinical gastrointestinal and neurological symptoms, combined with efficient highly sensitive molecular testing on feces, represent an efficient approach for detecting SARS-CoV-2, and for providing the correct therapy in challenging COVID-19 cases, like the one here reported.

Although wastewater-based epidemiology (WBE) successfully functioned as a tool for monitoring the coronavirus disease 2019 (COVID-19) pandemic globally, relatively little is known about its utility in low-income countries. This study aimed to quantify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in wastewater, estimate the number of infected individuals in the catchment areas, and correlate the results with the clinically reported COVID-19 cases in Addis Ababa, Ethiopia.

A total of 323 influent and 33 effluent wastewater samples were collected from three Wastewater Treatment Plants (WWTPs) using a 24-h composite Moore swab sampling method from February to November 2023. The virus was captured using Ceres Nanotrap® Enhancement Reagent 2 and Nanotrap® Microbiome A Particles, and then nucleic acids were extracted using the Qiagen QIAamp Viral RNA Mini Kit. The ThermoFisher TaqPath™ COVID-19 kit was applied to perform real-time reverse transcriptase polymerase chain reaction (qRT-PCR) to quantify the SARS-CoV-2 RNA. Wastewater viral concentrations were normalized using flow rate and number of people served. In the sampling period, spearman correlation was used to compare the SARS-CoV-2 target gene concentration to the reported COVID-19 cases. The numbers of infected individuals under each treatment plant were calculated considering the target genes' concentration, the flow rate of treatment plants, a gram of feces per person-day, and RNA copies per gram of feces.

SARS-CoV-2 was detected in 94% of untreated wastewater samples. All effluent wastewater samples (n = 22) from the upflow anaerobic sludge blanket (UASB) reactor and membrane bioreactor (MBR) technology were SARS-COV-2 RNA negative. In contrast, two out of 11 effluents from Waste Stabilization Pond were found positive. Positive correlations were observed between the weekly average SARS-CoV-2 concentration and the cumulative weekly reported COVID-19 cases in Addis Ababa. The estimated number of infected people in the Kality Treatment catchment area was 330 times the number of COVID-19 cases reported during the study period in Addis Ababa.

This study revealed that SARS-CoV-2 was circulating in the community and confirmed previous reports of more asymptomatic COVID-19 cases in Ethiopia. Additionally, this study provides further evidence of the importance of wastewater-based surveillance in general to monitor infectious diseases in low-income settings.

Wastewater-based surveillance of SARS-CoV-2 can be a useful method for tracking the increment of COVID-19 cases before it spreads widely throughout the community.

Different works suggest a close link between long COVID gastrointestinal (GI) manifestations and the post-infection disorders of gut-brain interaction (PI-DGBIs). However, the actual mechanisms underlying long-term GI sequelae are still not clear. Our study was aimed to assess both intestinal inflammation and permeability among subjects recovered from SARS-CoV-2 infection and their eventual correlation with long-term GI sequelae.

Eighty-six subjects attending the post-COVID service and recovered from SARS-CoV-2 infection for 6 months were investigated for long COVID manifestations. Those subjects complaining of long-term GI symptoms were further evaluated by Rome IV questionnaire to assess PI-DGBIs. Intestinal inflammation (by fecal calprotectin, FC) and permeability (by serum and fecal levels of zonulin) were evaluated in all subjects. The Hospital Anxiety and Depression Scale (HADS) and the Gastrointestinal Quality of Life Index (GIQLI) questionnaires were further provided to all participants.

Thirty-seven subjects (43%) complained of long-term GI symptoms, while 49 subjects (57%) did not. Thirty-three subjects fulfilled Rome IV criteria for PI-DGBIs. FC values resulted higher in those subjects who did not complain GI symptoms (p = 0.03), although remaining quite close to the normal range. No significant differences were shown regarding the assessment of intestinal permeability. By GIQLI, long-term GI sequelae were inversely correlated with quality of life (p = 0.009).

Long COVID GI complaints unlikely recognize underlying local inflammatory mechanisms. Since the healthcare, economic, and social burden of post-COVID DGBIs, a deeper understanding of this emerging condition should be encouraged to improve management of the affected subjects.

Background: Early detection and monitoring of SARS-CoV-2 infections in animal populations living in close proximity to humans is crucial for preventing reverse zoonosis of new viral strains. Evidence accumulated has revealed widespread SARS-CoV-2 infection among white-tailed deer (WTD), (Odocoileus virginianus) populations in the United States except in the southeast region. Therefore, the objective was to conduct surveillance for evidence of SARS-CoV-2 infection among WTD in Mississippi. Materials and Methods: Blood, kidney tissues, and nasal swab samples were collected in 17 counties from hunter-harvested deer during 2021-2022 and 2022-2023.Samples of kidney tissue were collected to evaluate for detecting antibody as a possible alternative to blood that is not always available from dead WTD. Nasal swab samples were tested for SARS-CoV-2 viral RNA by a RT-PCR assay. Sera and kidney tissue samples were tested for SARS-CoV-2 antibody by an enzyme-linked immunoassay (ELISA) and sera by a plaque reduction neutralization test (PRNT80). Results: The results of testing sera and kidney homogenate samples provided the first evidence of SARS-CoV-2 infection among WTD in Mississippi. The infection rate during 2021-2022 was 67% (10/15) based on the detection of neutralizing antibody by the PRNT80 and 26%(16/62) based on the testing of kidney tissue homogenates by an ELISA, and viral RNA was detected in 25% (3/12) of nasal swab samples. In 2022 to 2023, neutralizing antibody was detected in 62% (28/45) of WTD serum samples. In contrast, antibodies were not detected in 220 kidney homogenates by an ELISA nor was viral RNA detected in 220 nasal swab samples. Evidence of WTD activity was common in urban areas during the survey. Conclusion: Overall, the findings documented the first SARS-CoV-2 infection among WTD in Mississippi and showed that WTD commonly inhabited urban areas as a possible source of acquiring infection from humans infected with this virus.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been detected or isolated from domestic cats. It is unclear whether cats play an important role in the SARS-CoV-2 transmission cycle. In this study, we examined the susceptibility of cats to SARS-CoV-2, including wild type and variants, by animal experiments. Cats inoculated with wild type, gamma, and delta variants secreted a large amount of SARS-CoV-2 for 1 week after the inoculation from nasal, oropharyngeal, and rectal routes. Only 100 TCID50 of virus could infect cats and replicate well without severe clinical symptoms. In addition, one cat inoculated with wild type showed persistent virus secretion in feces for over 28 days post-inoculation (dpi). The titer of virus-neutralizing (VN) antibodies against SARS-CoV-2 increased from 11 dpi, reaching a peak at 14 dpi. However, the omicron variant could not replicate well in cat tissues and induced a lower titer of VN antibodies. It is concluded that cats were highly susceptible to SARS-CoV-2 infection, but not to the Omicron Variant, which caused the attenuated pathogenicity.

Coronavirus disease-2019 (COVID-19), caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), is an emergent disease that threatens global health. Public health structures and economic activities have been disrupted globally by the COVID-19 pandemic. Over 556.3 million confirmed cases and 6.3 million deaths have been reported. However, the exact mechanism of its emergence in humans remains unclear. SARS-CoV-2 is believed to have a zoonotic origin, suggesting a spillover route from animals to humans, which is potentially facilitated by wildlife farming and trade. The COVID-19 pandemic highlighted the importance of the One Health approach in managing threats of zoonosis in the human-animal-environment interaction. Implementing vigilant surveillance programs by adopting the One Health concept at the interfaces between wildlife, livestock, and humans is the most pertinent, practical, and actionable strategy for preventing and preparing for future pandemics of zoonosis, such as COVID-19 infection. This review summarizes the updated evidence of CoV infections in humans and animals and provides an appropriate strategy for preventive measures focused on surveillance systems through an On Health approach.

The impact of coronavirus disease 2019 (COVID-19) history on Crohn's disease (CD) is unknown. This investigation aimed to examine the effect of COVID-19 history on the disease course, oral-gut microbiota, and serum metabolomics in patients with CD. In this study, oral-gut microbiota and serum metabolomic profiles in 30 patients with CD and a history of mild COVID-19 (positive group, PG), 30 patients with CD without COVID-19 history (negative group, NG), and 60 healthy controls (HC) were assessed using 16S rDNA sequencing and targeted metabolomics. During follow-up, the CD activity index showed a stronger decrease in the PG than in the NG (p = 0.0496). PG patients demonstrated higher α-diversity and distinct β-diversity clustering in both salivary and fecal microbiota compared to NG and HC individuals. Notably, the gut microbiota composition in the PG patients showed a significantly greater similarity to that of HC than NG individuals. The interaction between oral and intestinal microbiota in the PG was reduced. Moreover, serum metabolome analysis revealed significantly increased anti-inflammatory metabolites, including short-chain fatty acids and N-Acetylserotonin, among PG patients; meanwhile, inflammation-related metabolites such as arachidonic acid were significantly reduced in this group. Our data suggest that the gut microbiota mediates a potential beneficial effect of a mild COVID-19 history in CD patients.

Since the coronavirus disease 2019 (COVID-19) pandemic, wastewater-based epidemiology (WBE) has been widely applied in many countries and regions for monitoring COVID-19 transmission in the population through testing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in wastewater. However, the amount of virus shed by individuals over time based on the stage of infection and accurate number of infections in the community creates challenges in predicting COVID-19 prevalence in the population and interpreting WBE results. In this study, we measured SARS-CoV-2, pepper mild mottle virus (PMMoV), and human mitochondrial DNA (mtDNA) in longitudinal fecal samples collected from 42 COVID-19 patients for up to 42 days after diagnosis. SARS-CoV-2 RNA was detected in 73.1% (19/26) of inpatient study participants in at least one of the collected fecal specimens during the sampling period. Most participants shed the virus within 3 weeks after diagnosis, but five inpatient participants still shed the virus between 20 and 60 days after diagnosis. The median concentration of SARS-CoV-2 in positive fecal samples was 1.08 × 105 genome copies (GC)/gram dry fecal material. PMMoV and mtDNA were detected in 99.4% (154/155) and 100% (155/155) of all fecal samples, respectively. The median concentrations of PMMoV RNA and mtDNA in fecal samples were 1.73 × 107 and 2.49 × 108 GC/dry gram, respectively. These results provide important information about the dynamics of fecal shedding of SARS-CoV-2 and two human fecal indicators in COVID-19 patients. mtDNA showed higher positive rates, higher concentrations, and less variability between and within individuals than PMMoV, suggesting that mtDNA could be a better normalization factor for WBE results than PMMoV.