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2.
Mediterr J Hematol Infect Dis ; 14(1): e2022050, 2022.
Article in English | MEDLINE | ID: covidwho-1988182

ABSTRACT

Background and Objective: In patients with mild-to-moderate COVID-19 and at high risk of progression, casirivimab/imdevimab and bamlanivimab/etesivimab were utilized in Umbria from late April to November 2021. This period was characterized by an initial prevalence of alpha (B1.1.1.7) and its progressive substitution with the delta variant (B1.617.2). Many delta infections occurred in patients already recently vaccinated.Our study aimed to observe the clinical outcome of patients treated with mAbs associations in a subgroup in which viral isolation was obtained, the pre and post-infusion neutralizing antibody activity against their viral isolate. Methods: In this retrospective observational study, the clinical outcome before and 30 days after infusion, the baseline neutralizing activity of sera against their viral isolate, and the titers of neutralizing antibodies (NAbTs) one-hour post-infusion relative to the type of mAbs associations were evaluated. Results: Better efficacy of the mAbs combinations relative to monotherapy regarding global hospitalization (p = 0.021) and 30 days symptoms (p<0.001) were seen. Infections after vaccination mostly occurred in the absence of neutralizing antibody titers (NAbT). SARS-CoV-2 delta variants were isolated within 2-4 months from vaccinations without NAbTs, or in the presence of high specific neutralizing activity after 5-6 months. NAbTs were higher after casirivimab/imdevimab infusion (p=0.001). Conclusions: Alpha infections occurred prevalently in unvaccinated patients or after 5-6 months, while delta infections prevailed in vaccinated ones. A poor neutralizing activity in most of these patients was seen. A higher NAbT after infusion of casirivimab/imdevimab was observed.

3.
Curr HIV Res ; 20(4): 296-300, 2022.
Article in English | MEDLINE | ID: covidwho-1974465

ABSTRACT

BACKGROUND: Vaccines have had a fundamental impact in containing the ongoing Coronavirus Disease 2019 (COVID-19) pandemic. However, there are few efficacy data relating to frail patients, including the HIV-positive patient. OBJECTIVE: This study evaluated the Severe Acute Respiratory Syndrome Coronavirus 2 (SARSCoV- 2) serum neutralization in People Living with HIV (PLWH) compared to a cohort of healthy volunteers both vaccinated with BNT162b2. METHODS: A serum sample was then withdrawn 14-21 days after the second dose of the vaccine and a serum neutralization assay was performed on Vero E6 cells. The experiments were performed using two strains of SARS-CoV-2 as 20A.EU1 and B.1.617.2. RESULTS: PLWH on Antiretroviral Therapy (ART) showed a vaccine response comparable to the healthy subjects. No correlation between CD4 count or CD4/CD8 and neutralizing antibodies (NTAbs) has been found. No differences in NT-Abs between patients with CD4 nadir above or under 200 cells/µl have been found. In both cohorts, vaccine-elicited serum better neutralized 20A.EU1 than B.1.617.2 strain. CONCLUSION: PLWH in ART and with good immuno-virological recovery showed a vaccine response comparable to that of healthy subjects and regardless of their immunological status at HIV infection diagnosis. However, larger studies are needed to confirm our results and to evaluate the vaccine response even in patients with low CD4 counts.


Subject(s)
COVID-19 , HIV Infections , Viral Vaccines , Humans , SARS-CoV-2 , Antibodies, Viral , BNT162 Vaccine , HIV Infections/drug therapy , Antibodies, Neutralizing
4.
Microorganisms ; 10(7)2022 Jul 21.
Article in English | MEDLINE | ID: covidwho-1957393

ABSTRACT

INTRODUCTION: The development of effective vaccines has partially mitigated the trend of the SARS-CoV-2 pandemic; however, the need for orally administered antiviral drugs persists. This study aims to investigate the activity of molnupiravir in combination with nirmatrelvir or GC376 on SARS-CoV-2 to verify the synergistic effect. METHODS: The SARS-CoV-2 strains 20A.EU, BA.1 and BA.2 were used to infect Vero E6 in presence of antiviral compounds alone or in combinations using five two-fold serial dilution of compound concentrations ≤EC90. After 48 and 72 h post-infection, viability was performed using MTT reduction assay. Supernatants were collected for plaque-assay titration. All experiments were performed in triplicate, each being repeated at least three times. The synergistic score was calculated using Synergy Finder version 2. RESULTS: All compounds reached micromolar EC90. Molnupiravir and GC376 showed a synergistic activity at 48 h with an HSA score of 19.33 (p < 0.0001) and an additive activity at 72 h with an HSA score of 8.61 (p < 0.0001). Molnupiravir and nirmatrelvir showed a synergistic activity both at 48 h and 72 h with an HSA score of 14.2 (p = 0.01) and 13.08 (p < 0.0001), respectively. CONCLUSION: Molnupiravir associated with one of the two protease-inhibitors nirmatrelvir and GC376 showed good additive-synergic activity in vitro.

5.
J Infect ; 83(4): 467-472, 2021 10.
Article in English | MEDLINE | ID: covidwho-1328766

ABSTRACT

OBJECTIVES: The emergence of new variants of concern (VOCs) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) around the world significantly complicated the exit from Coronavirus disease 2019 (COVID-19) pandemic. The aim of this study was to evaluate the serum neutralizing activity of three cohorts. METHODS: BNT162b2-elicited serum (N = 103), candidates as hyper-immune plasma donors (N = 90) and patients infected with the SARS-CoV-2 P1 variant (N = 22) were enrolled. Three strains of SARS-CoV-2 have been tested: 20A.EU1, B.1.1.7 (alpha) and P.1 (gamma). Neutralizing antibodies (NT-Abs) titers against SARS-CoV-2 were evaluated. RESULTS: B.1.1.7 and P.1 are less efficiently neutralized by convalescent wild-type infected serums if compared to 20A.EU1 strain (mean titer 1.6 and 6.7-fold lower respectively). BNT162b2 vaccine-elicited human sera show an equivalent neutralization potency on the B.1.1.7 but it is significantly lower for the P.1 variant (mean titer 3.3-fold lower). Convalescent P.1 patients are less protected from other SARS-CoV-2 strains with an important reduction of neutralizing antibodies against 20A.EU1 and B.1.1.7, about 12.2 and 10.9-fold, respectively. CONCLUSIONS: BNT162b2 vaccine confers immunity against all the tested VOCs, while previous SARS-CoV-2 infection may be less protective.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , COVID-19 Vaccines , Humans
6.
Redox Biol ; 45: 102041, 2021 09.
Article in English | MEDLINE | ID: covidwho-1263367

ABSTRACT

Viral infections sustain their replication cycle promoting a pro-oxidant environment in the host cell. In this context, specific alterations of the levels and homeostatic function of the tripeptide glutathione have been reported to play a causal role in the pro-oxidant and cytopathic effects (CPE) of the virus. In this study, these aspects were investigated for the first time in SARS-CoV2-infected Vero E6 cells, a reliable and well-characterized in vitro model of this infection. SARS-CoV2 markedly decreased the levels of cellular thiols, essentially lowering the reduced form of glutathione (GSH). Such an important defect occurred early in the CPE process (in the first 24 hpi). Thiol analysis in N-acetyl-Cys (NAC)-treated cells and membrane transporter expression data demonstrated that both a lowered uptake of the GSH biosynthesis precursor Cys and an increased efflux of cellular thiols, could play a role in this context. Increased levels of oxidized glutathione (GSSG) and protein glutathionylation were also observed along with upregulation of the ER stress marker PERK. The antiviral drugs Remdesivir (Rem) and Nelfinavir (Nel) influenced these changes at different levels, essentially confirming the importance or blocking viral replication to prevent GSH depletion in the host cell. Accordingly, Nel, the most potent antiviral in our in vitro study, produced a timely activation of Nrf2 transcription factor and a GSH enhancing response that synergized with NAC to restore GSH levels in the infected cells. Despite poor in vitro antiviral potency and GSH enhancing function, Rem treatment was found to prevent the SARS-CoV2-induced glutathionylation of cellular proteins. In conclusion, SARS-CoV2 infection impairs the metabolism of cellular glutathione. NAC and the antiviral Nel can prevent such defect in vitro.


Subject(s)
COVID-19 , Glutathione , Glutathione/metabolism , Glutathione Disulfide/metabolism , Humans , Oxidation-Reduction , RNA, Viral , SARS-CoV-2
7.
Viruses ; 13(3)2021 03 05.
Article in English | MEDLINE | ID: covidwho-1129784

ABSTRACT

The aim of this study was to establish the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on inanimate surfaces such as plastic, stainless steel, and glass during UV-C irradiation which is a physical means commonly utilized in sanitization procedures. The viral inactivation rate, virus half-life, and percentage of titer reduction after UV-C irradiation were assessed. Infectivity was maintained on plastic and glass until 120 h and on stainless steel until 72 h. The virus half-life was 5.3, 4.4, and 4.2 h on plastic, stainless steel, and glass, respectively. In all cases, titer decay was >99% after drop drying. UV-C irradiation efficiently reduced virus titer (99.99%), with doses ranging from 10.25 to 23.71 mJ/cm2. Plastic and stainless steel needed higher doses to achieve target reduction. The total inactivation of SARS-CoV-2 on glass was obtained with the lower dose applied. SARS-CoV-2 survival can be long lasting on inanimate surfaces. It is worth recommending efficient disinfection protocols as a measure of prevention of viral spread. UV-C can provide rapid, efficient and sustainable sanitization procedures of different materials and surfaces. The dosages and mode of irradiation are important parameters to consider in their implementation as an important means to fight the SARS-CoV-2 pandemic.


Subject(s)
COVID-19/virology , Disinfection/methods , SARS-CoV-2/radiation effects , Virus Inactivation/radiation effects , COVID-19/prevention & control , Disinfection/instrumentation , Glass/analysis , Humans , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Stainless Steel/analysis , Ultraviolet Rays , Viral Load/radiation effects
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