COVID-19 outcomes in patients with and without autoimmune rheumatic diseases: A multicenter comparative study.

BACKGROUND AND OBJECTIVE: People with rheumatic diseases are particularly concerned with the coronavirus disease 2019 (COVID-19) pandemic. Our work aimed to study the impact of pre-existing autoimmune rheumatic disease (AIRD) and its immunosuppressive drugs on COVID-19 severity and outcome. PATIENTS AND METHODS: This is a multicenter case-control study performed between September 2020 and February 2021 on 130 adults with COVID-19, including 66 patients with AIRD and 64 without AIRD, who served as a control group. RESULTS: Regarding COVID-19 clinical manifestations; diarrhea, fatigue, and headache were found with significantly higher frequency in the AIRD group while a higher frequency of cough was found in the control group. Comparing COVID-19 complications, only septic shock was significantly higher in the AIRD group (P = 0.013). Both groups were treated with similar COVID-19 drugs except for tocilizumab and anticoagulants, which were statistically significantly more frequently used in the control group (P < 0.001 for both). No statistically significant difference was found between the groups in the outcome or severity of COVID-19. There was no impact of previous immunosuppressive drugs before COVID-19 on the severity of the disease except for a longer duration of recovery in patients on steroids (P < 0.001). Patients with hypertension had severe COVID-19 compared with those without (odds ratio 2.8, 95% confidence interval 1.2-6.9; P = 0.020). CONCLUSION: AIRD may not affect COVID-19 severity and outcome. Similarly, immunosuppressive medications had no effect; except that patients on systemic steroids had longer duration for recovery. Comorbid conditions, such as hypertension, may be associated with more severe COVID-19 disease course.

Repurposing of drugs targeting the cytokine storm induced by SARS-CoV-2.

A cytokine storm is one of the leading causes of acute respiratory distress syndrome (ARDS) and sepsis-associated multiple organ failure in many respiratory viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The coronavirus disease 2019 (COVID-19) pandemic has caused millions of deaths worldwide, resulting in an urgent need for effective therapeutic interventions. Repurposing immunosuppressive drugs that target cytokines with immunomodulatory properties is a promising approach to counteract SARS-CoV-2-induced ARDS at the infective and post-infective stages. In this minireview, we examine drugs targeting IL-1ß, IL-4/IL-13, IL-6 and TNF-α tested in COVID-19 patients.

COVID-19 Disease in Kidney Transplantation Recipients: A Single- Center Study (Experience of Dr. Shariati Hospital)

Background: Coronavirus disease 2019 (COVID-19 disease) is caused by SARS-CoV-2. In December 2019, several outbreaks of severe and life-threatening pneumonia with unknown organism were reported in Wuhan, China and the disease spread rapidly all over the world and caused the biggest pandemic. There was no clear information regarding incidence, morbidity, and mortality rate of COVID-19 disease in kidney transplant recipients or other solid organ transplant recipients. Therefore, we designed a study to evaluate the factors that can have any impact on kidney transplant recipients infected with SARS-Cov2. Methods: Our research was a retrospective cross-sectional study. The study population was all adult kidney transplant recipients (>18 years old) who were hospitalized due to COVID-19 disease according to national guidelines from 1st March, 2020 to 20th April, 2020 in Shariati Hospital, Tehran, Iran. Demographic data, common clinical complaints, vital signs, types and dose of immunosuppressive drugs, comorbidity diseases, and basic laboratory tests were extracted from the medical records using a data collection form. Results: According to the results of our investigation, mortality rate was 69.2% in kidney transplant recipients who were admitted in our hospital. No one died under the age of 47 years, while no one survived over the age of 58 years. As a result, age can be a reliable predictor of survival rate in kidney transplant recipients with COVID-19 pneumonia. All patients in non- survivors' group were elderly and needed intubation, mechanical ventilation, and renal replacement. Conclusion: In addition to early referral and early start of appropriate and specific treatments of COVID-19 in patients with kidney transplantation, our general advice, is discontinuation of antimetabolite drugs at admission time, dose reduction of calcineurin inhibitors, and even withdrawal of all immunosuppressive drugs except steroids in critical cases. © 2022 by the Author(s).

Pneumocystis jirovecii Pneumonia Associated with COVID-19 in Patients with Interstitial Pneumonia.

Here, we report two cases of patients with interstitial pneumonia (IP) on steroids who developed Pneumocystis jirovecii pneumonia (PJP) following coronavirus disease 2019 (COVID-19) infection. Case 1: A 69-year-old man on 10 mg of prednisolone (PSL) daily for IP developed new pneumonia shortly after his COVID-19 infection improved and was diagnosed with PJP based on chest computed tomography (CT) findings and elevated serum ß-D-glucan levels. Trimethoprim-sulfamethoxazole (TMP-SMZ) was administered, and the pneumonia resolved. Case 2: A 70-year-old woman taking 4 mg/day of PSL for IP and rheumatoid arthritis developed COVID-19 pneumonia, which resolved mildly, but her pneumonia flared up and was diagnosed as PJP based on CT findings, elevated ß-D-glucan levels, and positive polymerase chain reaction for P. jirovecii DNA in the sputum. The autopsy revealed diffuse alveolar damage, increased collagen fiver and fibrotic foci, mucinous component accumulation, and the presence of a P. jirovecii cyst. In conclusion, steroids and immunosuppressive medications are well-known risk factors for PJP. Patients with IP who have been taking these drugs for a long time are frequently treated with additional steroids for COVID-19; thus, PJP complications should be avoided in such cases.

Immune Response after mRNA COVID-19 Vaccination in Lung Transplant Recipients: A 6-Month Follow-Up.

BACKGROUND AND OBJECTIVE: This prospective cohort study analyzed the immune response to COVID-19 mRNA vaccines in lung transplant recipients (LuTRs) compared to healthy controls (HCs) at a 6-month follow-up. METHODS: After the first two doses of either BNT162b2 or mRNA-1273, SARS-CoV-2 antibodies were measured in LuTRs (n = 57) and sex- and age-matched HCs (n = 57). Antibody kinetics during a 6-month follow-up and the effect of a third vaccine dose were evaluated. Humoral responses were assessed using the Elecsys® Anti-SARS-CoV-2 S immunoassay. In 16 LuTRs, SARS-CoV-2-specific T cell responses were quantified using IFN-γ ELISpot assays. RESULTS: Seroconversion rates were 94% and 100% after the first and second vaccine dose, respectively, in HCs, while only 19% and 56% of LuTRs developed antibodies. Furthermore, 22 of 24 LuTRs who received the third vaccine dose showed seroconversion (five of seven primary non-responders and 17 of 17 primary responders). A T cell response against SARS-CoV-2-spike S1 and/or S2 was detected in 100% (16/16) of HCs and 50% (8/16) of LuTRs. CONCLUSIONS: The data suggest that LuTRs have reduced humoral and cellular immune responses after two doses of COVID-19 mRNA vaccination when compared to HCs. A third dose may be of substantial benefit.

Impact of COVID-19 in immunosuppressive drug-naïve autoimmune disorders: Autoimmune gastritis, celiac disease, type 1 diabetes, and autoimmune thyroid disease.

Few conflicting data are currently available on the risk of SARS-CoV-2 infection in patients with autoimmune disorders. The studies performed so far are influenced, in most cases, by the treatment with immunosuppressive drugs, making it difficult to ascertain the burden of autoimmunity per se. For this reason, herein we assessed the susceptibility to COVID-19 in immunosuppressive drug-naïve patients with autoimmune diseases, such as autoimmune gastritis (AIG), celiac disease (CD), type 1 diabetes (T1D), and autoimmune thyroid disease (AITD). Telephone interviews were conducted on 400 patients-100 for each group-in May 2021 by looking at the positivity of molecular nasopharyngeal swabs and/or serology for SARS-CoV-2, the need for hospitalization, the outcome, and the vaccination status. Overall, a positive COVID-19 test was reported in 33 patients (8.2%), comparable with that of the Lombardy general population (8.2%). In particular, seven patients with AIG, 9 with CD, 8 with T1D, and 9 with AITD experienced COVID-19. Only three patients required hospitalization, none died, and 235 (58.7%) were vaccinated, 43 with AIG, 47 with CD, 91 with T1D, and 54 with AITD. These results seem to suggest that autoimmunity per se does not increase the susceptibility to COVID-19. Also, COVID-19 seems to be mild in these patients, as indicated by the low hospitalization rates and adverse outcomes, although further studies are needed to better clarify this issue.

Lipid rafts as viral entry routes and immune platforms: A double-edged sword in SARS-CoV-2 infection?

Lipid rafts are nanoscopic compartments of cell membranes that serve a variety of biological functions. They play a crucial role in viral infections, as enveloped viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can exploit rafts to enter or quit target cells. On the other hand, lipid rafts contribute to the formation of immune synapses and their proper functioning is a prerequisite for adequate immune response and viral clearance. In this narrative review we dissect the panorama focusing on this singular aspect of cell biology in the context of SARS-CoV-2 infection and therapy. A lipid raft-mediated mechanism can be hypothesized for many drugs recommended or considered for the treatment of SARS-CoV-2 infection, such as glucocorticoids, antimalarials, immunosuppressants and antiviral agents. Furthermore, the additional use of lipid-lowering agents, like statins, may affect the lipid composition of membrane rafts and thus influence the processes occurring in these compartments. The combination of drugs acting on lipid rafts may be successful in the treatment of more severe forms of the disease and should be reserved for further investigation.

Unexpected Positive Effects of Rituximab and Corticosteroids on COVID-19 in a Patient Suffering from Granulomatosis with Polyangiitis.

The COVID-19 pandemic has raised concerns among physicians and patients with autoimmune disorders about how this viral infection affects the patients receiving immunosuppressive drugs. There are speculations about a higher incidence and severity of COVID-19 in patients receiving a variety of immunosuppressant drugs. However, we reported the rapid recovery from COVID-19 in a 67-year-old male with granulomatosis with polyangiitis who did not experience severe symptoms of the COVID-19 as expected, despite having a history of serious lung involvement due to the autoimmune disease. He received conventional medications to treat COVID-19, though he had been receiving rituximab and corticosteroids before the onset of COVID-19 symptoms. Prevention of the cytokine storm caused by SARS-CoV-2 infection owing to taking the immunosuppressive drugs (rituximab and corticosteroids) could be a reason for these unexpected observations. Therefore, this case showed that taking immunosuppressive drugs is unlikely to be directly related to the increased severity of COVID-19.

COVID-19: Considerations about immune suppression and biologicals at the time of SARS-CoV-2 pandemic.

The extent of the profound immunological and nonimmunological responses linked to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is currently being investigated worldwide due to the large burden associated with death due to SARS-CoV-2 and the short-term consequences of coronavirus disease 2019 (COVID-19). It has been hypothesized that patients on immunosuppressive treatments, including biologics, may have an augmented risk of being infected by SARS-CoV-2; however, there are currently no definitive data about biological drugs and COVID-19 in immune-mediated inflammatory diseases. Current epidemiological models developed to understand how long the COVID-19 epidemic may last are not conclusive and range from sustained epidemics to complete elimination. Nevertheless, even in the best-case scenario of apparent elimination, there is concordance about a possible contagion resurgence as late as 2024. Therefore, knowledge of the impact of SARS-CoV-2 on immune-mediated diseases and among patients treated with biologicals, together with the results of novel and promising COVID-19 treatment strategies targeting the virus and the host immune response (or both), will help us to best manage our patients during this pandemic over the next few years.

The impact of COVID-19 pandemic on psoriasis patients, and their immunosuppressive treatment: a cross-sectional multicenter study from Turkey.

BACKGROUND: Immunosuppressive therapy has been a great concern during the pandemic. This study aimed to evaluate the pandemic's impact on psoriasis patients treated with immunosuppressive drugs. MATERIAL AND METHODS: The multicenter study was conducted in 14 tertiary dermatology centers. Demographic data, treatment status, disease course, and cases of COVID-19 were evaluated in patients with psoriasis using the immunosuppressive treatment. RESULTS: Of 1827 patients included, the drug adherence rate was 68.2%. Those receiving anti-interleukin (anti-IL) drugs were more likely to continue treatment than patients receiving conventional drugs (OR = 1.50, 95% CI, 1.181-1.895, p = .001). Disease worsening rate was 24.2% and drug dose reduction increased this rate 3.26 and drug withdrawal 8.71 times. Receiving anti-TNF or anti-IL drugs was associated with less disease worsening compared to conventional drugs (p = .038, p = .032; respectively). Drug withdrawal causes were 'unable to come' (39.6%), 'COVID concern' (25.3%), and 'physician's and patient's co-decision' (17.4%). Four patients had COVID-19 infection with mild symptoms. The incidence was 0.0022% while it was 0.0025% in the general population. CONCLUSION: Our study shows that psoriasis patients using systemic immunosuppressive do not have a higher, but even lower COVID-19 risk than the general population, and treatment compliance with biological drugs is higher.

Patients with inflammatory bowel disease on immunosuppressive drugs: perspectives' on COVID-19 and health care service during the pandemic.

BACKGROUND AND AIMS: Patients with inflammatory bowel diseases (IBD) have experienced changes to the routine management because of the SARS-CoV-2 pandemic. The aim of this study was to examine patients with IBD's adherence to the restrictions imposed by society and the hospital, worries and concerns regarding medical treatment and clinical follow-up under the pandemic. METHODS: IBD patients (≥18 years) at the outpatient clinic at Oslo University Hospital were included and answered a self-report questionnaire including concerns regarding their disease, medical therapy and follow-up during SARS-CoV-2 pandemic. RESULTS: In total, 522 IBD patients were included, 317 Crohn's disease, 205 ulcerative colitis, 386 patients <50 years. Eighteen percent were in obligatory quarantine, and more often patients <50 years compared to patients ≥50 years. Five patients tested positive to SARS- CoV-2. A higher proportion <50 years reported worries for their medical treatment and risk of COVID -19 disease compared to those ≥50 years. Forty percent avoided family, two-thirds avoided friends, and 4% cancelled their scheduled consultation at the hospital. The hospital changed physical consultation to telephone consultation for 15% of the patients. The preferred follow-up was physical consultation. A higher proportion of the patients <50 years preferred telephone consultation compared to those ≥50 years. Four out of five IBD patients were satisfied with the information about their IBD and COVID-19. CONCLUSIONS: SARS-CoV-2 pandemic affects the daily lives for patients with IBD. It is important to develop evidence-base guidelines in follow-up and treatment, as well as patient information about COVID-19and IBD.

Posterior Reversible Encephalopathy Syndrome.

PURPOSE OF REVIEW: This review provides an updated discussion on the clinical presentation, diagnosis and radiographic features, mechanisms, associations and epidemiology, treatment, and prognosis of posterior reversible encephalopathy syndrome (PRES). Headache is common in PRES, though headache associated with PRES was not identified as a separate entity in the 2018 International Classification of Headache Disorders. Here, we review the relevant literature and suggest criteria for consideration of its inclusion. RECENT FINDINGS: COVID-19 has been identified as a potential risk factor for PRES, with a prevalence of 1-4% in patients with SARS-CoV-2 infection undergoing neuroimaging, thus making a discussion of its identification and treatment particularly timely given the ongoing global pandemic at the time of this writing. PRES is a neuro-clinical syndrome with specific imaging findings. The clinical manifestations of PRES include headache, seizures, encephalopathy, visual disturbances, and focal neurologic deficits. Associations with PRES include renal failure, preeclampsia and eclampsia, autoimmune conditions, and immunosuppression. PRES is theorized to be a syndrome of disordered autoregulation and endothelial dysfunction resulting in preferential hyperperfusion of the posterior circulation. Treatment typically focuses on treating the underlying cause and removal of the offending agents.

Effect of immunosuppressive drugs in immune-mediated inflammatory disease during the coronavirus pandemic.

The safety of immunosuppressive treatment in patients with Immune-Mediated Inflammatory Diseases (IMIDs) during the Coronavirus pandemic is questioned and it is utmost important for public health. We searched studies trough MEDLINE/EMBASE database, including patient with IMID, undergoing immunosuppressive treatment with a positive diagnosis for SARS-CoV 2. We included 11 studies for the descriptive analysis and 10 studies for the pooled analysis, with a total population of 57 and 53 IMID-affected SARS-CoV-positive patients respectively. Overall no death was reported; 16 patients were hospitalized (30.2%) and only two cases were admitted to Intensive Care Unit (ICU) (3.8%). We found a significant association between the risk of hospitalization and older age (P .03), obesity (P .02), and presence of multi-comorbidity (P .03). No significant association was found between the risk of hospitalization and the use of biological or conventional DMARDs (respectively P .32 and .26), neither when they are used combined (P .85). We found consistent results in the sub-analysis of Psoriasis: 10 patients were hospitalized (31.3%) and only one case was admitted to Intensive Care Unit (ICU) (3.1%) Particular attention should be placed for patients with older age, obesity and multi-comorbidity that are at higher risk of hospitalization.

Management of patients with Behçet's disease during the COVID-19 pandemic.

Behçet's disease is a disease characterized by chronic inflammatory vasculitis. In the clinical symptoms of Behçet's disease, many immunosuppressive and immunomodulatory drugs are used. The suspicion that drugs used in chronic disease treatments such as Behçet's disease during pandemic will increase the risk of transmission of COVID-19 disease, and that the disease may progress more lethally in these patients after the infection caused clinicians to worry. As far as we know, there is no study in the literature about the management of patients with Behçet's disease in the pandemic period. Fifty-four patients with Behçet's disease who were admitted to the dermatology outpatient clinic between 11 March and July 14, 2020 were retrospectively analyzed. In this pandemic period, 44 of 54 patients were recommended to continue their previous treatment. While the dose of medication used by 7 patients was reduced, it was decided to change the treatment of 3 patients. No life-threatening activation was observed. None of the patients developed COVID-19 disease. This article is important in terms of being the first study in the literature examining the treatment of patients with Behçet's disease during the COVID-19. In this period, we know that the treatment practices in chronic diseases change frequently daily, and in this respect, we hope that our study will provide a perspective to other dermatology clinics in terms of the treatment of Behçet's disease during the pandemic.

Immunosuppressive and immunomodulator therapy for rare or uncommon skin disorders in pandemic days.

Immunosuppressive and immunomodulatory therapies are important in dermatology, but indications are influenced by SARS-CoV-2. We will focus on skin disorders such as autoimmune connective tissue disorders, neutrophilic dermatoses, and vasculitis. Immunomodulators such as colchicine and antimalarials can easily be preferred taking their beneficial effects on COVID-19 into consideration and also given their wide spectrum of action. Among the conventional therapies, methotrexate, azathioprine, and mycophenolate mofetil increase the risk of infection, and thus their use is recommended only when necessary and at low doses. On the other hand, use of cyclosporine is also not recommended as it increases the risk of hypertension, which is susceptible to COVID-19. Anti-TNF agents from among the biological therapies appear to be slightly risky in terms of susceptibility to infection. However, there are ongoing studies which suggest that some biological treatments may reduce cytokine storm impeding the COVID-19 progression as a result, in spite of their susceptibilities to COVID-19. Patients, who will be started on immunosuppressive therapy, should be tested for COVID-19 prior to the therapy, and in the event that COVID-19 is suspected, the therapy should be discontinued.

Immunosuppressive drugs for patients with psoriasis during the COVID-19 pandemic era. A review.

The COVID-19 has been spreading around the world. Concerns about the safety of administration of immunosuppressive drugs have been raised for treatment of psoriasis (PSO), and there is insufficient evidence for the risk of COVID-19 infection for psoriatic patients using these drugs, so we did a review, focusing on the risk of overall infection associated with the most commonly used immunosuppressive drugs, such as methotrexate, biologics, cyclosporin, Janus kinase inhibitors for the treatment of PSO. The data on the effect of immunosuppressive drugs on this virus may be ever-changing and remains to be clear. We recommend the initiation and continuation of low-risk immunomodulating drugs, such as Interleukin (IL)-17, IL-12/23, and IL-23 inhibitors, for treatment of PSO during COVID-19 era. For psoriatic patients with comorbidities switching to safer modalities such as systemic retinoids, apremilast, and home phototherapy is recommended. Immunosuppressive drugs should be withheld in psoriatic patients with the COVID-19 infection.

Immunosuppressive Drugs and COVID-19: A Review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is currently unknown whether immunosuppressive drugs are advantageous or detrimental in patients with COVID-19. Immunosuppressive drugs could be harmful in the initial phase of COVID-19. In this phase, the host immune response is necessary to inhibit viral replication. However, immunosuppressive drugs might have a beneficial effect in the later, more severe phase of COVID-19. In this phase, an overshoot of the host immune response (the "cytokine storm") can cause ARDS, multiorgan failure and mortality. AIM: To summarize the available evidence on the effect of immunosuppressive drugs on infection with SARS-CoV-2. The effects of immunosuppressive drugs on similar pandemic coronaviruses may resemble the effects on SARS-CoV-2. Thus, we also included studies on the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). METHODS: The study protocol was registered in PROSPERO (registration number CRD42020181137). We included randomized controlled trials (RCTs), cohort studies with a control group and case-control studies concerning humans ≥ 18 years old. We also included in-vitro studies and animal studies with a control group. RESULTS AND CONCLUSION: Sixty-nine studies were included. Interestingly, MPA inhibits SARS-CoV-2 replication in-vitro. Clinical studies are needed to confirm the inhibitory effect of MPA on SARS-CoV-2 replication in-vivo. There are indications that corticosteroids and IL-6 inhibitors, like tocilizumab, can reduce mortality and prevent mechanical ventilation in patients with COVID-19. However, observational studies have contradictory results and the risk of bias is high. Thus, these results have to be confirmed in high-quality clinical trials before these drugs can be implemented as standard care. Based on the positive results of CNIs, mTOR inhibitors and thiopurine analogues in in-vitro studies with SARS-CoV and MERS-CoV, it would be interesting to investigate their effects on SARS-CoV-2 replication.