SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2)-related pneumonia, referred to as COVID-19 (Coronavirus Disease 19), is a public health emergency as it carries high morbidity, mortality, ...and has no approved specific pharmacological treatments. In this case series, we aimed to report preliminary data obtained with anti-complement C5 therapy with eculizumab in COVID-19 patients admitted to intensive care unit (ICU) of ASL Napoli 2 Nord.
This is a case series of patients with a confirmed diagnosis of SARS-CoV2 infection and severe pneumonia or ARDS who were treated with up to 4 infusions of eculizumab as an off-label agent. Patients were also treated with anticoagulant therapy with Enoxaparin 4000 IU/day via subcutaneous injection, antiviral therapy with Lopinavir 800 mg/day + Ritonavir 200 mg/day, hydroxychloroquine 400 mg/day, ceftriaxone 2 g/day IV, vitamine C 6 g/day for 4 days, and were on Non-Invasive Ventilation (NIV).
We treated four COVID-19 patients admitted to the intensive care unit because of severe pneumonia or ARDS. All patients successfully recovered after treatment with eculizumab. Eculizumab induced a drop in inflammatory markers. Mean C Reactive Protein levels dropped from 14.6 mg/dl to 3.5 mg/dl and the mean duration of the disease was 12.8 days.
Eculizumab has the potential to be a key player in treatment of severe cases of COVID-19. Our results support eculizumab use as an off-label treatment of COVID-19, pending confirmation from the ongoing SOLID-C19 trial.
► The effect of 1α,25(OH)2D3 in MonoT0 and in MØT7 has been analyzed. ► 1α,25(OH)2D3 differently modulates the inflammatory response MonoT0 and in MØT7. ► 1α,25-(OH)2D3 has a well defined behavior ...during the early or tardive innate immune response.
Vitamin D3 1α,25-(OH)2D3, involved in the regulation of body calcium homeostasis, promotes immature myeloid precursor cells differentiation into monocytes/macrophages. In this study we compared the regulatory interaction between 1α,25-(OH)2D3 and tumor necrosis factor (TNF)-α or lipopolysaccharide (LPS) in the mRNA expression of interleukin (IL)-1β, (IL)-6, TNF-α, toll like receptors (TLR)-2 and (TLR)-4 in freshly isolated human monocyte (MonoT0) and in macrophages cultured for seven days (MØT7). Additionally, we detected the effect of 1α,25-(OH)2D3 on macrophages chemotaxis. The expression of IL-1β, IL-6 and TNF-α, as well as TLR-2 and TLR-4 in MonoT0 and in MØT7 was examined by real time RT-PCR. Macrophages chemotaxis was analyzed by using horizontal chemotaxis agarose spot assay.
We found that 1α,25-(OH)2D3 influences macrophages chemotaxis and differently modulates the expression of IL-1β, IL-6, TNF-α and TLRs in the two different stages of monocytes/macrophage maturation. In conclusion our data add new information about the role of 1α,25-(OH)2D3 on the expression of inflammatory mediators in human monocyte/macrophages, underlying the complex function of these cells. Investigating the differences in the pattern of expression of immune-mediators produced by MonoT0 and MØT7 may provide a new way to examine their biochemical and molecular function and may constitute a model system with well-defined behavior with respect to early or tardive events in the innate immune response.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The recent outbreak of SARS-CoV-2 greatly involves the resources of the global healthcare system, as it affects newborns, adults, and elders. This infection runs in three major stages: a mild ...cold-like illness, a moderate respiratory syndrome and a severe acute interstitial pneumonia. SARS-CoV-2 infection seems to have a more benign evolution in children. As a matter of fact, low susceptibility and minor aggressivity have been highlighted in most cases. There are currently no effective antiviral drugs treatment for the affected children. No sufficient results have been reached by the use of interferon (IFN), lopinavir/ritonavir, orbidol, and oseltamivir in the treatment of the coronaviruses infection. The aim of this short review is to highlight the differences existing between COVID-19 cases in adults and children.
In late December 2019 in Wuhan (China), Health Commission reported a cluster of pneumonia cases of unknown etiology, subsequently isolated and named Severe Acute Respiratory Syndrome (SARS) ...Coronavirus 2 (CoV-2). In this review, the main transmission routes and causes of mortality associated with COVID-19 were investigated.
A review was carried out to recognize relevant research available until 10 April 2020.
The main transmission routes of COVID-19 have been the following: animal to human and human-to-human pathways, namely: respiratory transmission; oro-fecal transmission; air, surface-human transmission. Transmission from asymptomatic persons, healthcare transmission, and interfamily transmission have been well documented.
SARS-CoV-2 possesses powerful pathogenicity and transmissibility. It is presumed to spread primarily via respiratory droplets and close contact. The most probable transmission pathway is definitely the inter-human one. Asymptomatic patients seem to play a crucial role in spreading the infection. Because of COVID-19 infection pandemic potential, careful surveillance is essential to monitor its future host adaptation, viral evolution, infectivity, transmissibility, and pathogenicity in order to gain an effective vaccine and flock immunity and reduce mortality as soon and as much as it is possible.
Transient elastography (TE) is adequate for a diagnosis of cirrhosis, but its accuracy for milder stages of fibrosis is much less satisfactory. The objective of this study was to compare the ...performance and the discordance rate of acoustic radiation force impulse (ARFI) and TE with liver biopsy in a cohort of chronic hepatitis C (CHC) patients.
One hundred thirty-nine consecutive patients with CHC were enrolled in two tertiary centers, and evaluated for histological (Metavir score) and biochemical features. All patients underwent TE and ARFI.
TE was unreliable in nine patients (6.5%), while in no cases (0%) were ARFI invalid measurements recorded (P=0.029). By area under receiver operating characteristic curve (AUROC), the best cutoff values for TE and ARFI for significant fibrosis (≥F2) were ≥6.5 kPa (AUROC: 0.78) and ≥1.3 m/s (AUROC: 0.86), respectively. For severe fibrosis (F3-F4), these cutoff values were 8.8 kPa (AUROC: 0.83) for TE and 1.7 m/s (AUROC: 0.94) for ARFI. For cirrhosis, TE had its best cutoff at ≥11 kPa (AUROC: 0.80) and ARFI at ≥2.0 m/s (AUROC: 0.89). By pairwise comparison of AUROC, ARFI was significantly more accurate than TE for a diagnosis of significant and severe fibrosis (P=0.024 and P=0.002, respectively), while this difference was only marginal for cirrhosis (P=0.09). By partial AUROC analysis, ARFI performance results significantly higher for all three stages of fibrosis. The average concordance rates of TE and ARFI vs. liver biopsy were 45.4 and 54.7%, respectively. By multivariate analysis, ARFI was not associated with alanine aminotransferase (ALT), body mass index, Metavir grade, and liver steatosis, while TE was significantly correlated with the ALT value (P=0.027).
In a cohort of patients with CHC, ARFI imaging was more accurate than TE for the non-invasive staging of both significant and severe classes of liver fibrosis.
Pregnant women and their infants are at high risk to develop a severe COVID-19, with increased rates of hospitalisation to intensive care units, need for mechanical ventilation and mortality. Preterm ...birth, fetal vascular malperfusion, and premature rupture of membrane have been the most reported adverse pregnancy outcomes and these effects have been especially associated with the onset of the disease at early gestational age. The early expression of ACE2 and TMPRSS2 in human embryos has been proven, determining an increased susceptibility to SARS-CoV-2. Preterm infants born to women infected by SARS-CoV-2 have a higher risk of need for specialist neonatal care with prolonged hospitalization. Moreover, inflammation of developing embryos could cause long-term defects, regardless of vertical transmission of SARS-CoV-2. Due to Maternal Immune Activation (MIA), in utero inflammation is associated with neurodevelopmental, cognitive and psychiatric disorders in affected offspring. Despite risks that COVID-19 could induce in pregnancy, there are not many published data describing the safety and/or efficacy of COVID-19 vaccines in pregnant women, commonly not included in vaccine research. The evidence from the few pregnant women unintentionally enrolled in clinical trials and vaccinated suggests that COVID-19 vaccines, both based on mRNA and viral vectors, do not pose significant risks to the fetus or breastfeeding infants. Moreover, human studies using mRNA-based vaccines against Zika virus, influenza, and rabies have reported good safety and immunogenicity during pregnancy. In this review, we evaluate the role of COVID-19 in adverse pregnancy and neonatal outcomes and the need to vaccinate pregnant women.
The new era of vaccines: the "nanovaccinology" Facciolà, A; Visalli, G; Laganà, P ...
European review for medical and pharmacological sciences,
08/2019, Volume:
23, Issue:
16
Journal Article
Peer reviewed
Vaccinations are the most effective preventive methods against infectious diseases and represent one of the most relevant successes of medicine. Vaccine development is constantly evolving; therefore, ...the number of vaccine candidates is progressively increasing. However, most of new potential vaccines are characterized by a lower immunogenicity, with the inability to stimulate powerful and long-lasting immune responses. Hence, to get modern and effective vaccines, we need adjuvants and innovative delivery systems that increase their immunogenicity. The use of nanotechnology in vaccinology is providing the opportunity to contrast these difficulties and develop effective vaccines. Particularly, nanoparticles used as vehicles of vaccine components, are able to increase the host's immune responses and, due to their size, to reach specific cellular districts. To date, a certain number of nanovaccines has been approved for human health and many are studied in clinical or pre-clinical trials. There are several types of nanoparticles considered as possible delivers of vaccine antigens. These nanoparticles-based synthetic delivery systems, in the size range of 20-200 nm, protect antigen from degradation, enhance its presentation and facilitate its uptake by professional antigen-presenting cells. Virus-like particles, self-assembled proteins, micelles, liposomes, inorganic nanoparticles, and polymers are the most studied of these systems. In this review, we provide a general overview of different types, methods of synthesis, characterizations, properties and applications of nanoparticles in vaccine production.
In an era when most individuals with treated HIV infection can expect to live into old age, clinicians should proactively review their patients’ current and future treatment needs and challenges. ...Clinical guidelines acknowledge that, in the setting of virological suppression, treatment switch may yield benefits in terms of tolerability, regimen simplification, adherence, convenience and long‐term health considerations, particularly in the context of ageing. In this paper, we review evidence from six key clinical studies on switching virologically suppressed patients to regimens based on integrase strand transfer inhibitors (INSTIs), the antiretroviral class increasingly preferred as initial therapy in clinical guidelines. We review these studies and focus on the virological efficacy, safety, and tolerability of switching to INSTI‐based regimens in suppressed HIV‐positive individuals. We review the early switch studies SWITCHMRK and SPIRAL assessing a switch from a ritonavir‐boosted protease inhibitor (PI/r) to raltegravir (RAL)‐containing regimens, together with data from STRATEGY‐PI assessing a switch to elvitegravir (EVG)‐containing regimens; EVG/cobicistat (COBI)/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) vs. remaining on a PI/r‐containing regimen, STRATEGY‐NNRTI assessing a switch to EVG/COBI/FTC/TDF vs. continuation of a nonnucleoside reverse transcriptase inhibitor (NNRTI) and two nucleoside reverse transcriptase inhibitors (NRTIs), STRIIVING assessing a switch to a dolutegravir (DTG)‐containing regimen (abacavir (ABC)/lamivudine (3TC)/DTG) vs. staying on the background regimen, and GS study 109 assessing a switch to EVG/COBI/FTC/tenofovir alafenamide fumarate (TAF) vs. continuation of FTC/TDF‐based regimens. Switching to INSTI‐containing regimens has been shown to support good virological efficacy, with evidence from two studies demonstrating superior virological efficacy for a switch to EVG‐containing regimens. In addition, switching to INSTI regimens was associated with improved tolerability and greater reported patient satisfaction and outcomes in some studies. INSTI‐based regimens offer an important contemporary switch option that may be tailored to meet and optimize the needs of many patients.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
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