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1.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-309520

ABSTRACT

Dysregulation of inflammation is hypothesized to play a crucial role for inducing the severe complications of Covid-19, with IL-1/IL-6 pathway being central in these events. Eight patients with severe Covid-19 pneumonia treated with the interleukin-1 receptor antagonist anakinra are reported;seven patients hospitalized in intensive care units (ICUs) in Greece and one non-ICU patient in the Netherlands. Patients scored positive for the hemophagocytosis score and they were diagnosed with secondary hemophagocytic lymphohistocytosis (sHLH). At the end-of-treatment with anakinra, ICU patients had less demands on vasopressors;they also had lower C-reactive protein, procalcitonin, troponin I, D-dimers, and ferritin - the hallmark marker of sHLH. All patients improved their respiratory function. Only two patients died. These data argue that the administration of anakinra may be a viable treatment in severe Covid-19 with sHLH, supporting for larger clinical studies to validate this concept.

2.
J Innate Immun ; : 1-11, 2021 Dec 01.
Article in English | MEDLINE | ID: covidwho-1546612

ABSTRACT

BACKGROUND: Macrophage activation-like syndrome (MALS) and complex immune dysregulation (CID) often underlie acute respiratory distress (ARDS) in COVID-19. We aimed to investigate the effect of personalized immunotherapy on clinical improvement of critical COVID-19. METHODS: In this open-label prospective trial, 102 patients with ARDS by SARS-CoV-2 were screened for MALS (ferritin >4,420 ng/mL) and CID (ferritin ≤4,420 ng/mL and low human leukocyte antigen (HLA)-DR expression on CD14-monocytes). Patients with MALS or CID with increased aminotransferases received intravenous anakinra; those with CID and normal aminotransferases received tocilizumab. The primary outcome was ≥25% decrease in the Sequential Organ Failure Assessment (SOFA) score and/or 50% increase in the respiratory ratio by day 8; 28-day mortality, change of SOFA score by day 28, serum biomarkers, and cytokine production by mononuclear cells were secondary endpoints. RESULTS: The primary study endpoint was met in 58.3% of anakinra-treated patients and in 33.3% of tocilizumab-treated patients (p: 0.01). Most patients in both groups received dexamethasone as standard of care. No differences were found in secondary outcomes, mortality, and SOFA score changes. Ferritin decreased among anakinra-treated patients; interleukin-6, soluble urokinase plasminogen activator receptor, and HLA-DR expression increased among tocilizumab-treated patients. Survivors by day 28 who received anakinra were distributed to lower severity levels of the WHO clinical progression scale. Greater incidence of secondary infections was found with tocilizumab treatment. CONCLUSION: Immune assessment resulted in favorable anakinra responses among critically ill patients with COVID-19 and features of MALS.

3.
Int J Environ Res Public Health ; 18(17)2021 08 30.
Article in English | MEDLINE | ID: covidwho-1390605

ABSTRACT

INTRODUCTION: Rapid antigen tests (RATs) are convenient for SARS-CoV-2 detection because they are simpler and faster than nucleic acid amplification tests (NAATs). This study aimed to assess the accuracy of a locally manufactured test; Rapid Test Ag 2019-nCoV (PROGNOSIS, BIOTECH, Larissa, Greece) in a clinical setting and during mass screening. METHODS: Nasopharyngeal samples from 624 individuals were analyzed. The results of the rapid test were compared to real-time reverse-transcription quantitative polymerase chain reaction (RT-qPCR). At the end of the test's procedure, positive test strips were scanned in an S-Flow reader in order to roughly estimate the antigen concentration. RESULTS: The lower limit of detection of the test was 468.75 genome copies/mL. The PROGNOSIS rapid test displayed a sensitivity of 85.5% (141/165) (95%CI: 79.1-90.5) and a specificity of 99.8% (458/459) (95%CI: 98.8-100.0%). The general inter-rater agreement was 0.89 (95%CI: 85.1-93.3). The regression analysis between the S-flow reader measurements (viral antigen) and the viral load of the positive samples demonstrated a weak correlation (R2 = 0.288, p < 0.001). CONCLUSION: The Rapid Test Ag 2019-nCoV demonstrated sufficient sensitivity, excellent specificity and could be available to be used with low overall cost. Thus, it could be used as point of care test, but also for mass screening for rapid detection of infected persons (e.g., for travelers).


Subject(s)
COVID-19 , SARS-CoV-2 , Biotechnology , COVID-19 Nucleic Acid Testing , COVID-19 Serological Testing , Greece , Hospitals , Humans , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and Specificity
4.
World J Clin Cases ; 9(19): 4918-4938, 2021 Jul 06.
Article in English | MEDLINE | ID: covidwho-1314989

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a major threat to global public health. The virus causes the clinical syndrome known as coronavirus disease 2019 (COVID-19), in which multiple organs can get affected. Apart from manifestations of the respiratory system, which predominate, its clinical presentation is frequently accompanied by symptoms of the gastro-intestinal (GI) tract and liver abnormalities. The correlation of symptoms and abnormalities with disease severity is discussed, leading to ambiguous results from international literature. Moreover, the disease infects patients with co-existing liver and GI disorders affecting both their health status and the availability of healthcare services provided to them. The risk of transmission of the disease during aerosol-generating procedures has changed the diagnostic approach and follow-up algorithms for liver and GI diseases. For the safety of both doctors and patients, telemedicine and distant evaluation have become everyday practice, whereas several routines and emergency visits at outpatient and emergency departments have been postponed or delayed. Vaccination against SARS-CoV-2 is underway, providing hope to humanity and the expectation that the post-COVID-19 era is near. This review aims to update knowledge about the manifestations of COVID-19 related to liver and GI diseases and the effect of the pandemic on the diagnostic and therapeutic procedures for these diseases with a special focus on how current practices have changed and what changes will possibly remain in the future.

5.
Int J Environ Res Public Health ; 18(6)2021 03 11.
Article in English | MEDLINE | ID: covidwho-1167512

ABSTRACT

A COVID-19 outbreak occurred among residents of a Roma settlement in Greece (8 April-4 June 2020). The aim of this study was to identify factors associated with an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and to evaluate the effectiveness of control measures implemented. Data were analyzed from individuals that were tested for SARS-CoV-2 during contact tracing, population screening or hospital visits. RT-PCR was used for the detection of SARS-CoV-2 in oropharyngeal samples. Risk factors for household secondary attack rates (SAR) and hospitalization with COVID-19 were examined using chi-square tests, Fisher's exact tests and logistic regression analyses. During the outbreak, 142 cases, 20 hospitalizations and 1 death were recorded, with a total of 2273 individuals tested. The risk of hospitalization was associated with age (OR: 1.04, 95% CI: 1.02-1.07) and Cycle threshold (Ct) values (OR for a decrease in Ct values by 1: 1.18, 95% CI: 1.07-1.31). Household SAR was estimated at 38.62% (95% CI: 32.50-45.01%). After the designation of an isolation facility for cases, household SAR declined from 74.42% to 31.03%. Household size was associated with the risk of infection (OR: 2.65, 95% CI: 1.00-7.07). The presence of COVID-19 symptoms among index cases was correlated with higher transmission (OR: 23.68, 95% CI 2.21-253.74) in multivariate analysis, while age was found to be associated with SAR only in univariate analysis. Roma communities can be particularly vulnerable to the spread of SARS-CoV-2. In similar settings, symptomatic cases are more important transmitters of SARS-CoV-2. Within these communities, immediate measures should be implemented to mitigate disease spread.


Subject(s)
COVID-19 , Roma , Disease Outbreaks , Greece/epidemiology , Humans , SARS-CoV-2
6.
Int J Infect Dis ; 97: 90-93, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-457203

ABSTRACT

In a proportion of patients, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a multisystem syndrome characterized by hyperinflammation, acute respiratory distress syndrome (ARDS), and hypercoagulability. A 68-year-old man with coronavirus disease 2019 (COVID-19) was admitted to the intensive care unit with respiratory failure, cytokine release syndrome (CRS), and skin ischemia - microthrombosis. Specific coagulation and inflammatory markers (D-dimer, ferritin, and C-reactive protein), along with the clinical picture, triggered the trial of recombinant tissue plasminogen activator (rt-PA) and tocilizumab. This was followed by resolution of the skin ischemia and CRS, while respiratory parameters improved. No major complications associated with rt-PA or tocilizumab occurred. The combination of rt-PA with targeted anti-inflammatory treatment could be a new therapeutic option for patients with COVID-19, ARDS, hyperinflammation, and increased blood viscosity.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Betacoronavirus , Coronavirus Infections/drug therapy , Fibrinolytic Agents/therapeutic use , Immunosuppressive Agents/therapeutic use , Pneumonia, Viral/drug therapy , Tissue Plasminogen Activator/therapeutic use , Aged , COVID-19 , Drug Combinations , Humans , Male , Pandemics , SARS-CoV-2
7.
Cell Host Microbe ; 28(1): 117-123.e1, 2020 07 08.
Article in English | MEDLINE | ID: covidwho-260325

ABSTRACT

Dysregulation of inflammation is hypothesized to play a crucial role in the severe complications of COVID-19, with the IL-1/IL-6 pathway being central. Here, we report on the treatment of eight severe COVID-19 pneumonia patients-seven hospitalized in intensive care units (ICUs) in Greece and one non-ICU patient in the Netherlands-with the interleukin-1 receptor antagonist Anakinra. All patients scored positive for the hemophagocytosis score (HScore) and were diagnosed with secondary hemophagocytic lymphohistocytosis (sHLH) characterized by pancytopenia, hyper-coagulation, acute kidney injury, and hepatobiliary dysfunction. At the end of treatment, ICU patients had less need for vasopressors, significantly improved respiratory function, and lower HScore. Although three patients died, the mortality was lower than historical series of patients with sHLH in sepsis. These data suggest that administration of Anakinra may be beneficial for treating severe COVID-19 patients with sHLH as determined by the HScore, and they support the need for larger clinical studies to validate this concept.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Lymphohistiocytosis, Hemophagocytic/drug therapy , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Aged , Aged, 80 and over , COVID-19 , Comorbidity , Female , Humans , Lymphohistiocytosis, Hemophagocytic/etiology , Male , Middle Aged , Off-Label Use , Oxygen/blood , Pandemics , Respiratory Insufficiency/prevention & control , SARS-CoV-2
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