Enhancing understanding of SARS-CoV-2 infection among individuals with Down syndrome: An integrative review

ABSTRACT BACKGROUND: Down syndrome (DS) is a non-rare genetic condition that affects approximately 1 in every 800 live births worldwide. Further, it is associated with comorbidities, anatomical alterations of the respiratory tract, and immunological dysfunctions that make individuals more susceptible to respiratory infections. OBJECTIVE: To systematize the current scientific knowledge about the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among individuals with DS. DESIGN AND SETTING: This integrative review was conducted at the Universidade Federal de São Carlos, São Paulo, Brazil. METHODS: This review was conducted in the following databases: the Virtual Health Library (Biblioteca Virtual em Saúde, BVS), PubMed, and Web of Science, using MeSH descriptors. The search included English or Portuguese studies published between January 1, 2020, and October 14, 2022. RESULTS: A total of 55 articles from 24 countries were selected, comprising 21 case-control or cohort studies, 23 case reports or series, and 11 narrative reviews or opinion studies. The articles were grouped into five categories: previous comorbidities, coronavirus disease 2019 (COVID-19) clinical features and evolution, cytokine storm and interleukins, living in institutions as a risk factor, and behavioral actions as a protective factor against SARS-CoV-2 infection. CONCLUSION: Individuals with DS are more susceptible to COVID-19 infection due to variables such as previous comorbidities, immunological factors, and their habitable environments. These aspects confer a higher risk of infection and an unfavorable clinical course. The precise pathways involved in the pathophysiology of COVID-19 in individuals with DS are not clear, thus requiring further studies. SYSTEMATIC REVIEW REGISTRATION: The Open Science Framework registered the research protocol (https://osf.io/jyb97/).

The Role of Oxidative Stress and Cytokine Storm in the Pathogenesis, Oral Manifestation, Progression and Adverse Effects Related to SARS-Cov2 Infection- A Review

Introduction: COVID-19 pandemic has been the most challenging global health concern that the world has ever seen and is the focus of active research around the world. The interaction of the SARS CoV2 virus with the target cells, their action on the immune system and the subsequent reaction has all been linked to the inflammatory processes that are taking place in the human body mainly the oxidative stress. Objective: Through this article we aim to analyse the effect of oxidative stress in the pathogenesis of COVID-19, highlighting the role of the same in the oral manifestations that are being reported in literature and its subsequent impact in the transmission and propagation of SARS-CoV2. The role of antioxidants in the control of the SARS-CoV2 infection has also been explored. Materials and Methods: Four reviewers independently collected the data pertaining to the topic from case reports and review articles published in electronic databases like PubMed, Scopus, Science Direct and Research gate. Conclusion: Increased release of cytokines known as cytokine storm has been associated with disease progression, oral manifestation as well as adverse effects in patients with COVID 19. However, as this is an ongoing pandemic with new mu- tations occurring frequently, further clinical trials are required to evaluate the exact mechanisms that may be at play in the pathogenesis of SARS-CoV2 infection.

Targeting TLR-4 Signaling to Treat COVID-19-induced Acute Kidney Injury

The newly discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has turned into a potentially fatal pandemic illness. Numerous acute kidney injury (AKI) cases have been reported, although diffuse alveolar destruction and acute respiratory failure are the major symptoms of SARS-CoV-2 infection. The AKI, often known as a sudden loss of kidney function, carries a greater risk of mortality and morbidity. AKI was the second most frequent cause of death after acute respiratory distress syndrome (ARDS) in critically ill patients with coronavirus disease 2019 (COVID-19). While most patients with COVID-19 have moderate symptoms, some have severe symptoms, such as septic shock and ARDS. Also, it has been proven that some patients have severe symptoms, such as the failure of several organs. The kidneys are often affected either directly or indirectly. The major signs of kidney involvement are proteinuria and AKI. It is hypothesized that multiple mechanisms contribute to kidney injury in COVID-19. Direct infection of podocytes and proximal tubular cells in the kidneys may lead to acute tubular necrosis and collapsing glomerulopathy. SARS-CoV2 may also trigger a cascade of immunological responses that lead to AKI, including cytokine storm (CS), macrophage activation syndrome, and Toll-like receptor type 4 activation (TLR-4). Other proposed processes of AKI include interactions between organs, endothelial failure, hypercoagulability, rhabdomyolysis, and sepsis. Furthermore, ischemic damage to the kidney might result from the decreased oxygen supply. This article focuses on kidney injury’s epidemiology, etiology, and pathophysiological processes. Specifically, it focuses on the CS and the role of TLR-4 in this process. To effectively manage and treat acute kidney damage and AKI in COVID-19, it is crucial to understand the underlying molecular pathways and pathophysiology.

Efficacy and safety of Ixekizumab vs. low-dose IL-2 vs. Colchicine vs. standard of care in the treatment of patients hospitalized with moderate-to-critical COVID-19: A pilot randomized clinical trial (STRUCK: Survival Trial Using Cytokine Inhibitors)

ABSTRACT Background: Cases of coronavirus disease 2019 (COVID-19) requiring hospitalization continue to appear in vulnerable populations, highlighting the importance of novel treatments. The hyperinflammatory response underlies the severity of the disease, and targeting this pathway may be useful. Herein, we tested whether immunomodulation focusing on interleukin (IL)-6, IL-17, and IL-2, could improve the clinical outcomes of patients admitted with COVID-19. Methods: This multicenter, open-label, prospective, randomized controlled trial was conducted in Brazil. Sixty hospitalized patients with moderate-to-critical COVID-19 received in addition to standard of care (SOC): IL-17 inhibitor (ixekizumab 80 mg SC/week) 1 dose every 4 weeks; low-dose IL-2 (1.5 million IU per day) for 7 days or until discharge; or indirect IL-6 inhibitor (colchicine) orally (0.5 mg) every 8 hours for 3 days, followed by 4 weeks at 0.5 mg 2x/day; or SOC alone. The primary outcome was accessed in the "per protocol" population as the proportion of patients with clinical improvement, defined as a decrease greater or equal to two points on the World Health Organization's (WHO) seven-category ordinal scale by day 28. Results: All treatments were safe, and the efficacy outcomes did not differ significantly from those of SOC. Interestingly, in the colchicine group, all participants had an improvement of greater or equal to two points on the WHO seven-category ordinal scale and no deaths or patient deterioration were observed. Conclusions: Ixekizumab, colchicine, and IL-2 were demonstrated to be safe but ineffective for COVID-19 treatment. These results must be interpreted cautiously because of the limited sample size.

A Covid-19 e as citocinas: uma revisão de literatura / Covid-19 and cytokines: a literature review / Covid-19 y citocinas: una revisión de la literatura

A COVID-19 surgiu em dezembro de 2019 na China, o contágio se espalhou rapidamente pelo mundo e já em março de 2020 a Organização Mundial da Saúde (OMS) declarou o surto como pandemia. A infecção causada por SARS-COV-2 mostrou-se com sintomatologia variada. Enquanto alguns infectados não tinham sintomas, outros apresentavam sinais que variam dos semelhantes a uma gripe, até uma possível evolução para síndrome do desconforto respiratório. Evidências indicam que, durante o curso da COVID-19 a rápida progressão e mortalidade pode ter sido associada à mecanismo hiperinflamatórios, com descontrole regulatório da produção de citocinas pró- inflamatórias, tanto em nível local, quanto sistêmico. Sendo assim, neste artigo revisamos a literatura sobre a COVID-19, seus aspectos epidemiológicos e clínicos, bem como a o papel das citocinas no contexto da infecção por SARS-CoV-2, já que a busca pelo entendimento dos mecanismos imunológicos que envolvem a COVID-19 e outras doenças de caráter inflamatório é de suma importância para o tratamento e o manejo de tais enfermidades.

COVID-19 emerged in December 2019 in China, the contagion spread rapidly around the world, and already in March 2020 the World Health Organization (WHO) declared the outbreak a pandemic. The infection caused by SARS-COV-2 was shown to have varied symptomatology. While some infected people had no symptoms, others showed signs ranging from flu-like to a possible evolution to respiratory distress syndrome. Evidence indicates that during the course of COVID-19 the rapid progression and mortality may have been associated with hyperinflammatory mechanisms, with regulatory uncontrolled production of pro-inflammatory cytokines at both local and systemic levels. Therefore, in this article we review the literature on COVID-19, its epidemiological and clinical aspects, as well as the role of cytokines in the context of SARS-CoV-2 infection, since the search for understanding the immunological mechanisms surrounding COVID-19 and other inflammatory diseases is of paramount importance for the treatment and management of such diseases.

El COVID-19 surgió en diciembre de 2019 en China, el contagio se extendió rápidamente por todo el mundo y ya en marzo de 2020 la Organización Mundial de la Salud (OMS) declaró el brote como pandemia. Se demostró que la infección causada por el SARS-COV-2 presentaba una sintomatología variada. Mientras que algunos infectados no presentaban síntomas, otros mostraban signos que iban desde similares a los de la gripe hasta una posible evolución a síndrome de dificultad respiratoria. Las pruebas indican que durante el curso del COVID-19 la rápida progresión y la mortalidad pueden haber estado asociadas a mecanismos hiperinflamatorios, con una producción descontrolada reguladora de citocinas proinflamatorias tanto a nivel local como sistémico. Por lo tanto, en este artículo revisamos la literatura sobre la COVID-19, sus aspectos epidemiológicos y clínicos, así como el papel de las citocinas en el contexto de la infección por SARS-CoV-2, ya que la búsqueda de la comprensión de los mecanismos inmunológicos que rodean la COVID-19 y otras enfermedades inflamatorias es de suma importancia para el tratamiento y la gestión de dichas enfermedades.

Establishment of Poly （I∶C）-induced Cytokine Storm Model in Mice and Intervention Effect of Artesunate and Qingfei Paidu Decoction / 中国实验方剂学杂志

ObjectiveTo observe the intervention effect of artesunate （ART） and Qingfei Paidu decoction （QFPD） on the mouse model of cytokine storm （CS） induced by viral mimic Poly （I∶C）. MethodEighty-four SPF male BALB/c mice were randomly divided into seven groups， with 12 mice in each group. Mice， except for those in the blank group （n=12）， were subjected to CS model induction by tail vein injection of Poly （I∶C） at 15 mg·kg-1， followed by drug treatments of low-dose ART （ART-l， 10 mg·kg-1）， medium-dose ART （ART-m， 20 mg·kg-1）， high-dose ART （ART-h， 40 mg·kg-1）， Qingfei Paidu Decoction （QFPD， 2.4 g·kg-1）， and dexamethasone （DXM， 10 mg·kg-1）. After 6 hours， lung tissues， bronchoalveolar lavage fluid （BALF）， spleen， lung， and peripheral blood were collected. The lung and spleen indexes were calculated and the number of inflammatory cells in BALF was detected. The pathological changes in lung tissues were observed by hematoxylin-eosin （HE） staining and the levels of tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin-1β （IL-1β）， and IL-6 in BALF were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of immune cells in BALF and peripheral blood was detected by flow cytometry. ResultThe analysis of lung and spleen indexes showed that compared with the blank group， the model group showed increased lung and spleen indexes to varying degrees （P<0.05）. Compared with the model group， the ART groups showed reduced spleen index （P<0.05） and the ART-l group showed reduced lung index （P<0.05）. Additionally， the QFPD group showed reduced lung and spleen indexes （P<0.05）. ELISA results showed that except for TNF-α， the levels of IFN-γ， IL-1β， and IL-6 in the model group increased compared with those in the blank group （P<0.05）. Compared with the model group， the ART-l group and the QFPD group showed reduced content of TNF-α （P<0.05）， and all groups with drug intervention showed reduced content of IFN-γ， IL-1β， and IL-6 （P<0.05）. The number of inflammatory cells in BALF showed a downward trend in the model group， and the number of cells increased in the groups with drug intervention except for the DXM group （P<0.05）. Flow cytometry showed that compared with the blank group， the model group showed decreased number of CD3 in the peripheral blood （P<0.05）， increased Ly-6G and F4/80 （P<0.05）， decreased expression of CD45， CD3， and F4/80 in BALF （P<0.05）， and increased expressions of Ly-6G （P<0.05）. Compared with the model group， the ART groups and QFPD group showed increased CD45 content in peripheral blood （P<0.05）， decreased Ly-6G and F4/80 content （P<0.05）， increased CD45 and F4/80 content in BALF （P<0.05）， and decreased expression of Ly-6G （P<0.05）. ConclusionART and QFPD have a good protective effect on Poly （I∶C）-induced CS in mice， and the mechanism is related to the effective intervention in immune cell disorder.

Application of immunosuppressive agents in crtical coronavirus disease / 中华危重病急救医学

The outbreak of novel coronavirus (SARS-CoV-2) infection has brought great harm to people's life and social development. Although SARS-CoV-2 infection is more common in mild patients at present, considering the characteristics of crtical disease, rapid progress and high mortality, the treatment of critical patients are the focus of clinical attention. Immune imbalance which is characterized by cytokine storm plays a vital role in SARS-CoV-2 induced acute respiratory distress syndrome (ARDS), extrapulmonary multiple organ failure and even death. Therefore, the application of immunosuppressive agent in crtical coronavirus disease patients has a promising prospect. In this paper, different immunosuppressive agents and their application in crtical SARS-CoV-2 infection are reviewed, so as to provide reference for crtical coronavirus disease therapy.

Inosine:A broad-spectrum anti-inflammatory against SARS-CoV-2 infection-induced acute lung injury via suppressing TBK1 phosphorylation / 药物分析学报

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)-induced cytokine storms constitute the primary cause of coronavirus disease 19(COVID-19)progression,severity,criticality,and death.Gluco-corticoid and anti-cytokine therapies are frequently administered to treat COVID-19,but have limited clinical efficacy in severe and critical cases.Nevertheless,the weaknesses of these treatment modalities have prompted the development of anti-inflammatory therapy against this infection.We found that the broad-spectrum anti-inflammatory agent inosine downregulated proinflammatory interleukin(IL)-6,upregulated anti-inflammatory IL-10,and ameliorated acute inflammatory lung injury caused by mul-tiple infectious agents.Inosine significantly improved survival in mice infected with SARS-CoV-2.It indirectly impeded TANK-binding kinase 1(TBK1)phosphorylation by binding stimulator of interferon genes(STING)and glycogen synthase kinase-3β(GSK3β),inhibited the activation and nuclear trans-location of the downstream transcription factors interferon regulatory factor(IRF3)and nuclear factor kappa B(NF-κB),and downregulated IL-6 in the sera and lung tissues of mice infected with lipopoly-saccharide(LPS),H1N1,or SARS-CoV-2.Thus,inosine administration is feasible for clinical anti-inflammatory therapy against severe and critical COVID-19.Moreover,targeting TBK1 is a promising strategy for inhibiting cytokine storms and mitigating acute inflammatory lung injury induced by SARS-CoV-2 and other infectious agents.

COVID-19-mediated pulmonary fibrosis: from mechanisms to medicines / 中国药理学通报

Coronavirus disease-19 (COVID-19), a global epidemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), lead to lung injury in millions of people. SARS-CoV-2 can not only cause cytokine storm, acute respiratory distress syndrome and respiratory failure in the phase of acute infection, but also have potential long-term effects on the lungs. Survivors of severe COVID-19 may develop pulmonary fibrosis, resulting in permanent lung injury. In this review we expound the occurrence and development of COVID-19-related pulmonary fibrosis, summarize the key roles of TGF-p/Smad, TGF-fV MAPK, JAK/STAT, Wnt/(3-catenin, YAP/TAZ, NF-KB and PI3K/Akt signal pathways in this process, and analyze the advantages and disadvantages of antiviral drugs, anti-fibrosis drugs, cytokine-targeted drugs, corticosteroids, spironolactone, traditional Chinese medicine prescriptions and lung transplantation in its treatment. This review may provide a reference for the study of pathological mechanism and clinical treatment of COVID-19-re-lated pulmonary fibrosis.

Selective inhibition of inflammatory cytokine storm in macrophages by α-momorcharin / 中国药理学通报

Aim To observe the inhibitory effect of Alpha-momorcharin (α-MMC) on the inflammatory cytokine storm of Ml-type inflammatory macrophages induced by LPS and explore its possible targeting mechanism. Methods Western blot was used to detect the expression of WIL2-S B lymphocytes, H9 T lymphocytes, THP-1 monocytes and M0 macrophages LRP1 receptor protein. CCK-8 method was used to detect the survival rate of the four cells. ELISA was used to detect the expression level of inflammatory cytokines in Ml macrophages. Western blot was used to detect the expression of TLR4 signaling pathway-related protein in Ml macrophages. Results Macrophages had a high density of LRP1 receptors consistent with monocytes; the survival rate of α-MMC on the four cells was positively correlated with the density of this receptor; α-MMC inhibited the expression of inflammatory cytokinesTNF-α, IL-lβ, IL-6, IL-8, MlP-lα and MCP-1 in Ml macrophages in a dose-and time-dependent manner; α-MMC showed significant inhibition to TAKl/pTAK1, p-JNK, p-APl and p-p65 signaling proteins of the TLR4 signaling pathway, and this inhibition could be blocked by the LRP1 receptor blocker RAP. Conclusions α-MMC selectively inhibits macrophage inflammatory cytokine synthesis by inhibiting TAK1 of the TLR4 signaling pathway, which in turn inhibits the downstream NF-ΚB and MAPK pathways, mediated by the LRP1 receptor. The selective immunosuppressive effect of α-MMC on macrophages may make it a very promising agent for the treatment of acute infectious macrophage activation syndrome (MAS).

Cytokine storm and translating IL-6 biology into effective treatments for COVID-19 / 医学前沿

As of May 3, 2023, the Coronavirus disease 2019 (COVID-19) pandemic has resulted in more than 760 million confirmed cases and over 6.9 million deaths. Several patients have developed pneumonia, which can deteriorate into acute respiratory distress syndrome. The primary etiology may be attributed to cytokine storm, which is triggered by the excessive release of proinflammatory cytokines and subsequently leads to immune dysregulation. Considering that high levels of interleukin-6 (IL-6) have been detected in several highly pathogenic coronavirus-infected diseases, such as severe acute respiratory syndrome in 2002, the Middle East respiratory syndrome in 2012, and COVID-19, the IL-6 pathway has emerged as a key in the pathogenesis of this hyperinflammatory state. Thus, we review the history of cytokine storm and the process of targeting IL-6 signaling to elucidate the pivotal role played by tocilizumab in combating COVID-19.

Hemophagocytic lymphohistiocytosis: presentation and outcome of twenty-one patients at a single institution

ABSTRACT Introduction: Hemophagocytic lymphohistiocytosis comprises a systemic hyperactivation of macrophages that requires prompt recognition of symptoms and early treatment. Objective and Method: In this context, we described clinical and laboratory characteristics, therapeutic modality and outcome of 21 patients with HLH treated at a pediatric oncology hospital between January 2000 and February 2019. Results: HLH mainly affected females, fever was the most frequent clinical sign and hyperferritinemia was the most prevalent laboratory abnormality. All patients were admitted to the intensive care unit (ICU) at some point. Fifteen (71.4%) patients presented resolution criteria and eight (53.3%) of them presented reactivation. The mortality rate was 57.1% and the mean time between diagnosis and death was 9.98 months. The 5-year overall survival (OS) was 36.7%. We observed a significant difference in prognosis associated with reactivation of HLH. These patients demonstrated an estimated 5-year OS of 25%, while all patients that did not reactivate were alive until the end of the follow-up. Conclusion: In conclusion, HLH is a rare disease with a high mortality rate, especially in patients with disease reactivation and those with familial- or immunodeficiency-associated forms, which makes early recognition and genetic testing crucial for appropriate management and prompt SCT indication.

Scientific Understanding of Cytokine Storm in Perspective of Ayurveda: A Review

Cytokine storm also known as cytokine releasing syndrome is due to elevate level of circulating cytokine and hyper action that can be triggered by some factor like virus, bacteria or other epigenetic factors. In this era of communicable disease, COVID-19 is such a disease which shows manifestation in the form of cytokine storm. Increase level of cytokine like interleukin-6 etc in the blood causes destruction of normally functioning cell leads to dangerous life-threatening condition like ARDs. Cytokines are immunomodulating agents composed of soluble proteins, peptides and glycoproteins secreted by haemopoietic and non-haemopoietic cells in response to various stimuli. Their main role is in molecular interaction between various cells of the immune system. Cytokines are nothing but just the immune markers which hyperactivation leads to cytokine storm. There is not any description of such pathogenesis in Ayurveda. But Ayurveda clearly defined some concepts of immunity such Asvyadhikshamatva, Oja, Bala, Vyadhibighatakarabhaba and Rasayana. In Covid-19, researcher found that such people are more vulnerable to disease and its severity. Such vulnerability depends upon person response to illness. Ayurveda may explain this vulnerability through its concepts of preventive, personalized and rejuvenation. The present review focused on cytokine storm and its understanding in perspective of Ayurvedic concepts of immunity

Periodontal Disease as a factor in morbidity of Covid-19: A Review

Background: Covid-19 is a worldwide pandemic causing considerable morbidity and mortality. Many studies have shown the influence of periodontal health on systemic disease. Aims: This article explores the association between periodontal disease (PD), oral dysbiosis and cytokine storm requiring proto- col of maintainence of oral hygiene in covid patients and also in healthy individuals during the pandemic. Covid patients need to be motivated to maintain proper oral hygiene measures to avoid risk of Covid related adverse outcomes. Methods: Data was collected and analyzed from recently published literature and electronic database searches of PubMed and Google Scholar. Results: Covid-19 leads to increased release of cytokines from host cells termed as cytokine storm, many of the components of which are common with the cytokine expression profile of periodontitis. It has been shown that periodontitis was significantly associated with increased risk of complications from the Covid-19 including ICU admission, need for assisted ventilation and death. Conclusion: Plaque control is important to prevent exchange of microorganisms between the oral cavity and the lungs and to reduce the chances of worsening respiratory disease during Covid-19 infection. Understanding this association may definitely help to identify individuals at high risk and deliver appropriate care at early stages.

COVID19: uncovering interindividual variability for tailoring appropriate therapeutic interventions / COVID19: a variabilidade individual da resposta imunoinflamatória

The severity of SARS-CoV2 infection, Covid19 disease, should account for the diversity of human individual immu-noinflammatory responses. Serum immunological markers during Covid19 illness may lead to individualized thera-peutics with better outcomes. Efficient treatment for Covid19 may require: 1) early disease detection, 2) combined drug therapy for 3) targeting the virus replication cycle, and 4) individualized drug treatment for specific immu-noinflammatory human profile responses administered in a 5) timely manner. Covid19 is unlikely to be the last emergent human disease with fast pandemic potential. Gathering knowledge on the individual human host profiles of immunoinflammatory responses is an opportunity that could lead us to understand individual differences in re-sponse to infection at the individual and population level, paving the way to faster, more efficient strategies to tack-le upcoming infectious diseases. This is a position paper based on an integrative non-exhaustive literature revision (AU)

A diversidade das respostas imunoinflamatórias individuais humanas muito provavelmente tem papel na gravidade da doença Covid19 causada pela infecção pelo vírus SARS-CoV2. Marcadores imunológicos séricos durante a Covid19 po-dem guiar a escolha de terapias individualizadas com melhores resultados. O tratamento eficiente para Covid19 pode exigir: 1) detecção precoce da doença, 2) terapia medicamentosa combinada com alvo ao 3) ciclo de replicação do ví-rus e 4) terapia anti-inflamatória individualizada para perfis de respostas imunoinflamatórias humanas, administradas em tempo hábil. É improvável que a Covid19 seja a última doença humana emergente com potencial de alastramento veloz pandêmico. Reunir conhecimento sobre perfis de respostas imunoinflamatórias individuais dos hospedeiros humanos é uma oportunidade ímpar que pode nos levar a entender as diferenças dessas respostas entre indivíduos, abrindo caminho para estratégias terapêuticas mais rápidas e eficientes no combate à futuras epidemias (AU)

Thrombocytopenia in COVID-19 : A Diagnostic and Therapeutic Challenge

The World started to experience the wrath of pandemic in the form of SARS-COV 2/COVID-19 infection since 2020. It is not the first time that we are experiencing such life threatening pandemics. But, what we forget to remember is the known diseases that are always there around us along with this pandemic. COVID-19 has its affect on almost every Organ System and one of its complications being Thrombogenicity. In order to combat this condition, we are using Anticoagulant Therapy mostly in the form of unfractionated Heparin or Low Molecular Weight heparin. But, it is also evident that heparin itself can result in state of Thrombosis in the form of heparin-induced Thrombocytopenia Complex and thus worsening the condition of the patient if not identified and treated early. In this report, we are going to discuss about a case of Thrombocytopenia Associated with COVID-19 which might be provoked by COVID-19 itself or use of Heparin and have given a brief review of literature on this topic

Clinical analysis of 36 children with pneumonia caused by coinfection of human adenovirus type 7 and Mycoplasma pneumoniae / 中华实用儿科临床杂志

Objective:To summarize the clinical features of children with pneumonia caused by coinfection of human adenovirus type 7 and Mycoplasma pneumoniae.Methods:A total of 36 children with pneumonia caused by coinfection of human adenovirus type 7 and Mycoplasma pneumoniae (coinfection group) diagnosed in the Wuhan Children′s Hospital from December 1, 2018 to September 1, 2019 were enrolled.Their clinical manifestations, laboratory examinations, and imaging findings were retrospectively analyzed.In the same period, 94 children with single human adenovirus type 7 infection pneumonia were selected as the single infection group.Differences between 2 groups were compared using the Student′s t-test, rank sum test and Chi- square test. Results:In the coinfection group, 25 cases were males, 11 cases were females, their mean age was 3.11 years.The main clinical manifestations included fever (97.2%) and cough (100.0%). The mean body temperature was 40.0 ℃, with the thermal peak of 4 times per day, and the mean course of fever of 11 days.The incidence of severe pneumonia was significantly higher in coinfection group (86.1%) than that of single infection group (69.1%) ( χ2=3.878, P<0.05). The common complications included myocardial damage (55.5%), heart failure (16.7%), liver function damage (25.0%), gastrointestinal bleeding (5.5%), toxic encephalopathy (11.0%), hemophagocytic syndrome (16.7%), and bronchiolitis obliterans (50.0%). The levels of cytokines like interleukin (IL)-6 [237.84(108.59, 606.36) ng/L], IL-10[31.44(12.13, 69.60) ng/L]and interferon-γ [(102.85±92.23) ng/L] were obviously elevated, and among them, IL-6 and IL-10 elevations were significantly pronounced in coinfection group than that of single infection group[148.35(57.43, 390.82); 19.67(10.96, 35.35)] ( Z=-1.984, -2.077, all P<0.05). Lung consolidation (50.0%) and pleural effusion (38.9%) were common in coinfection group, and the incidence of pleural effusion in coinfection group was significantly higher than that of single infection group (19.1%)( χ2=5.594, P<0.05). Conclusions:Most of the pneumonia caused by human adenovirus type 7 mixed Mycoplasma pneumoniae in children is severe pneumonia, which may be related to the cytokine storm.

Tanshinone IIA prevents acute lung injury by regulating macrophage polarization / 中西医结合学报

OBJECTIVE@#Acute lung injury (ALI) is a serious respiratory dysfunction caused by pathogen or physical invasion. The strong induced inflammation often causes death. Tanshinone IIA (Tan-IIA) is the major constituent of Salvia miltiorrhiza Bunge and has been shown to display anti-inflammatory effects. The aim of the current study was to investigate the effects of Tan-IIA on ALI.@*METHODS@#A murine model of lipopolysaccharide (LPS)-induced ALI was used. The lungs and serum samples of mice were extracted at 3 days after treatment. ALI-induced inflammatory damages were confirmed from cytokine detections and histomorphology observations. Effects of Tan-IIA were investigated using in vivo and in vitro ALI models. Tan-IIA mechanisms were investigated by performing Western blot and flow cytometry experiments. A wound-healing assay was performed to confirm the Tan-IIA function.@*RESULTS@#The cytokine storm induced by LPS treatment was detected at 3 days after LPS treatment, and alveolar epithelial damage and lymphocyte aggregation were observed. Tan-IIA treatment attenuated the LPS-induced inflammation and reduced the levels of inflammatory cytokines released not only by inhibiting neutrophils, but also by macrophage. Moreover, we found that macrophage activation and polarization after LPS treatment were abrogated after applying the Tan-IIA treatment. An in vitro assay also confirmed that including the Tan-IIA supplement increased the relative amount of the M2 subtype and decreased that of M1. Rebalanced macrophages and Tan-IIA inhibited activations of the nuclear factor-κB and hypoxia-inducible factor pathways. Including Tan-IIA and macrophages also improved alveolar epithelial repair by regulating macrophage polarization.@*CONCLUSION@#This study found that while an LPS-induced cytokine storm exacerbated ALI, including Tan-IIA could prevent ALI-induced inflammation and improve the alveolar epithelial repair, and do so by regulating macrophage polarization.

NLRP3 inflammasome: an important therapeutic target for SARS-CoV-2 infection / 中华微生物学和免疫学杂志

SARS-CoV-2, the pathogen of the COVID-19 pandemic, causes serious damage to human health and social stability. In severe COVID-19 cases, the infection triggers cytokine storm, resulting in multi-organ excessive inflammatory responses and even failure, which eventually leads to death. Recent studies have shown the activation of nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome plays an essential role in the pathogenesis of COVID-19. SARS-CoV-2 can activate NLRP3 inflammasome through several pathways, thereby inducing the release of a large number of pro-inflammatory cytokines. This article reviews the activation of NLRP3 inflammasome caused by SARS-CoV-2 infection and the possible molecular mechanisms, and summarizes the progress in targeted inhibition of NLRP3 inflammation, aiming to provide a new strategy for the treatment of SARS-CoV-2 infection.

Advance in research on application of endotoxin adsorption membrane in treatment of coronavirus disease 2019 / 中华危重病急救医学

The new type coronavirus disease 2019 (COVID-19) is a contagious disease of severe lung inflammation induced by 2019 novel coronavirus (2019-nCoV). The World Health Organization (WHO) nomenclature of the newly discovered coronavirus was 2019-nCoV and the disease caused by 2019-nCoV was named COVID-19 on January 12, 2020. After 2019-nCoV invasion into a human body, it can stimulate the human immune system and engender a large number of cytokines, triggering a cytokine storm, resulting in severe infection, acute lung injury, multiple organ dysfunction, etc. Therefore, theoretically, the removal of over-production of cytokines can avoid the occurrence of cytokine storm and reduce the incidence of severe critical COVID-19 and serious poor prognosis. In this review, the authors systematically reviewed the past published reports related to the occurrence of cytokine storm in sepsis resulting in deterioration of disease situation, and recently they analyzed the therapeutic effects of patients with severe critical COVID-19 using endotoxin adsorption membrane for treatment in the disease course, further providing the effective clinical evidence of applying endotoxin adsorption membrane for treatment of COVID-19.