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In addition to the respiratory symptoms associated with COVID-19, the disease has consistently been linked to many autoimmune diseases such as systemic lupus erythematous and antiphospholipid syndrome (APS). APS in particular was of paramount significance due to its devastating clinical sequela. In fact, the hypercoagulable state seen in patients with acute COVID-19 and the critical role of anticoagulant treatment in affected individuals shed light on the possible relatedness between APS and COVID-19. Moreover, the role of autoimmunity in the assumed association is not less important especially with the accumulated data available regarding the autoimmunity-triggering effect of SARS-CoV-2 infection. This is furtherly strengthened at the time patients with COVID-19 manifested antiphospholipid antibodies of different types following infection. Additionally, the severe form of the APS spectrum, catastrophic APS (CAPS), was shown to have overlapping characteristics with severe COVID-19 such as cytokine storm and multi-organ failure. Interestingly, COVID vaccine-induced autoimmune phenomena described in the medical literature have pointed to an association with APS. Whether the antiphospholipid antibodies were present or de novo, COVID vaccine-induced vascular thrombosis in certain individuals necessitates further investigations regarding the possible mechanisms involved. In our current paper, we aimed to focus on the associations mentioned, their implications, importance, and consequences. • Patients with COVID-19 have consistently demonstrated a hypercoagulable state. • Treatment with anticoagulants in patients with COVID-19 is among critical players in therapy. • COVID-19 patients were shown to have detected aPL antibodies. • The similarities between COVID-19 and APS resemble two sides of a coin. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) has resulted in a global pandemic. Most COVID-19 patients are asymptomatic or have flu-like symptoms. However, around 15% of the patients may have severe disease, including unilateral or bilateral pneumonia with acute respiratory distress syndrome and progressive hypoxemia that may require mechanical ventilation assistance. A systemic inflammatory response syndrome occurs in the most severe forms of COVID-19, with multiorgan involvement which can be life threatening caused by a cytokine storm. Although what best characterizes COVID-19 are the manifestations of the respiratory system, it has been shown that it also acts at the cardiovascular level, producing coagulation abnormalities, which causes thrombotic events mainly in the arteries/arterioles, microcirculation and venous system, and potentially increased mortality risk. This multiorgan vascular disease overlaps with other known microangiopathies, such as thrombotic microangiopathy or paroxysmal nocturnal hemoglobinuria, where complement overactivation plays an important role in the pathophysiology of thrombosis. Furthermore, coagulopathy secondary to COVID-19 occurs in the context of an uncontrolled inflammatory response, reminiscent of APS, especially in its catastrophic form. This review summarizes the current knowledge regarding the relationship between COVID-19 and the APS. • Coagulopathy secondary to COVID-19 occurs in the context of an uncontrolled inflammatory response, reminiscent of APS, especially in its catastrophic form. • During the first days of infection, there is an aPL-independent mechanism secondary to SARS-CoV2 infection. • The aPL carriers would have an additional later risk of thrombosis. [ABSTRACT FROM AUTHOR]

While autoimmunity is a branch of medicine linked to every single organ system via direct and indirect pathways, meeting in person to discuss autoimmunity during the 13th international congress on autoimmunity (AUTO13) with participants from all over the world had a very good reason. The mechanisms involved in autoimmune diseases are of extreme importance and in fact critical in understanding the course of diseases as well as selecting proper therapies. COVID-19 has served as a great example of how autoimmunity is deeply involved in the disease and directly correlated to severity, morbidity, and mortality. For instance, initially the term cytokine storm dominated, then COVID-19 was addressed as the new member of the hyperferritinemic syndrome, and also the use of immunosuppressants in patients with COVID-19 throughout the pandemic, all shed light on the fundamental role of autoimmunity. Unsurprisingly, SARS-CoV-2 was called the "autoimmune virus" during AUTO13. Subsequently, the correlation between autoimmunity and COVID-19 vaccines and post-COVID, all were discussed from different autoimmune aspects during the congress. In addition, updates on the mechanisms of diseases, autoantibodies, novel diagnostics and therapies in regard to autoimmune diseases such as antiphospholipid syndrome, systemic lupus erythematosus, systemic sclerosis and others, were discussed in dedicated sessions. Due to the magnificence of the topics discussed, we aimed to bring in our article hereby, the pearls of AUTO13 in terms of updates, new aspects of autoimmunity, and interesting findings. While more than 500 abstract were presented, concluding all the topics was not in reach, hence major findings were summarized. [ABSTRACT FROM AUTHOR]

From the introduction of hyperferritinemic syndrome concept, a growing body of evidence has suggested the role of ferritin as a pathogenic mediator and a relevant clinical feature in the management of patients with inflammatory diseases. From a pathogenic point of view, ferritin may directly stimulate the aberrant immune response by triggering the production of pro-inflammatory mediators in inducing a vicious pathogenic loop and contributing to the occurrence of cytokine storm syndrome. The latter has been recently defined as a clinical picture characterised by elevated circulating cytokine levels, acute systemic inflammatory symptoms, and secondary organ dysfunction beyond that which could be attributed to a normal response to a pathogen It is noteworthy that the occurrence of hyperferritinemia may be correlated with the development of the cytokine storm syndrome in the context of an inflammatory disease. In addition to adult onset Still's disease, macrophage activation syndrome, catastrophic anti-phospholipids syndrome, and septic shock, recent evidence has suggested this association between ferritin and life-threatening evolution in patients with systemic lupus erythematosus, with anti-MDA5 antibodies in the context of poly-dermatomyositis, with severe COVID-19, and with multisystem inflammatory syndrome. The possible underlying common inflammatory mechanisms, associated with hyperferritinemia, may led to the similar clinical picture observed in these patients. Furthermore, similar therapeutic strategies could be suggested inhibiting pro-inflammatory cytokines and improving long-term outcomes in these disorders. Thus, it could be possible to expand the spectrum of the hyperferritinemic syndrome to those diseases burdened by a dreadful clinical picture correlated with hyperferritinemia and the occurrence of the cytokine storm syndrome. In addition, the assessment of ferritin may provide useful information to the physicians in clinical practice to manage these patients. Therefore, ferritin may be considered a relevant clinical feature to be used as biomarker in dissecting the unmet needs in the management of these disorders. Novel evidence may thus support an expansion of the spectrum of the hyperferritinemic syndrome to these diseases burdened by a life-threatening clinical picture correlated with hyperferritinemia and the occurrence of the cytokine storm syndrome. • The concept of hyperferritinemic syndrome suggests ferritin pathogenic relevance. • Ferritin may stimulate the aberrant inflammatory response by triggering the immune system. • Hyperferritinemia may strictly correlate with cytokine storm syndrome development. • Ferritin assessment may provide useful clinical information in managing these patients. • The hyperferritinemic syndrome spectrum may be expanded to diseases burdened hyperferritinemia and cytokine storm syndrome. [ABSTRACT FROM AUTHOR]

The novel SARS-CoV-2 has been rattling the world since its outbreak in December 2019, leading to the COVID-19 pandemic. The learning curve of this new virus has been steep, with a global scientific community desperate to learn how the virus is transmitted, how it replicates, why it causes such a wide spectrum of disease manifestations, resulting in none or few symptoms in some. Others are burdened by an intense immune response that resembles the cytokine storm syndrome (CSS), which leads to severe disease manifestations, often complicated by fatal acute respiratory distress syndrome and death. Research efforts have been focusing on finding effective cures and vaccinations for this virus. The presence of SARS-CoV-2 in the gastrointestinal (GI) tract, represented by several GI manifestations, has led to its investigation as a target for the virus and as an indicator of disease severity. The response of the microbiome (which is heavily linked to immunity) to the novel SARS-CoV-2 virus, and its role in igniting the exaggerated immune response has therefore become a focus of interest. The objective of our study was to gather the data connecting between the microbiome, the GI tract and COVID-19 and to investigate whether these reported alterations in the gut microbiome bear any resemblance to those seen in lupus, the prototypical autoimmune disease. Confirming such changes may become the steppingstone to potential therapies that may prevent transmission, progression and immune related manifestations of COVID-19, via manipulation of the gut microbiota. We performed an extensive literature review, utilizing the Pubmed search engine and Google Scholar for studies evaluating the microbiome in COVID-19 patients and compared results with studies evaluating the microbiome in lupus. We searched for the terms: microbiome, dysbiosis, COVID-19, SARS-CoV-2, gastrointestinal as well as lupus and autoimmune. While there were hundreds of articles which referred to gastrointestinal manifestations in COVID-19, to date only 4 studies investigated the gastrointestinal microbiome in this setting. We compared the similarities between microbiome of COVID-19 patients and lupus patients. We found that there are several similar processes of immune dysregulation in patients with COVID-19 and in those with lupus, with several other alterations seen in other pathological states. Some of these similarities include loss of microbiota biodiversity, increased representation of pathobionts, which are microbes associated with inflammation and disease (i.e Proteobacteria) and a relative decrease of symbionts, which are protective microbes, associated with anti-inflammatory properties (i.e Lactobacillus). Compromise to the intestinal barrier has also been reported in both. We conclude that the gastrointestinal tract contributes to the disease manifestations in COVID-19. Whether gastrointestinal dysbiosis is the cause or effect of gastrointestinal manifestations and several severe systemic manifestations, which may be the response to an increased pro-inflammatory environment, is still debatable and warrants further investigation. Given the resemblance of the microbiome in COVID-19 patients to that seen in lupus patients, it becomes clearer why several therapies used in autoimmune conditions are currently under investigation for the treatment of COVID-19 patients. Moreover, these findings should promote further investigating the utility of manipulation of the microbiome, via nutritional supplementation or even fecal transplantations, interventions that may alter the course of the disease, and potentially prevent disease transmission at low cost and low risk. [ABSTRACT FROM AUTHOR]

The coronavirus disease-19 pandemic (COVID-19), which appeared in China in December 2019 and rapidly spread throughout the world, has forced clinicians and scientists to take up extraordinary challenges. This unprecedented situation led to the inception of numerous fundamental research protocols and many clinical trials. It quickly became apparent that although COVID-19, in the vast majority of cases, was a benign disease, it could also develop a severe form with sometimes fatal outcomes. Cytokines are central to the pathophysiology of COVID-19; while some of them are beneficial (type-I interferon, interleukin-7), others appear detrimental (interleukin-1β, -6, and TNF-α) particularly in the context of the so-called cytokine storm. Yet another characteristic of the disease has emerged: concomitant immunodeficiency, notably involving impaired type-I interferon response, and lymphopenia. This review provides an overview of current knowledge on COVID-19 immunopathology. We discuss the defective type-I IFN response, the theoretical role of IL-7 to restore lymphocyte repertoire, as well as we mention the two patterns observed in severe COVID-19 (i.e. interleukin-1β-driven macrophage activation syndrome vs. interleukin-6-driven immune dysregulation). Next, reviewing current evidence drawn from clinical trials, we examine a number of cytokine and anti-cytokine therapies, including interleukin-1, -6, and TNF inhibitors, as well as less targeted therapies, such as corticosteroids, chloroquine, or JAK inhibitors. • COVID-19 induces both impairment and hyperactivation of the immune system. • Early viral clearance by type-I IFN is a key to preventing further viral replication, T cell exhaustion, and cytokine storm. • Timely administration of treatments may reduce viral load and avoid hyperinflammation. [ABSTRACT FROM AUTHOR]

The severe form of COVID-19 share several clinical and laboratory features with four entities gathered under the term " hyperferritinemic syndromes " and including macrophage activation syndrome (MAS), adult-onset Still's disease (AOSD), catastrophic anti-phospholipid syndrome (CAPS) and septic shock. COVID-19 systemic inflammatory reaction and "hyperferritinemic syndromes " are all characterized by high serum ferritin and a life-threatening hyper-inflammation sustained by a cytokines storm which eventually leads to multi-organ failure. In this review, we analyze the possible epidemiological and molecular mechanisms responsible for hyper-inflammation in patients with severe COVID-19 and we underline the similarities between this condition and "hyperferritinemic syndromes" which would allow considering severe COVID-19 as a fifth member of this spectrum of inflammatory conditions. • COVID-19 infection share clinical/laboratory features with "hyperferritinemic syndromes". • A cytokine storm is responsible for COVID-19 systemic inflammatory response. • COVID-19 severe infection benefit from b-DMARDs targeting specific cytokines. [ABSTRACT FROM AUTHOR]

Now COVID-19 is causing a severe public health emergency and the mortality is rapidly increasing all over the world. In the current pandemic era, although there have been many efforts to diagnose a number of patients with symptoms or close contacts, there is no definite guideline for the initial therapeutic approach for them and therefore, many patients have been dying due to a hyperinflammatory immunological reaction labeled as "cytokine storm". Severe patients are hospitalized and the treatment is done, though they have not been established yet. Currently, however, no treatment is provided for those who are isolated at home or shelter until they get severe symptoms, which will increase the harms to the patients. In this review, we discuss some important points dedicated to the management of patients with COVID-19, which should help reducing morbidity and mortality. In this era, we suggest 7 recommendations to rescue the patients and to reduce the morbidity and mortality due to COVID-19 based on the immunological point of view. [ABSTRACT FROM AUTHOR]

Severe Acute Respiratory Syndrome related to Coronavirus-2 (SARS-CoV-2), coronavirus disease-2019 (COVID-19) may cause severe illness in 20% of patients. This may be in part due to an uncontrolled immune-response to SARS-CoV-2 infection triggering a systemic hyperinflammatory response, the so-called "cytokine storm". The reduction of this inflammatory immune-response could be considered as a potential therapeutic target against severe COVID-19. The relationship between inflammation and clot activation must also be considered. Furthermore, we must keep in mind that currently, no specific antiviral treatment is available for SARS-CoV-2. While moderate-severe forms need in-hospital surveillance plus antivirals and/or hydroxychloroquine; in severe and life-threating subsets a high intensity anti-inflammatory and immunomodulatory therapy could be a therapeutic option. However, right data on the effectiveness of different immunomodulating drugs are scarce. Herein, we discuss the pathogenesis and the possible role played by drugs such as: antimalarials, anti-IL6, anti-IL-1, calcineurin and JAK inhibitors, corticosteroids, immunoglobulins, heparins, angiotensin-converting enzyme agonists and statins in severe COVID-19. • Severe COVID-19 forms may be related to a hyperinflammatory syndrome. • Severe COVID-19 is associated with clot pathway hyperactivity and sometimes, with thromboses. • Immunosuppression may be a complementary therapy in COVID-19 patients. • Antimalarials, heparin, cytokine blockers, JAK-inhibitors, IVIG could be useful for treating severe COVID-19 patients. • In SARS-CoV-2 infections the effectiveness of the hyperimmune plasma remains uncertain. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible of the coronavirus disease 2019 (COVID-19) pandemic. Therapeutic options including antimalarials, antivirals, and vaccines are under study. Meanwhile the current pandemic has called attention over old therapeutic tools to treat infectious diseases. Convalescent plasma (CP) constitutes the first option in the current situation, since it has been successfully used in other coronaviruses outbreaks. Herein, we discuss the possible mechanisms of action of CP and their repercussion in COVID-19 pathogenesis, including direct neutralization of the virus, control of an overactive immune system (i.e. , cytokine storm, Th1/Th17 ratio, complement activation) and immunomodulation of a hypercoagulable state. All these benefits of CP are expected to be better achieved if used in non-critically hospitalized patients, in the hope of reducing morbidity and mortality. • Coronavirus disease 19 (COVID-19) is an emerging viral threat with major repercussions for public health. • There is not specific treatment for COVID-19. • Convalescent plasma (CP) emerges as the first option of management for hospitalized patients with COVID-19. • Transference of neutralizing antibodies helps to control COVID-19 infection and modulates inflammatory response. • Other plasma components may enhance the antiviral and anti-inflammatory properties of CP. [ABSTRACT FROM AUTHOR]

The outbreak of the new coronavirus infections COVID-19 in December 2019 in China has quickly become a global health emergency. Given the lack of specific anti-viral therapies, the current management of severe acute respiratory syndrome coronaviruses (SARS-CoV-2) is mainly supportive, even though several compounds are now under investigation for the treatment of this life-threatening disease. COVID-19 pandemic is certainly conditioning the treatment strategy of a complex disorder as rheumatoid arthritis (RA), whose infectious risk is increased compared to the general population because of an overall impairment of immune system typical of autoimmune diseases combined with the iatrogenic effect generated by corticosteroids and immunosuppressive drugs. However, the increasing knowledge about the pathophysiology of SARS-CoV-2 infection is leading to consider some anti-rheumatic drugs as potential treatment options for the management of COVID-19. In this review we will critically analyse the evidences on either positive or negative effect of drugs commonly used to treat RA in this particular scenario, in order to optimize the current approach to RA patients. [ABSTRACT FROM AUTHOR]