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1.
Brain Behav Immun ; 87: 34-39, 2020 07.
Article in English | MEDLINE | ID: covidwho-1719335

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/psychology
2.
Int J Biol Sci ; 18(2): 459-472, 2022.
Article in English | MEDLINE | ID: covidwho-1667649

ABSTRACT

The COVID-19 outbreak is emerging as a significant public health challenge. Excessive production of proinflammatory cytokines, also known as cytokine storm, is a severe clinical syndrome known to develop as a complication of infectious or inflammatory diseases. Clinical evidence suggests that the occurrence of cytokine storm in severe acute respiratory syndrome secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is closely associated with the rapid deterioration and high mortality of severe cases. In this review, we aim to summarize the mechanism of SARS-CoV-2 infection and the subsequent immunological events related to excessive cytokine production and inflammatory responses associated with ACE2-AngII signaling. An overview of the diagnosis and an update on current therapeutic regimens and vaccinations is also provided.


Subject(s)
COVID-19/complications , COVID-19/pathology , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/pathology , SARS-CoV-2 , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/therapy , Cytokines/genetics , Cytokines/metabolism , Gene Expression Regulation/immunology , Humans
3.
Exp Biol Med (Maywood) ; 247(4): 330-337, 2022 02.
Article in English | MEDLINE | ID: covidwho-1649719

ABSTRACT

Cytokine storm is an umbrella term that describes an inflammatory syndrome characterized by elevated levels of circulating cytokines and hyperactivation of innate and/or adaptive immune cells. One type of cytokine storm is hemophagocytic lymphohistiocytosis (HLH), which can be either primary or secondary. Severe COVID-19-associated pneumonia and acute respiratory distress syndrome (ARDS) can also lead to cytokine storm/cytokine release syndrome (CS/CRS) and, more rarely, meet criteria for the diagnosis of secondary HLH. Here, we review the immunobiology of primary and secondary HLH and examine whether COVID-19-associated CS/CRS can be discriminated from non-COVID-19 secondary HLH. Finally, we review differences in immunobiology between these different entities, which may inform both clinical diagnosis and treatment of patients.


Subject(s)
COVID-19/complications , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/therapy , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/etiology , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing/therapeutic use , Cytokine Release Syndrome/virology , Humans , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Lymphohistiocytosis, Hemophagocytic/immunology , Lymphohistiocytosis, Hemophagocytic/therapy
4.
Front Immunol ; 12: 631233, 2021.
Article in English | MEDLINE | ID: covidwho-1575223

ABSTRACT

Coronavirus disease-19 caused by the novel RNA betacoronavirus SARS-CoV2 has first emerged in Wuhan, China in December 2019, and since then developed into a worldwide pandemic with >99 million people afflicted and >2.1 million fatal outcomes as of 24th January 2021. SARS-CoV2 targets the lower respiratory tract system leading to pneumonia with fever, cough, and dyspnea. Most patients develop only mild symptoms. However, a certain percentage develop severe symptoms with dyspnea, hypoxia, and lung involvement which can further progress to a critical stage where respiratory support due to respiratory failure is required. Most of the COVID-19 symptoms are related to hyperinflammation as seen in cytokine release syndrome and it is believed that fatalities are due to a COVID-19 related cytokine storm. Treatments with anti-inflammatory or anti-viral drugs are still in clinical trials or could not reduce mortality. This makes it necessary to develop novel anti-inflammatory therapies. Recently, the therapeutic potential of phytocannabinoids, the unique active compounds of the cannabis plant, has been discovered in the area of immunology. Phytocannabinoids are a group of terpenophenolic compounds which biological functions are conveyed by their interactions with the endocannabinoid system in humans. Here, we explore the anti-inflammatory function of cannabinoids in relation to inflammatory events that happen during severe COVID-19 disease, and how cannabinoids might help to prevent the progression from mild to severe disease.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , COVID-19/therapy , Cannabinoids/therapeutic use , Cannabis/immunology , Cytokine Release Syndrome/therapy , Phytotherapy , SARS-CoV-2/physiology , Endocannabinoids/metabolism , Humans , Pandemics
5.
Inflammopharmacology ; 29(5): 1347-1355, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1557643

ABSTRACT

The natural pathway of antioxidant production is mediated through Kelch-like erythroid cell-derived protein with Cap and collar homology [ECH]-associated protein 1 (Keap1)-Nuclear factor erythroid 2-related factor 2 (Nrf2) system. Keap1 maintains a low level of Nrf2 by holding it in its protein complex. Also, Keap1 facilitates the degradation of Nrf2 by ubiquitination. In other words, Keap1 is a down-regulator of Nrf2. To boost the production of biological antioxidants, Keap1 has to be inhibited and Nrf2 has to be released. Liberated Nrf2 is in an unbound state, so it travels to the nucleus to stimulate the antioxidant response element (ARE) present on the antioxidant genes. AREs activate biosynthesis of biological antioxidants through genes responsible for the production of antioxidants. In some cases of coronavirus disease 2019 (COVID-19), there is an enormous release of cytokines. The antioxidant defense mechanism in the body helps in counteracting symptoms induced by the cytokine storm in COVID-19. So, boosting the production of antioxidants is highly desirable in such a condition. In this review article, we have compiled the role of Keap1-Nrf2 system in antioxidant production. We further propose its potential therapeutic use in managing cytokine storm in COVID-19.


Subject(s)
COVID-19/metabolism , COVID-19/therapy , Cytokine Release Syndrome/metabolism , Cytokine Release Syndrome/therapy , Kelch-Like ECH-Associated Protein 1/metabolism , NF-E2-Related Factor 2/metabolism , Animals , Antioxidants/metabolism , Antioxidants/pharmacology , Antioxidants/therapeutic use , Disease Management , Humans , Kelch-Like ECH-Associated Protein 1/antagonists & inhibitors , NF-E2-Related Factor 2/agonists , Oxidative Stress/drug effects , Oxidative Stress/physiology
7.
Int J Mol Sci ; 22(23)2021 Nov 26.
Article in English | MEDLINE | ID: covidwho-1551605

ABSTRACT

The "normal" immune response to an insult triggers a highly regulated response determined by the interaction of various immunocompetent cells with pro- and anti-inflammatory cytokines. Under pathologic conditions, the massive elevation of cytokine levels ("cytokine storm") could not be controlled until the recent development of hemoadsorption devices that are able to extract a variety of different DAMPs, PAMPs, and metabolic products from the blood. CytoSorb® has been approved for adjunctive sepsis therapy since 2011. This review aims to summarize theoretical knowledge, in vitro results, and clinical findings to provide the clinician with pragmatic guidance for daily practice. English-language and peer-reviewed literature identified by a selective literature search in PubMed and published between January 2016 and May 2021 was included. Hemoadsorption can be used successfully as adjunct to a complex therapeutic regimen for various conditions. To the contrary, this nonspecific intervention may potentially worsen patient outcomes in complex immunological processes. CytoSorb® therapy appears to be safe and useful in various diseases (e.g., rhabdomyolysis, liver failure, or intoxications) as well as in septic shock or cytokine release syndrome, although a conclusive assessment of treatment benefit is not possible and no survival benefit has yet been demonstrated in randomized controlled trials.


Subject(s)
Cytokine Release Syndrome/therapy , Cytokines , Shock, Septic/therapy , Animals , Anti-Bacterial Agents , COVID-19 , Cytokine Release Syndrome/immunology , Cytokines/blood , Databases, Factual , Humans , Hyperbilirubinemia , Rhabdomyolysis , Sepsis/blood , Shock, Septic/immunology
8.
Biomed Res Int ; 2021: 3178796, 2021.
Article in English | MEDLINE | ID: covidwho-1541947

ABSTRACT

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has seriously affected public health and social stability. The main route of the transmission is droplet transmission, where the oral cavity is the most important entry point to the body. Due to both the direct harmful effects of SARS-CoV-2 and disordered immune responses, some COVID-19 patients may progress to acute respiratory distress syndrome or even multiple organ failure. Genetic variants of SARS-CoV-2 have been emerging and circulating around the world. Currently, there is no internationally approved precise treatment for COVID-19. Mesenchymal stem cells (MSCs) can traffic and migrate towards the affected tissue, regulate both the innate and acquired immune systems, and participate in the process of healing. Here, we will discuss and investigate the mechanisms of immune disorder in COVID-19 and the therapeutic activity of MSCs, in particular human gingiva mesenchymal stem cells.


Subject(s)
COVID-19/therapy , Cytokine Release Syndrome/therapy , SARS-CoV-2/genetics , COVID-19/immunology , Cytokine Release Syndrome/immunology , Genetic Variation , Gingiva/cytology , Humans , Mesenchymal Stem Cell Transplantation , SARS-CoV-2/immunology
9.
J Cell Mol Med ; 26(1): 228-234, 2022 01.
Article in English | MEDLINE | ID: covidwho-1532813

ABSTRACT

The outbreak of COVID-19 has become a serious public health emergency. The virus targets cells by binding the ACE2 receptor. After infection, the virus triggers in some humans an immune storm containing the release of proinflammatory cytokines and chemokines followed by multiple organ failure. Several vaccines are enrolled, but an effective treatment is still missing. Mesenchymal stem cells (MSCs) have shown to secrete immunomodulatory factors that suppress this cytokine storm. Therefore, MSCs have been suggested as a potential treatment option for COVID-19. We report here that the ACE2 expression is minimal or nonexistent in MSC derived from three different human tissue sources (adipose tissue, umbilical cord Wharton`s jelly and bone marrow). In contrast, TMPRSS2 that is implicated in SARS-CoV-2 entry has been detected in all MSC samples. These results are of particular importance for future MSC-based cell therapies to treat severe cases after COVID-19 infection.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , COVID-19/therapy , Cell- and Tissue-Based Therapy/methods , Cytokine Release Syndrome/therapy , Mesenchymal Stem Cell Transplantation/methods , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/genetics , Adipose Tissue/cytology , Adipose Tissue/metabolism , Angiotensin-Converting Enzyme 2/metabolism , Bone Marrow Cells/cytology , Bone Marrow Cells/metabolism , COVID-19/genetics , COVID-19/pathology , COVID-19/virology , Cytokine Release Syndrome/genetics , Cytokine Release Syndrome/pathology , Cytokine Release Syndrome/virology , Gene Expression Profiling , Gene Expression Regulation , Humans , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Primary Cell Culture , Protein Binding , SARS-CoV-2/genetics , Serine Endopeptidases/genetics , Serine Endopeptidases/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Umbilical Cord/cytology , Umbilical Cord/metabolism
10.
Clin Transl Sci ; 14(6): 2146-2151, 2021 11.
Article in English | MEDLINE | ID: covidwho-1526353

ABSTRACT

Tocilizumab is an IL-6 receptor antagonist with the ability to suppress the cytokine storm in critically ill patients infected with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). We evaluated patients treated with tocilizumab for a SARS-CoV-2 infection who were admitted between March 13, 2020, and April 16, 2020. This was a multicenter study with data collected by chart review both retrospectively and concurrently. Parameters evaluated included age, sex, race, use of mechanical ventilation (MV), usage of steroids and vasopressors, inflammatory markers, and comorbidities. Early dosing was defined as a tocilizumab dose administered prior to or within 1 day of intubation. Late dosing was defined as a dose administered > 1 day after intubation. In the absence of MV, the timing of the dose was related to the patient's date of admission only. We evaluated 145 patients. The average age was 58.1 years, 64% were men, 68.3% had comorbidities, and 60% received steroid therapy. Disposition of patients was 48.3% discharged and 29.3% died, of which 43.9% were African American. MV was required in 55.9%, of which 34.5% died. Avoidance of MV (P = 0.002) and increased survival (P < 0.001) was statistically associated with early dosing. Tocilizumab therapy was effective at decreasing mortality and should be instituted early in the management of critically ill patients with coronavirus disease 2019) COVID-19).


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , COVID-19/therapy , Cytokine Release Syndrome/therapy , Respiration, Artificial/statistics & numerical data , COVID-19/immunology , COVID-19/mortality , COVID-19/virology , Critical Illness/mortality , Critical Illness/therapy , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/mortality , Cytokine Release Syndrome/virology , Female , Hospital Mortality , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/immunology , Severity of Illness Index , Time Factors , Time-to-Treatment , Treatment Outcome
12.
Pediatrics ; 148(5)2021 11.
Article in English | MEDLINE | ID: covidwho-1484901

ABSTRACT

A term infant girl with uneventful antenatal history had an erythematous rash followed by fever from day 8. She was diagnosed with late-onset sepsis and was treated accordingly. She received immunoglobulin for persistent thrombocytopenia, after which there was transient improvement. The patient was transferred to our hospital on day 25 after recurrence of fever, watery diarrhea, and a generalized maculopapular rash. On admission, she had tachycardia, tachypnoea, anemia, thrombocytopenia, hypoalbuminemia, and generalized edema. Reverse transcriptase-polymerase chain reaction results for coronavirus disease 2019 (COVID-19) was positive. Within 12 hours of admission, she developed cardiogenic shock with pulmonary edema and needed invasive ventilation. Echocardiography revealed ejection fraction of 40% with mild pericardial effusion. N-terminal pro-brain natriuretic peptide was 33000 g/L, D-dimer 16500 µg/L, and ferritin 16000 ng/mL. Methylprednisolone, immunoglobulin, and enoxaparin was started, with a diagnosis of multisystem inflammatory syndrome in children, associated with COVID-19. She developed seizures, pulmonary hemorrhage, and cardiac arrest the following day, along with acute kidney injury. She was extubated after 5 days. Steroid was stopped after 5 days because she developed hypertension and echocardiography had normalized. Five days after extubation, she again developed respiratory distress and was ventilated again for 2 days. Echocardiography revealed moderate left ventricular dysfunction, along with secondary elevation of ferritin. Methylprednisolone was restarted and continued for 5 days followed by tapering dose of oral prednisolone, on which she was finally discharged. Although mild myocarditis with COVID-19 has been reported, multisystem inflammatory syndrome in children in a newborn with refractory myocarditis, along with gastrointestinal and renal manifestations, is a rare entity. Dermatologic manifestation of neonatal COVID-19 is also unique.


Subject(s)
COVID-19/complications , Cytokine Release Syndrome , Systemic Inflammatory Response Syndrome , COVID-19/diagnosis , COVID-19/therapy , Cytokine Release Syndrome/diagnosis , Cytokine Release Syndrome/therapy , Cytokine Release Syndrome/virology , Female , Humans , Infant, Newborn , Systemic Inflammatory Response Syndrome/complications , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/therapy
13.
Cells ; 10(11)2021 10 25.
Article in English | MEDLINE | ID: covidwho-1480601

ABSTRACT

As the number of confirmed cases and deaths occurring from Coronavirus disease 2019 (COVID-19) surges worldwide, health experts are striving hard to fully comprehend the extent of damage caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although COVID-19 primarily manifests itself in the form of severe respiratory distress, it is also known to cause systemic damage to almost all major organs and organ systems within the body. In this review, we discuss the molecular mechanisms leading to multi-organ failure seen in COVID-19 patients. We also examine the potential of stem cell therapy in treating COVID-19 multi-organ failure cases.


Subject(s)
COVID-19/complications , COVID-19/therapy , Multiple Organ Failure/etiology , Multiple Organ Failure/therapy , Stem Cell Transplantation , COVID-19/immunology , Clinical Trials as Topic , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/therapy , Humans , Immunomodulation , Multiple Organ Failure/immunology , Regenerative Medicine , SARS-CoV-2/pathogenicity , Stem Cells/cytology , Stem Cells/immunology
14.
Front Immunol ; 12: 738697, 2021.
Article in English | MEDLINE | ID: covidwho-1477824

ABSTRACT

The severe respiratory consequences of the coronavirus disease 2019 (COVID-19) pandemic have prompted the urgent need for novel therapies. Cell-based therapies, primarily using mesenchymal stromal cells (MSCs), have demonstrated safety and potential efficacy in the treatment of critical illness, particularly sepsis and acute respiratory distress syndrome (ARDS). However, there are limited preclinical data for MSCs in COVID-19. Recent studies have shown that MSCs could decrease inflammation, improve lung permeability, enhance microbe and alveolar fluid clearance, and promote lung epithelial and endothelial repair. In addition, MSC-based therapy has shown promising effects in preclinical studies and phase 1 clinical trials in sepsis and ARDS. Here, we review recent advances related to MSC-based therapy in the context of sepsis and ARDS and evaluate the potential value of MSCs as a therapeutic strategy for COVID-19.


Subject(s)
COVID-19/therapy , Cell- and Tissue-Based Therapy/methods , Cytokine Release Syndrome/therapy , Mesenchymal Stem Cell Transplantation/methods , Cytokine Release Syndrome/pathology , Humans , Inflammation/therapy , Mesenchymal Stem Cells/immunology , SARS-CoV-2 , Sepsis/therapy
15.
Signal Transduct Target Ther ; 6(1): 367, 2021 10 20.
Article in English | MEDLINE | ID: covidwho-1475287

ABSTRACT

Cytokine release syndrome (CRS) embodies a mixture of clinical manifestations, including elevated circulating cytokine levels, acute systemic inflammatory symptoms and secondary organ dysfunction, which was first described in the context of acute graft-versus-host disease after allogeneic hematopoietic stem-cell transplantation and was later observed in pandemics of influenza, SARS-CoV and COVID-19, immunotherapy of tumor, after chimeric antigen receptor T (CAR-T) therapy, and in monogenic disorders and autoimmune diseases. Particularly, severe CRS is a very significant and life-threatening complication, which is clinically characterized by persistent high fever, hyperinflammation, and severe organ dysfunction. However, CRS is a double-edged sword, which may be both helpful in controlling tumors/viruses/infections and harmful to the host. Although a high incidence and high levels of cytokines are features of CRS, the detailed kinetics and specific mechanisms of CRS in human diseases and intervention therapy remain unclear. In the present review, we have summarized the most recent advances related to the clinical features and management of CRS as well as cutting-edge technologies to elucidate the mechanisms of CRS. Considering that CRS is the major adverse event in human diseases and intervention therapy, our review delineates the characteristics, kinetics, signaling pathways, and potential mechanisms of CRS, which shows its clinical relevance for achieving both favorable efficacy and low toxicity.


Subject(s)
Cytokine Release Syndrome , Signal Transduction/immunology , Acute Disease , Autoimmune Diseases/complications , Autoimmune Diseases/immunology , Autoimmune Diseases/therapy , COVID-19/complications , COVID-19/immunology , COVID-19/therapy , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/therapy , Graft vs Host Disease/complications , Graft vs Host Disease/immunology , Graft vs Host Disease/therapy , Hematopoietic Stem Cell Transplantation , Humans , Immunotherapy, Adoptive/adverse effects , Influenza, Human/complications , Influenza, Human/immunology , Neoplasms/complications , Neoplasms/immunology , Neoplasms/therapy , SARS Virus/immunology , SARS-CoV-2/immunology , Severe Acute Respiratory Syndrome/complications , Severe Acute Respiratory Syndrome/immunology , Severe Acute Respiratory Syndrome/therapy
16.
J Cell Mol Med ; 25(22): 10554-10564, 2021 11.
Article in English | MEDLINE | ID: covidwho-1462824

ABSTRACT

Acute respiratory distress syndrome (ARDS) is the most common cause of death in COVID-19 patients. The cytokine storm is the main driver of the severity and magnitude of ARDS. Placenta-derived decidua stromal cells (DSCs) have a stronger immunosuppressive effect than other sources of mesenchymal stromal cells. Safety and efficacy study included 10 patients with a median age of 50 (range 14-68) years with COVID-19-induced ARDS. DSCs were administered 1-2 times at a dose of 1 × 106 /kg. End points were safety and efficacy by survival, oxygenation and effects on levels of cytokines. Oxygenation levels increased from a median of 80.5% (range 69-88) to 95% (range 78-99) (p = 0.012), and pulmonary infiltrates disappeared in all patients. Levels of IL-6 decreased from a median of 69.3 (range 35.0-253.4) to 11 (range 4.0-38.3) pg/ml (p = 0.018), and CRP decreased from 69 (range 5-169) to 6 (range 2-31) mg/ml (p = 0.028). Two patients died, one of a myocardial infarction and the other of multiple organ failure, diagnosed before the DSC therapy. The other patients recovered and left the intensive care unit (ICU) within a median of 6 (range 3-12) days. DSC therapy is safe and capable of improving oxygenation, decreasing inflammatory cytokine level and clearing pulmonary infiltrates in patients with COVID-19.


Subject(s)
COVID-19/drug therapy , Cell Transplantation/methods , Cytokine Release Syndrome/therapy , Respiratory Distress Syndrome/virology , Stromal Cells/transplantation , Adolescent , Adult , Aged , COVID-19/complications , COVID-19/therapy , Cell Transplantation/adverse effects , Cytokine Release Syndrome/etiology , Cytokines/blood , Female , Humans , Length of Stay , Male , Middle Aged , Placenta/cytology , Pregnancy , Respiratory Distress Syndrome/therapy , Stromal Cells/physiology , Treatment Outcome
17.
J Zhejiang Univ Sci B ; 22(9): 701-717, 2021.
Article in English | MEDLINE | ID: covidwho-1405362

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic is a major public health event caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has spread widely all over the world. A high proportion of patients become severely or critically ill, and suffer high mortality due to respiratory failure and multiple organ dysfunction. Therefore, providing timely and effective treatment for critically ill patients is essential to reduce overall mortality. Convalescent plasma therapy and pharmacological treatments, such as aerosol inhalation of interferon-α (IFN-α), corticosteroids, and tocilizumab, have all been applied in clinical practice; however, their effects remain controversial. Recent studies have shown that extracorporeal therapies might have a potential role in treating critically ill COVID-19 patients. In this review, we examine the application of continuous renal replacement therapy (CRRT), therapeutic plasma exchange (TPE), hemoadsorption (HA), extracorporeal membrane oxygenation (ECMO), and extracorporeal carbon dioxide removal (ECCO2R) in critically ill COVID-19 patients to provide support for the further diagnosis and treatment of COVID-19.


Subject(s)
COVID-19/therapy , Extracorporeal Circulation/methods , Extracorporeal Membrane Oxygenation , SARS-CoV-2 , COVID-19/complications , Carbon Dioxide/isolation & purification , Critical Illness , Cytokine Release Syndrome/therapy , Hemoperfusion , Humans , Immunization, Passive , Plasma Exchange , Renal Replacement Therapy
18.
Hum Immunol ; 83(1): 86-98, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1401492

ABSTRACT

The global outbreak of coronavirus-2019 (COVID-19) still claims more lives daily around the world due to the lack of a definitive treatment and the rapid tendency of virus to mutate, which even jeopardizes vaccination efficacy. At the forefront battle against SARS-CoV-2, an effective innate response to the infection has a pivotal role in the initial control and treatment of disease. However, SARS-CoV-2 subtly interrupts the equations of immune responses, disrupting the cytolytic antiviral effects of NK cells, while seriously activating infected macrophages and other immune cells to induce an unleashed "cytokine storm", a dangerous and uncontrollable inflammatory response causing life-threatening symptoms in patients. Notably, the NK cell exhaustion with ineffective cytolytic function against the sources of exaggerated cytokine release, acts as an Achilles' heel which exacerbates the severity of COVID-19. Given this, approaches that improve NK cell cytotoxicity may benefit treatment protocols. As a suggestion, adoptive transfer of NK or CAR-NK cells with proper cytotolytic potentials and the lowest capacity of cytokine-release (for example CD56dim NK cells brightly express activating receptors), to severe COVID-19 patients may provide an effective cure especially in cases suffering from cytokine storms. More intriguingly, the ongoing evidence for persistent clonal expansion of NK memory cells characterized by an activating phenotype in response to viral infections, can benefit the future studies on vaccine development and adoptive NK cell therapy in COVID-19. Whether vaccinated volunteers or recovered patients can also be considered as suitable candidates for cell donation could be the subject of future research.


Subject(s)
Adoptive Transfer , COVID-19/therapy , Cytokine Release Syndrome/therapy , Cytokines/immunology , Killer Cells, Natural/transplantation , SARS-CoV-2/immunology , Adoptive Transfer/adverse effects , Animals , COVID-19/immunology , COVID-19/metabolism , COVID-19/virology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/metabolism , Cytokine Release Syndrome/virology , Cytokines/metabolism , Cytotoxicity, Immunologic , Host-Pathogen Interactions , Humans , Immunologic Memory , Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Killer Cells, Natural/virology , SARS-CoV-2/pathogenicity , Treatment Outcome
19.
Endocr Metab Immune Disord Drug Targets ; 21(8): 1392-1405, 2021.
Article in English | MEDLINE | ID: covidwho-1389051

ABSTRACT

The complications of the SARS-CoV-2 infection and its COVID-19 disease on mothers and their offspring are less known. This review aimed to determine the transmission, severity, and complications of SARS- CoV-2 infection during pregnancy. This review showed the influence of COVID-19 disease on neonatal neurogenesis. Owing medicines that were reported for the treatment of COVID-19 disease, this review suggested some control strategies like treatments (medicinal plants, antiviral therapy, cellular therapy, and immunotherapy), nutrition uptake, prevention, and recommendations. This overview showed that severe infection of SARS-CoV-2 during the early stage of pregnancy might increase the risk of stress, panic, and anxiety. This disorder can disturb the maternal immune system, and thus causing a neurodevelopmental disturbance. This hypothesis may be depending on the severity and intensity of the SARS-CoV-2 infection during pregnancy. However, vertical transmission of SARS-CoV-2 from dams to their fetuses is absent until now. During this global pandemic disease, maintaining safety during pregnancy, vaginal delivery, and breastfeeding may play a vital role in a healthy life for the offspring. Thus, international, and national organizations should be continuing for perinatal management, particularly during the next pandemic or disaster time.


Subject(s)
COVID-19/therapy , COVID-19/transmission , Infectious Disease Transmission, Vertical/prevention & control , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/therapy , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/immunology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/therapy , Female , Humans , Immunotherapy/methods , Pregnancy , SARS-CoV-2/drug effects , SARS-CoV-2/immunology
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