Interaction between gut microbiota and COVID-19 and its vaccines

The whole world has been continuously afflicted by the coronavirus disease 2019 (COVID-19) pandemic for the past 3 years. Many countries have tried many methods to control this virus infection with varying successes and failures. The gut microbiota is a biosystem spanning the entire length of the digestive tract and playing important roles in health and disease. It is much affected by COVID-19. In return it also substantially impacts infection. In particular, the gut microbiota has established a bidirectional interaction with the COVID-19 vaccines, enhancing or reducing vaccine efficacy by virtue of its varying components. Conversely, COVID-19 vaccines also make a substantial impact on the gut microbiota, re-ducing its overall population and biodiversity. It is hoped that by exploring and harnessing this bidirectional interaction we may break new ground and develop new methods to prevent and treat this formidable virus infection.     

Altered gut microbiota patterns in COVID-19: Markers for inflammation and disease severity

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to a severe respiratory illness and alters the gut microbiota, which dynamically interacts with the human immune system. Microbiota alterations include decreased levels of beneficial bacteria and augmentation of opportunistic pathogens. Here, we describe critical factors affecting the microbiota in coronavirus disease 2019 (COVID-19) patients. These include, such as gut microbiota imbalance and gastrointestinal symptoms, the pattern of altered gut microbiota composition in COVID-19 patients, and crosstalk between the microbiome and the gut-lung axis/gut-brain-lung axis. Moreover, we have illustrated the hypoxia state in COVID-19 associated gut microbiota alteration. The role of ACE2 in the digestive system, and control of its expression using the gut microbiota is discussed, highlighting the interactions between the lungs, the gut, and the brain during COVID-19 infection. Similarly, we address the gut microbiota in elderly or co-morbid patients as well as gut microbiota dysbiosis of in severe COVID-19. Several clinical trials to understand the role of probiotics in COVID-19 patients are listed in this review. Augmented inflammation is one of the major driving forces for COVID-19 symptoms and gut microbiome disruption and is associated with disease severity. However, understanding the role of the gut microbiota in immune modulation during SARS-CoV-2 infection may help improve therapeutic strategies for COVID-19 treatment.     

COVID-19 and splenectomy: Education matters

Whether COVID-19-related morbidity and mortality are increased in splenectomized patients is unknown. The study by Bianchi et al. suggests increased hospitalizations and mortality rates in splenectomized patients, despite observing similar infection rates when compared to the general population. Commentary on: Bianchi et al. Burden of COVID19 disease and vaccine coverages in Apulian splenectomized patients. A retrospective observational study. Br J Haematol 2023;201:1072–1080.     

Gastrointestinal and hepatic manifestations of COVID-19:A comprehensive review

The severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2) that causes coronavirus disease-2019(COVID-19) is a global pandemic, manifested by an infectious pneumonia. Although patients primarily present with fever, cough and dyspnea, some patients also develop gastrointestinal(GI) and hepatic manifestations. The most common GI symptoms reported are diarrhea, nausea,vomiting, and abdominal discomfort. Liver chemistry abnormalities are common and include elevation of aspartate transferase, alanine transferase, and total bilirubin. Studies have shown that SARS-CoV-2 infects the GI tract via its viral receptor angiotensin converting enzyme Ⅱ, which is expressed on enterocytes of the ileum and colon. Viral RNA has also been isolated from stool specimens of COVID-19 patients, which raised the concern for fecal-oral transmission in addition to droplet transmission. Although indirect evidence has suggested possible fecal-oral transmission of SARS-CoV-2, more effort is needed to establish the role of the fecal-oral transmission route. Further research will help elucidate the association between patients with underlying GI diseases, such as chronic liver disease and inflammatory bowel disease, and severity of COVID-19. In this review, we summarize the data on GI involvement to date, as well as the impact of COVID-19 on underlying GI diseases.     

Impact of COVID-19 Lockdown on the Nasopharyngeal Microbiota of Children and Adults Self-Confined at Home

The increased incidence of COVID-19 cases and deaths in Spain in March 2020 led to the declaration by the Spanish government of a state of emergency imposing strict confinement measures on the population. The objective of this study was to characterize the nasopharyngeal microbiota of children and adults and its relation to SARS-CoV-2 infection and COVID-19 severity during the pandemic lockdown in Spain. This cross-sectional study included family households located in metropolitan Barcelona, Spain, with one adult with a previous confirmed COVID-19 episode and one or more exposed co-habiting child contacts. Nasopharyngeal swabs were used to determine SARS-CoV-2 infection status, characterize the nasopharyngeal microbiota and determine common respiratory DNA/RNA viral co-infections. A total of 173 adult cases and 470 exposed children were included. Overall, a predominance of Corynebacterium and Dolosigranulum and a limited abundance of common pathobionts including Haemophilus and Streptococcus were found both among adults and children. Children with current SARS-CoV-2 infection presented higher bacterial richness and increased Fusobacterium, Streptococcus and Prevotella abundance than non-infected children. Among adults, persistent SARS-CoV-2 RNA was associated with an increased abundance of an unclassified member of the Actinomycetales order. COVID-19 severity was associated with increased Staphylococcus and reduced Dolosigranulum abundance. The stringent COVID-19 lockdown in Spain had a significant impact on the nasopharyngeal microbiota of children, reflected in the limited abundance of common respiratory pathobionts and the predominance of Corynebacterium, regardless of SARS-CoV-2 detection. COVID-19 severity in adults was associated with decreased nasopharynx levels of healthy commensal bacteria.     

Gastrointestinal manifestations of long-term effects after COVID-19 infection in patients with dialysis or kidney transplantation: An observational cohort study

BACKGROUND Prolonged symptoms after corona virus disease 2019(Long-COVID) in dialysisdependent patients and kidney transplant(KT) recipients are important as a possible risk factor for organ dysfunctions,especially gastrointestinal(GI)problems,during immunosuppressive therapy.AIM To identify the characteristics of GI manifestations of Long-COVID in patients with dialysis-dependent or KT status.METHODS This observational,prospective study included patients with COVID-19 infection,confirmed by rev...     

Immunoregulatory Intestinal Microbiota and COVID-19 in Patients with Type Two Diabetes: A Double-Edged Sword

Coronavirus disease 2019, or COVID-19, is a major challenge facing scientists worldwide. Alongside the lungs, the system of organs comprising the GI tract is commonly targeted by COVID-19. The dysbiotic modulations in the intestine influence the disease severity, potentially due to the ability of the intestinal microbiota to modulate T lymphocyte functions, i.e., to suppress or activate T cell subpopulations. The interplay between the lungs and intestinal microbiota is named the gut–lung axis. One of the most usual comorbidities in COVID-19 patients is type 2 diabetes, which induces changes in intestinal microbiota, resulting in a pro-inflammatory immune response, and consequently, a more severe course of COVID-19. However, changes in the microbiota in this comorbid pathology remain unclear. Metformin is used as a medication to treat type 2 diabetes. The use of the type 2 diabetes drug metformin is a promising treatment for this comorbidity because, in addition to its hypoglycemic action, it can increase amount of intestinal bacteria that induce regulatory T cell response. This dual activity of metformin can reduce lung damage and improve the course of the COVID-19 disease.     

COVID-19 vaccine-associated myocarditis

Myocarditis is now recognized as a rare complication of coronavirus disease 2019 (COVID-19) mRNA vaccination, particularly in adolescent and young adult males. Since the authorization of the Pfizer-BioNTech™ and Moderna™ mRNA vaccines targeting the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein, the Centers for Disease Control and Prevention (CDC) has reported 1175 confirmed cases of myocarditis after COVID-19 vaccination in individuals ages 30 years and younger as of January 2022. According to CDC data in June 2021, the incidence of vaccine-mediated myocarditis in males ages 12-29 years old was estimated to be 40.6 cases per million second doses of COVID-19 mRNA vaccination administered. Individuals with cases of COVID-19 vaccine-mediated myocarditis typically present with acute chest pain and elevated serum troponin levels, often within one week of receiving the second dose of mRNA COVID-19 vaccination. Most cases follow a benign clinical course with prompt resolution of symptoms. Proposed mechanisms of COVID-19 vaccine myocarditis include molecular mimicry between SARS-CoV-2 spike protein and self-antigens and the triggering of preexisting dysregulated immune pathways in predisposed individuals. The higher incidence of COVID-19 vaccine myocarditis in young males may be explained by testosterone and its role in modulating the immune response in myocarditis. There is limited data on long-term outcomes in these cases given the recency of their occurrence. The CDC continues to recommend COVID-19 vaccination for everyone 5 years of age and older given the greater risk of serious complications related to natural COVID-19 infection including hospitalization, multisystem organ dysfunction, and death. Further study is needed to better understand the immunopathology and long-term outcomes behind COVID-19 mRNA vaccine-mediated myocarditis.     

COVID-19 in Nursing Homes: Calming the Perfect Storm

The pandemic of viral infection with the severe acute respiratory syndrome coronavirus-2 that causes COVID-19 disease has put the nursing home industry in crisis. The combination of a vulnerable population that manifests nonspecific and atypical presentations of COVID-19, staffing shortages due to viral infection, inadequate resources for and availability of rapid, accurate testing and personal protective equipment, and lack of effective treatments for COVID-19 among nursing home residents have created a “perfect storm” in our countryʼs nursing homes. This perfect storm will continue as society begins to reopen, resulting in more infections among nursing home staff and clinicians who acquire the virus outside of work, remain asymptomatic, and unknowingly perpetuate the spread of the virus in their workplaces. Because of the elements of the perfect storm, nursing homes are like a tinderbox, and it only takes one person to start a fire that could cause many deaths in a single facility. Several public health interventions and health policy strategies, adequate resources, and focused clinical quality improvement initiatives can help calm the storm. The saddest part of this perfect storm is that many years of inaction on the part of policy makers contributed to its impact. We now have an opportunity to improve nursing homes to protect residents and their caregivers ahead of the next storm. It is time to reimagine how we pay for and regulate nursing home care to achieve this goal. J Am Geriatr Soc 68:2153–2162, 2020.     

Steroid resistance and rebound phenomena in patients with COVID-19

BackgroundIn patients with coronavirus disease (COVID-19) pneumonia, corticosteroids reduce progression to respiratory failure and death. Some patients, however, remain unresponsive to this treatment, or experience a rebound after termination.MethodsThis retrospective cohort study included COVID-19 patients treated with systemic corticosteroids in a Japanese hospital between June 1, 2020, and January 17, 2021. Patients were categorized into three groups: success, rebound, and refractory, and clinical characteristics and outcomes were compared.ResultsA total of 319 COVID-19 patients were admitted to our hospital and 113 patients met inclusion criteria. The success group had 83 patients (73.5%), the rebound group had nine patients (8.0%), and the refractory group had 21 patients (18.6%). Compared with the success group, the rebound group received corticosteroids earlier, for a shorter duration, and stopped them sooner. The median time from symptom onset to rebound was 12 days. There was no rebound after 20 days. Compared with the success group, the hazard ratio for the number of days from corticosteroid onset to an improvement of two points on a seven-point ordinal scale was 0.29 (95% confidence interval [CI], 0.14–0.60, P < .001) for the rebound group versus 0.13 (95% CI, 0.07–0.25, P < .001) for the refractory group.ConclusionsCOVID-19 patients treated with corticosteroids were classified into three response groups: success, rebound, and refractory, between which recovery time and prognosis differed. It was found that corticosteroid administration may prevent rebound phenomena if administered at least two weeks from symptom onset.     

COVID-19 cynomolgus macaque model reflecting human COVID-19 pathological conditions

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global threat to human health and life. A useful pathological animal model accurately reflecting human pathology is needed to overcome the COVID-19 crisis. In the present study, COVID-19 cynomolgus monkey models including monkeys with underlying diseases causing severe pathogenicity such as metabolic disease and elderly monkeys were examined. Cynomolgus macaques with various clinical conditions were intranasally and/or intratracheally inoculated with SARS-CoV-2. Infection with SARS-CoV-2 was found in mucosal swab samples, and a higher level and longer period of viral RNA was detected in elderly monkeys than in young monkeys. Pneumonia was confirmed in all of the monkeys by computed tomography images. When monkeys were readministrated SARS-CoV-2 at 56 d or later after initial infection all of the animals showed inflammatory responses without virus detection in swab samples. Surprisingly, in elderly monkeys reinfection showed transient severe pneumonia with increased levels of various serum cytokines and chemokines compared with those in primary infection. The results of this study indicated that the COVID-19 cynomolgus monkey model reflects the pathophysiology of humans and would be useful for elucidating the pathophysiology and developing therapeutic agents and vaccines.

At the end of 2019, cases of infection with a novel coronavirus, later named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that causes various respiratory symptoms expanded globally from China. On 11 March 2020, the World Health Organization declared a pandemic status based on the spread of infection worldwide and increase in the number of deaths. The outbreak of SARS-CoV-2 has resulted in a miserable reality for global health and life, and infection cases are continuing to increase worldwide. A detailed understanding of pathological conditions and development of effective therapeutic agents are needed to overcome the pandemic of diseases caused by SARS-CoV-2 infection, which has been named COVID-19. A new strategy including the development of pharmaceutical products and the use of appropriate animal models reflecting the human pathogenesis of COVID-19 is required.The common clinical features of COVID-19 are respiratory symptoms associated with pneumonia including fever, cough, myalgia, fatigue, dyspnea, and lymphopenia (1). COVID-19 symptoms range from no symptoms to severe symptoms. COVID-19 has shown severe pathogenicity in people with underlying diseases and in elderly people (2, 3). The period from onset of COVID-19 symptoms to death varies depending on the age of the patient and underlying disease status of the patient (4). Therefore, in addition to elucidating the pathological features in healthy individuals, it is necessary to elucidate the pathological conditions in patients with underlying diseases and in elderly patients.Cynomolgus monkeys (CMs), which are common laboratory animals among nonhuman primates (NHPs), show various human-like characteristics, including higher brain functions, long life span, single pregnancy, and regular menstrual periods, which are not found in other experimental animals. In the present study, COVID-19 model CMs, including healthy young CMs, elderly CMs (23 to 30 y of age, equivalent to 69 to 90 y of age in humans), and CMs with underlying diseases including diabetes and hyperlipidemia were experimentally infected with SARS-CoV-2 as animal models reflecting human pathology.     

COVID-19 and male infertility: An overview of the disease

Since SARS-CoV-2 infection was first discovered in December 2019 in Wuhan City in China, it spread rapidly and a global pandemic of COVID-19 has occurred. According to several recent studies on SARS-CoV-2, the virus primarily infects the respiratory system but may cause damage to other systems. ACE-2, the main receptor for entry into the target cells by SARS-CoV-2, was reported to abundantly express in testes, including spermatogonia, Leydig and Sertoli cells. Nevertheless, there is no clinical evidence in the literature about whether SARS-CoV-2 infection has an impact on male reproductive health. Therefore, this review highlights the effect of SARA-CoV-2 infection on male reproductive health, including the reproductive system and its functioning, as well as gamete and male gonadal function that might be affected by the virus itself or secondary to immunological and inflammatory response, as well as drug treatments and the psychological stress related to panic during the COVID-19 outbreak.