Summary
The effects of coronavirus disease 2019 (COVID‐19), a highly transmissible infectious respiratory disease that has initiated an ongoing pandemic since early 2020, do not always end in the ...acute phase. Depending on the study referred, about 10%–30% (or more) of COVID‐19 survivors may develop long‐COVID or post‐COVID‐19 syndrome (PCS), characterised by persistent symptoms (most commonly fatigue, dyspnoea, and cognitive impairments) lasting for 3 months or more after acute COVID‐19. While the pathophysiological mechanisms of PCS have been extensively described elsewhere, the subtypes of PCS have not. Owing to its highly multifaceted nature, this review proposes and characterises six subtypes of PCS based on the existing literature. The subtypes are non‐severe COVID‐19 multi‐organ sequelae (NSC‐MOS), pulmonary fibrosis sequelae (PFS), myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), postural orthostatic tachycardia syndrome (POTS), post‐intensive care syndrome (PICS) and medical or clinical sequelae (MCS). Original studies supporting each of these subtypes are documented in this review, as well as their respective symptoms and potential interventions. Ultimately, the subtyping proposed herein aims to provide better clarity on the current understanding of PCS.
The accumulating knowledge of the host-microbiota interplay gives rise to the microbiota-gut-brain (MGB) axis. The MGB axis depicts the interkingdom communication between the gut microbiota and the ...brain. This communication process involves the endocrine, immune and neurotransmitters systems. Dysfunction of these systems, along with the presence of gut dysbiosis, have been detected among clinically depressed patients. This implicates the involvement of a maladaptive MGB axis in the pathophysiology of depression. Depression refers to symptoms that characterize major depressive disorder (MDD), a mood disorder with a disease burden that rivals that of heart diseases. The use of probiotics to treat depression has gained attention in recent years, as evidenced by increasing numbers of animal and human studies that have supported the antidepressive efficacy of probiotics. Physiological changes observed in these studies allow for the elucidation of probiotics antidepressive mechanisms, which ultimately aim to restore proper functioning of the MGB axis. However, the understanding of mechanisms does not yet complete the endeavor in applying probiotics to treat MDD. Other challenges remain which include the heterogeneous nature of both the gut microbiota composition and depressive symptoms in the clinical setting. Nevertheless, probiotics offer some advantages over standard pharmaceutical antidepressants, in terms of residual symptoms, side effects and stigma involved. This review outlines antidepressive mechanisms of probiotics based on the currently available literature and discusses therapeutic potentials of probiotics for depression.
Long COVID or post-COVID-19 syndrome first gained widespread recognition among social support groups and later in scientific and medical communities. This illness is poorly understood as it affects ...COVID-19 survivors at all levels of disease severity, even younger adults, children, and those not hospitalized. While the precise definition of long COVID may be lacking, the most common symptoms reported in many studies are fatigue and dyspnoea that last for months after acute COVID-19. Other persistent symptoms may include cognitive and mental impairments, chest and joint pains, palpitations, myalgia, smell and taste dysfunctions, cough, headache, and gastrointestinal and cardiac issues. Presently, there is limited literature discussing the possible pathophysiology, risk factors, and treatments in long COVID, which the current review aims to address. In brief, long COVID may be driven by long-term tissue damage (e.g. lung, brain, and heart) and pathological inflammation (e.g. from viral persistence, immune dysregulation, and autoimmunity). The associated risk factors may include female sex, more than five early symptoms, early dyspnoea, prior psychiatric disorders, and specific biomarkers (e.g. D-dimer, CRP, and lymphocyte count), although more research is required to substantiate such risk factors. While preliminary evidence suggests that personalized rehabilitation training may help certain long COVID cases, therapeutic drugs repurposed from other similar conditions, such as myalgic encephalomyelitis or chronic fatigue syndrome, postural orthostatic tachycardia syndrome, and mast cell activation syndrome, also hold potential. In sum, this review hopes to provide the current understanding of what is known about long COVID.
Severe acute respiratory syndrome coronavirus 2 may inflict a post‐viral condition known as post‐COVID‐19 syndrome (PCS) or long‐COVID. Studies measuring levels of inflammatory and vascular ...biomarkers in blood, serum, or plasma of COVID‐19 survivors with PCS versus non‐PCS controls have produced mixed findings. Our review sought to meta‐analyse those studies. A systematic literature search was performed across five databases until 25 June 2022, with an updated search on 1 November 2022. Data analyses were performed with Review Manager and R Studio statistical software. Twenty‐four biomarkers from 23 studies were meta‐analysed. Higher levels of C‐reactive protein (Standardized mean difference (SMD) = 0.20; 95% CI: 0.02–0.39), D‐dimer (SMD = 0.27; 95% CI: 0.09–0.46), lactate dehydrogenase (SMD = 0.30; 95% CI: 0.05–0.54), and leukocytes (SMD = 0.34; 95% CI: 0.02–0.66) were found in COVID‐19 survivors with PCS than in those without PCS. After sensitivity analyses, lymphocytes (SMD = 0.30; 95% CI: 0.12–0.48) and interleukin‐6 (SMD = 0.30; 95% CI: 0.12–0.49) were also significantly higher in PCS than non‐PCS cases. No significant differences were noted in the remaining biomarkers investigated (e.g., ferritin, platelets, troponin, and fibrinogen). Subgroup analyses suggested the biomarker changes were mainly driven by PCS cases diagnosed via manifestation of organ abnormalities rather than symptomatic persistence, as well as PCS cases with duration of <6 than ≥6 months. In conclusion, our review pinpointed certain inflammatory and vascular biomarkers associated with PCS, which may shed light on potential new approaches to understanding, diagnosing, and treating PCS.
Gastroschisis has increased globally over recent decades, and this increase has not been explained by identified risk factors. We conducted a population-based study of infants born in Canada, ...2004-2020. We used "winter" months (i.e., September through June) and northern areas of residence as indicators of less sunlight/less active lifestyle, while "summer" (i.e., July and August) and southern areas were considered as reference. Rate of gastroschisis for infants conceived in winter (3.4 per 10,000) was higher than for infants conceived in summer (2.2 per 10,000; p < 0.001). Exposure to winter, and northern area, hypothyroidism, substance or tobacco uses and depressive disorder were initially identified as risk factors for gastroschisis. There was a significant interaction between women < 24 years of age and 2-month conception intervals (rate ratio (RR): 1.42 (95% confidence interval CI 1.19-1.70). The association of maternal depression (mean ratio 2.19, 95% CI 0.87-3.50, p = 0.001) with infant gastroschisis was mediated by hypothyroidism (mean ratio 1.04, 95% CI 1.01-1.07, p < 0.001), whereas substance use, hypothyroidism, tobacco smoking and gestational diabetes showed 5.5-, 3.1-, 2.7-, and 1.2-fold associations, respectively, with maternal depression. In contrast to the summer conception interval of low gastroschisis risk, an elevated risk of gastroschisis spans the other ten months in association with higher levels of stress adaptation, thermoregulation and metabolism, reproduction, and growth effector hormones. Our findings suggest that periconception depression with mediation by hypothyroidism, may play a causal role in offspring gastroschisis.
Long-COVID is a postviral illness that can affect survivors of COVID-19, regardless of initial disease severity or age. Symptoms of long-COVID include fatigue, dyspnea, gastrointestinal and cardiac ...problems, cognitive impairments, myalgia, and others. While the possible causes of long-COVID include long-term tissue damage, viral persistence, and chronic inflammation, the review proposes, perhaps for the first time, that persistent brainstem dysfunction may also be involved. This hypothesis can be split into two parts. The first is the brainstem tropism and damage in COVID-19. As the brainstem has a relatively high expression of ACE2 receptor compared with other brain regions, SARS-CoV-2 may exhibit tropism therein. Evidence also exists that neuropilin-1, a co-receptor of SARS-CoV-2, may be expressed in the brainstem. Indeed, autopsy studies have found SARS-CoV-2 RNA and proteins in the brainstem. The brainstem is also highly prone to damage from pathological immune or vascular activation, which has also been observed in autopsy of COVID-19 cases. The second part concerns functions of the brainstem that overlap with symptoms of long-COVID. The brainstem contains numerous distinct nuclei and subparts that regulate the respiratory, cardiovascular, gastrointestinal, and neurological processes, which can be linked to long-COVID. As neurons do not readily regenerate, brainstem dysfunction may be long-lasting and, thus, is long-COVID. Indeed, brainstem dysfunction has been implicated in other similar disorders, such as chronic pain and migraine and myalgic encephalomyelitis or chronic fatigue syndrome.
Abstract
Background
Liver diseases post-COVID-19 vaccination is extremely rare but can occur. A growing body of evidence has indicated that portal vein thrombosis, autoimmune hepatitis, raised liver ...enzymes and liver injuries, etc., may be potential consequence of COVID-19 vaccines.
Objectives
To describe the results of a systematic review for new-onset and relapsed liver disease following COVID-19 vaccination.
Methods
For this systematic review, we searched Proquest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature through the Preferred Reporting Items for Systematic Reviews and Meta Analyses PRISMA guideline for studies on the incidence of new onset or relapsed liver diseases post-COVID-19 vaccination, published from December 1, 2020 to July 31, 2022, with English language restriction.
Results
Two hundred seventy-five cases from one hundred and eighteen articles were included in the qualitative synthesis of this systematic review. Autoimmune hepatitis (138 cases) was the most frequent pathology observed post-COVID-19 vaccination, followed by portal vein thrombosis (52 cases), raised liver enzymes (26 cases) and liver injury (21 cases). Other cases include splanchnic vein thrombosis, acute cellular rejection of the liver, jaundice, hepatomegaly, acute hepatic failure and hepatic porphyria. Mortality was reported in any of the included cases for acute hepatic failure (n = 4, 50%), portal vein thrombosis (n = 25, 48.1%), splanchnic vein thrombosis (n = 6, 42.8%), jaundice (n = 1, 12.5%), raised liver enzymes (n = 2, 7.7%), and autoimmune hepatitis (n = 3, 2.2%). Most patients were easily treated without any serious complications, recovered and did not require long-term hepatic therapy.
Conclusion
Reported evidence of liver diseases post-COIVD-19 vaccination should not discourage vaccination against this worldwide pandemic. The number of reported cases is relatively very small in relation to the hundreds of millions of vaccinations that have occurred and the protective benefits offered by COVID-19 vaccination far outweigh the risks.
Herpes simplex virus type 1 (HSV-1) as a possible infectious etiology in Alzheimer’s disease (AD) has been proposed since the 1980s. The accumulating research thus far continues to support the ...association and a possible causal role of HSV-1 in the development of AD. HSV-1 has been shown to induce neuropathological and behavioral changes of AD, such as amyloid-beta accumulation, tau hyperphosphorylation, as well as memory and learning impairments in experimental settings. However, a neuroanatomical standpoint of HSV-1 tropism in the brain has not been emphasized in detail. In this review, we propose that the hippocampal vulnerability to HSV-1 infection plays a part in the development of AD and amnestic mild cognitive impairment (aMCI). Henceforth, this review draws on human studies to bridge HSV-1 to hippocampal-related brain disorders, namely AD and aMCI/MCI. Next, experimental models and clinical observations supporting the neurotropism or predilection of HSV-1 to infect the hippocampus are examined. Following this, factors and mechanisms predisposing the hippocampus to HSV-1 infection are discussed. In brief, the hippocampus has high levels of viral cellular receptors, neural stem or progenitor cells (NSCs/NPCs), glucocorticoid receptors (GRs) and amyloid precursor protein (APP) that support HSV-1 infectivity, as well as inadequate antiviral immunity against HSV-1. Currently, the established diseases HSV-1 causes are mucocutaneous lesions and encephalitis; however, this review revises that HSV-1 may also induce and/or contribute to hippocampal-related brain disorders, especially AD and aMCI/MCI.
Given the increasing anti-vaccine movements erroneously touting vaccine danger, this review has investigated the rare adverse events potentially associated with BNT162b2 (Pfizer-BioNTech), an mRNA ...vaccine against the severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2). Only real-world surveillance studies with at least 0.1 million BNT162b2-vaccinated participants and one unvaccinated control group were selected for review. A total of 21 studies examining the potential association of BNT162b2 with cardiovascular, herpetic, thrombotic or thrombocytopenic, neurological, mortality, and other miscellaneous rare adverse events were described in this review. Only myocarditis is consistently associated with BNT162b2. An unclear direction of association was seen with stroke (hemorrhagic and ischemic), herpes zoster, and paresthesia from BNT162b2, which may require more studies to resolve. Fortunately, most surveillance studies detected no increased risks of the remaining rare adverse events reviewed herein, further reassuring the safety of BNT162b2. In conclusion, this review has concisely summarized the current rare adverse events related and unrelated to BNT162b2, arguably for the first time in sufficient depth, to better communicate vaccine safety to the public.
Background: Solid organ rejection post-SARS-CoV-2 vaccination or COVID-19 infection is extremely rare but can occur. T-cell recognition of antigen is the primary and central event that leads to the ...cascade of events that result in rejection of a transplanted organ. Objectives: To describe the results of a systematic review for solid organ rejections following SARS-CoV-2 vaccination or COVID-19 infection. Methods: For this systematic review and meta-analysis, we searched Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, Scopus and Nature through the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines for studies on the incidence of solid organ rejection post-SARS-CoV-2 vaccination or COVID-19 infection, published from 1 December 2019 to 31 May 2022, with English language restriction. Results: One hundred thirty-six cases from fifty-two articles were included in the qualitative synthesis of this systematic review (56 solid organs rejected post-SARS-CoV-2 vaccination and 40 solid organs rejected following COVID-19 infection). Cornea rejection (44 cases) was the most frequent organ observed post-SARS-CoV-2 vaccination and following COVID-19 infection, followed by kidney rejection (36 cases), liver rejection (12 cases), lung rejection (2 cases), heart rejection (1 case) and pancreas rejection (1 case). The median or mean patient age ranged from 23 to 94 years across the studies. The majority of the patients were male (n = 51, 53.1%) and were of White (Caucasian) (n = 51, 53.7%) and Hispanic (n = 15, 15.8%) ethnicity. A total of fifty-six solid organ rejections were reported post-SARS-CoV-2 vaccination Pfizer-BioNTech (n = 31), Moderna (n = 14), Oxford Uni-AstraZeneca (n = 10) and Sinovac-CoronaVac (n = 1). The median time from SARS-CoV-2 vaccination to organ rejection was 13.5 h (IQR, 3.2–17.2), while the median time from COVID-19 infection to organ rejection was 14 h (IQR, 5–21). Most patients were easily treated without any serious complications, recovered and did not require long-term allograft rejection therapy graft success (n = 70, 85.4%), graft failure (n = 12, 14.6%), survived (n = 90, 95.7%) and died (n = 4, 4.3%). Conclusion: The reported evidence of solid organ rejections post-SARS-CoV-2 vaccination or COIVD-19 infection should not discourage vaccination against this worldwide pandemic. The number of reported cases is relatively small in relation to the hundreds of millions of vaccinations that have occurred, and the protective benefits offered by SARS-CoV-2 vaccination far outweigh the risks.
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