Figure 2 - available via license: Creative Commons Attribution 4.0 International
Content may be subject to copyright.
Immunological responses in H−/S+ vs H+/S+ individuals. (A) Plasma cytokine/chemokine concentrations (pg/mL) in H−/S+ (white bars) and H+/S+ (black bars) patients; (B) Plasma IL6/IL10 ratio in H−/S+ and H+/S+ patients; (C) mRNA expression of genes involved in the antimicrobial immune response analyzed on unstimulated (left panel) and SARS-CoV-2 (N+S)-stimulated (right panel) PBMCs isolated from H−/S+ and H+/S+ individuals; gene expression (mean values) is shown as a color scale from white to blue/black (Heatmap). Results are indicated as mean ± SEM values and statistically significant differences (p < 0.05) are indicated; * p < 0.05, ** p < 0.01. In line with the results of the comparison between HIV-positive individuals, HIV/SARS-CoV-2 coinfection was associated with higher IL10 expression than in HIVnegative SARS-CoV-2-positive individuals.
Source publication
While the risk of SARS-CoV-2 infection and/or COVID-19 disease progression in the general population has been largely assessed, its impact on HIV-positive individuals remains unclear. We present clinical and immunological data collected in a cohort of HIV-infected young individuals during the first wave of COVID-19 pandemic. SARS-CoV-2 RNA, virus-s...
Contexts in source publication
Context 1
... widespread hyper-activation characterized H+/S+ when they were compared to H−/S+ infected individuals, as the concentration of several cytokines and chemokines was significantly upregulated in the plasma of coinfected patients (IL-8, IL-12, IL-13, IL-17, GM-and CSF, p < 0.05; IL-10, IFNγ, and VEGF, p < 0.01) (Figure 2A). These results were confirmed by gene expression analysis in basal condition (IL6, IL10, IFNG, TLR3, NLRP3, and ERAP2; p < 0.05) and upon SARS-CoV-2 specific stimulation (IL10, CD69 and ERAP2; p < 0.05) ( Figure 2C). ...
Context 2
... widespread hyper-activation characterized H+/S+ when they were compared to H−/S+ infected individuals, as the concentration of several cytokines and chemokines was significantly upregulated in the plasma of coinfected patients (IL-8, IL-12, IL-13, IL-17, GM-and CSF, p < 0.05; IL-10, IFNγ, and VEGF, p < 0.01) (Figure 2A). These results were confirmed by gene expression analysis in basal condition (IL6, IL10, IFNG, TLR3, NLRP3, and ERAP2; p < 0.05) and upon SARS-CoV-2 specific stimulation (IL10, CD69 and ERAP2; p < 0.05) ( Figure 2C). Notably, the IL-6/IL-10 ratio in plasma was significantly reduced in H+/S+ compared to H−/S+ patients (p < 0.05) ( Figure 2B). ...
Context 3
... results were confirmed by gene expression analysis in basal condition (IL6, IL10, IFNG, TLR3, NLRP3, and ERAP2; p < 0.05) and upon SARS-CoV-2 specific stimulation (IL10, CD69 and ERAP2; p < 0.05) ( Figure 2C). Notably, the IL-6/IL-10 ratio in plasma was significantly reduced in H+/S+ compared to H−/S+ patients (p < 0.05) ( Figure 2B). ...
Context 4
... widespread hyper-activation characterized H+/S+ when they were compared to H−/S+ infected individuals, as the concentration of several cytokines and chemokines was significantly upregulated in the plasma of coinfected patients (IL-8, IL-12, IL-13, IL-17, GM-and CSF, p < 0.05; IL-10, IFNγ, and VEGF, p < 0.01) (Figure 2A). These results were confirmed by gene expression analysis in basal condition (IL6, IL10, IFNG, TLR3, NLRP3, and ERAP2; p < 0.05) and upon SARS-CoV-2 specific stimulation (IL10, CD69 and ERAP2; p < 0.05) ( Figure 2C). ...
Context 5
... widespread hyper-activation characterized H+/S+ when they were compared to H−/S+ infected individuals, as the concentration of several cytokines and chemokines was significantly upregulated in the plasma of coinfected patients (IL-8, IL-12, IL-13, IL-17, GM-and CSF, p < 0.05; IL-10, IFNγ, and VEGF, p < 0.01) (Figure 2A). These results were confirmed by gene expression analysis in basal condition (IL6, IL10, IFNG, TLR3, NLRP3, and ERAP2; p < 0.05) and upon SARS-CoV-2 specific stimulation (IL10, CD69 and ERAP2; p < 0.05) ( Figure 2C). Notably, the IL-6/IL-10 ratio in plasma was significantly reduced in H+/S+ compared to H−/S+ patients (p < 0.05) ( Figure 2B). ...
Context 6
... results were confirmed by gene expression analysis in basal condition (IL6, IL10, IFNG, TLR3, NLRP3, and ERAP2; p < 0.05) and upon SARS-CoV-2 specific stimulation (IL10, CD69 and ERAP2; p < 0.05) ( Figure 2C). Notably, the IL-6/IL-10 ratio in plasma was significantly reduced in H+/S+ compared to H−/S+ patients (p < 0.05) ( Figure 2B). ...
Citations
... The impaired JAK/STAT signalling pathway is however restored in the presence of uninterrupted combined Antiretroviral therapy (cART) for more than 6 months [51]. Per our search, we found one study available on HIV/COVID-19 signalling pathway that investigated STAT3 but did not look at other STAT pathways [52], and therefore creates a gap that needs to be researched. Understanding the viral coinfection, immune response, and signalling pathway dynamics will help identify particulate markers that predisposes to severity of disease. ...
People living with HIV (PLWH) usually suffer from co-infections and co-morbidities including respiratory tract infections. SARS-CoV-2 has been reported to cause respiratory infections. There are uncertainties in the disease severity and immunological response among PLWH who are co-infected with COVID-19. This review outlines the current knowledge on the clinical outcomes and immunological response to SARS-CoV-2 among PLWH. Literature was searched in Google scholar, Scopus, PubMed, and Science Direct conforming with the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines from studies published from January 2020 to June 2023. A total of 81 studies from 25 countries were identified, and RT-PCR was used in confirming COVID-19 in 80 of the studies. Fifty-seven studies assessed risk factors and clinical outcomes in HIV patients co-infected with COVID-19. Thirty-nine of the studies indicated the following factors being associated with severe outcomes in HIV/SARS-CoV-2: older age, the male sex, African American race, smoking, obesity, cardiovascular diseases, low CD4 ⁺ count, high viral load, tuberculosis, high levels of inflammatory markers, chronic kidney disease, hypertension, diabetes, interruption, and delayed initiation of ART. The severe outcomes are patients’ hospitalization, admission at intensive care unit, mechanical ventilation, and death. Twenty (20) studies, however, reported no difference in clinical presentation among co-infected compared to mono-infected individuals. Immune response to SARS-CoV-2 infection was investigated in 25 studies, with some of the studies reporting high levels of inflammatory markers, T cell exhaustion and lower positive conversion rate of IgG in PLWH. There is scanty information on the cytokines that predisposes to severity among HIV/SARS-CoV-2 co-infected individuals on combined ART. More research work should be carried out to validate co-infection-related cytokines and/or immune markers to SARS-CoV-2 among PLWH.
... In line with these data, preliminary experiments mimicking a more physiological condition of the pulmonary milieu were carried out by setting up a co-culture system of PBMC-epithelial lung cells, as previously described [39]. This model was used to investigate potential associations between SNCA expression in immune cells, and epithelial cell susceptibility to SARS-CoV-2 infection. ...
... Eventually, a co-culture system of PBMCs and CaLu-3 was set up as previously described [39]. Briefly, 1.25 × 10 5 Calu-3 cells were cultured in the lower chamber of a 12 well plate with 0.4 µm pore polycarbonate membrane inserts (Costar, Corning Incorporated, Corning, NY, USA) in 1 mL medium with 10% FBS. ...
Background
Increasing evidence suggests a double-faceted role of alpha-synuclein (α-syn) following infection by a variety of viruses, including SARS-CoV-2. Although α-syn accumulation is known to contribute to cell toxicity and the development and/or exacerbation of neuropathological manifestations, it is also a key to sustaining anti-viral innate immunity. Consistently with α-syn aggregation as a hallmark of Parkinson's disease, most studies investigating the biological function of α-syn focused on neural cells, while reports on the role of α-syn in periphery are limited, especially in SARS-CoV-2 infection.
Results
Results herein obtained by real time qPCR, immunofluorescence and western blot indicate that α-syn upregulation in peripheral cells occurs as a Type-I Interferon (IFN)-related response against SARS-CoV-2 infection. Noteworthy, this effect mostly involves α-syn multimers, and the dynamic α-syn multimer:monomer ratio. Administration of excess α-syn monomers promoted SARS-CoV-2 replication along with downregulation of IFN-Stimulated Genes (ISGs) in epithelial lung cells, which was associated with reduced α-syn multimers and α-syn multimer:monomer ratio. These effects were prevented by combined administration of IFN-β, which hindered virus replication and upregulated ISGs, meanwhile increasing both α-syn multimers and α-syn multimer:monomer ratio in the absence of cell toxicity. Finally, in endothelial cells displaying abortive SARS-CoV-2 replication, α-syn multimers, and multimer:monomer ratio were not reduced following exposure to the virus and exogenous α-syn, suggesting that only productive viral infection impairs α-syn multimerization and multimer:monomer equilibrium.
Conclusions
Our study provides novel insights into the biology of α-syn, showing that its dynamic conformations are implicated in the innate immune response against SARS-CoV-2 infection in peripheral cells. In particular, our results suggest that promotion of non-toxic α-syn multimers likely occurs as a Type-I IFN-related biological response which partakes in the suppression of viral replication. Further studies are needed to replicate our findings in neuronal cells as well as animal models, and to ascertain the nature of such α-syn conformations.
... PLWH and HC were divided into two sub-groups, based on the detection or lack thereof of serum anti-SARS-CoV-2-Nucleocapsid-specific IgG, as previously described (23) or on a positive result with an antigenic test or RT-PCR test performed on a nasopharyngeal exudate sample: 1) SARS-CoV-2-vaccinated individuals with a previous history of SARS-CoV-2 infection (SIV); and 2) SARS-CoV-2-vaccinated individuals with no history of previous SARS-CoV-2 natural infection (SV). ...
Background
Data on the efficacy of three SARS-CoV-2 mRNA BNT162b2 vaccine doses and the role of previous SARS-CoV-2-infection in enhancing vaccine immunogenicity in HIV-vertically-infected people living with HIV (PLWH) are limited, as is the duration of vaccine-induced responses.
Methods
SARS-CoV-2 plasma neutralizing activity (NA) against the European (B.1), Delta (B.1.617.2) and Omicron (B.1.1.529) variants and cell-mediated immunity (CMI) were analyzed in 29 ART-treated young PLWH (mean age 27.9 years) and 30 healthy controls (HC) who received three BNT162b2 vaccine doses. Individuals were stratified based on the presence/absence of previous SARS-CoV-2 infection (infected and vaccinated -SIV-; uninfected and vaccinated -SV-). Analyses were performed before vaccination (T0), 25 days from the second dose (T1), the day the third dose was administered (T2), and 3 months after the third dose (T3).
Results
In PLWH: i) NA against all variants was higher in SIV compared to SV at T2 and was increased at T3; ii) switched-memory plasmablasts were augmented in SIV alone at T2 and T3; iii) a SARS-CoV-2 specific T cell memory was generated; iv) IFN-γ-secreting CD4+ and CD8+ T lymphocytes were boosted at T3 mainly in SV. CMI magnitude was reduced in PLWH compared to HC. Notably, after the third dose of vaccine viremia was unmodified, but CD4 T cell counts were reduced>20% in 3/29 PHLW.
Conclusion
A third dose of BNT162b2 vaccine induces strong humoral and CMI responses in young ART-treated PLWH independently from a previous SARS-CoV-2 natural infection. The lower magnitude of CMI responses should be considered when planning mRNA vaccine booster doses in PLWH.
... Also, the dynamics of the immune system in response to SARS-CoV-2 mRNA vaccine are still largely undefined in subjects bearing underlying conditions, namely patients diagnosed with malignancies, chronic infections (HIV, HCV, etc.), neurological disorders, immunological disorders, or even in the particular setting of pregnancy. Understanding the vaccine-elicited immune reactions would possibly be of paramount importance for clinical management of these cohorts and for defining appropriate public health guidelines for vulnerable populations, including dedicated fine-tuned specific vaccinal plans [80,[157][158][159][160]. ...
Messenger RNA (mRNA) vaccines belong to a new class of medications, RNA therapeutics, including both coding and non-coding RNAs. The use of mRNA as a therapy is based on the biological role of mRNA itself, namely its translation into a functional protein. The goal of mRNA vaccines is to produce a specific antigen in cells to elicit an immune response that might be prophylactic or therapeutic. The potential of mRNA as vaccine has been envisaged for years but its efficacy has been clearly demonstrated with the approval of COVID-19 vaccines in 2021. Since then, mRNA vaccines have been in the pipeline for diseases that are still untreatable. There are many advantages of mRNA vaccines over traditional vaccines, including easy and cost-effective production, high safety, and high-level antigen expression. However, the nature of mRNA itself and some technical issues pose challenges associated with the vaccines’ development and use. Here we review the immunological and pharmacological features of mRNA vaccines by discussing their pharmacokinetics, mechanisms of action, and safety, with a particular attention on the advantages and challenges related to their administration. Furthermore, we present an overview of the areas of application and the clinical trials that utilize a mRNA vaccine as a treatment.
... For example, a study performed in Italy on 85 PLWH found that they do not develop higher clinical severity or demonstrate increased risk for COVID-19. Moreover, HIV-1-and SARS-CoV-2-positive patients have higher levels of IL-10, thus suggesting an IL-10-mediated role in SARS-CoV-2 infection in PLWH [35]. Another important issue that has been poorly addressed is the prevalence of long-COVID-19 in PLWH taking cART. ...
Human immunodeficiency virus type 1 (HIV-1) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have caused two major viral outbreaks during the last century. Two major aspects of HIV-1 and SARS-CoV-2 co-infection have been extensively investigated and deserve attention. First, the impact of the co-infection on the progression of disease caused by HIV-1 or SARS-CoV-2. Second, the impact of the HIV-1 anti-retroviral treatment on SARS-CoV-2 infection. In this review, we aim to summarize and discuss the works produced since the beginning of the SARS-CoV-2 pandemic ranging from clinical studies to in vitro experiments in the context of co-infection and drug development.
... In our study, the IL-10 pathway was consistently activated in HBECs upon all treatments (S1, HIV, and combination). This finding is consistent with observed increases in IL-10 expression in HIV-infected young individuals who contracted SARS-CoV-2 [45]. There is evidence that IL-10 regulation of HIV-specific CD4 and CD8 T cell functions [46], which may help explain why decreased SARS-CoV2 replication was associated with increased IL-10 in co-infection assays performed in vitro by Vanetti et al. [45]. ...
... This finding is consistent with observed increases in IL-10 expression in HIV-infected young individuals who contracted SARS-CoV-2 [45]. There is evidence that IL-10 regulation of HIV-specific CD4 and CD8 T cell functions [46], which may help explain why decreased SARS-CoV2 replication was associated with increased IL-10 in co-infection assays performed in vitro by Vanetti et al. [45]. Our results are also consistent with those observations, as there was no indication of increased risk of COVID-19 illness in HIV young individuals [45]. ...
... There is evidence that IL-10 regulation of HIV-specific CD4 and CD8 T cell functions [46], which may help explain why decreased SARS-CoV2 replication was associated with increased IL-10 in co-infection assays performed in vitro by Vanetti et al. [45]. Our results are also consistent with those observations, as there was no indication of increased risk of COVID-19 illness in HIV young individuals [45]. ...
The SARS-CoV-2 pandemic provides a natural opportunity for the collision of coronavirus disease-2019 (COVID-19) with chronic infections, which place numerous individuals at high risk of severe COVID-19. Infection with Human Immunodeficiency Virus (HIV), a global epidemic, remains a major public health concern. Whether prior HIV+ status exacerbates COVID-19 warrants investigation. Herein, we characterized the impact of SARS-CoV-2 in human bronchial epithelial cells (HBECs) previously exposed to HIV. We optimized the air-liquid interface (ALI) cell culture technique to allow for challenges with HIV at the basolateral cell surface and SARS-CoV-2 spike protein on the apical surface, followed by genetic analyses for cellular stress/toxicity and innate/adaptive immune responses. Our results suggest that the IL-10 pathway was consistently activated in HBECs treated with spike, HIV, or a combination. Recombinant spike protein elicited COVID-19 cytokine storms while HIV activated different signaling pathways. HIV-treated HBECs could no longer activate NF-kB, pro-inflammatory TRAF-6 ubiquitination nor RIP1 signaling. Combinations of HIV and SARS-CoV-2 spike increased gene expression for activation of endoplasmic reticulum-phagosome pathway and downregulated non-canonical NF-kB pathways that are key in functional regulatory T cells and RNA Polymerase II transcription. Our in vitro studies suggest that prior HIV infection may not exacerbate COVID-19. Further in vivo studies are warranted to advance this field.
... However, CD4+ T-cell recovery is incomplete despite viral suppression in some PLWH [4]. There is conflicting evidence as to whether PLWH have an increased risk of SARS-CoV-2 infection [5,6]. Several systematic reviews and non-systematic reviews found comparable mortality and morbidity of SARS-CoV-2 between PLWH and HIV-negative individuals [7][8][9][10][11]. ...
This study compared the immunogenicity of inactivated SARS-CoV-2 vaccines between people living with HIV (PLWH) and HIV-negative individuals. We recruited 120 PLWH and 53 HIV-negative individuals aged 18–59 years who had received an inactivated SARS-CoV-2 vaccine in two Chinese cities between April and June 2021. Blood samples were tested for immunogenicity of the inactivated SARS-CoV-2 vaccines. The prevalence and severity of adverse events associated with SARS-CoV-2 vaccines were similar between PLWH and HIV-negative individuals. The seropositivity of neutralizing activity against authentic SARS-CoV-2, of the total amount of antibody (total antibody) and of S-IgG were 71.3%, 81.9%, and 92.6%, respectively, among fully vaccinated PLWH. Among all participants, PLWH had lower neutralizing activity, total antibody, S-IgG, and T-cell-specific immune response levels, compared to HIV-negative individuals, after controlling for types of vaccine, time interval between first and second dose, time after receiving the second dose, and sociodemographic factors. PLWH with a longer interval since HIV diagnosis, who received their second dose 15–28 days prior to study commencement, and who had an interval of ≥21 days between first and second dose had higher neutralizing activity levels. The immunogenicity of the inactivated SARS-CoV-2 vaccines was lower among PLWH as compared to HIV-negative individuals. Vaccination guideline specific for PLWH should be developed.
... In a non-human primate model of HIV infection, the authors identified a dysregulated expression of the immunosuppressive molecule transforming growth factor (TGF) β, along with its cellular source, as a correlate of HIV pathogenesis in the intestine, one of the major sites supporting HIV replication and harboring latently infected cells. In Vanetti's manuscript, HIV infection was leveraged as a platform to study host-pathogen interactions in the context of COVID-19, identifying increased levels of the immunosuppressive cytokine IL-10 driven by co-infection as a protective factor against SARS-CoV-2 in vivo as well as in vitro [6]. ...
Effective antiviral immune responses rely on the host’s genetic background and its interaction with the surrounding environment [...]
The safety and immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in people living with HIV (PLWH) in real world studies remain controversial. Thus, we conducted a comprehensive systematic review and meta-analysis to address this issue. Data search were conducted from PubMed, Web of science, and Embase. Adverse events following vaccination, the risk ratio (RR) of SARS-CoV-2-specific IgG seroconversion, and the level of anti-SARS-CoV-2 neutralizing antibodies were compared between the PLWH group and a healthy control group. A total of 10,582 PLWH from 22 studies were included. In our analysis, the incidence of local or systemic adverse events after the first SARS-CoV-2 vaccine dose was not statistically different between PLWH and healthy controls. However, there was a statistical difference after the second dose (RR = 0.83, 95% CI: 0.71 – 0.98). The seroconversion rate of SARS-CoV-2 IgG antibodies in PLWH was significantly lower than that in the healthy control group (RR = 0.94, 95% CI: 0.89-0.98; I2 = 80%, P < 0.01). The anti-SARS-CoV-2 neutralizing antibody titers in PLWH after full immunization were also significantly lower than that in the healthy control group (RR = 0.91, 95% CI: 0.85-0.98; I2 = 81%, P < 0.01). The safety and tolerance of COVID-19 vaccines in PLWH are acceptable. However, their immunogenicity may be impaired to a certain extent, characterized by a lower IgG seroconversion rate and neutralizing antibody titers compared with healthy individuals. These findings should provide guidance for optimizing future COVID-19 vaccination strategies among PLWH.
