On January 9th, 2020, the “World Health Organization” (WHO) declared the identification, by Chinese Health authorities, of a novel coronavirus, further classified as SARS-CoV-2 responsible of a ...diseases (COVID-19) ranging from asymptomatic cases to severe respiratory involvement. On March 9th, 2020, WHO declared COVID-19 a global pandemic. Italy is the second most affected country by COVID-19 infection after China. The “L. Spallanzani” National Institute for the Infectious Diseases, IRCCS has been the first Italian hospital to admit and manage patients affected by COVID-19. Hereby, we show our recommendations for the management of COVID-19 patients, based on very limited clinical evidences; these recomendations should be considered as expert opinions, which may be modified according to newly produced literature data. *for the INMI COVID-19 Treatment Group – ICOTREG Abdeddaim A, Agrati C, Albarello F, Antinori A, Ascoli Bartoli T, Baldini F, Bellagamba R, Bevilacqua N, Bibas M, Biava G, Boumis E, Busso D, Camici M, Capobianchi MR, Capone A, Caravella I, Cataldo A, Cerilli S, Chinello G, Cicalini S, Corpolongo A, Cristofaro M, D’Abramo A, Dantimi C, De Angelis G, De Palo MG, D’Offizi G, De Zottis F, Di Lorenzo R, Di Stefano F, Fusetti M, Galati V, Gagliardini R, Garotto G, Gebremeskel Tekle Saba, Giancola ML, Giansante F, Girardi E, Goletti D, Granata G, Greci MC, Grilli E, Grisetti S, Gualano G, Iacomi F, Iannicelli G, Ippolito G, Lepore L, Libertone R, Lionetti R, Liuzzi G, Loiacono L, Macchione M, Marchioni L, Mariano A, Marini MC, Maritti M, Mastrobattista A, Mazzotta V, Mencarini P, Migliorisi-Ramazzini P, Mondi A, Montalbano M, Mosti S, Murachelli S, Musso M, Nicastri E, Noto P, Oliva A, Palazzolo C, Palmieri F, Pareo C, Petrone A, Pianura E, Pinnetti C, Pontarelli A, Puro V, Rianda A, Rosati S, Sampaolesi A, Santagata C, Scarcia D’Aprano S, Scarabello A, Schininà V, Scorzolini L, Stazi GV, Taibi C, Taglietti F, Tonnarini R, Topino S, Vergori A, Vincenzi L, Visco-Comandini U, Vittozzi P, Zaccarelli M, Zaccaro G.
•A mortality gap remains for late presenters, particularly, AIDS presenters, in recent years.•Increased mortality for AIDS presenters was driven by AIDS events in the first year.•Two-year immune ...recovery is the key for long-term mortality in short-term AIDS survivors.•Late and AIDS presenters still show a higher risk treatment failure.•Urgent public health strategies are needed for emerging unknown HIV infections.
Limited data are available on the long-term outcomes in recent years for late HIV diagnosis (LD).
All subjects with HIV enrolled in the ICONA cohort in 2009-2022 who started antiretroviral treatment (ART) within 4 months from diagnosis were included and divided into: (i) pre-ART CD4 count ≥350/mm3 without AIDS (non-LD), (ii) pre-ART CD4 count <350/mm3 without AIDS (LD asymptomatic), and (iii) with AIDS events pre-ART (LD-AIDS). The estimated probability and independent risk for mortality (all-cause and cause-specific) and treatment failure were evaluated.
Of 6813 participants (2448 non-LD, 3198 LD asymptomatic, and 1167 LD-AIDS), 161 (2.4%) died after ART initiation. At survival analysis, a higher probability of all-cause mortality has been identified for LD than non-LD (P <0.001) and within the former, for LD-AIDS over LD asymptomatic (P <0.001). After adjusting for confounders, LD showed a higher risk of all-cause mortality (vs non-LD adjusted hazard ratio (aHR) 5.51, P <0.001) and, in particular, being an AIDS presenter predicted a greater risk of all-cause (aHR = 4.42, P <0.001), AIDS-related (adjusted subhazard ratio aSHR = 16.86, P <0.001), and non-AIDS–related mortality (aSHR = 1.74, P = 0.022) than the rest of the late presenters. Among the short-term survivors in the LD-AIDS group, the long-term mortality was mediated by the lack of immune recovery at 2 years. Finally, LD compared with non-LD and, particularly, among the former, LD-AIDS over LD asymptomatic showed a greater risk of treatment failure.
In recent years, LD subjects, particularly, AIDS presenters, remained at a higher risk of poorer outcomes. Public health strategies for early HIV diagnosis are urgently needed to constrain the mortality gap.
Abstract Since spring 2022, the global epidemiology of the monkeypox virus (MPXV) has changed. The unprecedented increase of human clade II MPXV cases worldwide heightened concerns about this ...emerging zoonotic disease. We analysed the positivity rates, viral loads, infectiousness, and persistence of MPXV DNA for up to 4 months in several biological samples from 89 MPXV-confirmed cases. Our data showed that viral loads and positivity rates were higher during the first two weeks of symptoms for all sample types. Amongst no-skin-samples, respiratory specimens showed higher MPXV DNA levels and median time until viral clearance, suggesting their usefulness in supporting MPXV diagnosis, investigating asymptomatic patients, and monitoring viral shedding. Infectious virus was cultured from respiratory samples, semen, and stools, with high viral loads and collected within the first 10 days. Notably, only one saliva and one semen were found positive for viral DNA after 71 and 31 days from symptoms, respectively. The focus on bloodstream samples showed the best testing sensitivity in plasma, reporting the overall highest MPXV DNA detection rate and viral loads during the 3-week follow-up as compared to serum and whole-blood. The data here presented can be useful for MPXV diagnostics and a better understanding of the potential alternative routes of its onward transmission.
We report the follow-up laboratory investigation of three MPXV cases infected in May-June 2022 from diagnosis to disease resolution, monitoring viral shedding in different body fluids and antibody ...kinetics. Out of 138 non-lesion samples, viral DNA was found in 92.3% saliva, 85.7% semen, 86.2% oropharyngeal swabs, 51.7% plasma, 46.1% stool, and 9.5% urine samples. Viral load quantified by digital PCR widely varied, but tend to be higher in oropharyngeal swabs, saliva, and stool. Replication competent virus was recovered from four out of seventeen samples, including 1 saliva, 1 oropharyngeal swabs, 1 semen, and 1 stool. The analysis of the antibody kinetics revealed that IgM, IgA, and IgG antibodies were detected within two weeks post-symptoms onset for all three patients, with IgG detected early on at day 4-8 and IgM and IgA showing lower titers along the time frame of the study. Antibody levels increased during the second week of illness with IgG reaching high titers.
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•Follow-up study on three patients with MPXV infected during the 2022 global outbreak•Frequent detection of MPXV DNA in saliva, oro-pharynx, and semen•Infectious MPXV cultured from oral swab, saliva, stool, and semen samples•Early seroconversion of specific IgM, IgA, and IgG in MPXV infection
Immunology; Virology
The WHO advised that the impact of COVID-19 pandemic on TB services was estimated to be dramatic due to the disruption of TB services.
A retrospective data collection and evaluation was conducted to ...include all the patients hospitalized for TB at INMI from 9 March to 31 August 2020 (lockdown period and three months thereafter). For the purpose of the study, data from patients hospitalized in the same period of 2019 were also collected.
In the period of March-August 2019, 201 patients were hospitalized with a diagnosis of TB, while in the same period of 2020, only 115 patients, with a case reduction of 43%. Patients with weight loss, acute respiratory failure, concurrent extrapulmonary TB, and higher Timika radiographic scores were significantly more frequently hospitalized during 2020 vs. 2019. The median patient delay was 75 days (IQR: 40-100) in 2020 compared to 30 days (IQR: 10-60) in 2019 (
< 0.01). Diagnostic delays in 2020 remain significant in the multiple logistic model (AOR = 6.93, 95%CI: 3.9-12.3).
Our experience suggests that COVID-19 pandemic had an impact on TB patient care in terms of higher diagnostic delay, reduction in hospitalization, and a greater severity of clinical presentations.
Human and viral microRNAs (miRNAs) are involved in the regulation of gene transcription, and the establishment of their profiles in acute (AHI) and chronic (CHI) HIV infections may shed light on the ...pathogenetic events related to different phases of HIV disease. Next-generation sequencing (NGS) of miRNA libraries was performed, and the reads were used to analyze miRNA differential expression in the plasma with AHI and CHI. Functional analysis was then undertaken to investigate the biological processes characterizing the two phases of HIV infection. Except for hsa-miR-122-5p, which was found in 3.39% AHI vs. 0.18% CHI, the most represented human miRNAs were similarly represented in AHI and CHI. However, when considering the overall detected miRNAs in AHI and CHI, 15 displayed differential expression (FDR
< 0.05). Functional analysis identified 163 target mRNAs involved in promoting angiogenesis activation in AHI versus CHI through the action of hsa-miR10b-5p, hsa-miR1290, hsa-miR1-3p, and hsa-miR296-5p. The viral miRNAs detected, all belonging to herpesviruses, accounted for only 0.014% of total reads. The present data suggest that AHI patients exhibit strong innate immune activation through the upregulation of hsa-miR-122-5p and early activation of angiogenesis. More specific investigations are needed to study the role of viral miRNAs in HIV pathogenesis.
•Risk of in-hospital COVID-19 mortality in people living with HIV (PLWH) and the general population was assessed.•PLWH <65 years with clusters of differentiation (CD)4 ≤350 cells/mm3 are at higher ...risk of worse COVID-19 outcomes.•This risk is further increased in PLWH <65 years with CD4 count ≤200 cells/mm3.•The evidence was insufficient for PLWH aged ≥65 years.•PLWH with low CD4 counts should be prioritized for preventive interventions.
We aimed to study whether people living with HIV (PLWH) are at higher risk of in-hospital COVID-19 mortality compared to the general population (GenPop).
This was a retrospective study in 19 Italian centers (February 2020 to November 2022) including hospitalized PLWH and GenPop with SARS-CoV-2 infection. The main outcome was in-hospital mortality. Competing risk analyses by Fine-Gray regression model were used to estimate the association between in-hospital mortality and HIV status/age.
A total of 7399 patients with COVID-19 were included, 239 (3.2%) PLWH, and 7160 (96.8%) GenPop. By day 40, in-hospital death occurred in 1283/7160 (17.9%) among GenPop and 34/239 (14.2%) among PLWH. After adjusting for potential confounders, compared to GenPop <65 years, a significantly higher risk of death was observed for GenPop ≥65 (adjusted subdistribution hazard ratio aSHR 1.79 95% CI 1.39-2.31), PLWH ≥65 (aSHR 2.16 95% CI 1.15-4.04), PLWH <65 with CD4 ≤200 (aSHR 9.69 95% CI 5.50-17.07) and PLWH <65 with CD4 201-350 (aSHR 4.37 95% CI 1.79-10.63), whereas no evidence for a difference for PLWH <65 with CD4 >350 (aSHR 1.11 95% CI 0.41-2.99).
In PLWH aged <65 years a CD4 ≤350 rather than HIV itself seems the driver for the observed higher risk of in-hospital mortality. We cannot however rule out that HIV infection per se is the risk factor in those aged ≥65 years.
•Monkeypox (Mpox) virus has been recently recognized as a cause of proctitis in men who have sex with men.•Mpox proctitis may lead to hospitalization for severe anorectal pain.•Sigmoidoscopy showed ...inflamed and friable mucosa, ulcerations, and granular areas.•Rectal biopsies revealed for the first time progressive transformation of germinal centers associated with Mpox proctitis.•Careful diagnostic workouts and follow-ups are indicated in Mpox proctitis.
In the recent 2022 monkeypox (Mpox) global outbreak, cases have been mostly documented among men who have sex with men. Proctitis was reported in almost 14% of cases. In this study, four Mpox-confirmed cases requiring hospitalizations for severe proctitis were characterized by clinical, virological, microbiological, endoscopic, and histological aspects. The study showed the presence of lymphofollicular lesions associated with Mpox virus rectal infection for the first time.
Torquetenovirus (TTV) is the most abundant component of the human blood virome and its replication is controlled by a functioning immune system. In this study, TTV replication was evaluated in 21 ...people with acute HIV infection (AHI) and immune reconstitution following antiretroviral therapy (ART). PBMC-associated TTV and HIV-1 DNA, as well as plasma HIV-1 RNA, were measured by real-time PCR. CD4 and CD8 differentiation, activation, exhaustion, and senescence phenotypes were analyzed by flow cytometry. Thirteen healthy donors (HD) and twenty-eight chronically infected HIV individuals (CHI), late presenters at diagnosis, were included as control groups. TTV replication in AHI seems to be controlled by the immune system being higher than in HD and lower than in CHI. During ART, a transient increase in TTV DNA levels was associated with a significant perturbation of activation and senescence markers on CD8 T cells. TTV loads were positively correlated with the expansion of CD8 effector memory and CD57+ cells. Our results shed light on the kinetics of TTV replication in the context of HIV acute infection and confirm that the virus replication is strongly regulated by the modulation of the immune system.
Myeloid-derived suppressor cells (MDSC) are expanded during HIV-1 infection and correlated with disease progression. MDSC expand in the early phase of primary infection depending on TRAIL level. In ...this study we evaluated the effect of ART on the frequency of MDSC in patients with primary HIV infection (PHI), and their impact on CD4 T cell reconstitution. MDSC frequency was evaluated by flow-cytometry in 60 PHI patients at 12, 24 and 48 weeks after ART initiation. Cytokine plasma levels were evaluated by Luminex technology at the same time points. The capacity of MDSC to modulate hematopoietic early progenitor cells' expansion was evaluated using the OP9/Dl1
system. As previously described, polymorphonuclear-MDSC (PMN-MDSC) frequency was higher in PHI compared to healthy donors. Interestingly, 48 weeks of successful ART failed to normalize the PMN-MDSC frequency. Moreover, PMN-MDSC frequency was not correlated with residual viral load, suggesting that the persistence of PMN-MDSC was not due to residual viral replication. Interestingly, patients with low PMN-MDSC frequency (<6%) at T0 had a higher HIV DNA at the same time point than individuals with high PMN-MDSC frequency (>6%). We also found an inverse correlation between PMN-MDSC frequency and CD4-T cell count at 48 weeks post-ART, which was confirmed by multivariate analysis adjusting for age and CD4 T cell number at baseline. These data suggest that the persistence of PMN-MDSC may impact CD4 T cell recovery. Indeed,
PMN-MDSC impaired the expansion of CD34+CD38- hematopoietic early progenitors. Further, a balance between TRAIL and GM-CSF may be necessary to maintain a low MDSC level. In conclusion, early ART initiation was not able to normalize PMN-MDSC frequency that might impact the CD4 T cell recovery. These data open new questions regarding the clinical impact of MDSC persistence in HIV+ patients, in particular on non-AIDS related diseases.
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