The prognostic impact of monocyte fluorescence, immunosuppressive monocytes and peripheral blood immune cell numbers in HIV-associated Diffuse Large B-cell Lymphoma.

INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is a high grade non-Hodgkin lymphoma which is common among immunodeficient people. Derangements of peripheral blood immune cells have been described to have a prognostic impact in DLBCL in high income countries, including a monocytosis, the ratios of lymphocytes to both monocytes (L:M) and neutrophils (N:L), as well as the numbers of regulatory T-cells (Tregs) and immunosuppressive monocytes (HLA-DRlow monos). To date, the impact of these variables has not been assessed in the setting of HIV-associated DLBCL (HIV-DLBCL), which is among the most common malignancies seen in people living with HIV. In this study, we assessed these factors in a cohort of South African patients with DLBCL and a high HIV-seropositivity-rate. In addition, we evaluated the prognostic value of monocyte activation (as reflected by monocyte fluorescence (MO-Y) on a Sysmex haematology analyser). This parameter has to date not been assessed in the setting of DLBCL. METHODS: A full blood count and differential count as well as flow cytometry for HLA-DRlow monocyte and Treg enumeration were performed in patients with incident DLBCL referred to the Chris Hani Baragwanath Academic Hospital in Johannesburg, South Africa between November 2019 and May 2022. Additional clinical and laboratory data were recorded from the patient charts and laboratory information system. RESULTS: Seventy-six patients were included, of whom 81.3% were people living with HIV with a median CD4 count of 148 cells/ul. Most patients had advanced stage disease (74.8%) and were predominantly treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy (without Rituximab). At a median follow-up period of 19 months, the median survival time was 3.5 months, with a 12-month survival rate of 27.0%. All of the immune-cell-related variables (with the exception of the CD4 count) were similar between the people living with HIV and the HIV-negative individuals. In contrast to previous studies, a high monocyte count, the L:M and increased numbers of HLA-DRlow monocytes were not significantly associated with survival in HIV-DLBCL, while a neutrophilia (>8 x 109/L), the N:L (>6:1), high numbers of Tregs (≥5.17% of CD4s) and lymphopenia (<1.3 x 109/L) were. In addition, increased monocyte fluorescence (MO-Y >115.5) was associated with superior outcomes, which we speculate to reflect a more robust antitumour immune response among individuals with high levels of monocyte activation. On Cox Proportional hazard analysis, immune-cell factors independently associated with survival included a CD4 count <150 cells/ul and a neutrophilia. CONCLUSION: The monocyte count, L:M and the number of HLA-DRlow monos are not strong prognostic indicators in HIV-DLBCL, while a low CD4 count and neutrophilia are. Elevation of the MO-Y shows some promise as a potential biomarker of antitumour immunity; further study in this regard would be of interest.

Severe Pancytopenia After COVID-19 Revealing a Case of Primary Bone Marrow Diffuse Large B Cell Lymphoma.

BACKGROUND Diffuse large B cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL). While bone marrow (BM) involvement is common in lymphoma, primary bone marrow (PBM) DLBCL is extremely rare. We present a case of PBM DLBCL discovered in a patient with COVID-19. CASE REPORT An 80-year-old man presented with generalized abdominal pain, weight loss, fever, fatigue, anorexia, and watery diarrhea over a 3-month period. Physical examination was unremarkable. Laboratory workup revealed anemia, thrombocytopenia, and elevated inflammation markers. SARS-COV-2 PCR was positive, while blood cultures were negative. A rapid decline in the white blood cell count in the following days prompted a BM biopsy, confirming the diagnosis of PBM DLBCL. Computed tomography (CT) did not show thoracic or abdominal lymphadenopathy. The patient received packed red blood cell and platelet transfusions, granulocyte colony-stimulating factor (G-CSF) for pancytopenia, and empirical antibiotics for suspected infection. Due to active COVID-19 and advanced age, cytotoxic chemotherapy was delayed. Rituximab and prednisone were initiated on day 9, followed by an infusion reaction, which led to treatment discontinuation. He died 2 days later. CONCLUSIONS Diagnosing PBM malignancy is challenging, especially with coexisting infection. It is essential to suspect underlying BM malignancy in patients with clinical deterioration and worsening pancytopenia despite adequate treatment. The diagnosis of PBM DLBCL requires the absence of lymphadenopathy, and the presence of histologically confirmed DLBCL. Prompt management with combination chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with/without hematopoietic stem cell transplant can improve the prognosis.

Aseptic Abscess Syndrome in Rheumatoid Arthritis Patient.

Aseptic abscess syndrome (AAS) is a rare, potentially life-threatening disorder, with numerous features of neutrophilic dermatoses. The main symptoms include aseptic abscess-like collections in internal organs (spleen, liver, lungs), lack of microbes (bacteria, viruses, or parasites) after an exhaustive search, ineffectiveness of antibiotics, and high sensitivity to corticosteroid therapy. AAS is characterized by the development of deep, inflammatory abscesses and systemic symptoms (weight loss, abdominal pain, fever, and leukocytosis). They may be associated with inflammatory bowel disease (IBD) and autoimmune diseases. The patient in this study is a 67-year-old man, suffering from rheumatoid arthritis (RA), with numerous purulent abscesses in the mediastinum, within the subcutaneous tissue above the extension surfaces of the joints, and on the dorsum of the hands. The lesions are accompanied by bone destruction. The patient was treated with prednisone 40 mg and adalimumab, which resulted in a quick reduction of inflammatory markers and clinical improvement, as well as the healing and absorption of abscesses. Despite COVID-19 infection, treatment with remdesivir, prednisone, and adalimumab was continued, with the complete resolution of the lesions. AAS is difficult to recognize, so practitioners have to be aware of this condition, especially in patients with RA.

A case report of possible concurrent vasculitis in vertebral bodies and partial transverse myelitis following COVID-19 vaccination.

INTRODUCTION: Cases with organ-specific and systemic vasculitis associated with corona virus disease 2019 (COVID-19) vaccination have been reported. However, acute partial transverse myelitis (APTM) is rare adverse events following received COVID-19 vaccines. To the best of our knowledge, there is no report on vaccine-associated APTM accompanied by possible concurrent vasculitis. Herein we present a case with possible concurrent spinal vasculitis and APTM following the second dose of inactivated COVID-19 vaccine. CASE SUMMARY: A 33-year-old man presented with weakness of left lower limb and aberrant sensation of his left lower trunk and limb (from T9 level to toes) for 2 days following receipt of an inactivated COVID-19 vaccine. Remarkable demyelinating lesion at T7 spinal cord was showed by 3.0T magnetic resonance imaging (MRI) scan. Moreover, vertebral bodies of T3-T7 also presented high signal in T-2 weighted imaging (T2WI) accompanied by multiple sites of flowing void effect indicating possible vasculitis. Oligoclonal band was positive in cerebrospinal fluid (CSF) while it was negative in sera. Intravenous methylprednisolone (1 g/d) was administrated for 5 days followed by subsequent dose-tapering prednisone. His limb weakness and aberrant sensation both improved and he was able to walk unaided after treatment. The MRI recheck also showed remarkable improvement on the lesions in spinal cord and vertebral bodies. CONCLUSION: this case illustrates the concurrence of possible vasculitis in vertebral bodies and acute transverse myelitis (ATM) following COVID-19 vaccination.

Immunogenicity and safety of the mRNA-based BNT162b2 vaccine in systemic autoimmune rheumatic diseases patients.

BACKGROUND: The COVID-19 outbreak has led to the rapid development and administration of the COVID-19 vaccines worldwide. Data about the immunogenicity and adverse effects of the vaccine on patients with systemic autoimmune rheumatic diseases (SARDs) is emerging. AIM: To evaluate Pfizer/BioNTech (BNT162b2) mRNA-based vaccine second-dose immunogenicity and safety, and the relation between them, in patients with SARDs. METHODS: A total of one hundred forty tow adults who received two doses of the BNT162b2 vaccine were included in the study. The SARDs group included Ninety-nine patients and the control group (forty-three participants) comprised a mixture of healthy participants and patients who were seen at the rheumatology clinic for non-SARDs. Anti-SARS-CoV-2 IgG antibodies against the Spike protein were evaluated using a SARS-CoV-2 IgG immunoassay. A level of > 150 AU/mL was considered positive. An adverse effects questionnaire was given to the participants upon their first visit to the clinic after their BNT162b2 vaccination. RESULTS: Of the 142 participants, 116 were seropositive (81.7%) and 26 (18.3%) were seronegative. Of the seronegative participants, 96.2% were SARDs patients. The proportion of seropositivity in the SARDs patients treated with any immunosuppressant was significantly lower (69.9%) compared to the control group and SARDs patients not receiving immunosuppressants (96.8%). A significant negative correlation between seronegativity and treatment with rituximab, mycophenolate mofetil (MMF), and prednisone was found in the SARDs group (p = 0.004, 0.044, 0.007 respectively). No fever was observed following the BNT162b2 vaccine in seronegative patients, and the frequency of musculoskeletal adverse effects upon the second dose of the BNT162b2 vaccine was significantly higher in seropositive compared to seronegative patients and in the control group compared to the SARDs patients (p = 0.045, p = 0.02 respectively). CONCLUSION: A decline in the immunogenicity to the second dose of BNT162b2 mRNA is seen in patients with SARDs, especially in patients treated with rituximab, MMF, and prednisone. Adverse effects of the vaccine including fever and musculoskeletal symptoms might be a signal for the acquisition of immunity in those patients. KEY POINTS: • BNT162b2 mRNA vaccine is less immunogenic in SARDs patients compared to the control group. • Rituximab, prednisone, and mycophenolate mofetil significantly reduced immunogenicity to the vaccine. • There is a correlation between immunogenicity and adverse effects of the vaccine.

Association between Immunosuppressive Drugs and Coronavirus Disease 2019 Outcomes in Patients with Noninfectious Uveitis in a Large US Claims Database.

PURPOSE: To determine the dose-dependent risk of systemic corticosteroids (SCs) and the risk of other immunosuppressive therapies on coronavirus disease 2019 (COVID-19) infection, hospitalization, and death in patients with noninfectious uveitis (NIU). DESIGN: A retrospective cohort study from January 20, 2020, to December 31, 2020 (an era before widespread COVID-19 vaccination), using the Optum Labs Data Warehouse, a US national de-identified claims database. PARTICIPANTS: Patients who had at least 1 NIU diagnosis from January 1, 2017. METHODS: Unadjusted and adjusted hazard ratios (HRs) were estimated for each variable and COVID-19 outcome using Cox proportional hazards models, with time-updated dichotomous indicators for outpatient immunosuppressive medication exposure. To assess the dose-dependent effect of SC exposure, the average daily dose of prednisone over the exposed interval was included in the adjusted models as a continuous variable, in addition to the dichotomous variable. MAIN OUTCOME MEASURES: Incidence rates of COVID-19 infection, COVID-19-related hospitalization, and COVID-19-related in-hospital death. RESULTS: This study included 52 286 NIU patients of whom 12 000 (23.0%) were exposed to immunosuppressive medications during the risk period. In adjusted models, exposure to SCs was associated with increased risk of COVID-19 infection (HR, 2.66; 95% confidence interval [CI], 2.19-3.24; P < 0.001), hospitalization (HR, 3.26; 95% CI, 2.46-4.33; P < 0.001), and in-hospital death (HR, 1.99; 95% CI, 0.93-4.27; P = 0.08). Furthermore, incremental increases in the dosage of SCs were associated with a greater risk for these outcomes. Although tumor necrosis factor-α (TNF-α) inhibitors were associated with an increased risk of infection (HR, 1.48; 95% CI, 1.08-2.04; P = 0.02), other immunosuppressive treatments did not increase the risk of COVID-19 infection, hospitalization, or death. CONCLUSIONS: This study from an era before widespread COVID-19 vaccination demonstrates that outpatient SC exposure is associated with greater risk of COVID-19 infection and severe outcomes in patients with NIU. Future studies should evaluate the impact of immunosuppression in vaccinated NIU patients. Limiting exposure to SCs and use of alternative therapies may be warranted.

Reactivation of minimal change disease after Pfizer vaccine against COVID-19.

This case follows a 54-year-old woman with a medical history of hypertension who experienced reactivation of minimal change disease (MCD) after receiving the Pfizer vaccine against COVID-19. She had her first episode of MCD 15 days after receiving the influenza vaccine in 2018. She remained in remission for over 3 years following treatment with steroids. She experienced foamy urine and leg edema after receiving the first dose of the Pfizer vaccine, but she did not consult medical professionals until she received the second dose. She wanted to be fully vaccinated because she worked in healthcare. Her initial diagnosis of MCD in 2018 was made following a kidney biopsy. The diagnosis of reactivation following COVID-19 vaccine was made with labs and presenting symptoms. At presentation, her urine protein was 9,977 mg/day. She was treated with prednisone 50 mg/day following her relapse with improvement in her urine protein to 85 mg/g within 4 weeks of starting treatment. She is currently undergoing treatment with prednisone with improvement in her presenting symptoms, which included foaming of urine and edema of legs. This case demonstrates the importance of vigilance in patients with a history of MCD when receiving the COVID-19 vaccine, particularly if they have a history of such reactions to other vaccines. Patients should discuss the benefits and risks of receiving the vaccine with their medical professionals and stay cognizant about the possibility of reactivation after receiving the COVID-19 vaccine.

Giant cell arteritis with spontaneous remission.

The case of a 75-year-old woman diagnosed with polymyalgia rheumatica (PMR), treated with low doses of prednisone, and with clinical and analytical remission is reported. Two years later, she presented with a clinical picture of giant cell arteritis (GCA), including headache, diplopia, jaw pain, feeling of swelling in both temples, and elevation of acute phase reactants. Symptoms spontaneously subsided 2 weeks later, while analytical parameters improved without any treatment. A high-resolution colour Doppler ultrasound showed thickening of the intima-media complex with 'halo' sign in the right temporal artery. A biopsy of the right temporal artery was performed, although it was not successful, as no artery could be found, and the procedure became more complicated with an eyebrow ptosis due to a lesion in the frontal branch of the facial nerve. GCA diagnosis was based on the clinical, laboratory, and ultrasound findings. The patient was treated with prednisone and methotrexate, without clinical or analytical relapse. Comments are presented on the described cases of GCA with spontaneous remission, and the most appropriate treatments in these cases are discussed. Other peculiarities of the case, such as the progression to GCA more than 2 years after the onset of PMR, and the complications from the temporal artery biopsy are also mentioned.

Safety and efficacy of a dose-dense short-term therapy in patients with MYC-translocated aggressive lymphoma.

Patients with aggressive B-cell lymphoma and MYC rearrangement at fluorescence in situ hybridization exhibit poor outcome after R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). In the last decade, 68 patients with Burkitt lymphoma ([BL] n = 46) or high-grade B-cell lymphoma ([HGBCL] single, double, or triple hit; n = 22) were treated with a dose-dense, short-term therapy termed "CARMEN regimen" at 5 Italian centers. Forty-six (68%) patients were HIV+. CARMEN included a 36-day induction with sequential, single weekly doses of cyclophosphamide, vincristine, rituximab, methotrexate, etoposide, and doxorubicin plus intrathecal chemotherapy, followed by high-dose-cytarabine-based consolidation. Patients who did not achieve complete remission (CR) after induction received BEAM (carmustina, etoposide, cytarabine, melfalan)-conditioned autologous stem cell transplantation (ASCT) after consolidation. Sixty-one (90%) patients completed induction, and 59 (87%) completed consolidation. Seventeen patients received ASCT. Grade 4 hematological toxicity was common but did not cause treatment discontinuation; grade 4 nonhematological toxicity was recorded in 11 (16%) patients, with grade 4 infections in 6 (9%). Six (9%) patients died of toxicity (sepsis in 4, COVID-19, acute respiratory distress syndrome). CR rate after the whole treatment was 73% (95% confidence interval [CI], 55% to 91%) for patients with HGBCL and 78% (95% CI, 66% to 90%) for patients with BL. At a median follow-up of 65 (interquartile range, 40-109) months, 48 patients remain event free, with a 5-year progression-free survival of 63% (95% CI, 58% to 68%) for HGBCL and 72% (95% CI, 71% to 73%) for BL, with a 5-year overall survival (OS) of 63% (95% CI, 58% to 68%) and 76% (95% CI, 75% to 77%), respectively. HIV seropositivity did not have a detrimental effect on outcome. This retrospective study shows that CARMEN is a safe and active regimen both in HIV-negative and -positive patients with MYC-rearranged lymphomas. Encouraging survival figures, attained with a single dose of doxorubicin and cyclophosphamide, deserve further investigation in HGBCL and other aggressive lymphomas.

Coronavirus Disease 2019 Positivity Immediately After Lung Transplantation: A Case Report.

Management of COVID-19 in lung transplant recipients is challenging. We report a case of a 71-year-old male who underwent bilateral lung transplantation with an unexpected case of COVID-19. The patient had been fully vaccinated. The patient and donor tested negative for pretransplant COVID-19. On routine bronchoscopy on day 1 after transplant, the COVID-19 test was positive. Mycophenolic mofetil and the second dose of basiliximab were skipped, but tacrolimus and prednisone were continued. He was treated with casirivimab/imdevimab and remdesivir. He was discharged on day 14 and has had no episodes of acute rejection during the 3 months.

Transition to Virtual Asthma Care During the COVID-19 Pandemic: An Observational Study.

BACKGROUND: The COVID-19 pandemic increased reliance on virtual care for patients with persistent asthma. OBJECTIVE: This retrospective cohort study assessed changes from in-person to virtual care during the pandemic. In patients with persistent asthma, compared with the same period before the pandemic. METHODS: Kaiser Permanente Colorado members aged 18 to 99 years with persistent asthma were evaluated during two periods (March to October 2019 and March to October 2020). Comparison of asthma exacerbations (hospitalizations, emergency department visits, and courses of oral prednisone) and asthma medication metrics were evaluated between the two periods and by type of care received during the pandemic (no care, virtual care only, in-person care only, or a mix of virtual and in-person care). Population characteristics by type of care received during the pandemic were also evaluated. RESULTS: Among 7,805 adults with persistent asthma, those who used more virtual care or sought no care during the pandemic were younger and had fewer comorbidities, mental health diagnoses, or financial barriers. Exacerbations decreased (0.264 to 0.214; P <.001) as did courses of prednisone (0.213 to 0.169). Asthma medication adherence (0.53 to 0.54; P <.001) and the asthma medication ratio, a quality-of-care metric (0.755 to 0.762; P = .019), increased slightly. Patients receiving a mix of in-person and virtual care had the highest rate of exacerbations (0.83) and a lower asthma medication ratio (0.74) despite having the highest adherence (.57). CONCLUSIONS: Despite an increase in virtual care, asthma exacerbations decreased except among individuals who received both in-person and virtual care, likely because they had more severe disease.

Characteristics associated with poor COVID-19 outcomes in individuals with systemic lupus erythematosus: data from the COVID-19 Global Rheumatology Alliance.

AIM: To determine characteristics associated with more severe outcomes in a global registry of people with systemic lupus erythematosus (SLE) and COVID-19. METHODS: People with SLE and COVID-19 reported in the COVID-19 Global Rheumatology Alliance registry from March 2020 to June 2021 were included. The ordinal outcome was defined as: (1) not hospitalised, (2) hospitalised with no oxygenation, (3) hospitalised with any ventilation or oxygenation and (4) death. A multivariable ordinal logistic regression model was constructed to assess the relationship between COVID-19 severity and demographic characteristics, comorbidities, medications and disease activity. RESULTS: A total of 1606 people with SLE were included. In the multivariable model, older age (OR 1.03, 95% CI 1.02 to 1.04), male sex (1.50, 1.01 to 2.23), prednisone dose (1-5 mg/day 1.86, 1.20 to 2.66, 6-9 mg/day 2.47, 1.24 to 4.86 and ≥10 mg/day 1.95, 1.27 to 2.99), no current treatment (1.80, 1.17 to 2.75), comorbidities (eg, kidney disease 3.51, 2.42 to 5.09, cardiovascular disease/hypertension 1.69, 1.25 to 2.29) and moderate or high SLE disease activity (vs remission; 1.61, 1.02 to 2.54 and 3.94, 2.11 to 7.34, respectively) were associated with more severe outcomes. In age-adjusted and sex-adjusted models, mycophenolate, rituximab and cyclophosphamide were associated with worse outcomes compared with hydroxychloroquine; outcomes were more favourable with methotrexate and belimumab. CONCLUSIONS: More severe COVID-19 outcomes in individuals with SLE are largely driven by demographic factors, comorbidities and untreated or active SLE. Patients using glucocorticoids also experienced more severe outcomes.

Rheumatologic Manifestations of Post SARS-CoV-2 Infection: A Case Series.

BACKGROUND: It has been over a year since the first documented case of the COVID-19 virus was recorded. Since then, our understanding of this virus has continually evolved, however, its wide-ranging effects are still unfolding. Similar to previously studied viral infections, severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2) has been shown to lead to a degree of autoimmunity in patients who are recovering from its effects. Due to its effects on the innate immune system, such as the toll-like receptors and complement system, a varying degree of proinflammatory markers can become widespread in those who continue to recover from the virus. This case series offers a unique perspective on how COVID-19 has had dramatic effects on those already suffering from inflammatory rheumatic conditions, such as rheumatoid arthritis, systemic lupus erythematosus, or fibromyalgia. As the ever-lasting effects of COVID-19 are still unfolding, this case series is one of few to discuss the development and changes of patients with rheumatic conditions. This study hopes to encourage larger studies to be conducted on the effects of COVID- 19 on autoimmune conditions. CASE PRESENTATION: Seven patients were identified with new manifestations of rheumatic conditions, which included 3 cases of rheumatoid arthritis, 2 cases of polymyalgia rheumatica, 1 case of reactive arthritis, and 1 case of cutaneous lupus. Post-COVID syndrome was also diagnosed in 7 other patients. Patients with rheumatoid arthritis presented with symptoms 4-5 weeks after being diagnosed with COVID-19. Symptoms of polyarticular joint pain, swelling, and morning stiffness were reported in this group. These patients were treated with disease-modifying anti-rheumatic drugs and experienced an improvement in symptoms on follow-up. Two cases of polymyalgia rheumatica were identified in patients that were previously diagnosed with COVID-19 six weeks prior. One patient had no significant past medical history and the other patient had a history of rheumatoid arthritis, which was well controlled. These patients experienced weakness and tenderness in the proximal joints with elevated levels of ESR and CRP. They were treated with prednisone and showed improvement. Reactive arthritis was diagnosed in 1 patient who presented with swelling in both hands and wrists 2 days after being diagnosed with COVID-19. This patient began to experience symptoms of reactive arthritis 2 days after resolution of initial COVID-19 symptoms and this persisted for 3 months. The patient was managed with methylprednisolone injections and NSAIDs, which improved her symptoms. Post-COVID syndrome was identified in 7 patients. All patients were female and had a history of well-controlled fibromyalgia. Patients generally experienced fatigue, headaches, and memory fog, which had variable onset from a few days and up to 4 weeks after being diagnosed with COVID-19. One patient had a complete recovery of her symptoms at follow-up 3 months after the initial presentation. The other 6 patients continued to report symptoms of post-COVID syndrome at follow-up. Patients were managed with lifestyle modifications and their previous fibromyalgia treatment. CONCLUSION: While cases of COVID-19 continue to rise, complications of this disease are still being discovered. Those who initially recover from COVID-19 may experience new-onset rheumatic conditions, worsening of previously diagnosed rheumatic conditions, or post-COVID syndrome. As we continue to learn more about the effects of COVID-19, the awareness of these manifestations will play a key role in the appropriate management of these patients.

Use of glucocorticoids megadoses in SARS-CoV-2 infection in a spanish registry: SEMI-COVID-19.

OBJECTIVE: To describe the impact of different doses of corticosteroids on the evolution of patients with COVID-19 pneumonia, based on the potential benefit of the non-genomic mechanism of these drugs at higher doses. METHODS: Observational study using data collected from the SEMI-COVID-19 Registry. We evaluated the epidemiological, radiological and analytical scenario between patients treated with megadoses therapy of corticosteroids vs low-dose of corticosteroids and the development of complications. The primary endpoint was all-cause in-hospital mortality according to use of corticosteroids megadoses. RESULTS: Of a total of 14,921 patients, corticosteroids were used in 5,262 (35.3%). Of them, 2,216 (46%) specifically received megadoses. Age was a factor that differed between those who received megadoses therapy versus those who did not in a significant manner (69 years [IQR 59-79] vs 73 years [IQR 61-83]; p < .001). Radiological and analytical findings showed a higher use of megadoses therapy among patients with an interstitial infiltrate and elevated inflammatory markers associated with COVID-19. In the univariate study it appears that steroid use is associated with increased mortality (OR 2.07 95% CI 1.91-2.24 p < .001) and megadose use with increased survival (OR 0.84 95% CI 0.75-0.96, p 0.011), but when adjusting for possible confounding factors, it is observed that the use of megadoses is also associated with higher mortality (OR 1.54, 95% CI 1.32-1.80; p < .001). There is no difference between megadoses and low-dose (p .298). Although, there are differences in the use of megadoses versus low-dose in terms of complications, mainly infectious, with fewer pneumonias and sepsis in the megadoses group (OR 0.82 95% CI 0.71-0.95; p < .001 and OR 0.80 95% CI 0.65-0.97; p < .001) respectively. CONCLUSION: There is no difference in mortality with megadoses versus low-dose, but there is a lower incidence of infectious complications with glucocorticoid megadoses.

Case Report: Home-based Management of Severe COVID-19 with Low-dose Tofacitinib.

Human lives and nations' economies have been adversely affected worldwide by the COVID-19 pandemic. The hyperinflammatory state associated with the disease may be related to mortality. Systemic glucocorticoid is the first-line therapy for cytokine storm. Various immunomodulatory drugs such as tocilizumab and baricitinib have been used in those not responding to glucocorticoid monotherapy. Amid the peak crisis of COVID-19 in India, there was an extreme paucity of medications, oxygen, and hospital beds. We describe three patients with COVID-19 who received low-dose tofacitinib (an oral Janus kinase inhibitor) in addition to moderate-dose glucocorticoid. These patients were treated at their homes, as the hospitals were short of beds. Rapid reduction in hypoxemia along with gradual resolution of other signs of the disease were observed. The results are reassuring regarding the feasibility of managing of severe COVID-19 outside the hospital setting when healthcare resources are overwhelmed by pandemic-related caseload.

Limited increase in antibody titers following mRNA SARS-CoV-2 vaccination for more than 3 years after final dose of anti-CD20 antibody.

We investigated the efficacy of BNT162b2 mRNA COVID-19 vaccine in patients with B-cell malignancies treated with anti-CD20 antibody. Although T-cell-mediated immune responses were detected even in patients receiving R-CHOP treatment, the S1 antibody titer following BNT162b2 vaccination remained only marginally increased for more than 3 years after the final dose of anti-CD20 antibody. We found no relationship between the percent of B-cells and S1 antibody titer. The duration of this suppression was much longer than we anticipated. Further protection and treatment strategies against COVID-19 for these patients are warranted.

Evaluation of Immune Response and Disease Status in Systemic Lupus Erythematosus Patients Following SARS-CoV-2 Vaccination.

OBJECTIVE: To evaluate seroreactivity and disease flares after COVID-19 vaccination in a multiethnic/multiracial cohort of patients with systemic lupus erythematosus (SLE). METHODS: Ninety SLE patients and 20 healthy controls receiving a complete COVID-19 vaccine regimen were included. IgG seroreactivity to the SARS-CoV-2 spike receptor-binding domain (RBD) and SARS-CoV-2 microneutralization were used to evaluate B cell responses; interferon-γ (IFNγ) production was measured by enzyme-linked immunospot (ELISpot) assay in order to assess T cell responses. Disease activity was measured by the hybrid SLE Disease Activity Index (SLEDAI), and flares were identified according to the Safety of Estrogens in Lupus Erythematosus National Assessment-SLEDAI flare index. RESULTS: Overall, fully vaccinated SLE patients produced significantly lower IgG antibodies against SARS-CoV-2 spike RBD compared to fully vaccinated controls. Twenty-six SLE patients (28.8%) generated an IgG response below that of the lowest control (<100 units/ml). In logistic regression analyses, the use of any immunosuppressant or prednisone and a normal anti-double-stranded DNA antibody level prior to vaccination were associated with decreased vaccine responses. IgG seroreactivity to the SARS-CoV-2 spike RBD strongly correlated with the SARS-CoV-2 microneutralization titers and correlated with antigen-specific IFNγ production determined by ELISpot. In a subset of patients with poor antibody responses, IFNγ production was similarly diminished. Pre- and postvaccination SLEDAI scores were similar in both groups. Postvaccination flares occurred in 11.4% of patients; 1.3% of these were severe. CONCLUSION: In a multiethnic/multiracial study of SLE patients, 29% had a low response to the COVID-19 vaccine which was associated with receiving immunosuppressive therapy. Reassuringly, severe disease flares were rare. While minimal protective levels remain unknown, these data suggest that protocol development is needed to assess the efficacy of booster vaccination.

Leukocytoclastic vasculitis (cutaneous small-vessel vasculitis) after COVID-19 vaccination.

Vaccinations may induce cutaneous adverse events, due to nonspecific inflammation or immuno-mediated reactions. Several types of vasculitis have been observed. We report on a 71-year-old woman who developed cutaneous small-vessel vasculitis after the second dose of Vaxzevria COVID-19 vaccination, showing leukocytoclastic vasculitis on histopathological examination of a skin biopsy. Cutaneous small-vessel vasculitis is a rare condition which can be idiopathic or secondary to underlying infections, connective tissue disorders, malignancy, and medications. The pathogenesis involves immune complex deposition in small blood vessels, leading to activation of the complement system and recruitment of leukocytes. Exacerbation of small-vessel vasculitis has been reported following the administration of various vaccines, particularly influenza vaccine. It is expected that SARS-CoV-2 vaccine results in the activation of B- and T-cells and antibody formation. We hypothesize that leukocytoclastic vasculitis caused by immune complex deposition within cutaneous small vessels could be a rare side effect of Vaxzevria COVID-19 vaccination.

Complete response in a frail patient with high-grade B-cell lymphoma to only one cycle of R-CHOP or to prolonged COVID-19?

BACKGROUND: COVID-19 infection increases mortality in hematological malignancies. In a large meta-analysis, patients aged 60 years and older had a significantly higher risk of death than patients under 60 years of age [1]. Furthermore, a high risk of death and reduced survival in patients receiving B cell depletion therapy with prolonged COVID-19 infection was reported in a recent study [2]. High-grade B-cell lymphomas are classified as morphologically aggressive lymphomas with the presence of a high mitotic index and Ki-67 proliferation rates. They demonstrate aggressive behavior clinically as well as morphologically, and COVID-19 infection is an important factor that increases mortality in these patients. Herein, we present an elderly patient with a diagnosis of high-grade B-cell lymphoma, in whom a complete response was observed after prolonged COVID-19 infection. CASE SUMMARY: An 81-year-old female patient received her first cycle of R-CHOP (rituximab, cyclophosphamide, vincristine, and prednisolone) treatment after being diagnosed with high- grade B-cell lymphoma. After being discharged from the hospital, the patient was referred to the emergency department with complaints of fever and fatigue when she came for the second cycle of chemotherapy. Her COVID-19 PCR test was found positive. She was admitted to the infectious diseases service and favipiravir treatment was started. On the 24th day of hospitalization, it was decided to perform interim FDG-PET/CT (Fluorodeoxyglucose - Positron Emission Tomography/Computed Tomography) scan at a time that her PCR (Polymerase Chain Reaction) test was still positive. A complete metabolic response was detected in her imaging. On the 26th day, the PCR test became negative and the patient was transferred to the oncology service and received the second cycle of R-CHOP treatment. CONCLUSION: Our case emphasizes that antitumor effect could be seen in a patient with SARS-CoV-2 infection and a hematologic malignancy. It also highlights being alert to prolonged COVID-19 infection in patients receiving B-cell depletion therapy.