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1.
J Med Virol ; 94(1): 291-297, 2022 01.
Article in English | MEDLINE | ID: covidwho-1544344

ABSTRACT

Due to current advances and growing experience in the management of coronavirus Disease 2019 (COVID-19), the outcome of COVID-19 patients with severe/critical illness would be expected to be better in the second wave compared with the first wave. As our hospitalization criteria changed in the second wave, we aimed to investigate whether a favorable outcome occurred in hospitalized COVID-19 patients with only severe/critical illness. Among 642 laboratory-confirmed hospitalized COVID-19 patients in the first wave and 1121 in the second wave, those who met World Health Organization (WHO) definitions for severe or critical illness on admission or during follow-up were surveyed. Data on demographics, comorbidities, C-reactive protein (CRP) levels on admission, and outcomes were obtained from an electronic hospital database. Univariate analysis was performed to compare the characteristics of patients in the first and second waves. There were 228 (35.5%) patients with severe/critical illness in the first wave and 681 (60.7%) in the second wave. Both groups were similar in terms of age, gender, and comorbidities, other than chronic kidney disease. Median serum CRP levels were significantly higher in patients in the second wave compared with those in the first wave [109 mg/L (interquartile range [IQR]: 65-157) vs. 87 mg/L (IQR: 39-140); p < 0.001]. However, intensive care unit admission and mortality rates were similar among the waves. Even though a lower mortality rate in the second wave has been reported in previous studies, including all hospitalized COVID-19 patients, we found similar demographics and outcomes among hospitalized COVID-19 patients with severe/critical illness in the first and second wave.


Subject(s)
COVID-19/drug therapy , COVID-19/mortality , Critical Care/statistics & numerical data , Severity of Illness Index , Aged , Amides/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Azithromycin/therapeutic use , C-Reactive Protein/analysis , COVID-19/epidemiology , COVID-19/pathology , Comorbidity , Drug Combinations , Enoxaparin/therapeutic use , Female , Hospital Mortality , Hospitalization/statistics & numerical data , Humans , Hydroxychloroquine/therapeutic use , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Lopinavir/therapeutic use , Male , Methylprednisolone/therapeutic use , Middle Aged , Pyrazines/therapeutic use , Retrospective Studies , Ritonavir/therapeutic use , SARS-CoV-2 , Treatment Outcome , Turkey/epidemiology
4.
Nat Med ; 27(10): 1752-1760, 2021 10.
Article in English | MEDLINE | ID: covidwho-1392877

ABSTRACT

Early increase of soluble urokinase plasminogen activator receptor (suPAR) serum levels is indicative of increased risk of progression of coronavirus disease 2019 (COVID-19) to respiratory failure. The SAVE-MORE double-blind, randomized controlled trial evaluated the efficacy and safety of anakinra, an IL-1α/ß inhibitor, in 594 patients with COVID-19 at risk of progressing to respiratory failure as identified by plasma suPAR ≥6 ng ml-1, 85.9% (n = 510) of whom were receiving dexamethasone. At day 28, the adjusted proportional odds of having a worse clinical status (assessed by the 11-point World Health Organization Clinical Progression Scale (WHO-CPS)) with anakinra, as compared to placebo, was 0.36 (95% confidence interval 0.26-0.50). The median WHO-CPS decrease on day 28 from baseline in the placebo and anakinra groups was 3 and 4 points, respectively (odds ratio (OR) = 0.40, P < 0.0001); the respective median decrease of Sequential Organ Failure Assessment (SOFA) score on day 7 from baseline was 0 and 1 points (OR = 0.63, P = 0.004). Twenty-eight-day mortality decreased (hazard ratio = 0.45, P = 0.045), and hospital stay was shorter.


Subject(s)
COVID-19/drug therapy , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Receptors, Urokinase Plasminogen Activator/blood , Aged , COVID-19/virology , Double-Blind Method , Female , Humans , Interleukin 1 Receptor Antagonist Protein/adverse effects , Male , Middle Aged , Placebos , SARS-CoV-2/isolation & purification
5.
J Pediatr ; 229: 33-40, 2021 02.
Article in English | MEDLINE | ID: covidwho-1382573

ABSTRACT

OBJECTIVE: To describe the similarities and differences in the evaluation and treatment of multisystem inflammatory syndrome in children (MIS-C) at hospitals in the US. STUDY DESIGN: We conducted a cross-sectional survey from June 16 to July 16, 2020, of US children's hospitals regarding protocols for management of patients with MIS-C. Elements included characteristics of the hospital, clinical definition of MIS-C, evaluation, treatment, and follow-up. We summarized key findings and compared results from centers in which >5 patients had been treated vs those in which ≤5 patients had been treated. RESULTS: In all, 40 centers of varying size and experience with MIS-C participated in this protocol survey. Overall, 21 of 40 centers required only 1 day of fever for MIS-C to be considered. In the evaluation of patients, there was often a tiered approach. Intravenous immunoglobulin was the most widely recommended medication to treat MIS-C (98% of centers). Corticosteroids were listed in 93% of protocols primarily for moderate or severe cases. Aspirin was commonly recommended for mild cases, whereas heparin or low molecular weight heparin were to be used primarily in severe cases. In severe cases, anakinra and vasopressors frequently were recommended; 39 of 40 centers recommended follow-up with cardiology. There were similar findings between centers in which >5 patients vs ≤5 patients had been managed. Supplemental materials containing hospital protocols are provided. CONCLUSIONS: There are many similarities yet key differences between hospital protocols for MIS-C. These findings can help healthcare providers learn from others regarding options for managing MIS-C.


Subject(s)
COVID-19/therapy , Clinical Protocols , Practice Patterns, Physicians'/statistics & numerical data , Systemic Inflammatory Response Syndrome/therapy , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Anticoagulants/therapeutic use , Antirheumatic Agents/therapeutic use , Aspirin/therapeutic use , COVID-19/diagnosis , Child , Cross-Sectional Studies , Glucocorticoids/therapeutic use , Heparin/therapeutic use , Hospitals , Humans , Immunoglobulins, Intravenous , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Surveys and Questionnaires , Systemic Inflammatory Response Syndrome/diagnosis , United States/epidemiology , Vasoconstrictor Agents/therapeutic use
6.
Indian J Pharmacol ; 53(3): 226-228, 2021.
Article in English | MEDLINE | ID: covidwho-1282691

ABSTRACT

Although many potent drugs have been used for cytokine storm, mortality is high for patients with coronavirus disease-2019 (COVID-19), which is followed up in the intensive care unit. Interferons (IFNs) are the major cytokines of the antiviral defense system released from many cell types. However, IFN-γ plays a key role in both primary and secondary cytokine storms. If the cytokine storm is not treated urgently, it will be fatal; therefore, it should be treated immediately. Anakinra, an interleukin-1 (IL-1) antagonist, tocilizumab, an IL-6 antagonist, and Janus kinase (JAK) inhibitors are successfully used in cytokine storm caused by COVID-19. However, sometimes, despite these treatments, the patient's clinical course does not improve. Emapalumab (Eb) is the human immunoglobulin G1 monoclonal antibody and is a potent and noncompetitive antagonist of IFN-γ. Eb can be life saving for cytokine storm caused by COVID-19, which is resistant to anakinra, tocilizumab, and JAK inhibitors.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing/therapeutic use , COVID-19/drug therapy , Cytokine Release Syndrome/drug therapy , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Janus Kinase Inhibitors/therapeutic use , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal, Humanized/pharmacology , Antibodies, Neutralizing/pharmacology , Antirheumatic Agents/pharmacology , Antirheumatic Agents/therapeutic use , COVID-19/epidemiology , COVID-19/immunology , Cytokine Release Syndrome/epidemiology , Cytokine Release Syndrome/immunology , Disease Progression , Drug Resistance, Viral , Humans , Interferon-gamma/antagonists & inhibitors , Interferon-gamma/immunology , Interleukin 1 Receptor Antagonist Protein/pharmacology , Interleukins/antagonists & inhibitors , Interleukins/immunology , Janus Kinase Inhibitors/pharmacology , Recurrence
7.
Exp Dermatol ; 30 Suppl 1: 18-22, 2021 06.
Article in English | MEDLINE | ID: covidwho-1258931

ABSTRACT

The reported incidence of COVID-19 among cohorts of patients with inflammatory bowel and skin diseases under treatment with biologicals is low. Treatment may further modify disease severity as some biological modifiers, such as anakinra, are also proposed for the management of COVID-19 patients potentially providing HS patients with an advantage. The above preliminary evidence suggests that hidradenitis suppurativa (HS) does probably not provide an increased susceptibility for COVID-19 and that any susceptibility is unlikely to be modified negatively by treatment with biologicals. On the occasion of its 10th International Conference, experts of the European Hidradenitis Suppurativa Foundation e.V. have prepared a consensus statement regarding anti-COVID-19 measurements for HS patients. Based on the available knowledge, patients with HS may be vaccinated against SARS-CoV2 and patients affected by metabolic syndrome constitute a high-risk group for COVID-19 and should be vaccinated at the earliest convenient point in time. HS patients on treatment with adalimumab can be vaccinated with non-living virus anti-SARS-CoV2 vaccines. A possible suboptimal effect of the vaccine may be suspected but might not be expected universally. The management of the biological treatment in HS patients is at the discretion of the dermatologist / responsible physician.


Subject(s)
COVID-19/complications , Hidradenitis Suppurativa/complications , Hidradenitis Suppurativa/drug therapy , SARS-CoV-2 , Adalimumab/therapeutic use , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/immunology , COVID-19 Vaccines/pharmacology , Cohort Studies , Disease Susceptibility , Europe , Foundations , Hidradenitis Suppurativa/immunology , Humans , Incidence , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Metabolic Syndrome/complications , Metabolic Syndrome/immunology , Pandemics , Severity of Illness Index
8.
Mol Cells ; 44(6): 408-421, 2021 Jun 30.
Article in English | MEDLINE | ID: covidwho-1249737

ABSTRACT

The outbreak of coronavirus disease 2019 (COVID-19) has not only affected human health but also diverted the focus of research and derailed the world economy over the past year. Recently, vaccination against COVID-19 has begun, but further studies on effective therapeutic agents are still needed. The severity of COVID-19 is attributable to several factors such as the dysfunctional host immune response manifested by uncontrolled viral replication, type I interferon suppression, and release of impaired cytokines by the infected resident and recruited cells. Due to the evolving pathophysiology and direct involvement of the host immune system in COVID-19, the use of immune-modulating drugs is still challenging. For the use of immune-modulating drugs in severe COVID-19, it is important to balance the fight between the aggravated immune system and suppression of immune defense against the virus that causes secondary infection. In addition, the interplaying events that occur during virus-host interactions, such as activation of the host immune system, immune evasion mechanism of the virus, and manifestation of different stages of COVID-19, are disjunctive and require thorough streamlining. This review provides an update on the immunotherapeutic interventions implemented to combat COVID-19 along with the understanding of molecular aspects of the immune evasion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may provide opportunities to develop more effective and promising therapeutics.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/therapy , Immune Evasion/drug effects , Immunologic Factors/therapeutic use , Virus Replication/drug effects , COVID-19/immunology , COVID-19/pathology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , Clinical Trials as Topic , Cytokines/antagonists & inhibitors , Cytokines/biosynthesis , Dexamethasone/therapeutic use , Drug Combinations , Humans , Immunity, Innate/drug effects , Immunization, Passive/methods , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Peptides/therapeutic use , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Virus Replication/immunology
9.
Int J Infect Dis ; 108: 209-211, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1240393

ABSTRACT

Multisystem inflammatory syndrome in adults (MIS-A) came to attention back in June 2020, when the United States Center for Disease Control and Prevention (CDC) received initial reports regarding patients who had presented delayed and multisystem involvement of the disease, with clinical course resembling multisystem inflammatory syndrome in children (MIS-C). This study introduces a case of MIS-A, where the patient presented 3 weeks after initial COVID-19 exposure. His clinical course was consistent with the working definition of MIS-A as specified by the CDC. Aggressive supportive care in the intensive care unit, utilization of advanced heart failure devices, and immunomodulatory therapeutics (high-dose steroids, anakinra, intravenous immunoglobulin) led to clinical recovery. Management of MIS-A is a topic of ongoing research and needs more studies to elaborate on treatment modalities and clinical predictors.


Subject(s)
COVID-19 , Adult , Child , Humans , Immunoglobulins, Intravenous/therapeutic use , Interleukin 1 Receptor Antagonist Protein/therapeutic use , SARS-CoV-2 , Systemic Inflammatory Response Syndrome , United States
10.
J Immunother Cancer ; 9(5)2021 05.
Article in English | MEDLINE | ID: covidwho-1228897

ABSTRACT

COVID-19, the syndrome caused by the infection with SARS-CoV-2 coronavirus, is characterized, in its severe form, by interstitial diffuse pneumonitis and acute respiratory distress syndrome (ARDS). ARDS and systemic manifestations of COVID-19 are mainly due to an exaggerated immune response triggered by the viral infection. Cytokine release syndrome (CRS), an inflammatory syndrome characterized by elevated levels of circulating cytokines, and endothelial dysfunction are systemic manifestations of COVID-19. CRS is also an adverse event of immunotherapy (IMTX), the treatment of diseases using drugs, cells, and antibodies to stimulate or suppress the immune system. Graft-versus-host disease complications after an allogeneic stem cell transplant, toxicity after the infusion of chimeric antigen receptor-T cell therapy and monoclonal antibodies can all lead to CRS. It is hypothesized that anti-inflammatory drugs used for treatment of CRS in IMTX may be useful in reducing the mortality in COVID-19, whereas IMTX itself may help in ameliorating effects of SARS-CoV-2 infection. In this paper, we focused on the potential shared mechanisms and differences between COVID-19 and IMTX-related toxicities. We performed a systematic review of the clinical trials testing anti-inflammatory therapies and of the data published from prospective trials. Preliminary evidence suggests there might be a benefit in targeting the cytokines involved in the pathogenesis of COVID-19, especially by inhibiting the interleukin-6 pathway. Many other approaches based on novel drugs and cell therapies are currently under investigation and may lead to a reduction in hospitalization and mortality due to COVID-19.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , COVID-19/therapy , Cytokine Release Syndrome/drug therapy , Immunotherapy/methods , Interleukin-6/antagonists & inhibitors , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/pathology , Cytokine Release Syndrome/pathology , Humans , Immunization, Passive/methods , Immunotherapy/adverse effects , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Interleukin-1beta/blood , Interleukin-6/blood , Nitriles , Pyrazoles/therapeutic use , Pyrimidines , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , Tumor Necrosis Factor-alpha/blood
11.
J Med Virol ; 93(3): 1532-1537, 2021 03.
Article in English | MEDLINE | ID: covidwho-1196470

ABSTRACT

COVID-19 pandemic has been affecting the whole world by increasing morbidity and mortality rates day by day. Treatment algorithms have been attempted as parallel to the increasing experience with COVID-19. In the pathogenesis of this virus pro-inflammatory cytokine storm has been called to have the main role. The right timing should be made for treatments. We proposed IL- 1 blocking by anakinra in seventeen COVID-19 patients at high risk of worsening. Patients were assessed according to HScore, SOFA (Sequential Organ Failure Assessment Score = SOFA), MuLBSTA Score (multilobular infiltration, hypo-lymphocytosis, bacterial coinfection, smoking history, hyper-tension, and age), Brescia-COVID respiratory severity scale (BCRSS). In our study, the mortality rate was 17.6%. Consequently, 1 (5.9%) patient was receiving low-flow oxygen supply, 3 (17.6%) patients needed no longer oxygen supply and 10 (58.8%) patients were discharged from the hospital. According to the results of our study in the manner of general evaluation; we found that SOFA, MuLBSTA, and BCRSS scores were one step ahead according to HScore being insufficient to determine early phases of the disease. In our opinion, the prominent factors that emphasize the use of anakinra could be listed as comorbidity, risk, or presence of secondary infection, ongoing malignant disease. However, the other factors that enhance the use of anakinra in the situation of viremia also could be sorted as no response to full dose antivirals, antiviral side effects, or no success to antiviral treatment.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Pneumonia/drug therapy , COVID-19/virology , Comorbidity , Female , Humans , Male , Middle Aged , Oxygen/administration & dosage , Pandemics/prevention & control , Severity of Illness Index
12.
Cytokine ; 143: 155544, 2021 07.
Article in English | MEDLINE | ID: covidwho-1188449

ABSTRACT

The overproduction of proinflammatory cytokines, resulting in what has been described as a cytokine storm or cytokine release syndrome (CRS), may be the key factor in the pathology of severe coronavirus disease 2019 (COVID-19) and is also a crucial cause of death from COVID-19. With the purpose of finding effective and low-toxicity drugs to mitigate CRS, IL-1 blockade agents, which are one of the safest ways to stop this overwhelming innate immune response, are already available in several preliminary reports or are under observational trials and may offer an important treatment option in hyperinflammatory COVID-19. In this review, we described the key information in both case reports and clinical studies on the potential beneficial features of IL-1 inhibitors in COVID-19 patients.


Subject(s)
COVID-19/drug therapy , Cytokine Release Syndrome/drug therapy , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Receptors, Interleukin-1 Type I/antagonists & inhibitors , Receptors, Interleukin-1/antagonists & inhibitors , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/mortality , COVID-19/pathology , Cytokine Release Syndrome/pathology , Female , Humans , Male , Middle Aged , Recombinant Fusion Proteins/therapeutic use , SARS-CoV-2/drug effects
13.
Medicine (Baltimore) ; 100(12): e25170, 2021 Mar 26.
Article in English | MEDLINE | ID: covidwho-1150007

ABSTRACT

RATIONALE: The immunologic syndrome induced by severe acute coronavirus disease 2019 (COVID-19) is yet not fully understood. Typical patterns of clinical and laboratory features match secondary hemophagocytic lymphohistiocytosis (sHLH). However, the optimal approach to COVID-19 patients testing positive for sHLH is still unclear. PATIENT CONCERNS: Three patients with COVID-19 are reviewed. All showed hyperinflammation and cytokine storm, necessitating intensive care treatment including mechanical ventilation. DIAGNOSIS: Secondary hemophagocytic lymphohistiocytosis due to severe COVID-19; diagnosed via HScore. INTERVENTIONS: A treatment regimen of methylprednisolone, pentaglobin, and anakinra was developed and administered. OUTCOMES: One patient survived the ICU stay. Two other patients, in whom sHLH was diagnosed too late, deceased. LESSONS: A routine screening of COVID-19 patients for secondary HLH by using the HScore is feasible; especially those patients deteriorating clinically with no sufficient response to shock management might be at particular high risk. A stepwise therapeutic approach comprising corticosteroids, immunoglobulins and anakinra, accompanied by immunoadsorption, may dampen cytokine storm effects, and potentially reduce mortality.


Subject(s)
COVID-19/complications , Lymphohistiocytosis, Hemophagocytic/drug therapy , Lymphohistiocytosis, Hemophagocytic/etiology , Aged , Anti-Inflammatory Agents/therapeutic use , COVID-19/physiopathology , COVID-19/therapy , Combined Modality Therapy , Critical Care , Cytokine Release Syndrome/drug therapy , Delayed Diagnosis , Fatal Outcome , Female , Humans , Immunoglobulin A/therapeutic use , Immunoglobulin M/therapeutic use , Immunoglobulins, Intravenous/therapeutic use , Immunosuppressive Agents/therapeutic use , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Lymphohistiocytosis, Hemophagocytic/diagnosis , Male , Methylprednisolone/therapeutic use , Middle Aged , Respiration, Artificial , SARS-CoV-2
14.
Pediatr Rheumatol Online J ; 19(1): 29, 2021 Mar 16.
Article in English | MEDLINE | ID: covidwho-1136233

ABSTRACT

BACKGROUND: There is mounting evidence on the existence of a Pediatric Inflammatory Multisystem Syndrome-temporally associated to SARS-CoV-2 infection (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining whether KD and PIMS are two distinct entities. METHODS: The Rheumatology Study Group of the Italian Pediatric Society launched a survey to enroll patients diagnosed with KD (Kawasaki Disease Group - KDG) or KD-like (Kawacovid Group - KCG) disease between February 1st 2020, and May 31st 2020. Demographic, clinical, laboratory data, treatment information, and patients' outcome were collected in an online anonymized database (RedCAP®). Relationship between clinical presentation and SARS-CoV-2 infection was also taken into account. Moreover, clinical characteristics of KDG during SARS-CoV-2 epidemic (KDG-CoV2) were compared to Kawasaki Disease patients (KDG-Historical) seen in three different Italian tertiary pediatric hospitals (Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste; AOU Meyer, Florence; IRCCS Istituto Giannina Gaslini, Genoa) from January 1st 2000 to December 31st 2019. Chi square test or exact Fisher test and non-parametric Wilcoxon Mann-Whitney test were used to study differences between two groups. RESULTS: One-hundred-forty-nine cases were enrolled, (96 KDG and 53 KCG). KCG children were significantly older and presented more frequently from gastrointestinal and respiratory involvement. Cardiac involvement was more common in KCG, with 60,4% of patients with myocarditis. 37,8% of patients among KCG presented hypotension/non-cardiogenic shock. Coronary artery abnormalities (CAA) were more common in the KDG. The risk of ICU admission were higher in KCG. Lymphopenia, higher CRP levels, elevated ferritin and troponin-T characterized KCG. KDG received more frequently immunoglobulins (IVIG) and acetylsalicylic acid (ASA) (81,3% vs 66%; p = 0.04 and 71,9% vs 43,4%; p = 0.001 respectively) as KCG more often received glucocorticoids (56,6% vs 14,6%; p < 0.0001). SARS-CoV-2 assay more often resulted positive in KCG than in KDG (75,5% vs 20%; p < 0.0001). Short-term follow data showed minor complications. Comparing KDG with a KD-Historical Italian cohort (598 patients), no statistical difference was found in terms of clinical manifestations and laboratory data. CONCLUSION: Our study suggests that SARS-CoV-2 infection might determine two distinct inflammatory diseases in children: KD and PIMS-TS. Older age at onset and clinical peculiarities like the occurrence of myocarditis characterize this multi-inflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths.


Subject(s)
COVID-19/physiopathology , Coronary Artery Disease/physiopathology , Hypotension/physiopathology , Lymphopenia/physiopathology , Mucocutaneous Lymph Node Syndrome/physiopathology , Myocarditis/physiopathology , Systemic Inflammatory Response Syndrome/physiopathology , Age Distribution , Antirheumatic Agents/therapeutic use , Aspirin/therapeutic use , C-Reactive Protein/metabolism , COVID-19/epidemiology , COVID-19/metabolism , COVID-19/therapy , Child , Child, Preschool , Cough/physiopathology , Diarrhea/physiopathology , Dyspnea/physiopathology , Female , Glucocorticoids/therapeutic use , Heart Failure/physiopathology , Humans , Hyperferritinemia/metabolism , Hyperferritinemia/physiopathology , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Infant , Intensive Care Units, Pediatric , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Italy/epidemiology , Male , Mucocutaneous Lymph Node Syndrome/epidemiology , Mucocutaneous Lymph Node Syndrome/metabolism , Mucocutaneous Lymph Node Syndrome/therapy , Platelet Aggregation Inhibitors/therapeutic use , SARS-CoV-2 , Shock/physiopathology , Systemic Inflammatory Response Syndrome/epidemiology , Systemic Inflammatory Response Syndrome/metabolism , Systemic Inflammatory Response Syndrome/therapy , Tachypnea/physiopathology , Troponin T/metabolism , Vomiting/physiopathology
15.
Int J Infect Dis ; 105: 756-762, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1135367

ABSTRACT

OBJECTIVES: Disease severity, previous medications and immunosuppressive agents could affect the antibody response against SARS-CoV-2. This study aimed to analyze variables affecting the humoral response to SARS-CoV-2. METHODS: This prospective cohort study included adult patients who recovered from COVID-19 and were admitted to a COVID-19 follow-up unit. Eight patient groups were defined in accordance with the results of thoracic computed tomography (CT), SARS-CoV-2 PCR test, and tocilizumab or anakinra use during active disease. Anti-S IgG antibodies were determined by ELISA in serum samples. Anti-S positive and negative cases were compared. RESULTS: A total of 518 patients were included in the study. SARS-CoV-2 IgG antibodies were positive in 82.8% of patients. SARS-CoV-2 PCR positivity, extent of lung involvement on CT, and time to antibody testing were independently associated with antibody positivity. Tocilizumab, anakinra or prednisolone use was not a factor affecting the antibody response. The rate of antibody response and sample/CO values among antibody-positive patients showed a linear relationship with the extent of lung involvement on CT. CONCLUSIONS: The use of tocilizumab, anakinra and prednisolone for COVID-19 did not affect the antibody response against SARS-CoV-2. The main driver of antibody response among patients with COVID-19 was the extent of pulmonary involvement on CT.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Viral/blood , COVID-19/drug therapy , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Prednisolone/therapeutic use , SARS-CoV-2/immunology , Antibodies, Viral/immunology , Cohort Studies , Drug Therapy, Combination , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Male , Middle Aged , Multivariate Analysis , Prospective Studies , Severity of Illness Index , Tomography, X-Ray Computed
16.
Rheumatol Int ; 41(1): 205-211, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1130760

ABSTRACT

Amyloidosis is described by the deposition of misfolded proteins in the tissues. Amyloidoses are classified into two as systemic and localized. Out of the systemic forms, AL (light chain) amyloidosis is the most prevalent type; however, amyloid A (AA) amyloidosis is more frequently encountered in the rheumatology practice. AA amyloidosis stands out as a major complication of familial Mediterranean fever (FMF). Splenic and renal involvement is more likely in FMF-associated systemic amyloidosis. The involvement of thyroid and adrenal glands has also been described, although infrequently. Amyloidoses have a heterogeneous plethora of clinical manifestations, with certain phenotypes associated with specific amyloid forms. Gynecological amyloidosis is a rare condition. Uterine involvement may occur in a localized fashion or may also arise as a part of systemic involvement, albeit at a lesser ratio. Several cases of uterine AL amyloidosis have been documented so far as an organ involvement in systemic AL amyloidosis. On the other hand, uterine amyloidosis associated with AA amyloidosis has been described merely in one case with rheumatoid arthritis (RA). Here, we presented a 40-year-old female patient with FMF known for 38 years who underwent splenectomy and hysterectomy due to massive splenomegaly, deep anemia, and persistent menometrorrhagia. Histological examinations of materials revealed uterine and splenic AA amyloidosis. This case report is first-of-its-kind to describe FMF-associated uterine AA amyloidosis and also provides a discussion of possible mechanisms of amyloidosis-induced uterine bleeding.


Subject(s)
Amyloidosis/etiology , Familial Mediterranean Fever/complications , Menorrhagia/etiology , Adult , Amyloidosis/drug therapy , Amyloidosis/pathology , Female , Humans , Interleukin 1 Receptor Antagonist Protein/therapeutic use
20.
Arthritis Rheumatol ; 73(4): e13-e29, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1086276

ABSTRACT

OBJECTIVE: To provide guidance on the management of Multisystem Inflammatory Syndrome in Children (MIS-C), a condition characterized by fever, inflammation, and multiorgan dysfunction that manifests late in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Recommendations are also provided for children with hyperinflammation during coronavirus disease 2019 (COVID-19), the acute, infectious phase of SARS-CoV-2 infection. METHODS: The Task Force was composed of 9 pediatric rheumatologists and 2 adult rheumatologists, 2 pediatric cardiologists, 2 pediatric infectious disease specialists, and 1 pediatric critical care physician. Preliminary statements addressing clinical questions related to MIS-C and hyperinflammation in COVID-19 were developed based on evidence reports. Consensus was built through a modified Delphi process that involved anonymous voting and webinar discussion. A 9-point scale was used to determine the appropriateness of each statement (median scores of 1-3 for inappropriate, 4-6 for uncertain, and 7-9 for appropriate). Consensus was rated as low, moderate, or high based on dispersion of the votes. Approved guidance statements were those that were classified as appropriate with moderate or high levels of consensus, which were prespecified before voting. RESULTS: The first version of the guidance was approved in June 2020, and consisted of 40 final guidance statements accompanied by a flow diagram depicting the diagnostic pathway for MIS-C. The document was revised in November 2020, and a new flow diagram with recommendations for initial immunomodulatory treatment of MIS-C was added. CONCLUSION: Our understanding of SARS-CoV-2-related syndromes in the pediatric population continues to evolve. This guidance document reflects currently available evidence coupled with expert opinion, and will be revised as further evidence becomes available.


Subject(s)
COVID-19/diagnosis , COVID-19/therapy , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/therapy , Adolescent , Advisory Committees , Anticoagulants/therapeutic use , Antirheumatic Agents/therapeutic use , Child , Child, Preschool , Delphi Technique , Diagnosis, Differential , Glucocorticoids/therapeutic use , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Infant , Infant, Newborn , Inflammation , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Mucocutaneous Lymph Node Syndrome/diagnosis , Platelet Aggregation Inhibitors/therapeutic use , Rheumatology , SARS-CoV-2 , Young Adult
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