Patients recovering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection demonstrate impaired lung function and those requiring chemotherapy after recovering from SARS-CoV-2 ...infection have yet to be explored. In this study, we sought to investigate the possible pulmonary functional changes during and after administering chemotherapy in patients with prior SARS-CoV-2 infection.
In this study, a total of 37 SARS-CoV-2 infected patients with cancer who were discharged from hospital and received subsequent cytotoxic chemotherapy were enrolled and prospectively followed-up. The following parameters were prospectively measured before (P1), after first chemotherapy cycle (P2), and 10 weeks after the end of chemotherapy (P3), to assess their impact on respiratory complications in terms of diffusion capacity of the lungs for carbon monoxide (DLCO), forced expiratory volume in 1-s (FEV1), forced vital capacity (FVC), 6-min walking distance (6MWD) test and levels of key inflammatory markers.
All patients completed at least 2 cycles of chemotherapy without showing overt respiratory complications. Six patients (16%) complained about dyspnea during chemotherapy or at follow-up period. DLCO was significantly impaired during follow-up period from P1 78 to P3 60% of predicted values; interquartile range (IQR) 55-89 and in 32 of 37 (86% of patients) from P1 to P2 (65% of predictive value; IQR 58-70;
< 0.001). Several patients experienced post-chemotherapy respiratory complications. As expected, all patients from control groups showed persistent improved pulmonary functions.
The risk of pulmonary impairments due to cytotoxic chemotherapy in prior SARS-CoV-2 infected patients is linked to the loss of DLCO. Accordingly, we recommend that for patients with cancer requiring chemotherapy after recovering from prior SARS-CoV-2 infection, pulmonary tests to be performed routinely before and during chemotherapy treatment to monitor the pulmonary performance.
Clinical characteristics of HIV-1 infection in people inhabiting Western, Sub-Saharan African, and South-East Asian countries are well recognized. However, very little information is available with ...regard to HIV-1 infection and treatment outcome in MENA countries including the Gulf Cooperation Council (GCC) states.
Clinical, demographic and epidemiologic characteristics of 602 HIV-1 infected patients followed in the adult Infectious Diseases Clinic of King Faisal Specialist Hospital and Research Centre, in Riyadh, Kingdom of Saudi Arabia a tertiary referral center were longitudinally collected from 1989 to 2010.
Of the 602 HIV-1 infected patients in this observation period, 70% were male. The major mode of HIV-1 transmission was heterosexual contact (55%). At diagnosis, opportunistic infections were found in 49% of patients, most commonly being pneumocysitis. AIDS associated neoplasia was also noted in 6% of patients. A hundred and forty-seven patients (24%) died from the cohort by the end of the observation period. The mortality rate peaked in 1992 at 90 deaths per 1000 person-year, whereas the mortality rate gradually decreased to <1% from 1993-2010. In 2010, 71% of the patients were receiving highly active retroviral therapy.
These data describe the clinical characteristic of HIV-1-infected patients at a major tertiary referral hospital in KSA over a 20-year period. Initiation of antiretroviral therapy resulted in a significant reduction in both morbidity and mortality. Future studies are needed in the design and implementation of targeted treatment and prevention strategies for HIV-1 infection in KSA.
HIV-1 infection is associated with profound dysfunction of myeloid dendritic cells, for reasons that remain ill-defined. Soluble HLA class I molecules can have important inhibitory effects on T cells ...and NK cells, but may also contribute to reduced functional properties of professional antigen-presenting cells. Here, we investigated the expression of soluble HLA class I isoforms during HIV-1 infection and assessed their functional impact on antigen-presenting characteristics of dendritic cells.
Soluble HLA class I molecules were highly upregulated in progressive HIV-1 infection as determined by quantitative Western blots. This was associated with strong increases of intracellular expression of HLA class I isoforms in dendritic cells and monocytes. Using mixed lymphocyte reactions, we found that soluble HLA class I molecules effectively inhibited the antigen-presenting properties of dendritic cells, however, there was no significant influence of HLA class I molecules on the cytokine-secretion properties of these cells. The immunomodulatory effects of soluble HLA class I molecules were mediated by interactions with inhibitory myelomonocytic MHC class I receptors from the Leukocyte Immunoglobulin Like Receptor (LILR) family.
During progressive HIV-1 infection, soluble HLA class I molecules can contribute to systemic immune dysfunction by inhibiting the antigen-presenting properties of myeloid dendritic cells through interactions with inhibitory myelomonocytic HLA class I receptors.
Human Immunodeficiency Virus infection continue to represent a global health concern influenced by various social, economic, and cultural factors. The MENA are among the top regions in the world with ...the fastest-growing HIV epidemic. Thus, adequate knowledge and a positive attitude of people toward HIV/AIDS are of utmost importance to prevent the spreading of the disease. Accordingly, this study aims to evaluate the knowledge and attitude of the public and healthcare population toward HIV/AIDs.
A cross-sectional analysis was conducted among residents within our population from October 2018 until August 2019. An anonymous online questionnaire was used to investigate the population's demographic characteristics, HIV/AIDS-related knowledge, and attitudes toward HIV-infected patients. Participants completed a 40-item questionnaire designed to measure their knowledge and attitude toward HIV/AIDS. The data was collected via surveys, administered through electronic tablets to the participants at public places (n = 5,757) and through an online version of the questionnaire on Google Forms (n = 2500), which was sent through social media platforms. Descriptive statistics were used to analyse the data using the R-statistical software program.
A total of 8,257 participants were included in our analysis. Saudi Arabian citizens represented 79% of the participants, while participants from the MENA countries represented 11.7% and 3% from the other Gulf Cooperation Council countries. Fifty-nine (59%) knew that HIV is a contagious infection, and 13.8% were unaware that HIV could be transmitted sexually. A few healthcare professionals reported negative attitudes toward HIV infected patients. Many risk factors, including age, gender, nationality, and education, significantly affected the knowledge and attitude scores. In this survey, we found that social media is the primary source of participants' information.
Overall correct knowledge score of individuals about HIV/AIDS was relatively low. This study showed that the general population was knowledgeable to a certain degree about HIV/AIDS and its modes of transmission. Nevertheless, they lack a detailed understanding of the disease's nature, modes of transmission, and existing treatment. Policymakers in the region should further eliminate social discrimination and stigma in HIV-infected patients.
Middle East respiratory syndrome coronavirus (MERS-CoV) first emerged in 2012 and causes human infections in endemic regions. Vaccines and therapeutics in development against MERS-CoV focus on the ...spike (S) glycoprotein to prevent viral entry into target cells. These efforts are limited by a poor understanding of antibody responses elicited by infection. Here, we analyze S-directed antibody responses in plasma collected from MERS-CoV-infected individuals. We observe that binding and neutralizing antibodies peak 1–6 weeks after symptom onset/hospitalization, persist for at least 6 months, and neutralize human and camel MERS-CoV strains. We show that the MERS-CoV S1 subunit is immunodominant and that antibodies targeting S1, particularly the receptor-binding domain (RBD), account for most plasma neutralizing activity. Antigenic site mapping reveals that plasma antibodies frequently target RBD epitopes, whereas targeting of S2 subunit epitopes is rare. Our data reveal the humoral immune responses elicited by MERS-CoV infection, which will guide vaccine and therapeutic design.
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•MERS-CoV-infection-elicited antibodies against the S protein persist for at least 6 months•Infection-elicited antibodies cross-neutralize human and camel MERS-CoV variants•Antibodies targeting the MERS-CoV RBD account for most of the plasma neutralizing activity•Neutralizing antibodies directed to the S2 subunit are rarely elicited by MERS-CoV infection
Addetia et al. examine the durability, breadth, and domain and epitope specificity of antibodies directed against the MERS-CoV spike glycoprotein by analyzing plasma samples collected from individuals infected with MERS-CoV. Neutralizing antibodies elicited by infection primarily target the S1 subunit and, more specifically, the receptor-binding domain of the spike protein.
In Saudi Arabia, the epidemiology and clinical significance of Torque Teno virus (TTV) infection alone and in patients with hepatitis virus infections have not been determined in a single study. In ...this paper, we molecularly investigated the rate and genotypes of TTV infection among Saudi Arabian blood donors and patients with viral hepatitis. The effect of TTV coinfection on viral hepatitis was also examined.
DNA was extracted from the sera of 200 healthy blood volunteers, 45 hepatitis B virus patients, 100 hepatitis C virus patients, 19 hepatitis G virus patients, and 56 non-A-G hepatitis patients. TTV DNA was amplified using primers derived from the ORF1 and 5'UTR regions. The alanine aminotransferase (ALT) level was determined for each specimen. Sequencing of ORF1 amplicons was carried out to investigate TTV genotypes.
Using primers derived from ORF1 and 5'UTR, TTV DNA was detected in 5.5% and 50.5%, respectively, of healthy blood donors, in 2.2% and 88.8% in hepatitis B patients, in 2.0% and 70% of hepatitis C patients, in 15.8% and 100% of hepatitis G patients, in 5.4% and 12.5% of non-A-G hepatitis patients and in 4.8% and 56.4% overall. No detrimental effect of TTV coinfection in viral hepatitis patients was noted. An overall prevalence of 4.8% and 56.4% was established. Phylogenetic analysis indicated that the most common genotype of TTV among Saudis is 2c.
The rate of TTV infection among Saudi Arabians seems to be lower than that stated in previous reports on Saudi Arabia and in some other countries. The virus does not seem to worsen the status of those who are suffering from viral hepatitis infection.
This study aimed to understand the pathophysiology of host responses to infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/(COVID-19) and Middle East respiratory ...syndrome coronavirus (MERS-CoV) and to identify proteins for patient stratification with different grades of illness severity.
Peripheral blood samples from 43 patients with different grades of COVID-19, 7 MERS-CoV patients admitted to the ICU, and 10 healthy subjects were analyzed using label-free quantitative liquid chromatography-mass spectrometry (LC-MS).
We identified 193 and 91 proteins that differed significantly between COVID-19 and MERS-CoV sample groups, respectively, and 49 overlapped between datasets. Only 10 proteins are diagnostic of asymptomatic cases, 12 are prognostic of recovery from severe illness, and 28 are prognostic of a fatal outcome of COVID-19. These proteins are implicated in virus-specific/related signaling networks. Notable among the top canonical pathways are humoral immunity, inflammation, acute-phase response signaling, liver X receptor/retinoid X receptor (LXR/RXR) activation, coagulation, and the complement system. Furthermore, we confirmed positive viral shedding in 11.76% of 51 additional peripheral blood samples, indicating that caution should be taken to avoid the possible risk of transfusion of infected blood products.
We identified COVID-19 and MERS-CoV protein panels that have potential as biomarkers and might assist in the prognosis of SARS-CoV-2 infection. The identified markers further our understanding of COVID-19 disease pathophysiology and may have prognostic or therapeutic potential in predicting or managing host cell responses to human COVID-19 and MERS-CoV infections.
Dendritic cells (DCs) are the most potent antigen-presenting cells capable of priming naïve T-cells. Its C-type lectin receptor, DC-SIGN, regulates a wide range of immune functions. Along with its ...role in HIV-1 pathogenesis through complement opsonization of the virus, DC-SIGN has recently emerged as an adaptor for complement protein C1q on the surface of immature DCs
a trimeric complex involving gC1qR, a receptor for the globular domain of C1q. Here, we have examined the nature of interaction between C1q and DC-SIGN in terms of domain localization, and implications of C1q-DC-SIGN-gC1qR complex formation on HIV-1 transmission. We first expressed and purified recombinant extracellular domains of DC-SIGN and its homologue DC-SIGNR as tetramers comprising of the entire extra cellular domain including the α-helical neck region and monomers comprising of the carbohydrate recognition domain only. Direct binding studies revealed that both DC-SIGN and DC-SIGNR were able to bind independently to the recombinant globular head modules ghA, ghB, and ghC, with ghB being the preferential binder. C1q appeared to interact with DC-SIGN or DC-SIGNR in a manner similar to IgG. Mutational analysis using single amino acid substitutions within the globular head modules showed that Tyr
and Lys
were critical for the C1q-DC-SIGN/DC-SIGNR interaction. Competitive studies revealed that gC1qR and ghB shared overlapping binding sites on DC-SIGN, implying that HIV-1 transmission by DCs could be modulated due to the interplay of gC1qR-C1q with DC-SIGN. Since C1q, gC1qR, and DC-SIGN can individually bind HIV-1, we examined how C1q and gC1qR modulated HIV-1-DC-SIGN interaction in an infection assay. Here, we report, for the first time, that C1q suppressed DC-SIGN-mediated transfer of HIV-1 to activated pooled peripheral blood mononuclear cells, although the globular head modules did not. The protective effect of C1q was negated by the addition of gC1qR. In fact, gC1qR enhanced DC-SIGN-mediated HIV-1 transfer, suggesting its role in HIV-1 pathogenesis. Our results highlight the consequences of multiple innate immune pattern recognition molecules forming a complex that can modify their functions in a way, which may be advantageous for the pathogen.
Elite controllers spontaneously control HIV-1 replication, which in many cases is associated with preservation of normal CD4 T-cell counts. However, a subset of elite controllers has progressive CD4 ...T-cell losses despite undetectable viral loads, for reasons that remain undefined. Here, we assessed mechanisms of CD4 T-cell homeostasis in elite controllers with progressive vs. nonprogressive HIV-1 disease courses.
Flow cytometry assays were used to determine the proliferation, activation and apoptosis levels of naive T cells in elite controllers with high or low CD4 T-cell counts and reference cohorts of HIV-1-negative and HAART-treated persons. Thymic output was measured by single-joint T-cell receptor excision circle (sjTREC)/β T-cell receptor excision circle (βTREC) ratios, and the frequency of circulating recent thymic emigrants was flow cytometrically determined by surface expression of protein tyrosine kinase 7.
Proportions of naive T cells in elite controllers were severely reduced and closely resemble those of HIV-1 patients with progressive disease. Despite reductions in naive T cells, most elite controllers were able to maintain normal total CD4 T-cell counts by preservation of uncompromised thymic function in conjunction with extrathymic processes that led to elevated levels of circulating recent thymic emigrants. In contrast, elite controllers with low CD4 T-cell counts had reduced thymic output that mirrored thymic dysfunction during untreated progressive HIV-1 infection.
These results indicate that both thymic and extrathymic mechanisms contribute to CD4 T-cell maintenance in elite controllers and support the idea that CD4 T-cell homeostasis and control of viral replication are distinct but frequently coinciding processes.
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