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1.
COVID-19 and kidney: role of SARS-CoV-2 infection in the induction of renal damage.
Perrotta, AM, Rotondi, S, Mazzaferro, S, Bosi, L, Letizia, C, Muscaritoli, M, Gigante, A, Salciccia, S, Pasculli, P, Ciardi, MR, et al
European review for medical and pharmacological sciences. 2023;(16):7861-7867
Abstract
OBJECTIVE SARS-CoV-2 causes acute respiratory disease, interstitial and alveolar pneumonia, and involves numerous organs and systems such as the kidney, heart, digestive tract, blood, and nervous system. We aimed to evaluate the incidence of renal manifestations in patients diagnosed with COVID-19 infection. PATIENTS AND METHODS We performed a monocentric, cross-sectional, observational study, conducted on 114 patients with SARS-CoV-2. Clinical and laboratory parameters [renal function, serum electrolytes, inflammatory state, blood gas analysis, Interleukin 6 (IL-6) and urinalysis] were evaluated. The same values were checked out after two months (T1), however after negativization. RESULTS We enrolled 114 patients (59 males) with a mean age of 63.8 ± 13.9 years. We found hematuria in 48 patients (55.8%), proteinuria in 33 patients (38.4%), leukocyturia in 61 patients (70.9%), acute kidney injury (AKI) in 28 patients (24.6%), AKI in chronic kidney disease (CKD) in 24 patients (21.1%). Moreover, we found a significant increase of inflammatory indexes as C Reactive Protein (CRP), lactic dehydrogenase (LDH), alpha 1 and alpha 2 globulins with a subsequent reduction at T1 (p = 0.016, p < 0.001, p = 0.005, p = 0.007; respectively). Hemoglobin and erythrocyte values significantly decreased (p < 0.001, p = 0.003, respectively), and we found lymphopenia (p < 0.001). Also, we found elevated levels of the D-Dimer (p < 0.001) and a significant increase in the International Normalized Ratio (INR) (p = 0.038). We also showed a significant improvement after negativization in oxygen partial pressure (p = 0.001) and oxygen saturation (p < 0.001) and a significant increase in pH (p = 0.018) and bicarbonate concentration (p = 0.042). Moreover, we found a significant increase in IL-6 (p = 0.004). Also, we reported mild hyponatremia and hypokalemia with subsequent significant recovery (p < 0.001, p < 0.001, respectively) and mild hypochloremia with a recovery to the limits of statistical significance (p = 0.053). At the entrance, we found an increase in serum glucose with a significant reduction during recovery (p < 0.001). CONCLUSIONS The prevalence of AKI and/or CKD and/or abnormal urinalysis in patients diagnosed with COVID-19 on admission seems to be high and appears as a negative prognostic factor. Urinalysis appears to be very useful in unveiling the potential kidney impairment of COVID-19 patients; therefore, urinalysis could be used to reflect and predict the disease severity. We also recommend a careful evaluation of metabolic alterations, inflammatory states, and electrolytic disorders in COVID-19 patients.
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2.
Efficacy of antiseptic mouthrinses against SARS-CoV-2: A prospective randomized placebo-controlled pilot study.
Fantozzi, PJ, Pampena, E, Pierangeli, A, Oliveto, G, Sorrentino, L, Di Vanna, D, Pampena, R, Lazzaro, A, Gentilini, E, Mastroianni, CM, et al
American journal of otolaryngology. 2022;(6):103549
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Abstract
OBJECTIVES Coronavirus-disease-19 (COVID-19) continues to affect millions of individuals worldwide. Antiviral activity of mouthrinses remains an important research area as the oral cavity is a site of SARS-CoV-2 initial replication. The aim of this study was to assess the effectiveness of three different mouthrinses in reducing the oral/oropharyngeal SARS-CoV-2 viral load. METHODS Adult patients, hospitalized with confirmed COVID-19 were recruited for the study. Oral/oropharyngeal baseline SARS-CoV-2 samples were collected and analyzed by Real-Time-PCR. Subsequently, patients were instructed to rinse with 1 % hydrogen peroxide (H2O2), 0.12 % chlorhexidine (CHX), 1 % povidone‑iodine (PVP-I) or Sodium Chloride 0.9 % (placebo). Viral loads were measured right after (T1), and at 45 min (T2) from the rinse. RESULTS In the PVP-I 1 % group, 5/8 (62.5 %) patients at T1, and 3/8 (37.5 %) patients at T2, SARS-CoV-2 was not detectable in the swab specimens. In the H2O2 1 % group, 2/11 (18.2 %) patients at T1, and 2/11 (18.2 %) other patients at T2 showed no SARS-CoV-2 loads. One (12.5 %) patient in the CHX 0.12 % group showed SARS-CoV-2 negativity at T2. One (9.1 %) patient at T1, and another (9.1 %) patient at T2 showed no SARS-CoV-2 loads in the placebo group. CONCLUSIONS Oral SARS-CoV-2 loads were reduced at T1 in the PVP-I 1 % and H2O2 1 % groups. CLINICAL RELEVANCE PVP-I 1 % was the most effective rinse especially in patients with low viral copy numbers at baseline.
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Beyond Bone: Infectious Diseases and Immunity in Parathyroid Disorders.
Hasenmajer, V, Puliani, G, Minnetti, M, Sbardella, E, Mastroianni, CM, D'Ettorre, G, Isidori, AM, Gianfrilli, D
Advances in experimental medicine and biology. 2022;:17-32
Abstract
Parathyroid disorders are characterized by alterations in calcium and phosphate homeostasis due to inappropriately high or low levels of parathyroid hormone (PTH). Despite PTH receptor type 1 has been described in almost all immune lineages and calcium signalling has been confirmed as a crucial mediator for immune response, in vitro studies on the physiological interactions between PTH and immunity are conflicting and not representative of the clinical scenarios seen in patients with parathyroid disorders. Infectious diseases are among the main causes of increased morbidity and mortality in patients with secondary hyperparathyroidism and chronic kidney disease. More, immune alterations have been described in primary hyperparathyroidism. Recent studies have unveiled an increased risk of infections also in hypoparathyroidism, suggesting that not only calcium, but also physiological levels of PTH may be necessary for a proper immune response. Finally, calcium/phosphate imbalance could affect negatively the prognosis of infectious diseases. Our review aimed to collect available data on infectious disease prevalence in patients with parathyroid disorders and new evidence on the role of PTH and calcium in determining the increased risk of infections observed in these patients.
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Neuro-Axonal Damage and Alteration of Blood-Brain Barrier Integrity in COVID-19 Patients.
Zingaropoli, MA, Iannetta, M, Piermatteo, L, Pasculli, P, Latronico, T, Mazzuti, L, Campogiani, L, Duca, L, Ferraguti, G, De Michele, M, et al
Cells. 2022;(16)
Abstract
Neurofilament light chain (NfL) is a specific biomarker of neuro-axonal damage. Matrix metalloproteinases (MMPs) are zinc-dependent enzymes involved in blood-brain barrier (BBB) integrity. We explored neuro-axonal damage, alteration of BBB integrity and SARS-CoV-2 RNA presence in COVID-19 patients with severe neurological symptoms (neuro-COVID) as well as neuro-axonal damage in COVID-19 patients without severe neurological symptoms according to disease severity and after recovery, comparing the obtained findings with healthy donors (HD). Overall, COVID-19 patients (n = 55) showed higher plasma NfL levels compared to HD (n = 31) (p < 0.0001), especially those who developed ARDS (n = 28) (p = 0.0005). After recovery, plasma NfL levels were still higher in ARDS patients compared to HD (p = 0.0037). In neuro-COVID patients (n = 12), higher CSF and plasma NfL, and CSF MMP-2 levels in ARDS than non-ARDS group were observed (p = 0.0357, p = 0.0346 and p = 0.0303, respectively). SARS-CoV-2 RNA was detected in four CSF and two plasma samples. SARS-CoV-2 RNA detection was not associated to increased CSF NfL and MMP levels. During COVID-19, ARDS could be associated to CNS damage and alteration of BBB integrity in the absence of SARS-CoV-2 RNA detection in CSF or blood. CNS damage was still detectable after discharge in blood of COVID-19 patients who developed ARDS during hospitalization.
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Targeting Microbiome: An Alternative Strategy for Fighting SARS-CoV-2 Infection.
Spagnolello, O, Pinacchio, C, Santinelli, L, Vassalini, P, Innocenti, GP, De Girolamo, G, Fabris, S, Giovanetti, M, Angeletti, S, Russo, A, et al
Chemotherapy. 2021;(1-2):24-32
Abstract
Respiratory and gastrointestinal symptoms are the predominant clinical manifestations of the coronavirus disease 2019 (COVID-19). Infecting intestinal epithelial cells, the severe acute respiratory syndrome coronavirus-2 may impact on host's microbiota and gut inflammation. It is well established that an imbalanced intestinal microbiome can affect pulmonary function, modulating the host immune response ("gut-lung axis"). While effective vaccines and targeted drugs are being tested, alternative pathophysiology-based options to prevent and treat COVID-19 infection must be considered on top of the limited evidence-based therapy currently available. Addressing intestinal dysbiosis with a probiotic supplement may, therefore, be a sensible option to be evaluated, in addition to current best available medical treatments. Herein, we summed up pathophysiologic assumptions and current evidence regarding bacteriotherapy administration in preventing and treating COVID-19 pneumonia.
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Key mutations in the C-terminus of the HBV surface glycoprotein correlate with lower HBsAg levels in vivo, hinder HBsAg secretion in vitro and reduce HBsAg structural stability in the setting of HBeAg-negative chronic HBV genotype-D infection.
Salpini, R, Battisti, A, Piermatteo, L, Carioti, L, Anastasiou, OE, Gill, US, Di Carlo, D, Colagrossi, L, Duca, L, Bertoli, A, et al
Emerging microbes & infections. 2020;(1):928-939
Abstract
Increasing evidences suggest that HBsAg-production varies across HBV-genotypes. HBsAg C-terminus plays a crucial role for HBsAg-secretion. Here, we evaluate HBsAg-levels in different HBV-genotypes in HBeAg-negative chronic infection, the correlation of specific mutations in HBsAg C-terminus with HBsAg-levels in-vivo, their impact on HBsAg-secretion in-vitro and on structural stability in-silico.HBsAg-levels were investigated in 323 drug-naïve HBeAg-negative patients chronically infected with HBV genotype-D(N = 228), -A(N = 65) and -E(N = 30). Genotype-D was characterized by HBsAg-levels lower than genotype-A and -E (3.3[2.7-3.8]IU/ml; 3.8[3.5-4.2]IU/ml and 3.9[3.7-4.2]IU/ml, P < 0.001). Results confirmed by multivariable analysis correcting for patients'demographics, HBV-DNA, ALT and infection-status.In genotype-D, specific C-terminus mutations (V190A-S204N-Y206C-Y206F-S210N) significantly correlate with HBsAg<1000IU/ml(P-value from <0.001 to 0.04). These mutations lie in divergent pathways involving other HBsAg C-terminus mutations: V190A + F220L (Phi = 0.41, P = 0.003), S204N + L205P (Phi = 0.36, P = 0.005), Y206F + S210R (Phi = 0.47, P < 0.001) and S210N + F220L (Phi = 0.40, P = 0.006). Notably, patients with these mutational pairs present HBsAg-levels 1log lower than patients without them(P-value from 0.003 to 0.02). In-vitro, the above-mentioned mutational pairs determined a significant decrease in HBsAg secretion-efficiency compared to wt(P-value from <0.001 to 0.02). Structurally, these mutational pairs reduced HBsAg C-terminus stability and determined a rearrangement of this domain.In conclusion, HBsAg-levels in genotype-D are significantly lower than in genotype-A and -E in HBeAg-negative patients. In genotype-D, specific mutational clusters in HBsAg C-terminus correlate with lower HBsAg-levels in-vivo, hamper HBsAg-release in-vitro and affect its structural stability, supporting their detrimental role on HBsAg-secretion. In this light, genotypic-testing can be a valuable tool to optimize the clinical interpretation of HBsAg in genotype-D and to provide information on HBV-pathogenicity and disease-progression.
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Diet Supplementation, Probiotics, and Nutraceuticals in SARS-CoV-2 Infection: A Scoping Review.
Infusino, F, Marazzato, M, Mancone, M, Fedele, F, Mastroianni, CM, Severino, P, Ceccarelli, G, Santinelli, L, Cavarretta, E, Marullo, AGM, et al
Nutrients. 2020;(6)
Abstract
The severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2) global pandemic is a devastating event that is causing thousands of victims every day around the world. One of the main reasons of the great impact of coronavirus disease 2019 (COVID-19) on society is its unexpected spread, which has not allowed an adequate preparation. The scientific community is fighting against time for the production of a vaccine, but it is difficult to place a safe and effective product on the market as fast as the virus is spreading. Similarly, for drugs that can directly interfere with viral pathways, their production times are long, despite the great efforts made. For these reasons, we analyzed the possible role of non-pharmacological substances such as supplements, probiotics, and nutraceuticals in reducing the risk of Sars-CoV-2 infection or mitigating the symptoms of COVID-19. These substances could have numerous advantages in the current circumstances, are generally easily available, and have negligible side effects if administered at the already used and tested dosages. Large scientific evidence supports the benefits that some bacterial and molecular products may exert on the immune response to respiratory viruses. These could also have a regulatory role in systemic inflammation or endothelial damage, which are two crucial aspects of COVID-19. However, there are no specific data available, and rigorous clinical trials should be conducted to confirm the putative benefits of diet supplementation, probiotics, and nutraceuticals in the current pandemic.
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Real word outcomes associated with use of raltegravir in older people living with HIV: results from the 60 months follow-up of the RAL-age cohort.
Santinelli, L, Ceccarelli, G, Borrazzo, C, Celani, L, Pavone, P, Innocenti, GP, Spagnolello, O, Fimiani, C, Ceci, F, Di Sora, F, et al
Expert review of anti-infective therapy. 2020;(5):485-492
Abstract
Objective: In people living with HIV (PLWH), antiretroviral treatments have increased the median life expectancy. Raltegravir (RAL) represents a long-term safe regimen used both in the first-line antiretroviral treatments and in the optimization strategies. Aim of the study was to evaluate the real-life efficacy, tolerability, and safety of the long-term RAL use in a multicenter cohort of elderly PLWH.Methods: A 60-month follow-up observational study was carried out in the RAL-AGE Cohort including aged PLWH (≥60 years old) treated with RAL-based regimens (n = 96). The control group was a cohort of PLWH aged less than 60 years (n = 50).Results: RAL treated aged HIV population experiences an increase of CD4+ cells and a stable control of viral load at 60 months of follow-up. A significant improvement in lipid metabolism profile, a decrease of platelet count and a reduction in cardiovascular risk levels were observed in the older population. Immune activation markers expressed on CD4+ T cells decreased compared to baseline, but this difference was greater in the control group.Conclusion: A 60-month treatment with RAL-containing regimens is safe and highly effective in the older PLWH and these data give new insights on the elderly population.Clinical trial registration: NCT02765776 and NCT03579485.
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Genetic divergence of HIV-1 B subtype in Italy over the years 2003-2016 and impact on CTL escape prevalence.
Alteri, C, Fabeni, L, Scutari, R, Berno, G, Di Carlo, D, Gori, C, Bertoli, A, Vergori, A, Mastrorosa, I, Bellagamba, R, et al
Scientific reports. 2018;(1):15739
Abstract
HIV-1 is characterized by high genetic variability, with implications for spread, and immune-escape selection. Here, the genetic modification of HIV-1 B subtype over time was evaluated on 3,328 pol and 1,152 V3 sequences belonging to B subtype and collected from individuals diagnosed in Italy between 2003 and 2016. Sequences were analyzed for genetic-distance from consensus-B (Tajima-Nei), non-synonymous and synonymous rates (dN and dS), CTL escapes, and intra-host evolution over four time-spans (2003-2006, 2007-2009, 2010-2012, 2013-2016). Genetic-distance increased over time for both pol and V3 sequences (P < 0.0001 and 0.0003). Similar results were obtained for dN and dS. Entropy-value significantly increased at 16 pol and two V3 amino acid positions. Seven of them were CTL escape positions (protease: 71; reverse-transcriptase: 35, 162, 177, 202, 207, 211). Sequences with ≥3 CTL escapes increased from 36.1% in 2003-2006 to 54.0% in 2013-2016 (P < 0.0001), and showed better intra-host adaptation than those containing ≤2 CTL escapes (intra-host evolution: 3.0 × 10-3 [2.9 × 10-3-3.1 × 10-3] vs. 4.3 × 10-3 [4.0 × 10-3-5.0 × 10-3], P[LRT] < 0.0001[21.09]). These data provide evidence of still ongoing modifications, involving CTL escape mutations, in circulating HIV-1 B subtype in Italy. These modifications might affect the process of HIV-1 adaptation to the host, as suggested by the slow intra-host evolution characterizing viruses with a high number of CTL escapes.
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10.
Impact of switching from lopinavir/ritonavir to boosted and un-boosted atazanavir on glucose metabolism: the ATAzanavir & GLUcose metabolism (ATAGLU) study.
d'Ettorre, G, Ceccarelli, G, Zaccarelli, M, Ascoli-Bartoli, T, Bianchi, L, Bellelli, V, De Girolamo, G, Serafino, S, Giustini, N, Mastroianni, CM, et al
International journal of STD & AIDS. 2016;(8):638-43
Abstract
Previous studies have reported that protease inhibitors (PIs) can contribute to glycaemic alterations. However, there are few trials examining the direct effect of a single PI. The objective of the study was to evaluate the modifications of glucose and lipid profiles after a switch from lopinavir/ritonavir (LPV/r) to atazanavir, used as ritonavir-boosted (ATV/r) or un-boosted. We conducted a retrospective observational cohort study on the effect of ATV/(r) on glycaemic metabolism (ATAGLU) in patients with undetectable levels of HIV-RNA who switched from LPV/r. In total, 235 patients treated for 48 weeks with LPV/r plus two nucleoside reverse transcriptase inhibitors (NRTIs) and with undetectable HIV-RNA were included: 134 continued LPV/r after the initial 48 weeks and 101 switched to ATV(/r) (18.3% to ATV; 24.7% to ATV/r). A significant decrease in mean glucose level and insulin resistance was observed in patients who switched to ATV(/r). The mean cholesterol triglyceride levels increased in the LPV/r group and decreased among the patients who switched. A significant increase of CD4 T cells with undetectable levels of HIV-RNA was observed in all groups. The long-term results obtained in this real-life study suggest that patients who have achieved initial suppression on a regimen including LPV/r + two NRTIs can switch to ATV/(r) + two NRTIs with an improvement in lipid and glycaemic metabolism.