ABSTRACT
On September 10, 2021, a special tribunal established by the French government launched an inquiry into the activities of former health minister Dr. Agnes Buzyn who was charged with "endangering the lives of others". It is surprising to learn of this accusation and inquiry into the actions of a public health official whose response to the epidemic was, to all appearances, exemplary.
ABSTRACT
As of this writing, it is estimated that there have been nearly 600 million cases of coronavirus disease 2019 (COVID-19) around the world with over six million deaths. While shocking, these figures do not fully illustrate the morbidity associated with this disease. It is also estimated that between 10% and 30% of those who survive COVID-19 develop persistent symptoms after the acute infection has passed. These individuals, who most often experienced initial infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) considered mild to moderate in severity, often display a broad array of symptoms. Collectively, this disorder or syndrome is now referred to as Long COVID (among other designations), and it represents a national/international health crisis. The most frequently reported symptoms associated with Long COVID include chronic fatigue with post exertional features, neurocognitive dysfunction, breathlessness, and somatic pain. Long COVID can range in severity from mild to severely debilitating, with resultant loss of quality of life and productivity. For now, there are many unanswered questions surrounding Long COVID: how can it be best defined, what is needed for accurate diagnosis, what is causing it, and how should it be best managed. How rheumatologists will engage in the Long COVID pandemic is another question; at the minimum, we will be called upon to evaluate and manage our own patients with immune-mediated inflammatory diseases who have developed it. This review focuses on addressing the disease essentials, providing both declarative and procedural knowledge to prepare rheumatologists for how to address Long COVID: understanding its origins, its current case definitions, epidemiology, pathobiology and clinical manifestations. Finally, it will provide an outline on how to clinically approach patients with possible Long COVID and initiate treatment and/or guide them on how to best manage it.
ABSTRACT
OBJECTIVE: Patients with immune-mediated inflammatory diseases (IMIDs) receiving B cell-depleting therapy (BCDT) are among the most vulnerable to severe COVID-19, as well as the most likely to suboptimally respond to SARS-CoV-2 vaccines. However, little is known about the frequency or severity of breakthrough infection in this population. We retrospectively analyzed a large group of vaccinated IMID patients undergoing BCDT in order to identify breakthrough COVID-19 infections and assess their outcomes. METHODS: In this retrospective cohort study, the pharmacy records and COVID-19 registry at the Cleveland Clinic were searched using specific International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes to identify IMIDs patients who 1) received treatment with BCDT, 2) were vaccinated against SARS-CoV-2, and 3) experienced breakthrough infections. Each electronic medical record was reviewed to extract clinical data and outcomes. Univariate and multivariable logistic/proportional odds regression models were used to examine the risk factors for severe outcomes. RESULTS: Of 1,696 IMID patients receiving BCDT, 74 developed breakthrough COVID-19 prior to December 16, 2021. Outcomes were severe, with 29 patients hospitalized (39.2%), 11 patients requiring critical care (14.9%), and 6 deaths (8.1%). Outpatient anti-SARS-CoV-2 monoclonal antibodies were used to treat 21 patients, with 1 hospitalization and no deaths. A comparator analysis examining 1,437 unvaccinated IMID patients receiving BCDT over the same time period identified 57 COVID-19 cases (4.0%), with 28 requiring hospitalization (49.1%), including 7 deaths (12.3%). CONCLUSION: IMID patients receiving BCDT regardless of vaccine status appear to be vulnerable to infection with SARS-CoV-2, and use of BCDT is frequently associated with severe outcomes. Outpatient use of anti-SARS-CoV-2 monoclonal antibody therapy appears to be associated with enhanced clinical outcomes.
ABSTRACT
BACKGROUND: The role of humoral immunity has been well established in reducing infection risk and facilitating viral clearance in patients with COVID-19. However, the relationship between specific antibody responses and severity of COVID-19 is less well understood. METHODS: To address this question and identify gaps in knowledge, we utilized the methodology of a scoping review to interrogate risk of infection and clinical outcomes of COVID-19 in patients with iatrogenic and inborn humoral immunodeficiency states based on existing literature. RESULTS: Among patients with iatrogenic B-cell depletion, particularly with agents targeting CD20, our analysis found increased risk of severe COVID-19 and death across a range of underlying disease states. Among patients with humoral inborn errors of immunity with COVID-19, our synthesis found that patients with dysregulated humoral immunity, predominantly common variable immunodeficiency (CVID), may be more susceptible to severe COVID-19 than patients with humoral immunodeficiency states due to X-linked agammaglobulinemia and other miscellaneous forms of humoral immunodeficiency. There were insufficient data to appraise the risk of COVID-19 infection in both populations of patients. CONCLUSIONS: Our work identifies potentially significant predictors of COVID-19 severity in patients with humoral immunodeficiency states and highlights the need for larger studies to control for clinical and biologic confounders of disease severity.
ABSTRACT
The coronavirus disease 2019 (COVID-19; caused by SARS-CoV-2) pandemic has affected the healthcare system on a global scale, and we utilized the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2020 annual meeting to examine how COVID-19 might affect patients with psoriatic disease (PsD) and the clinicians who care for them. Pressing issues and concerns identified included whether having psoriasis increased the risk of acquiring COVID-19, vaccine safety, and the acceptability of telehealth. The general message from rheumatologists, dermatologists, infectious disease specialists, and patient research partners was that data did not suggest that having PsD or its treatment significantly increased risk of infection or more severe disease course, and that the telehealth experience was a success overall.
ABSTRACT
This review focuses on an alternative strategy utilizing small molecules to inhibit a key signal-transduction pathway, the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway. The JAK-STAT pathway mediates biologic activity for a large number of inflammatory cytokines and mediators.
ABSTRACT
The glucocorticoid dexamethasone is the standard of care in critically ill patients with COVID-19 to suppress the inappropriately heightened inflammatory response (cytokine storm), but the Janus kinase inhibitor baricitinib combined with remdesivir has received emergency use authorization for the same indication. As of this writing, in a hospitalized patient with COVID-19 who has evidence of pneumonitis or hypoxia, we recommend using either regimen, but not both together. Both regimens have shown benefit in randomized controlled trials, but we cannot state with certainty that either is superior to the other, nor whether they should be used together. Further trials are underway.
ABSTRACT
Numerous immunomodulating agents are currently being studied in clinical trials for the treatment of COVID-19, including interferon therapies. Interferons are naturally occurring host antiviral proteins upstream of the inflammatory pathway that are released by host cells in response to the presence of viral pathogens. It is known that beta coronaviruses deploy anti-interferon defenses to escape host innate immunity early in the infection course, and thus interferons have become attractive candidates for treatment of COVID-19. Questions surrounding timing, type of interferon, and route of administration all remain unanswered. Here we discuss the role of interferons in host antiviral immunity, and review the current data surrounding use of interferons in COVID-19.
Subject(s)
Betacoronavirus , Coronavirus Infections , Pandemics , Periodicals as Topic , Pneumonia, Viral , Rheumatic Diseases , COVID-19 , Humans , SARS-CoV-2ABSTRACT
Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been used experimentally in patients with acute respiratory distress syndrome. Recombinant GM-CSF administered by direct inhalation is currently being studied in a cohort of patients with advanced COVID-19.
ABSTRACT
Interleukin 1 (IL-1) is a potential target of therapy in COVID-19 during the severe respiratory-inflammatory phase ("cytokine release syndrome"), when pulmonary macrophages are hyperactivated, releasing IL-1 and other cytokines. Preliminary evidence indicates that anakinra and canakinumab, drugs that block the action of IL-1 and have a good safety profile, improve the outcomes of patients with COVID-19 cytokine release syndrome. Results from large, randomized clinical trials are pending.
ABSTRACT
Knowledge about the pathobiology of SARS-CoV-2 as it interacts with immune defenses is limited. SARS-CoV-2 is spread by droplets that come into contact with mucous membranes. COVID-19 is characterized by 2 or 3 stages: most patients who recover experience 2 stages of illness commencing with an asymptomatic or paucisymptomatic incubation period, followed by a nonsevere symptomatic illness lasting for several weeks, occurring in about 80% of those infected. In the remainder, a third phase marked by a severe respiratory illness, often accompanied by multisystem dysfunction, coagulopathy, and shock is observed. This phase of the illness is characterized by hypercytokinemic inflammation and is often referred to as "cytokine storm." While the immunopathogenesis remains unclear, prospects of treating this severe phase of the illness with immunotherapy are evolving, with some treatments showing promise.