ERN ReCONNET points to consider for treating patients living with autoimmune rheumatic diseases with antiviral therapies and anti-SARS-CoV-2 antibody products.

Recent studies have shown that people who are immunocompromised may inadvertently play a role in spurring the mutations of the virus that create new variants. This is because some immunocompromised individuals remain at risk of getting COVID-19 despite vaccination, experience more severe disease, are susceptible to being chronically infected and remain contagious for longer if they become infected and considering that immunocompromised individuals represent approximately 2% of the overall population, this aspect should be carefully considered. So far, some autoimmune rheumatic disease (ARD) patients with COVID-19 have been treated with antiviral therapies or anti-SARS-CoV-2 antibody products. However, there is no homogeneous approach to these treatment strategies. This issue was addressed within the European Reference Network (ERN) on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ReCONNET) in a discussion among experts and patient's representatives in the context of the rare and complex connective tissue diseases (rCTDs) covered by the Network. ERN ReCONNET is one of the 24 ERNs launched by the European Commission in 2017 with the aim of tackling low prevalence and rare diseases that require highly specialised treatment and promoting concentration of knowledge and resources through virtual networks involving healthcare providers (HCPs) across the European Union (EU). Considering the urgent need to provide guidance not only to the rCTDs community, but also to the whole ARDs community, a multidisciplinary Task Force, including expert clinicians and European Patient Advocacy Group (ePAG) Advocates, was created in the framework of ERN ReCONNET with the aim of developing overarching principles (OP) and points-to-consider (PtC) on a homogenous approach to treat immunocompromised patients with ARDs (with a particular focus on CTDs) affected by COVID-19 using antiviral therapies and anti-SARS-CoV-2 antibody products. The present work reports the final OP and PtC agreed by the Task Force.

Intravenous Immunoglobulins at the Crossroad of Autoimmunity and Viral Infections.

Intravenous immunoglobulins (IVIG) are blood preparations pooled from the plasma of donors that have been first employed as replacement therapy in immunodeficiency. IVIG interact at multiple levels with the different components of the immune system and exert their activity against infections. Passive immunotherapy includes convalescent plasma from subjects who have recovered from infection, hyperimmune globulin formulations with a high titer of neutralizing antibodies, and monoclonal antibodies (mAbs). IVIG are used for the prevention and treatment of several infections, especially in immunocompromised patients, or in case of a poorly responsive immune system. The evolution of IVIG from a source of passive immunity to a powerful immunomodulatory/anti-inflammatory agent results in extensive applications in autoimmune diseases. IVIG composition depends on the antibodies of the donor population and the alterations of protein structure due to the processing of plasma. The anti-viral and anti-inflammatory activity of IVIG has led us to think that they may represent a useful therapeutic tool even in COVID-19. The human origin of IVIG carries specific criticalities including risks of blood products, supply, and elevated costs. IVIG can be useful in critically ill patients, as well as early empirical treatment. To date, the need for further well-designed studies stating protocols and the efficacy/tolerability profile of IVIG and convalescent plasma in selected situations are awaited.

The anti-viral facet of anti-rheumatic drugs: Lessons from COVID-19.

The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has posed the world at a pandemic risk. Coronavirus-19 disease (COVID-19) is an infectious disease caused by SARS-CoV-2, which causes pneumonia, requires intensive care unit hospitalization in about 10% of cases and can lead to a fatal outcome. Several efforts are currently made to find a treatment for COVID-19 patients. So far, several anti-viral and immunosuppressive or immunomodulating drugs have demonstrated some efficacy on COVID-19 both in vitro and in animal models as well as in cases series. In COVID-19 patients a pro-inflammatory status with high levels of interleukin (IL)-1B, IL-1 receptor (R)A and tumor necrosis factor (TNF)-α has been demonstrated. Moreover, high levels of IL-6 and TNF-α have been observed in patients requiring intensive-care-unit hospitalization. This provided rationale for the use of anti-rheumatic drugs as potential treatments for this severe viral infection. Other agents, such as hydroxychloroquine and chloroquine might have a direct anti-viral effect. The anti-viral aspect of immunosuppressants towards a variety of viruses has been known since long time and it is herein discussed in the view of searching for a potential treatment for SARS-CoV-2 infection.