ABSTRACT
The coronavirus disease 19 (COVID-19) pandemic is a significant psychological stressor in addition to its tremendous impact on every facet of individuals' lives and organizations in virtually all social and economic sectors worldwide. Fear of illness and uncertainty about the future precipitate anxiety- and stress-related disorders, and several groups have rightfully called for the creation and dissemination of robust mental health screening and treatment programs for the general public and front-line healthcare workers. However, in addition to pandemic-associated psychological distress, the direct effects of the virus itself (several acute respiratory syndrome coronavirus; SARS-CoV-2), and the subsequent host immunologic response, on the human central nervous system (CNS) and related outcomes are unknown. We discuss currently available evidence of COVID-19 related neuropsychiatric sequelae while drawing parallels to past viral pandemic-related outcomes. Past pandemics have demonstrated that diverse types of neuropsychiatric symptoms, such as encephalopathy, mood changes, psychosis, neuromuscular dysfunction, or demyelinating processes, may accompany acute viral infection, or may follow infection by weeks, months, or longer in recovered patients. The potential mechanisms are also discussed, including viral and immunological underpinnings. Therefore, prospective neuropsychiatric monitoring of individuals exposed to SARS-CoV-2 at various points in the life course, as well as their neuroimmune status, are needed to fully understand the long-term impact of COVID-19, and to establish a framework for integrating psychoneuroimmunology into epidemiologic studies of pandemics.
Subject(s)
Coronavirus Infections/psychology , Cytokine Release Syndrome/psychology , Mental Disorders/psychology , Nervous System Diseases/psychology , Pneumonia, Viral/psychology , Acute Disease , Anxiety/etiology , Anxiety/immunology , Anxiety/psychology , Bacterial Translocation , Betacoronavirus , COVID-19 , Chronic Disease , Coronavirus Infections/complications , Coronavirus Infections/immunology , Coronavirus Infections/therapy , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/therapy , Demyelinating Diseases/etiology , Demyelinating Diseases/immunology , Demyelinating Diseases/physiopathology , Demyelinating Diseases/psychology , Depression/etiology , Depression/immunology , Depression/psychology , Humans , Immunologic Factors/adverse effects , Mental Disorders/etiology , Mental Disorders/immunology , Mental Health , Nervous System Diseases/etiology , Nervous System Diseases/immunology , Nervous System Diseases/physiopathology , Neurodegenerative Diseases/etiology , Neurodegenerative Diseases/immunology , Neurodegenerative Diseases/physiopathology , Neurodegenerative Diseases/psychology , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/immunology , Pneumonia, Viral/therapy , Psychoneuroimmunology , Psychotic Disorders/etiology , Psychotic Disorders/immunology , Psychotic Disorders/psychology , Public Health , SARS-CoV-2 , Stress Disorders, Post-Traumatic/etiology , Stress Disorders, Post-Traumatic/immunology , Stress Disorders, Post-Traumatic/psychologyABSTRACT
Mucosal barrier alterations may play a role in the pathogenesis of several diseases, including COVID-19. In this study we evaluate the association between bacterial translocation markers and systemic inflammation at the earliest time-point after hospitalization and at the last 72 h of hospitalization in survivors and non-survivors COVID-19 patients. Sixty-six SARS-CoV-2 RT-PCR positive patients and nine non-COVID-19 pneumonia controls were admitted in this study. Blood samples were collected at hospital admission (T1) (Controls and COVID-19 patients) and 0-72 h before hospital discharge (T2, alive or dead) to analyze systemic cytokines and chemokines, lipopolysaccharide (LPS) concentrations and soluble CD14 (sCD14) levels. THP-1 human monocytic cell line was incubated with plasma from survivors and non-survivors COVID-19 patients and their phenotype, activation status, TLR4, and chemokine receptors were analyzed by flow cytometry. COVID-19 patients presented higher IL-6, IFN-γ, TNF-α, TGF-ß1, CCL2/MCP-1, CCL4/MIP-1ß, and CCL5/RANTES levels than controls. Moreover, LPS and sCD14 were higher at hospital admission in SARS-CoV-2-infected patients. Non-survivors COVID-19 patients had increased LPS levels concomitant with higher IL-6, TNF-α, CCL2/MCP-1, and CCL5/RANTES levels at T2. Increased expression of CD16 and CCR5 were identified in THP-1 cells incubated with the plasma of survivor patients obtained at T2. The incubation of THP-1 with T2 plasma of non-survivors COVID-19 leads to higher TLR4, CCR2, CCR5, CCR7, and CD69 expression. In conclusion, the coexistence of increased microbial translocation and hyperinflammation in patients with severe COVID-19 may lead to higher monocyte activation, which may be associated with worsening outcomes, such as death.
Subject(s)
COVID-19/immunology , Inflammation/etiology , Lipopolysaccharides/blood , Monocytes/physiology , SARS-CoV-2 , Aged , Aged, 80 and over , Bacterial Translocation , COVID-19/mortality , Female , Hospitalization , Humans , Inflammation Mediators/blood , Male , Middle Aged , Severity of Illness Index , THP-1 CellsABSTRACT
The microbiota-gut-liver-lung axis plays a bidirectional role in the pathophysiology of a number of infectious diseases. During the course of severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and 2 (SARS-CoV-2) infection, this pathway is unbalanced due to intestinal involvement and systemic inflammatory response. Moreover, there is convincing preliminary evidence linking microbiota-gut-liver axis perturbations, proinflammatory status, and endothelial damage in noncommunicable preventable diseases with coronavirus disease 2019 (Covid-19) severity. Intestinal damage due to SARS-CoV-2 infection, systemic inflammation-induced dysfunction, and IL-6-mediated diffuse vascular damage may increase intestinal permeability and precipitate bacterial translocation. The systemic release of damage- and pathogen-associated molecular patterns (e.g. lipopolysaccharides) and consequent immune-activation may in turn auto-fuel vicious cycles of systemic inflammation and tissue damage. Thus, intestinal bacterial translocation may play an additive/synergistic role in the cytokine release syndrome in Covid-19. This review provides evidence on gut-liver axis involvement in Covid-19 as well as insights into the hypothesis that intestinal endotheliitis and permeability changes with bacterial translocation are key pathophysiologic events modulating systemic inflammatory response. Moreover, it presents an overview of readily applicable measures for the modulation of the gut-liver axis and microbiota in clinical practice.