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1.
J Autoimmun ; 129: 102827, 2022 Apr 11.
Article in English | MEDLINE | ID: covidwho-1783457

ABSTRACT

OBJECTIVE: To evaluate B-cell- and T-cell-mediated immune response to SARS-CoV-2 mRNA vaccination in patients with complex or rare systemic autoimmune diseases previously been treated with or under continuous treatment with B-cell-targeted therapies including rituximab (RTX) and belimumab (BEL). MATERIALS AND METHODS: Twenty-eight consecutive patients receiving RTX (n = 11) or BEL (n = 17) treatment and 13 age-/sex-matched controls (non-rheumatic healthcare personnel) were recruited. None of the patients had detectable anti-SARS-CoV-2 antibodies caused by prior exposure to the virus. All the patients and controls received mRNA vaccines and were tested three to four weeks after completion of vaccination. In all the RTX patients, vaccination was started within 5 months from the last infusion, and B-cell depletion was confirmed in all but one of them. Total anti-SARS-CoV-2 RBD antibodies were analyzed using a diagnostic assay, while T-cell response was evaluated using the interferon-gamma release assay (IGRA). Further, SARS-CoV-2 pseudoviruses were employed to verify the strain-specific neutralizing capacity of the antibodies. RESULTS: Detectable anti-SARS-CoV-2 antibodies were documented in 1 out of the 11 RTX patients and 16 of the 17 BEL patients. The median concentration in the RTX and BEL patients was significantly lower than that in the controls (39.6 AU/ml vs. 1133 AU/ml, p = 0.002). The result of IGRA was positive in 8 of the 11 (72.7%) RTX patients and 16 of the 17 (94.1%) BEL patients, and interferon release in both the RTX and BEL patients was comparable to that in the control participants. CONCLUSION: B-cell-targeted therapies do not preclude SARS-CoV-2 vaccination, since virus-specific cellular immunity can be induced even in the absence of circulating B cells. An important finding was that lupus patients treated with BEL developed immune responses to SARS-CoV-2; this indicates retention of the immunogenicity of the COVID-19 vaccine.

2.
Lancet Rheumatol ; 4(2): e135-e144, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1555786

ABSTRACT

In patients with moderate-to-severe COVID-19 pneumonia, an aberrant post-viral alveolitis with excessive inflammatory responses and immunothrombosis underpins use of immunomodulatory therapy (eg, corticosteroids and interleukin-6 receptor antagonism). By contrast, immunosuppression in individuals with mild COVID-19 who do not require oxygen therapy or in those with critical disease undergoing prolonged ventilation is of no proven benefit. Furthermore, a window of opportunity is thought to exist for timely immunosuppression in patients with moderate-to-severe COVID-19 pneumonia shortly after clinical presentation. In this Viewpoint, we explore the shortcomings of a universal immunosuppression approach in patients with moderate-to-severe COVID-19 due to disease heterogeneity related to ongoing SARS-CoV-2 replication, which can manifest as RNAaemia in some patients treated with immunotherapy. By contrast, immunomodulatory therapy has overall benefits in patients with rapid SARS-CoV-2 clearance, via blunting of multifaceted, excessive innate immune responses in the lungs, potentially uncontrolled T-cell responses, possible autoimmune responses, and immunothrombosis. We highlight this therapeutic dichotomy to better understand the immunopathology of moderate-to-severe COVID-19, particularly the role of RNAaemia, and to refine therapy choices.

3.
Lancet Rheumatol ; 3(12): e855-e864, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1500370

ABSTRACT

BACKGROUND: Patients with primary systemic vasculitis or polymyalgia rheumatica might be at a high risk for poor COVID-19 outcomes due to the treatments used, the potential organ damage cause by primary systemic vasculitis, and the demographic factors associated with these conditions. We therefore aimed to investigate factors associated with COVID-19 outcomes in patients with primary systemic vasculitis or polymyalgia rheumatica. METHODS: In this retrospective cohort study, adult patients (aged ≥18 years) diagnosed with COVID-19 between March 12, 2020, and April 12, 2021, who had a history of primary systemic vasculitis (antineutrophil cytoplasmic antibody [ANCA]-associated vasculitis, giant cell arteritis, Behçet's syndrome, or other vasculitis) or polymyalgia rheumatica, and were reported to the COVID-19 Global Rheumatology Alliance registry were included. To assess COVID-19 outcomes in patients, we used an ordinal COVID-19 severity scale, defined as: (1) no hospitalisation; (2) hospitalisation without supplemental oxygen; (3) hospitalisation with any supplemental oxygen or ventilation; or (4) death. Multivariable ordinal logistic regression analyses were used to estimate odds ratios (ORs), adjusting for age, sex, time period, number of comorbidities, smoking status, obesity, glucocorticoid use, disease activity, region, and medication category. Analyses were also stratified by type of rheumatic disease. FINDINGS: Of 1202 eligible patients identified in the registry, 733 (61·0%) were women and 469 (39·0%) were men, and their mean age was 63·8 years (SD 17·1). A total of 374 (31·1%) patients had polymyalgia rheumatica, 353 (29·4%) had ANCA-associated vasculitis, 183 (15·2%) had giant cell arteritis, 112 (9·3%) had Behçet's syndrome, and 180 (15·0%) had other vasculitis. Of 1020 (84·9%) patients with outcome data, 512 (50·2%) were not hospitalised, 114 (11·2%) were hospitalised and did not receive supplemental oxygen, 239 (23·4%) were hospitalised and received ventilation or supplemental oxygen, and 155 (15·2%) died. A higher odds of poor COVID-19 outcomes were observed in patients who were older (per each additional decade of life OR 1·44 [95% CI 1·31-1·57]), were male compared with female (1·38 [1·05-1·80]), had more comorbidities (per each additional comorbidity 1·39 [1·23-1·58]), were taking 10 mg/day or more of prednisolone compared with none (2·14 [1·50-3·04]), or had moderate, or high or severe disease activity compared with those who had disease remission or low disease activity (2·12 [1·49-3·02]). Risk factors varied among different disease subtypes. INTERPRETATION: Among patients with primary systemic vasculitis and polymyalgia rheumatica, severe COVID-19 outcomes were associated with variable and largely unmodifiable risk factors, such as age, sex, and number of comorbidities, as well as treatments, including high-dose glucocorticoids. Our results could be used to inform mitigation strategies for patients with these diseases. FUNDING: American College of Rheumatology and the European Alliance of Associations for Rheumatology.

4.
Ann Rheum Dis ; 81(1): 34-40, 2022 01.
Article in English | MEDLINE | ID: covidwho-1462913

ABSTRACT

OBJECTIVES: To update the EULAR points to consider (PtCs) on the use of immunomodulatory therapies in COVID-19. METHODS: According to the EULAR standardised operating procedures, a systematic literature review up to 14 July 2021 was conducted and followed by a consensus meeting of an international multidisciplinary task force. The new statements were consolidated by formal voting. RESULTS: We updated 2 overarching principles and 12 PtC. Evidence was only available in moderate to severe and critical patients. Glucocorticoids alone or in combination with tocilizumab are beneficial in COVID-19 cases requiring oxygen therapy and in critical COVID-19. Use of Janus kinase inhibitors (baricitinib and tofacitinib) is promising in the same populations of severe and critical COVID-19. Anti-SARS-CoV-2 monoclonal antibodies and convalescent plasma may find application in early phases of the disease and in selected subgroups of immunosuppressed patients. There was insufficient robust evidence for the efficacy of other immunomodulators with further work being needed in relation to biomarker-based stratification for IL-1 therapy CONCLUSIONS: Growing evidence supports incremental efficacy of glucocorticoids alone or combined with tocilizumab/Janus kinase inhibitors in moderate to severe and critical COVID-19. Ongoing studies may unmask the potential application of other therapeutic approaches. Involvement of rheumatologists, as systemic inflammatory diseases experts, should be encouraged in clinical trials of immunomodulatory therapy in COVID-19.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , Glucocorticoids/therapeutic use , Janus Kinase Inhibitors/therapeutic use , Azetidines/therapeutic use , Consensus Development Conferences as Topic , Drug Therapy, Combination , Humans , Immunomodulation , Piperidines/therapeutic use , Purines/therapeutic use , Pyrazoles/therapeutic use , Pyrimidines/therapeutic use , SARS-CoV-2 , Sulfonamides/therapeutic use
5.
Rev Rhum Ed Fr ; 88(5): 377-381, 2021 Oct.
Article in French | MEDLINE | ID: covidwho-1447100

ABSTRACT

OBJECTIF: Cette étude a pour objectif de déterminer la prévalence du coronavirus 2 du syndrome respiratoire aigu sévère (SARS-CoV-2) 2019 (COVID-19) chez des patients adultes traités par biothérapies ou inhibiteurs des JAK pour des rhumatismes inflammatoires chroniques, en particulier des arthrites inflammatoires chroniques. MÉTHODES: Pour cela, une étude basée sur la population, dans la province d'Udine (466 700 habitants d'âge > 15 ans, région du Frioul-Vénétie-Julienne, Italie) a été planifiée. Le critère principal de jugement était la prévalence du COVID-19 durant les deux premiers mois de l'épidémie. Tous les patients de notre province atteints de maladies rhumatismales et traités par biothérapies ou inhibiteurs des JAK au cours des 6 mois précédents ont été inclus (n = 1051). RÉSULTATS: Du 29 février au 25 avril 2020, 4 patients adultes (4/1051, 3,8/1000, IC 95 % 1,5-9,7/1000) ont été testés positifs au COVID-19 par RT-PCR et écouvillon. Au total, 47/1051 patients (4,5 %) ont été soumis au test COVID-19 par RT-PCR durant la même période, en raison de symptômes compatibles avec le COVID-19 pour 15 d'entre eux. Dans la population générale, la prévalence était de 937 cas/466700 (2/1000, IC 95 % 1,9-2,1/1000, valeur p = 0,33, test du Chi2), et 20 179/466 700 (4,3 %) prélèvements COVID-19 sur écouvillon ont été effectués. CONCLUSION: Le risque de COVID-19 chez les patients atteints de maladies rhumatismales et traités par biothérapies ou inhibiteurs des JAK n'apparaît pas différent de celui observé dans la population générale. Les patients doivent être encouragés à poursuivre en toute sécurité leur traitement et à respecter les mesures de prévention et de protection contre le COVID-19.

6.
Viruses ; 13(8)2021 08 06.
Article in English | MEDLINE | ID: covidwho-1348696

ABSTRACT

Severe acute respiratory coronavirus-2 syndrome (SARS-CoV-2) is a well-known pandemic infectious disease caused by an RNA virus belonging to the coronaviridae family. The most important involvement during the acute phase of infection concerns the respiratory tract and may be fatal. However, COVID-19 may become a systemic disease with a wide spectrum of manifestations. Herein, we report the natural history of sacroiliac inflammatory involvement in two females who developed COVID-19 infection with mild flu-like symptoms. After the infection they reported inflammatory back pain, with magnetic resonance imaging (MRI) studies showing typical aspects of sacroiliitis. Symptoms improved with NSAIDs therapy over the following months while MRI remained positive. A literature review was performed on this emerging topic. To our knowledge, this is the first MRI longitudinal study of post-COVID-19 sacroiliitis with almost one year of follow-up. Predisposing factors for the development of articular involvement are unclear but a long-lasting persistence of the virus, demonstrated by nasopharyngeal swab, may enhance the probability of altering the immune system in a favourable background.


Subject(s)
Arthritis/etiology , COVID-19/complications , Sacroiliitis/etiology , Arthritis/diagnostic imaging , Female , Humans , Longitudinal Studies , Magnetic Resonance Imaging , Middle Aged , Sacroiliitis/diagnostic imaging
7.
J Multidiscip Healthc ; 14: 1475-1488, 2021.
Article in English | MEDLINE | ID: covidwho-1278269

ABSTRACT

OBJECTIVE: To compare the psychological impact of the lockdown measures contrasting the COVID-19 outbreak between systemic lupus erythematosus (SLE) and general population. PATIENTS AND METHODS: From July 15th to August 15th 2020, a retrospective survey referring to the period March 9th to May 18th 2020 was administered to SLE patients and the results of the survey, called LEPRE (Lupus Erythematosus PREsto) study, were compared with those from the PRESTO (imPact of quaRantine mEasures againST cOvid19) project, the same survey provided to the general population. Consecutive patients >18 years old affected by SLE and regularly followed in a single rheumatologic centre were involved. Primary outcome was to compare the scores of the Impact of Events Scale-Revised (IES-R), the General Health Questionnaire 12 (GHQ-12) and the Center for Epidemiological Depression Scale (CES-D) between patients and general population. RESULTS: A total of 64 patients completed the survey. After a propensity score matching, they were compared to 128 people from PRESTO project. The median age among patients was 43 years (I-III interquartile range 35-54.5), 88% were female and 100% Caucasian. IES-R [(score>23: 57% (34) vs 49% (58)], GHQ-12 [(score>13: 85% (52) vs 88% (106)], and CES-D [(score>15: 45% (28) vs 40% (46)] scores were not statistically different between patients and controls (p>0.05). CONCLUSION: Restrictive measures for COVID-19 pandemic had no greater impact on patients with SLE than in the general population. Strategy for coping to the SLE might be useful during lockdown measures and may be helpful for other chronic conditions.

8.
Rev Rhum Ed Fr ; 88(5): 377-381, 2021 Oct.
Article in French | MEDLINE | ID: covidwho-1233600

ABSTRACT

OBJECTIF: Cette étude a pour objectif de déterminer la prévalence du coronavirus 2 du syndrome respiratoire aigu sévère (SARS-CoV-2) 2019 (COVID-19) chez des patients adultes traités par biothérapies ou inhibiteurs des JAK pour des rhumatismes inflammatoires chroniques, en particulier des arthrites inflammatoires chroniques. MÉTHODES: Pour cela, une étude basée sur la population, dans la province d'Udine (466 700 habitants d'âge > 15 ans, région du Frioul-Vénétie-Julienne, Italie) a été planifiée. Le critère principal de jugement était la prévalence du COVID-19 durant les deux premiers mois de l'épidémie. Tous les patients de notre province atteints de maladies rhumatismales et traités par biothérapies ou inhibiteurs des JAK au cours des 6 mois précédents ont été inclus (n = 1051). RÉSULTATS: Du 29 février au 25 avril 2020, 4 patients adultes (4/1051, 3,8/1000, IC 95 % 1,5-9,7/1000) ont été testés positifs au COVID-19 par RT-PCR et écouvillon. Au total, 47/1051 patients (4,5 %) ont été soumis au test COVID-19 par RT-PCR durant la même période, en raison de symptômes compatibles avec le COVID-19 pour 15 d'entre eux. Dans la population générale, la prévalence était de 937 cas/466700 (2/1000, IC 95 % 1,9-2,1/1000, valeur p = 0,33, test du Chi2), et 20 179/466 700 (4,3 %) prélèvements COVID-19 sur écouvillon ont été effectués. CONCLUSION: Le risque de COVID-19 chez les patients atteints de maladies rhumatismales et traités par biothérapies ou inhibiteurs des JAK n'apparaît pas différent de celui observé dans la population générale. Les patients doivent être encouragés à poursuivre en toute sécurité leur traitement et à respecter les mesures de prévention et de protection contre le COVID-19.

10.
Ann Rheum Dis ; 2021 Feb 05.
Article in English | MEDLINE | ID: covidwho-1066833

ABSTRACT

OBJECTIVES: Severe systemic inflammation associated with some stages of COVID-19 and in fatal cases led therapeutic agents developed or used frequently in Rheumatology being at the vanguard of experimental therapeutics strategies. The aim of this project was to elaborate EULAR Points to consider (PtCs) on COVID-19 pathophysiology and immunomodulatory therapies. METHODS: PtCs were developed in accordance with EULAR standard operating procedures for endorsed recommendations, led by an international multidisciplinary Task Force, including rheumatologists, translational immunologists, haematologists, paediatricians, patients and health professionals, based on a systemic literature review up to 15 December 2020. Overarching principles (OPs) and PtCs were formulated and consolidated by formal voting. RESULTS: Two OPs and fourteen PtCs were developed. OPs highlight the heterogeneous clinical spectrum of SARS-CoV-2 infection and the need of a multifaceted approach to target the different pathophysiological mechanisms. PtCs 1-6 encompass the pathophysiology of SARS-CoV-2 including immune response, endothelial dysfunction and biomarkers. PtCs 7-14 focus on the management of SARS-CoV-2 infection with immunomodulators. There was evidence supporting the use of glucocorticoids, especially dexamethasone, in COVID-19 cases requiring oxygen therapy. No other immunomodulator demonstrated efficacy on mortality to date, with however inconsistent results for tocilizumab. Immunomodulatory therapy was not associated with higher infection rates. CONCLUSIONS: Multifactorial pathophysiological mechanisms, including immune abnormalities, play a key role in COVID-19. The efficacy of glucocorticoids in cases requiring oxygen therapy suggests that immunomodulatory treatment might be effective in COVID-19 subsets. Involvement of rheumatologists, as systemic inflammatory diseases experts, should continue in ongoing clinical trials delineating optimal immunomodulatory therapy utilisation in COVID-19.

11.
Cytokine ; 140: 155438, 2021 04.
Article in English | MEDLINE | ID: covidwho-1032450

ABSTRACT

BACKGROUND: Patients infected by SARS-CoV-2 can develop interstitial pneumonia, requiring hospitalisation or mechanical ventilation. Increased levels of inflammatory biomarkers are associated with development of acute respiratory distress syndrome (ARDS). The aim of the present study was to determine which cytokines are associated with respiratory insufficiency in patients hospitalised for COVID-19. PATIENTS AND METHODS: Data on 67 consecutive patients were collected between March 8 and March 30, 2020. PaO2/FiO2 ratio (P/F) was calculated at hospital admission. The following cytokines were analysed: interleukin (IL)-6, IL-1α, IL-18, tumour necrosis factor (TNF)-ß, macrophage colony-stimulating factor (M-CSF), macrophage migration inhibitory factor (MIF), soluble IL-2 receptor alpha (sIL-2Rα; CD25), IL-12ß, IL-3, interferon (IFN) α2a, monokine induced by gamma interferon (MIG), monocyte-chemotactic protein 3 (MCP3) and hepatocyte growth factor (HGF). RESULTS: P/F lower than 300 was recorded in 22 out of 67 patients (32.8%). P/F strongly correlated with IL-6 (r = -0.62, P < 0.0001), M-CSF (r = -0.63, P < 0.0001), sIL-2Rα (r = -0.54, P < 0.0001), and HGF (r = -0.53, P < 0.0001). ROC curve analyses for IL-6 (AUC 0.83, 95% CI 0.73-0.93, P < 0.0001), M-CSF (AUC 0.87, 95% CI 0.79-0.96, P < 0.0001), HGF (AUC 0.81, 95% CI 0.70-0.93, P < 0.0001), and sIL-2Rα (AUC 0.80, 95% CI, 0.69-0.90, P < 0.0001) showed that these four soluble factors were highly significant. All four soluble factors correlated with LDH, white blood cell count, neutrophil count, lymphocyte count, and CRP. CONCLUSION: IL-6, M-CSF, sIL-2Rα, and HGF are possibly involved in the main biological processes of severe COVID-19, mirroring the level of systemic hyperinflammatory state, the level of lung inflammation, and the severity of organ damage.


Subject(s)
COVID-19/blood , Cytokines/blood , Immunity, Innate/immunology , Inflammation/blood , Interleukin-2 Receptor alpha Subunit/blood , Multiple Organ Failure/blood , Pneumonia/blood , Aged , COVID-19/complications , COVID-19/virology , Female , Hepatocyte Growth Factor/blood , Host-Pathogen Interactions , Humans , Inflammation/complications , Interleukin-6/blood , Macrophage Colony-Stimulating Factor/blood , Male , Middle Aged , Multiple Organ Failure/complications , Pneumonia/complications , Pneumonia/virology , Retrospective Studies , SARS-CoV-2/physiology
13.
J Med Virol ; 92(11): 2852-2856, 2020 11.
Article in English | MEDLINE | ID: covidwho-866098

ABSTRACT

INTRODUCTION: The most serious COVID-19 deriving from severe acute respiratory syndrome coronavirus 2 causes a cytokine release storm and it is associated with worse outcomes. In COVID-19 patients, interleukin-6 (IL-6) levels are significantly elevated. Blocking IL-6 preliminarily resulted in the improvement of this hyperinflammatory state. It is unknown which patients could require higher doses of tocilizumab to get out of the cytokine storm. MATERIALS AND METHODS: Twenty-four patients affected by COVID-19 pneumonia were included. All the patients underwent tocilizumab 8 mg/kg intravenously and were tested for serum IL-6 24 to 48 hours before and 12 to 48 hours after tocilizumab infusion. Comparisons between survivors and nonsurvivors were performed. RESULTS: Eighteen patients were discharged, while six patients died, with no clinical or laboratory differences between the two groups at baseline. IL-6 was not different at baseline (P = .41), while 24 to 48 hours post-tocilizumab IL-6 serum levels were significantly higher in nonsurvivors than in survivors (2398.5 [430.5-9372] vs 290.5 [58.5-1305.5] pg/mL, P = .022). Serum IL-6 post-tocilizumab showed a good predictive ability to discriminate survivors from nonsurvivors (area under the curve, 0.815; 95% confidence interval, 0.63-0.99, P = .02). CONCLUSION: Repeated measurement of the serum level of IL-6 early after tocilizumab may distinguish nonsurvivors from survivors and support the choice of deeper targeting IL-6 in COVID-19 pneumonia.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , Interleukin-6/blood , Survivors/statistics & numerical data , Administration, Intravenous , Aged , Biomarkers/blood , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/virology , Female , Humans , Male , Middle Aged , Retrospective Studies , Severity of Illness Index
16.
Riv. Ital. Med. Labor. ; 1(16): 7-17, 20200301.
Article in Italian | WHO COVID, ELSEVIER | ID: covidwho-659439

ABSTRACT

COVID-19 infection (SARS-CoV-2) is a viral disease first encountered in Wuhan, China, in December 2019, then rapidly spreading around the world. During this current public health emergency of international concern, screening and diagnosing patients quickly in order to aid containment is a priority. Most of our knowledge on diagnostics comes from previous studies on SARSCoV. Since SARS-CoV-2 belongs to the same large family of viruses as those that cause the MERS and SARS outbreak, we could assume that its antibody generation process should be similar. The high contagiousness and the characteristics of high lethality of the epidemic require efficient diagnostics, able to quickly identify the sources of the infection. The identification of patients with active SARS-CoV-2 infection is currently based on the amplification of a viral genome sequence using molecular biology techniques (real-time polymerase chain reaction), which can be subsequently confirmed by gene sequencing. However, the variability linked to the execution of the swab and the limitations of the test (complexity, biosecurity levels, costs and long response times) makes molecular diagnostics unsuitable for use in the field. Consequently, new tools such as serological tests capable of tracking the virus through each phase of the disease are in great demand. Serological antibody tests are already being developed and have already been introduced to the market. To date, however, there is no robust scientific evidence on the clinical-diagnostic reliability of these tests which therefore, at the moment, cannot replace the molecular test. The few studies in the literature are of limited thickness, sometimes discordant with each other and conducted on a small scale mainly on the Chinese population. In the absence of specific references, there is an open debate on the best use of these serological tests and on the ideal moment of their execution. In this review we describe the main characteristics of the SARS-CoV-2 virus, the diagnostic molecular strategies available today, and the first experimental data on the determination of antibodies directed towards SARS-CoV-2.

18.
Isr Med Assoc J ; 22(6): 335-339, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-607449

ABSTRACT

BACKGROUND: In the absence of definitive anti-viral therapy, there is considerable interest in mitigating against severe inflammatory reactions in coronavirus disease-2019 (COVID-19) pneumonia to improve survival. These reactions are sometimes termed cytokine storm. PDE4 inhibitors (PDE4i) have anti-inflammatory properties with approved indications in inflammatory skin and joint diseases as well as chronic obstructive pulmonary disease (COPD). Furthermore, multiple animal models demonstrate strong anti-inflammatory effects of PDE4i in respiratory models of viral and bacterial infection and also after chemically mediated lung injury. The rationale for PDE4i use in COVID-19 patients comes from the multimodal mechanism of action with cytokine, chemokine, and other key pathway inhibition all achieved with an excellent safety profile. We highlight how PDE4i could be an overlooked treatment from the rheumatologic and respiratory armamentarium, which has potential beneficial immune-modulation for treating severe COVID-19 pneumonia associated with cytokine storms. The proposed use of PDE4i is also supported by age-related immune changes in inflammation severity in PDE4i modifiable pathways in primate coronavirus disease. In conclusion, over-exuberant anti-viral immune responses in older patients with COVID-19 may pose a substantial risk to patient survival and mitigation against such hyper-inflammation with PDE4i, especially with anti-viral agents, is a strategy that need to be pursed, especially in older patients.


Subject(s)
Anti-Inflammatory Agents/administration & dosage , Communicable Diseases, Emerging/drug therapy , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Disease Outbreaks , Phosphodiesterase 4 Inhibitors/administration & dosage , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Adult , Age Factors , Aged , Animals , Betacoronavirus , COVID-19 , Communicable Diseases, Emerging/mortality , Coronavirus Infections/diagnosis , Female , Humans , Italy , Male , Middle Aged , Pandemics , Phosphodiesterase 4 Inhibitors/pharmacology , Pneumonia, Viral/diagnosis , Prognosis , Risk Assessment , SARS-CoV-2 , Survival Analysis , Treatment Outcome , United Kingdom
19.
Immunol Res ; 68(3): 161-168, 2020 06.
Article in English | MEDLINE | ID: covidwho-592322

ABSTRACT

The recent COVID-19 pandemic has had a significant impact on our lives and has rapidly expanded to reach more than 4 million cases worldwide by May 2020. These cases are characterized by extreme variability, from a mild or asymptomatic form lasting for a few days up to severe forms of interstitial pneumonia that may require ventilatory therapy and can lead to patient death.Several hypotheses have been drawn up to understand the role of the interaction between the infectious agent and the immune system in the development of the disease and the most severe forms; the role of the cytokine storm seems important.Innate immunity, as one of the first elements of guest interaction with different infectious agents, could play an important role in the development of the cytokine storm and be responsible for boosting more severe forms. Therefore, it seems important to study also this important arm of the immune system to adequately understand the pathogenesis of the disease. Research on this topic is also needed to develop therapeutic strategies for treatment of this disease.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/immunology , Cytokine Release Syndrome/virology , Cytokines/metabolism , Immunity, Innate , Pneumonia, Viral/immunology , Asymptomatic Diseases/epidemiology , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Coronavirus Infections/virology , Cytokine Release Syndrome/diagnosis , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/mortality , Cytokines/immunology , Humans , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , SARS-CoV-2 , Severity of Illness Index
20.
J Clin Virol ; 129: 104444, 2020 08.
Article in English | MEDLINE | ID: covidwho-276355

ABSTRACT

OBJECTIVE: Approximately 5% of patients with coronavirus disease 2019 (COVID-19) develop a life-threatening pneumonia that often occurs in the setting of increased inflammation or "cytokine storm". Anti-cytokine treatments are being evaluated but optimal patient selection remains unclear, and the aim of our study is to address this point. METHODS: Between February 29 to April 6, 2020, 111 consecutive hospitalized patients with COVID-19 pneumonia were evaluated in a single centre retrospective study. Patients were divided in two groups: 42 severe cases (TOCI) with adverse prognostic features including raised CRP and IL-6 levels, who underwent anti-cytokine treatments, mostly tocilizumab, and 69 standard of care patients (SOC). RESULTS: In the TOCI group, all received anti-viral therapy and 40% also received glucocorticoids. In TOCI, 62% of cases were ventilated and there were three deaths (17.8 ± 10.6 days, mean follow up) with 7/26 cases remaining on ventilators, without improvement, and 17/26 developed bacterial superinfection. One fatality occurred in the 15 TOCI cases treated on noninvasive ventilation and one serious bacterial superinfection. Of the 69 cases in SOC, there was no fatalities and no bacterial complications. The TOCI group had higher baseline CRP and IL-6 elevations (p < 0.0001 for both) and higher neutrophils and lower lymphocyte levels (p = 0.04 and p = 0.001, respectively) with the TOCI ventilated patients having higher markers than non-ventilated TOCI patients. CONCLUSION: Higher inflammatory markers, more infections and worse outcomes characterized ventilated TOCI cases compared to ward based TOCI. Despite the confounding factors, this suggests that therapy time in anti-cytokine randomized trials will be key.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Coronavirus Infections/complications , Coronavirus Infections/therapy , Cytokine Release Syndrome/drug therapy , Immunologic Factors/therapeutic use , Pneumonia, Viral/complications , Pneumonia, Viral/therapy , Standard of Care , Adult , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , COVID-19 , Female , Glucocorticoids/therapeutic use , Hospitals , Humans , Inpatients , Italy , Male , Middle Aged , Pandemics , Retrospective Studies , Treatment Outcome , Young Adult
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