Immunosuppressants exert differential effects on pan-coronavirus infection and distinct combinatory antiviral activity with molnupiravir and nirmatrelvir.

BACKGROUND: Immunocompromised populations, such as organ transplant recipients and patients with inflammatory bowel disease (IBD) receiving immunosuppressive/immunomodulatory medications, may be more susceptible to coronavirus infections. However, little is known about how immunosuppressants affect coronavirus replication and their combinational effects with antiviral drugs. OBJECTIVE: This study aims to profile the effects of immunosuppressants and the combination of immunosuppressants with oral antiviral drugs molnupiravir and nirmatrelvir on pan-coronavirus infection in cell and human airway organoids (hAOs) culture models. METHODS: Different coronaviruses (including wild type, delta and omicron variants of SARS-CoV-2, and NL63, 229E and OC43 seasonal coronaviruses) were used in lung cell lines and hAOs models. The effects of immunosuppressants were tested. RESULTS: Dexamethasone and 5-aminosalicylic acid moderately stimulated the replication of different coronaviruses. Mycophenolic acid (MPA), 6-thioguanine (6-TG), tofacitinib and filgotinib treatment dose-dependently inhibited viral replication of all tested coronaviruses in both cell lines and hAOs. The half maximum effective concentration (EC50) of tofacitinib against SARS-CoV-2 was 0.62 µM and the half maximum cytotoxic concentration (CC50) was above 30 µM, which resulted in a selective index (SI) of about 50. The anti-coronavirus effect of the JAK inhibitors tofacitinib and filgotinib is dependent on the inhibition of STAT3 phosphorylation. Combinations of MPA, 6-TG, tofacitinib, and filgotinib with the oral antiviral drugs molnupiravir or nirmatrelvir exerted an additive or synergistic antiviral activity. CONCLUSIONS: Different immunosuppressants have distinct effects on coronavirus replication, with 6-TG, MPA, tofacitinib and filgotinib possessing pan-coronavirus antiviral activity. The combinations of MPA, 6-TG, tofacitinib and filgotinib with antiviral drugs exerted an additive or synergistic antiviral activity. Thus, these findings provide an important reference for optimal management of immunocompromised patients infected with coronaviruses.

Approaches to vaccination against coronavirus infection in patients with autoimmune inflammatory rheumatic diseases

The problem of COVID-19 vaccination in patients with autoimmune inflammatory rheumatic diseases is discussed. There is an increased risk of viral infections in these patients. Attending physicians should provide patients with rheumatic diseases with complete information about the risks and benefits of COVID-19 immunoprophylaxis. The use of immunosuppressive drugs, rather than the diseases themselves, can reduce the level of post-vaccination immune response. This requires choosing the optimal time for carrying out COVID-19 vaccination in this group of patients. Fragments of European and American recommendations on vaccination against COVID-19 in patients with rheumatic diseases are given.Copyright © 2022 Infectious Diseases: News, Opinions, Training.

Pre-existing autoimmunity is associated with increased severity of COVID-19: A retrospective cohort study using data from the National COVID Cohort Collaborative (N3C).

BACKGROUND: Identifying individuals with a higher risk of developing severe COVID-19 outcomes will inform targeted or more intensive clinical monitoring and management. To date, there is mixed evidence regarding the impact of pre-existing autoimmune disease (AID) diagnosis and/or immunosuppressant (IS) exposure on developing severe COVID-19 outcomes. METHODS: A retrospective cohort of adults diagnosed with COVID-19 was created in the National COVID Cohort Collaborative enclave. Two outcomes, life-threatening disease, and hospitalization were evaluated by using logistic regression models with and without adjustment for demographics and comorbidities. RESULTS: Of the 2,453,799 adults diagnosed with COVID-19, 191,520 (7.81%) had a pre-existing AID diagnosis and 278,095 (11.33%) had a pre-existing IS exposure. Logistic regression models adjusted for demographics and comorbidities demonstrated that individuals with a pre-existing AID (OR = 1.13, 95% CI 1.09 - 1.17; P< 0.001), IS (OR= 1.27, 95% CI 1.24 - 1.30; P< 0.001), or both (OR = 1.35, 95% CI 1.29 - 1.40; P< 0.001) were more likely to have a life-threatening COVID-19 disease. These results were consistent when evaluating hospitalization. A sensitivity analysis evaluating specific IS revealed that TNF inhibitors were protective against life-threatening disease (OR = 0.80, 95% CI 0.66- 0.96; P=0.017) and hospitalization (OR = 0.80, 95% CI 0.73 - 0.89; P< 0.001). CONCLUSIONS: Patients with pre-existing AID, exposure to IS, or both are more likely to have a life-threatening disease or hospitalization. These patients may thus require tailored monitoring and preventative measures to minimize negative consequences of COVID-19.

Medication Adherence among Allogeneic Haematopoietic Stem Cell Transplant Recipients: A Systematic Review.

Recipients of a haematopoietic stem cell transplantation (HSCT) may experience issues in medication adherence (MA) when discharged. The primary aim of this review was to describe the oral MA prevalence and the tools used to evaluate it among these patients; the secondary aims were to summarise factors affecting medication non-adherence (MNA), interventions promoting MA, and outcomes of MNA. A systematic review (PROSPERO no. CRD42022315298) was performed by searching the Cumulative Index of Nursing and Allied Health (CINAHL), Cochrane Library, Excerpta Medica dataBASE (EMBASE), PsycINFO, PubMed and Scopus databases, and grey literature up to May 2022 by including (a) adult recipients of allogeneic HSCT, taking oral medications up to 4 years after HSCT; (b) primary studies published in any year and written in any language; (c) with an experimental, quasi-experimental, observational, correlational, and cross-sectional design; and (d) with a low risk of bias. We provide a qualitative narrative synthesis of the extracted data. We included 14 studies with 1049 patients. The median prevalence of MA was 61.8% and it has not decreased over time (immunosuppressors 61.5% [range 31.3-88.8%] and non-immunosuppressors 65.2% [range 48-100%]). Subjective measures of MA have been used most frequently (78.6%) to date. Factors affecting MNA are younger age, higher psychosocial risk, distress, daily immunosuppressors, decreased concomitant therapies, and experiencing more side effects. Four studies reported findings about interventions, all led by pharmacists, with positive effects on MA. Two studies showed an association between MNA and chronic graft-versus-host disease. The variability in adherence rates suggests that the issues are relevant and should be carefully considered in daily practice. MNA has a multifactorial nature and thus requires multidisciplinary care models.

Infections after organ transplantation and immune response.

Organ transplantation has provided another chance of survival for end-stage organ failure patients. Yet, transplant rejection is still a main challenging factor. Immunosuppressive drugs have been used to avoid rejection and suppress the immune response against allografts. Thus, immunosuppressants increase the risk of infection in immunocompromised organ transplant recipients. The infection risk reflects the relationship between the nature and severity of immunosuppression and infectious diseases. Furthermore, immunosuppressants show an immunological impact on the genetics of innate and adaptive immune responses. This effect usually reactivates the post-transplant infection in the donor and recipient tissues since T-cell activation has a substantial role in allograft rejection. Meanwhile, different infections have been found to activate the T-cells into CD4+ helper T-cell subset and CD8+ cytotoxic T-lymphocyte that affect the infection and the allograft. Therefore, the best management and preventive strategies of immunosuppression, antimicrobial prophylaxis, and intensive medical care are required for successful organ transplantation. This review addresses the activation of immune responses against different infections in immunocompromised individuals after organ transplantation.

Case report: One pediatric liver-transplant recipient with SARS-CoV-2 infection suffering unexplained mixed acidosis.

Background: The management of LT patients during COVID-19 pandemic is important. Immunosuppressants (IS) are key therapy agents after liver transplant. Different ISs have different side effects. Calcineurin inhibitor (CNI) may lead to metabolic acidosis while mycophenolate mofetil (MMF) showed rare nephrotoxicity. We report a post-liver transplant girl who was infected with SARS-CoV-2, developing a severe mixed acidosis 3 months after the transplantation. Her acidosis was improved after withdrawing of MMF, leading the suspicion that acidosis maybe a rare side effect of MMF. Case presentation: A girl was admitted to our hospital due to SARS-CoV-2 infection, 3 months before admission the patient received LT due to Niemann-Pick disease (NPD). During hospitalization, blood gas analysis showed severe mixed acidosis. To relieve mixed acidosis, the patient was given oral rehydration salt and liquid replacement therapy. Considering that immunosuppressants may cause metabolic acidosis, dose of CsA was decreased and MMF was discontinued. Results: However, liquid replacement therapy and decreased CsA dose cannot improve the condition. As an attempt, MMF was discontinued, and 3 days later, the girl's acidosis was relieved, the latest blood gas analysis was normal with the original dose of CsA and no use of MMF or other IS. In addition, we used Naranjo Scale to see if adverse drug reactions (ADRs) existed. The final score was 6 which means MMF contributes to acidosis probably. Conclusion: The girl's mixed acidosis cannot be explained by Niemann-Pick disease and SARS-CoV-2 infection. CNIs could cause metabolic acidosis but declining the dose of CsA didn't improve her acidosis while withdrawing MMF showed a good effect. Together with the Naranjo Scale result, we suspect that acidosis maybe a rare side effect of MMF.

Considerations on Immunization and Immunosuppression of Patients With Autoimmune Blistering Diseases During COVID-19 Pandemic in Brazil: Case Report.

Autoimmune blistering diseases comprise a rare group of potentially life-threatening dermatoses. Management of autoimmune disorders poses a challenge in terms of achieving disease control and preventing adverse events. Treatment often requires an individualized approach considering disease severity, age, comorbidities, and infectious risk especially in the context of the ongoing COVID-19 pandemic. Knowledge regarding SARS-CoV-2 infection is still evolving and no specific antiviral therapy is available yet. We report four patients with active disease that required adjustment of treatment during the pandemic to discuss the use of immunosuppressants and immunobiologics, weighing potential risks and benefits of each therapy modality and vaccination status.

Approaches to vaccination against coronavirus infection in patients with autoimmune inflammatory rheumatic diseases

The problem of COVID-19 vaccination in patients with autoimmune inflammatory rheumatic diseases is discussed. There is an increased risk of viral infections in these patients. Attending physicians should provide patients with rheumatic diseases with complete information about the risks and benefits of COVID-19 immunoprophylaxis. The use of immunosuppressive drugs, rather than the diseases themselves, can reduce the level of post-vaccination immune response. This requires choosing the optimal time for carrying out COVID-19 vaccination in this group of patients. Fragments of European and American recommendations on vaccination against COVID-19 in patients with rheumatic diseases are given. © 2022 Infectious Diseases: News, Opinions, Training.

Inflammation as an exacerbation marker and target for prophylaxis against Coronavirus Disease 2019-related thrombosis.

Objectives: There are currently no appropriate markers and target for prophylaxis against COVID-19-related thrombosis, especially in the not-severe cases. We tested the hypothesis that inflammation is a suitable marker and target for prophylaxis against COVID-19-related thrombosis. Methods: Data of all 32 COVID-19 patients admitted to Saitama Medical Center between January 1 and March 30, 2021, were analyzed. Patients were divided into severe (requiring oxygen, n=12) and non-severe (no requirement for oxygen, n=20), and also those with high C-reactive protein (CRP) level (cutoff value: 30 mg/L, n=21) and low-CRP (n=11). We also compared the clinical and laboratory data of a 46-year-old post-liver transplant male patient, who was treated with a combination of immunosuppressants (methylprednisolone, fludrocortisone, cyclosporine, and everolimus) with those of other COVID-19 patients, using the Smirnoff-Grubbs and Box plots tests. Results: The levels of CRP, ferritin, lactate dehydrogenase, aspartate aminotransferase, and thrombin-antithrombin complex (TAT) were significantly higher in the high-severity group than the low-severity group; while other coagulation parameters were comparable. The time between onset of illness and blood levels of lactate dehydrogenase, fibrinogen, D-dimer, TAT, and plasmin alpha2-plasmin inhibitor complex (PIC) were significantly higher whereas lymphocyte count was significantly lower in the high-CRP group. Extremely low levels of TAT, PIC, and plasminogen activator inhibitor-1 (PAI-1) were recorded in the liver transplant patient treated with immunosuppressants. The TAT, PIC, and PAI-1 levels were deemed outliers. Conclusions: Inflammation is a potentially suitable marker and target for prophylaxis against COVID-19-related thrombosis.

Encephalopathy in 2 paediatric patients with SARS-CoV-2 infection benefited from early immunosuppressive treatment: A case report

Background Reports of neurological involvement are building up ever since COVID-19 has become a pandemic. Although rare, SARS-CoV-2 encephalopathy is a devastating complication associated with poor prognosis. Cytokine storm has been implicated in its pathophysiology. Case presentation We are reporting two paediatric patients who have contracted with COVID-19 and developed encephalopathy, who presented with status epilepticus and altered consciousness. Early aggressive immunosuppressive treatment was initiated promptly and both of them were able to recover without neurological deficit. Conclusion Patients with SARS-CoV-2 encephalopathy should be put on immunosuppressive therapy early for better neurological outcome. This improvement after the use of immunosuppressants further strengthened the cytokine storm theory in SARS-CoV-2 encephalopathy.

[Translated article] Practical Guide to New Treatments for SARS-CoV-2 Infection in Dermatology Patients Being Treated With Common Immunomodulators.

Immunosuppressants and immunomodulators are widely used in dermatology. Some of these drugs, however, can increase the risk of severe COVID-19. New antivirals against SARS-CoV-2 have been shown to reduce progression to COVID-19 pneumonia in susceptible patients, but their availability is limited. On May 23, 2022, the Spanish Agency for Medicines and Medical Devices (AEMPS) updated its priority eligibility criteria for SARS-CoV-2 antiviral therapy. In this practical guide, we review the indications for these new drugs and provide guidance on which patients with mild to moderate COVID might benefit from their use in dermatology.

Informe de un caso de infección por coronavirus en un trasplantado renal

Introducción: La infección por coronavirus favorece el desarrollo de alteraciones respiratorias. En trasplantados renales el pronóstico de la neumonía por SARS-CoV-2 puede ser diferente al resto de la población. Muchos pacientes trasplantados tienen de base linfopenia inducida por fármacos, por lo que la detección y el tratamiento precoz son determinantes en este grupo de población. Presentación del caso: Varón de 50 años con ERC no filiada, trasplantado renal en 2016 que acudió a urgencias por fiebre de 38ºC, tos, rinorrea, diarrea con pérdida de peso y molestia en injerto renal en fosa iliaca derecha. Se diagnosticó de COVID-19 positivo tras realización de placa de tórax y PCR SARS-CoV-2. Ingresó en nuestra unidad de trasplante renal. Plan de cuidados: Se realizó una valoración inicial mediante los patrones funcionales de Gordon. Posteriormente identificamos Diagnósticos de Enfermería según la taxonomía NANDA con sus correspondientes criterios de resultados e intervenciones. Evaluación del plan: Tras la realización de las intervenciones y la evaluación de los indicadores de resultados observamos una disminución de la temperatura corporal y de la dificultad respiratoria con mejoría en el patrón respiratorio. En cuanto a la función renal, no se ha visto significativamente alterada a pesar de la retirada temporal de la inmunosupresión. Conclusión: El paciente se fue de alta con una función renal similar a la previa y con la inmunosupresión reintroducida. Se lograron los objetivos planteados dejando patente que el papel de enfermería ha sido fundamental en el proceso de recuperación y afrontamiento de la enfermedad.Alternate : Introduction: Coronavirus infection favours the development of respiratory disorders. In kidney transplant patients, the prognosis of SARS-CoV-2 pneumonia may be different from the rest of the population. Many transplant patients have drug-induced lymphopenia, so early detection and treatment are crucial in this population group. Case description: A 50-year-old man with unknown CKD and a kidney transplant in 2016 who came to the emergency room due to fever of 38ºC, cough, rhinorrhea, diarrhea with weight loss and discomfort in a kidney graft in the right iliac fossa. He was diagnosed with COVID-19 positive after performing a chest X-ray and SARS-CoV-2 PCR. He was admitted to our kidney transplant unit. Description of the care plan: An initial assessment was made using Gordon’s functional patterns. Subsequently, we identify Nursing Diagnoses according to the NANDA taxonomy with their corresponding outcome and intervention criteria. Evaluation of the care plan: After carrying out the interventions and evaluating the outcome indicators, we observed a decrease in body temperature and respiratory distress with improvement in the respiratory pattern. Regarding renal function, it has not been significantly altered despite the temporary withdrawal of immunosuppression. Conclusion: The patient is discharged with a renal function similar to the previous one and with reintroduced immunosuppression. The objectives set were achieved, making it clear that the role of nursing has been vital in the process of recovery and coping with the disease.

The use of azathioprine in atopic dermatitis: A review.

Most patients with atopic dermatitis (AD) have a good response to topical treatment. However, some need systemic therapy in order to satisfactorily control the disease. Azathioprine is an accessible drug for patients in many countries, including underdeveloped countries, and therefore it is used by many dermatologists in moderate and severe AD. It is important to have a deep knowledge and understanding about this drug since it is an alternative therapy as a steroid-sparing agent and an affordable one. However, when it comes to systemic therapy for AD, it is not always clear its indications and it is necessary to have a closer follow-up of the patient. In this paper, we describe thoroughly its indications in AD, the mechanism of action of the drug, as well as the interactions, adverse effects, adequate monitoring, and precautions in special population that must be considered when prescribing azathioprine. This review will help dermatologists prescribe it safely to all patients who require it.

Practical Guide to New Treatments for SARS-CoV-2 Infection in Dermatology Patients Being Treated With Common Immunomodulators. / Guía práctica de las nuevas alternativas terapéuticas frente a SARS-CoV-2 en pacientes con inmunomoduladores de uso frecuente en dermatología.

Immunosuppressants and immunomodulators are widely used in dermatology. Some of these drugs, however, can increase the risk of severe COVID-19. New antivirals against SARS-CoV-2 have been shown to reduce progression to COVID-19 pneumonia in susceptible patients, but their availability is limited. On May 23, 2022, the Spanish Agency for Medicines and Medical Devices (AEMPS) updated its priority eligibility criteria for SARS-CoV-2 antiviral therapy. In this practical guide, we review the indications for these new drugs and provide guidance on which patients with mild to moderate COVID might benefit from their use in dermatology.

A prospective longitudinal study evaluating the influence of immunosuppressives and other factors on COVID-19 in autoimmune rheumatic diseases.

BACKGROUND: We conducted this study to identify the influence of prolonged use of hydroxychloroquine (HCQ), glucocorticoids and other immunosuppressants (IS) on occurrence and outcome of COVID-19 in patients with autoimmune rheumatic diseases (AIRDs). METHODS: This was a prospective, multicenter, non-interventional longitudinal study across 15 specialist rheumatology centers. Consecutive AIRD patients on treatment with immunosuppressants were recruited and followed up longitudinally to assess parameters contributing to development of COVID-19 and its outcome. RESULTS: COVID-19 occurred in 314 (3.45%) of 9212 AIRD patients during a median follow up of 177 (IQR 129, 219) days. Long term HCQ use had no major impact on the occurrence or the outcome of COVID-19. Glucocorticoids in moderate dose (7.5-20 mg/day) conferred higher risk (RR = 1.72) of infection. Among the IS, Mycophenolate mofetil (MMF), Cyclophosphamide (CYC) and Rituximab (RTX) use was higher in patients with COVID 19. However, the conventional risk factors such as male sex (RR = 1.51), coexistent diabetes mellitus (RR = 1.64), pre-existing lung disease (RR = 2.01) and smoking (RR = 3.32) were the major contributing risk factors for COVID-19. Thirteen patients (4.14%) died, the strongest risk factor being pre-existing lung disease (RR = 6.36, p = 0.01). Incidence (17.5 vs 5.3 per 1 lakh (Karnataka) and 25.3 vs 7.9 per 1 lakh (Kerala)) and case fatality (4.1% vs 1.3% (Karnataka) and 4.3% vs 0.4% (Kerala)) rate of COVID-19 was significantly higher (p < 0.001) compared to the general population of the corresponding geographic region. CONCLUSIONS: Immunosuppressants have a differential impact on the risk of COVID-19 occurrence in AIRD patients. Older age, males, smokers, hypertensive, diabetic and underlying lung disease contributed to higher risk. The incidence rate and the case fatality rate in AIRD patients is much higher than that in the general population.

Outcomes of COVID-19 in Inflammatory Rheumatic Diseases: A Retrospective Cohort Study.

Background Similar to coronavirus disease 2019 (COVID-19), the pathogenesis of inflammatory rheumatic diseases includes cytokines dysregulation and increased expression of pro-inflammatory cytokines. Although current data from international studies suggest that rheumatic diseases are associated with a higher risk of COVID-19 infection and worse outcomes, there is limited literature in Saudi Arabia. This study aims to evaluate the outcomes and length of hospital stay of COVID-19 patients with inflammatory rheumatic diseases in Saudi Arabia. Method This was a single-center retrospective cohort study that included 122 patients with inflammatory rheumatic diseases and documented coronavirus disease 2019 (COVID-19) infection from 2019 to 2021. Patients with suspected COVID-19 infection, non-inflammatory diseases, such as osteoarthritis, or inflammatory diseases but without or with weak systemic involvement, such as gout, were excluded. Results The vast majority (81.1%) of the patients were females. Rheumatoid arthritis was the most common primary rheumatological diagnosis. The admission rate was 34.5% with an overall mortality rate of 11.5%. Number of episodes of COVID-19 infection, mechanical ventilation, cytokine storm syndrome, secondary bacterial infection, number of comorbidities, rituximab, diabetes mellitus, hypertension, chronic kidney disease, and heart failure were significantly associated with a longer hospital stay. Additionally, hypertension, heart failure, rituximab, mechanical ventilation, cytokine storm syndrome, and secondary bacterial infection were significantly associated with higher mortality. Predictors of longer hospitalization were obesity, number of episodes of COVID-19 infection, mechanical ventilation, number of comorbidities, and chronic kidney disease, whereas, hypertension was the only predictor of mortality. Conclusion Obesity, number of episodes of COVID-19 infection, mechanical ventilation, number of comorbidities, and chronic kidney disease were significantly associated with higher odds of longer hospitalization, whereas, hypertension was significantly associated with higher odds of mortality. We recommend that these patients should be prioritized for the COVID-19 vaccine booster doses, and rituximab should be avoided unless its benefit clearly outweighs its risk.

COVID-19 infection and vaccination against COVID-19: Impact on managing demyelinating CNS disorders in Southern India- experience from a demyelinating disease registry.

BACKGROUND AND OBJECTIVE: The impact of COVID-19 infection and the effect of COVID-19 vaccinations on patients with demyelinating central nervous system disease in low middle income countries (LMIC's) have not been reported in detail earlier. We sought to identify risk factors associated with COVID-19 infection and the role of vaccination in order to develop management guidelines relevant to our patients. METHODS: A total of 621 patients from our registry that included 297 MS and 324 non MS disorders (Aquaporin- 4 antibody positive [50], Myelin oligodendrocyte glycoprotein antibody positive [81], seronegative [162] and clinically isolated syndrome [31]) were contacted. COVID-19 infection and vaccination status were queried. Patients who self reported COVID-19 infection based on a positive RT PCR report were compared with non infected patients to identify factors associated with susceptibility for COVID-19 infection. Univariate and multivariate analysis of potential risk factors included demographic and clinical features, body mass index (BMI), presence of comorbidities, absolute lymphocyte count, treatment types and vaccination status. RESULTS: Sixty seven patients with MS and 27 with non MS disorders developed COVID-19 infection. Among them 81 patients had mild infection and remained quarantined at home. All 13 patients who needed hospitalization recovered. Vaccination status was known in 582 patients among whom 69.8% had completed or taken one dose of vaccine at the time of inquiry. Majority of treated patients (61.3%) were on nonspecific immunosuppressants. In univariate analysis, presence of ≥1 comorbidity was significantly associated with COVID-19 infection in both MS (p value 0.01, OR-2.28, 95%CI- 1.18-4.4) and non MS patients (p- 0.001, OR-4.4, 95% CI-1.88-10.24). In the latter, BMI ≥ 30 (p-0.04, OR-3.27, 95% CI- 0.98-10.87) and EDSS score ≥ 3 (p-0.02, OR- 2.59,95% CI- 1.08-6.23) were other significant associations. History of prior COVID-19 vaccination was associated with reduced frequency of COVID-19 infection among MS (p- 0.001,OR- 0.24,95% CI- 0.13-0.43) and non MS patients (p- 0.0001,OR-0.14, 95% CI- 0.058-0.35). In multivariate analysis presence of comorbidities significantly increased and prior vaccination significantly reduced frequency of COVID-19 infection for both MS and related disorders. Concurrent disease modifying treatments showed a trend for association with infection. In the unvaccinated group, patients on disease modifying treatment were significantly at risk of infection, 81.5% unvaccinated and treated versus 18.5% who were unvaccinated and untreated (p- 0.0001, OR-10.1, 95% CI-0.56-2.11). CONCLUSION: Frequency and severity of COVID-19 infection was low among our patient cohort. Higher rate of infection in the treated group was significantly seen among unvaccinated patients. Our preliminary results suggests that in LMIC's, where "off label therapies" with inexpensive immunosuppressives are the main disease modifying drugs, mRNA vaccinations appear safe and effective against severe COVID-19 infection.

COVID-19 and Fungal Diseases.

Coronavirus Disease-2019 (COVID-19) can cause secondary bacterial and fungal infections by affecting the expression of pro-inflammatory markers, such as tumor necrosis alpha and certain cytokines, as well as the numbers of CD4 and CD8 cells. In particular, in the head and neck, various fungal species are naturally present, making it the main route of secondary infection. It is difficult to clearly distinguish whether secondary infection is caused by COVID-19 directly or indirectly as a result of the immunocompromised state induced by drugs used to treat the disease. However, the risk of fungal infection is high in patients with severe COVID-19, and lymphopenia is observed in most patients with the disease. Patients with COVID-19 who are immunosuppressed or have other pre-existing comorbidities are at a significantly higher risk of acquiring invasive fungal infections. In order to reduce morbidity and mortality in these patients, early diagnosis is required, and treatment with systemic antifungal drugs or surgical necrotic tissue resection is essential. Therefore, this review aimed to examine the risk of fungal infection in the head and neck of patients with COVID-19 and provide information that could reduce the risk of mortality.

Evaluation of COVID-19 cases who received immunosuppressive therapy at a tertiary care hospital

Objective: Immunosuppressive drugs are included in the treatment protocols of severe COVID-19 cases that may present with cytokine storm. In this study, we aimed to examine the characteristics of COVID-19 patients who received immunosuppressive therapy Methods: Patients diagnosed with COVID-19 and followed in the quarantine wards of our hospital between 01.03.2020-24.05.2020 were included in the study. Patient information was obtained retrospectively from patient files and discharge reports, and 263 COVID-19 patients -aged 18 and over- were included in the study.

The association between immunosuppressants use and COVID-19 adverse outcomes: national COVID-19 cohort in South Korea.

BACKGROUND: There is uncertainty of the effect of immunosuppression, including corticosteroids, before COVID-19 infection on COVID-19 outcomes. The aim of this study was to investigate the relationship between prehospitalization immunosuppressants use (exposure) and COVID-19 patient outcomes. METHODS: We conducted a population-based retrospective cohort study using a nationwide healthcare claims database of South Korea as of May 15, 2020. Confirmed COVID-19 infection in hospitalized individuals aged 40 years or older were included for analysis. We defined exposure variable by using inpatient and outpatient prescription records of immunosuppressants from the database. Our primary endpoint was a composite endpoint of all-cause death, intensive care unit (ICU) admission, and mechanical ventilation use. Inverse probability of treatment weighting (IPTW)-adjusted logistic regression analyses were used, to estimate odds ratio (OR) and 95% confidence intervals (CI), comparing immunosuppressants users and non-users. RESULTS: We identified 4,349 patients, for which 1,356 were immunosuppressants users and 2,993 were non-users. Patients who used immunosuppressants were at increased odds of the primary endpoint of all-cause death, ICU admission and mechanical ventilation use (IPTW OR =1.32; 95% CI: 1.06-1.63), driven by higher odds of all-cause mortality (IPTW OR =1.63; 95% CI: 1.21-2.26). Patients who used corticosteroids (n=1,340) were at increased odds of the primary endpoint (IPTW OR =1.33; 95% CI: 1.07-1.64). CONCLUSIONS: Immunosuppressant use was associated with worse outcomes among COVID-19 patients. These findings support the latest guidelines from the CDC that people on immunosuppressants are at high risk of severe COVID-19 and that immunocompromised people may benefit from booster COVID-19 vaccinations.