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1.
Medicine (Baltimore) ; 100(41): e27418, 2021 Oct 15.
Article in English | MEDLINE | ID: covidwho-1501202

ABSTRACT

ABSTRACT: The occurrence of COVID-19 pandemic had a significant negative effect on health care systems over the last year. Health care providers were forced to focus mainly on COVID-19 patients, neglecting in many cases equally important diseases, both acute and chronic. Therefore, also screening and diagnostic strategies for HIV could have been significantly impaired.This retrospective, multicenter, observational study aimed at assessing the number and characteristics of new HIV/AIDS diagnoses during COVID-19 pandemic in Italy and compared characteristics of people living with HIV at diagnosis between pre- and post-COVID-19 era (2019 vs 2020).Our results showed a significant reduction of HIV diagnoses during pandemic. By contrast, people living with HIV during pandemic were older and were diagnosed in earlier stage of disease (considering CD4+ T cell count) compared to those who were diagnosed the year before. Moreover, there was a significant decrease of new HIV diagnoses among men who have sex with men, probably for the impact of social distancing and restriction applied by the Italian Government. Late presentation incidence, if numbers in 2020 were lower than those in 2019, is still an issue.Routinely performing HIV testing in patients with suspected SARS-CoV-2 infection is identifying and linking to care underdiagnosed people living with HIV earlier. Thus, combined tests (HIV and SARS-CoV-2) should be implemented in patients with SARS-CoV-2 symptoms overlapping HIV's ones. Lastly, our results lastly showed how urgent implementation of a national policy for HIV screening is necessary.


Subject(s)
Delivery of Health Care/organization & administration , HIV Infections/epidemiology , Mass Screening/statistics & numerical data , Adult , CD4 Lymphocyte Count/statistics & numerical data , COVID-19/epidemiology , Cross-Sectional Studies , Female , HIV Infections/diagnosis , Humans , Italy/epidemiology , Male , Mass Screening/organization & administration , Middle Aged , Pandemics , Retrospective Studies , Risk Factors , SARS-CoV-2
2.
Clin Immunol ; 230: 108824, 2021 09.
Article in English | MEDLINE | ID: covidwho-1482503

ABSTRACT

The current intersection of the COVID-19 and HIV-1 pandemics, has raised concerns about the risk for poor COVID-19 outcomes particularly in regions like sub-Saharan Africa, disproportionally affected by HIV. DPP4/CD26 has been suggested to be a potential therapeutic target and a biomarker for risk in COVID-19 patients with high risk co-morbidities. We therefore evaluated soluble DPP4 (sDPP4) levels and activity in plasma of 131 HIV-infected and 20 HIV-uninfected South African individuals. Flow cytometry was performed to compare cell surface expression of DPP4/CD26 and activation markers on peripheral blood mononuclear cells of extreme clinical phenotypes. Progressors had lower specific DPP4 activity and lower frequency of CD3+ T-cells expressing CD26 than HIV-1 controllers, but more activated CD3+CD26+ T-cells. The frequency of CD26-expressing T-cells negatively correlated with HLA-DR+ and CD38+ T-cells. Divergent DPP4/CD26 expression between HIV-1 controllers and progressors may have implications for risk and treatment of COVID-19 in people living with HIV.


Subject(s)
COVID-19/complications , Dipeptidyl Peptidase 4/metabolism , HIV Infections/complications , HIV-1 , SARS-CoV-2 , Adult , CD4 Lymphocyte Count , Case-Control Studies , Comorbidity , Cross-Sectional Studies , Disease Susceptibility , Female , Humans , Male , Risk Factors , South Africa , Viral Load , Young Adult
3.
Front Immunol ; 12: 727850, 2021.
Article in English | MEDLINE | ID: covidwho-1477821

ABSTRACT

Mass SARS-Cov-2 vaccination campaign represents the only strategy to defeat the global pandemic we are facing. Immunocompromised patients represent a vulnerable population at high risk of developing severe COVID-19 and thus should be prioritized in the vaccination programs and in the study of the vaccine efficacy. Nevertheless, most data on efficacy and safety of the available vaccines derive from trials conducted on healthy individuals; hence, studies on immunogenicity of SARS-CoV2 vaccines in such populations are deeply needed. Here, we perform an observational longitudinal study analyzing the humoral and cellular response following the BNT162b2 mRNA COVID-19 vaccine in a cohort of patients affected by inborn errors of immunity (IEI) compared to healthy controls (HC). We show that both IEI and HC groups experienced a significant increase in anti-SARS-CoV-2 Abs 1 week after the second scheduled dose as well as an overall statistically significant expansion of the Ag-specific CD4+CD40L+ T cells in both HC and IEI. Five IEI patients did not develop any specific CD4+CD40L+ T cellular response, with one of these patients unable to also mount any humoral response. These data raise immunologic concerns about using Ab response as a sole metric of protective immunity following vaccination for SARS-CoV-2. Taken together, these findings suggest that evaluation of vaccine-induced immunity in this subpopulation should also include quantification of Ag-specific T cells.


Subject(s)
Antibodies, Viral/blood , CD4-Positive T-Lymphocytes/immunology , COVID-19 Vaccines/immunology , Immunogenicity, Vaccine/immunology , Primary Immunodeficiency Diseases/immunology , SARS-CoV-2/immunology , Adolescent , Adult , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , CD4 Lymphocyte Count , COVID-19/prevention & control , Female , Humans , Immunity, Cellular/immunology , Immunity, Humoral/immunology , Immunocompromised Host/immunology , Longitudinal Studies , Male , Middle Aged , Vaccination , Young Adult
4.
Front Immunol ; 12: 715023, 2021.
Article in English | MEDLINE | ID: covidwho-1477819

ABSTRACT

Emerging evidence has unveiled the secondary infection as one of the mortal causes of post-SARS-CoV-2 infection, but the factors related to secondary bacterial or fungi infection remains largely unexplored. We here systematically investigated the factors that might contribute to secondary infection. By clinical examination index analysis of patients, combined with the integrative analysis with RNA-seq analysis in the peripheral blood mononuclear cell isolated shortly from initial infection, this study showed that the antibiotic catabolic process and myeloid cell homeostasis were activated while the T-cell response were relatively repressed in those with the risk of secondary infection. Further monitoring analysis of immune cell and liver injury analysis showed that the risk of secondary infection was accompanied by severe lymphocytopenia at the intermediate and late stages and liver injury at the early stages of SARS-CoV-2. Moreover, the metagenomics analysis of bronchoalveolar lavage fluid and the microbial culture analysis, to some extent, showed that the severe pneumonia-related bacteria have already existed in the initial infection.


Subject(s)
Bacterial Infections/epidemiology , COVID-19/pathology , Coinfection/epidemiology , Coinfection/mortality , Mycoses/epidemiology , Adult , Aged , Aged, 80 and over , Bacterial Infections/mortality , Bronchoalveolar Lavage Fluid/microbiology , CD4 Lymphocyte Count , Female , Humans , Leukocytes, Mononuclear/immunology , Liver/injuries , Liver/virology , Lymphopenia/immunology , Male , Middle Aged , Mycoses/mortality , Retrospective Studies , Risk Factors , SARS-CoV-2/immunology , T-Lymphocytes/immunology
5.
J Immunol Res ; 2021: 8669098, 2021.
Article in English | MEDLINE | ID: covidwho-1476888

ABSTRACT

Objective: This study explored the consistency and differences in the immune cells and cytokines between patients with COVID-19 or cancer. We further analyzed the correlations between the acute inflammation and cancer-related immune disorder. Methods: This retrospective study involved 167 COVID-19 patients and 218 cancer patients. COVID-19 and cancer were each further divided into two subgroups. Quantitative and qualitative variables were measured by one-way ANOVA and chi-square test, respectively. Herein, we carried out a correlation analysis between immune cells and cytokines and used receiver operating characteristic (ROC) curves to discover the optimal diagnostic index. Results: COVID-19 and cancers were associated with lymphopenia and high levels of monocytes, neutrophils, IL-6, and IL-10. IL-2 was the optimal indicator to differentiate the two diseases. Compared with respiratory cancer patients, COVID-19 patients had lower levels of IL-2 and higher levels of CD3+CD4+ T cells and CD19+ B cells. In the subgroup analysis, IL-6 was the optimal differential diagnostic parameter that had the ability to identify if COVID-19 patients would be severely affected, and severe COVID-19 patients had lower levels of lymphocyte subsets (CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+T cells, and CD19+ B cells) and CD16+CD56+ NK cells and higher level of neutrophils. There were significant differences in the levels of CD3+CD4+ T cells and CD19+ B cells between T1-2 and T3-4 stages as well as IL-2 and CD19+ B cells between N0-1 and N2-3 stages while no significant differences between the metastatic and nonmetastatic cancer patients. Additionally, there were higher correlations between IL-2 and IL-4, TNF-α and IL-2, TNF-α and IL-4, TNF-α and IFN-γ, and CD16+CD56+NK cells and various subsets of T cells in COVID-19 patients. There was a higher correlation between CD3+CD4+ T cells and CD19+ B cells in cancer patients. Conclusion: Inflammation associated with COVID-19 or cancer had effects on patients' outcomes. Accompanied by changes in immune cells and cytokines, there were consistencies, differences, and satisfactory correlations between patients with COVID-19 and those with cancers.


Subject(s)
COVID-19/immunology , Cytokines/blood , Lymphopenia/blood , Monocytes/immunology , Neoplasms/immunology , Neutrophils/immunology , Adolescent , Adult , Aged , Aged, 80 and over , B-Lymphocytes/immunology , CD4 Lymphocyte Count , CD4-Positive T-Lymphocytes/immunology , COVID-19/diagnosis , COVID-19/pathology , Female , Humans , Inflammation/blood , Inflammation/pathology , Killer Cells, Natural/immunology , Lymphocyte Subsets/immunology , Male , Middle Aged , Neoplasms/diagnosis , Neoplasms/pathology , Retrospective Studies , SARS-CoV-2/immunology , Young Adult
6.
Viruses ; 13(10)2021 10 13.
Article in English | MEDLINE | ID: covidwho-1470992

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the coronavirus disease 2019 (COVID-19) pandemic, severely affecting public health and the global economy. Adaptive immunity plays a crucial role in fighting against SARS-CoV-2 infection and directly influences the clinical outcomes of patients. Clinical studies have indicated that patients with severe COVID-19 exhibit delayed and weak adaptive immune responses; however, the mechanism by which SARS-CoV-2 impedes adaptive immunity remains unclear. Here, by using an in vitro cell line, we report that the SARS-CoV-2 spike protein significantly inhibits DNA damage repair, which is required for effective V(D)J recombination in adaptive immunity. Mechanistically, we found that the spike protein localizes in the nucleus and inhibits DNA damage repair by impeding key DNA repair protein BRCA1 and 53BP1 recruitment to the damage site. Our findings reveal a potential molecular mechanism by which the spike protein might impede adaptive immunity and underscore the potential side effects of full-length spike-based vaccines.


Subject(s)
Adaptive Immunity/immunology , COVID-19/pathology , DNA Repair/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , V(D)J Recombination/genetics , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , BRCA1 Protein/antagonists & inhibitors , CD4 Lymphocyte Count , CD8-Positive T-Lymphocytes/immunology , COVID-19 Vaccines/immunology , Cell Line , DNA Damage/genetics , HEK293 Cells , Humans , Immunity, Humoral/immunology , Immunosuppression , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes, Helper-Inducer/immunology , Tumor Suppressor p53-Binding Protein 1/antagonists & inhibitors
7.
Int J Immunopathol Pharmacol ; 35: 20587384211048567, 2021.
Article in English | MEDLINE | ID: covidwho-1463208

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) had become a worldwide health threat. Early prediction of the severity of COVID-19 patients was important for reducing death rate and controlling this disease. METHODS AND MATERIALS: A total of 301 patients confirmed with COVID-19 in Wuhan from 8 February to 10 April 2020 were included. Clinical data were collected and analyzed. Diagnostic and prognostic utility of blood cell counts and lymphocyte subsets in COVID-19 patients were investigated. The receiver operator characteristic curve (ROC) was used in discriminating the mild and severe/critical cases. RESULTS: There were difference in blood cell counts and lymphocyte subsets among mild, severe and critical patients, which were also influenced by comorbidities and duration of disease. The area under the ROC of lymphocyte, CD3+ T cells, CD4+ T cells, and CD8+ T cells were 0.718, 0.721, 0.718, and 0.670, which were higher than that of other hematological parameters. The optimal threshold was 1205, 691, 402, and 177 per µl, respectively. Patients with higher counts of lymphocyte, CD3+ T cells, CD4+ T cells, or CD8+ T cells were correlated with shorter length of stay in hospital (p < 0.05). Multivariable Cox regression analysis showed disease severity, CD3+ T cells counts and time when the nucleic acid turned negative were independent risk factors for in-hospital death of COVID-19 patients (p < 0.05). CONCLUSION: Blood cell counts and lymphocyte subsets correlated with severity of COVID-19.


Subject(s)
COVID-19/immunology , Lymphocyte Subsets/immunology , Adult , Aged , Aged, 80 and over , CD4 Lymphocyte Count , COVID-19/diagnosis , COVID-19/mortality , COVID-19/virology , China , Female , Hospital Mortality , Host-Pathogen Interactions , Humans , Lymphocyte Subsets/virology , Male , Middle Aged , Phenotype , Predictive Value of Tests , Prognosis , Retrospective Studies , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Severity of Illness Index , Time Factors , Young Adult
8.
Front Immunol ; 12: 709759, 2021.
Article in English | MEDLINE | ID: covidwho-1450807

ABSTRACT

The clinical features of SARS-CoV-2 infection range from asymptomatic to severe disease with life-threatening complications. Understanding the persistence of immune responses in asymptomatic individuals merit special attention because of their importance in controlling the spread of the infections. We here studied the antibody and T cell responses, and a wide range of inflammation markers, in 56 SARS-CoV-2 antibody-positive individuals, identified by a population screen after the first wave of SARS-CoV-2 infection. These, mostly asymptomatic individuals, were reanalyzed 7-8 months after their infection together with 115 age-matched seronegative controls. We found that 7-8 months after the infection their antibodies to SARS-CoV-2 Nucleocapsid (N) protein declined whereas we found no decrease in the antibodies to Spike receptor-binding domain (S-RBD) when compared to the findings at seropositivity identification. In contrast to antibodies to N protein, the antibodies to S-RBD correlated with the viral neutralization capacity and with CD4+ T cell responses as measured by antigen-specific upregulation of CD137 and CD69 markers. Unexpectedly we found the asymptomatic antibody-positive individuals to have increased serum levels of S100A12, TGF-alpha, IL18, and OSM, the markers of activated macrophages-monocytes, suggesting long-term persistent inflammatory effect associated with the viral infection in asymptomatic individuals. Our results support the evidence for the long-term persistence of the inflammation process and the need for post-infection clinical monitoring of SARS-CoV-2 infected asymptomatic individuals.


Subject(s)
Antibodies, Viral/blood , Asymptomatic Infections , CD4-Positive T-Lymphocytes/immunology , COVID-19/pathology , Inflammation Mediators/blood , SARS-CoV-2/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , CD4 Lymphocyte Count , Coronavirus Nucleocapsid Proteins/immunology , Humans , Inflammation/immunology , Interleukin-18/blood , Macrophages/immunology , Monocytes/immunology , Oncostatin M/blood , Phosphoproteins/immunology , Protein Domains/immunology , S100A12 Protein/blood , Spike Glycoprotein, Coronavirus/immunology , Transforming Growth Factor alpha/blood
9.
J Int AIDS Soc ; 24 Suppl 5: e25778, 2021 09.
Article in English | MEDLINE | ID: covidwho-1427127

ABSTRACT

INTRODUCTION: The Spectrum/AIM model is used by national HIV programs and UNAIDS to prepare annual estimates of key HIV indicators. This article describes key updates to paediatric and adult models for the 2021 round of HIV estimates. METHODS: Potential updates to Spectrum arise due to newly available data, new analyses of existing data, and the need for new issues to be addressed. Updates are guided by experts through the UNAIDS Reference Group on Estimates, Modelling and Projections. Changes are tested and assessed for impact before being accepted into the final model. RESULTS: Spectrum tracks children living with HIV by CD4% for ages 0-4 and CD4 count for ages 5-14. Data from IeDEA treatment sites have been used to map the transition from CD4% to CD4 count at age 5. Breastfeeding patterns in sub-Saharan Africa have been updated with the latest survey data and estimates of continuation on antiretroviral therapy (ART) with breastfeeding have been revised based on recent studies. Model assumptions about the CD4 counts of people who drop out of ART have been revised to account for CD4 count increases while on treatment. If available, monthly data on numbers on ART can now be used to estimate the effects of COVID-19-related disruptions during 2020. CONCLUSIONS: These changes are intended to provide more accurate estimates of HIV burden. The effects of these changes on paediatric indicators are small except in countries with new surveys that might have updated patterns of breastfeeding. Changes to the adult model have little effect on total new infections. AIDS-related deaths will be somewhat lower in countries that have data on ART drop out but might be increased by HIV care disruptions due to COVID-19. The updated model uses newly available data to improve the estimation of paediatric and adult HIV indicators.


Subject(s)
COVID-19 , HIV Infections , Adolescent , Adult , Anti-HIV Agents/therapeutic use , CD4 Lymphocyte Count , Child , Child, Preschool , Female , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Incidence , Infant , Infant, Newborn , Prevalence , SARS-CoV-2
10.
Front Immunol ; 12: 720952, 2021.
Article in English | MEDLINE | ID: covidwho-1417084

ABSTRACT

The ongoing COVID-19 pandemic has increased awareness about sex-specific differences in immunity and outcomes following SARS-CoV-2 infection. Strong evidence of a male bias in COVID-19 disease severity is hypothesized to be mediated by sex differential immune responses against SARS-CoV-2. This hypothesis is based on data from other viral infections, including influenza viruses, HIV, hepatitis viruses, and others that have demonstrated sex-specific immunity to viral infections. Although males are more susceptible to most viral infections, females possess immunological features that render them more vulnerable to distinct immune-related disease outcomes. Both sex chromosome complement and related genes as well as sex steroids play important roles in mediating the development of sex differences in immunity to viral infections.


Subject(s)
COVID-19/pathology , Severity of Illness Index , Sex Characteristics , CD4 Lymphocyte Count , CD4-CD8 Ratio , Cytokines/blood , Female , Humans , Immunity, Innate/genetics , Immunity, Innate/immunology , Male , SARS-CoV-2/immunology , Sex Factors
11.
Am J Case Rep ; 22: e932467, 2021 Aug 11.
Article in English | MEDLINE | ID: covidwho-1404093

ABSTRACT

BACKGROUND Neurosyphilis is a bacterial infection of the brain and the spinal cord, caused by Treponema pallidum. Its nonspecific clinical presentation includes cognitive impairment and motor and/or sensory function compromise. Neurosyphilis infections in patients with HIV have increased over the past few years and many cases of neurosyphilis manifest in patients with HIV who have low CD4 T-cell counts and high viral loads (VL). However, there is extremely limited acknowledgement in the literature about neurosyphilis presentations in patients with HIV who have normal CD4 counts. CASE REPORT We present a neurosyphilis and HIV coinfection in a patient with a normal CD4 count and an undetectable VL. A 69-year-old woman with a medical history of HIV was on a prescribed antiretroviral treatment regimen. She presented in the Emergency Room in an unresponsive state, although this had been preceded by a period of rapidly progressive cognitive decline. Her brain computed tomography scan without contrast was unremarkable. Laboratory test results were within normal limits, except for a positive result for the microhemagglutination assay for Treponema pallidum antibodies and rapid plasma regain (RPR) test, which was highly suggestive of neurosyphilis as a presumed diagnosis. She showed remarkable clinical improvement after the initiation of conventional treatment for neurosyphilis, which is a 14-day regimen of intravenous penicillin G. CONCLUSIONS Given the broad neurological manifestations of neurosyphilis and its increasing incidence in patients with HIV, it is important to consider neurosyphilis in the differential diagnosis after ruling out other causes of encephalopathy, especially in patients with an undetectable VL and a normal CD4 count.


Subject(s)
HIV Infections , Neurosyphilis , Aged , CD4 Lymphocyte Count , Female , HIV , HIV Infections/complications , Humans , Neurosyphilis/complications , Neurosyphilis/diagnosis , Neurosyphilis/drug therapy , Penicillins , Viral Load
12.
Front Immunol ; 12: 693269, 2021.
Article in English | MEDLINE | ID: covidwho-1389185

ABSTRACT

Chronic immune activation has been considered as the driving force for CD4+ T cell depletion in people infected with HIV-1. Interestingly, the normal immune profile of adult HIV-negative individuals living in Africa also exhibit chronic immune activation, reminiscent of that observed in HIV-1 infected individuals. It is characterized by increased levels of soluble immune activation markers, such as the cytokines interleukin (IL)-4, IL-10, TNF-α, and cellular activation markers including HLA-DR, CD-38, CCR5, coupled with reduced naïve and increased memory cells in CD4+ and CD8+ subsets. In addition, it is accompanied by low CD4+ T cell counts when compared to Europeans. There is also evidence that mononuclear cells from African infants secrete less innate cytokines than South and North Americans and Europeans in vitro. Chronic immune activation in Africans is linked to environmental factors such as parasitic infections and could be responsible for previously observed immune hypo-responsiveness to infections and vaccines. It is unclear whether the immunogenicity and effectiveness of anti-SARS-CoV-2 vaccines will also be reduced by similar mechanisms. A review of studies investigating this phenomenon is urgently required as they should inform the design and delivery for vaccines to be used in African populations.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , COVID-19 Vaccines/immunology , Immunogenicity, Vaccine/immunology , Lymphocyte Activation/immunology , SARS-CoV-2/immunology , ADP-ribosyl Cyclase 1/blood , Africa , CD4 Lymphocyte Count , CD8-Positive T-Lymphocytes/immunology , COVID-19/prevention & control , HLA-DR Antigens/blood , Humans , Interleukin-10/blood , Interleukin-4/blood , Leukocytes, Mononuclear/metabolism , Membrane Glycoproteins/blood , Receptors, CCR5/blood , Tumor Necrosis Factor-alpha/blood
14.
J Clin Lab Anal ; 35(9): e23923, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1353465

ABSTRACT

BACKGROUND: The dynamic alteration and comparative study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA shedding pattern during treatment are limited. This study explores the potential risk factors influencing prolonged viral shedding in COVID-19. METHODS: A total of 126 COVID-19 patients were enrolled in this retrospective longitudinal study. A multivariate logistic regression analysis was carried out to estimate the potential risk factors. RESULTS: 38.1% (48/126) cases presented prolonged respiratory tract viral shedding, and 30 (23.8%) cases presented prolonged rectal swab viral shedding. Obesity (OR, 3.31; 95% CI, 1.08-10.09), positive rectal swab (OR, 3.43; 95% CI, 1.53-7.7), treatment by lopinavir/ritonavir with chloroquine phosphate (OR, 2.5; 95% CI, 1.04-6.03), the interval from onset to antiviral treatment more than 7 days (OR, 2.26; 95% CI, 1.04-4.93), lower CD4+ T cell (OR, 0.92; 95% CI, 0.86-0.99) and higher NK cells (OR, 1.11; 95% CI, 1.02-1.20) were significantly associated with prolonged respiratory tract viral shedding. CD3-CD56+ NK cells (OR, 0.87; 95% CI, 0.76-0.99) were related with prolonged fecal shedding. CONCLUSIONS: Obesity, delayed antiviral treatment, and positive SARS-CoV-2 for stool were independent risk factors for prolonged SARS-CoV-2 RNA shedding of the respiratory tract. A combination of LPV/r and abidol as the initial antiviral regimen was effective in shortening the duration of viral shedding compared with LPV/r combined with chloroquine phosphate. CD4+ T cell and NK cells were significantly associated with prolonged viral shedding, and further studies are to be warranted to determine the mechanism of immunomodulatory response in virus clearance.


Subject(s)
COVID-19/virology , Feces/virology , SARS-CoV-2/physiology , Virus Shedding/physiology , Adult , Animals , Antiviral Agents/administration & dosage , CD4 Lymphocyte Count , COVID-19/epidemiology , Chloroquine/administration & dosage , Chloroquine/adverse effects , Chloroquine/analogs & derivatives , Female , Humans , Killer Cells, Natural , Longitudinal Studies , Lopinavir/administration & dosage , Lynx , Male , Obesity/epidemiology , Respiratory System/virology , Retrospective Studies , Risk Factors , Ritonavir/administration & dosage , Time Factors , Virus Shedding/drug effects
15.
Viral Immunol ; 34(5): 330-335, 2021 06.
Article in English | MEDLINE | ID: covidwho-1343605

ABSTRACT

The aim of this study was to analyze the correlation between dynamic changes in the nasopharyngeal viral load of patients infected with the new coronavirus causing pneumonia and lymphocyte count disease severity. Cases newly diagnosed with COVID-19 at the First Affiliated Hospital of Nanchang University from January 2020 to February 2020 were analyzed retrospectively. Quantitative real-time polymerase chain reaction was used to determine severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from throat swab sample ΔCT values; lymphocyte and lymphocyte subset counts, coagulation system factor levels, myocardial injury indexes, and laboratory biochemical indicators were compared between the mild group and the severe group. The correlation between the relative load of nasopharyngeal SARS-CoV-2 RNA and severe disease symptoms was analyzed. Of the 76 patients, 49 were male and 27 were female. The lymphocyte, CD4+ T lymphocyte, and CD8+ T lymphocyte counts all differed significantly between the two groups (p < 0.001), as did differences in interleukin (IL)-2R, IL-6, and IL-8 levels (p = 0.022, 0.026, and 0.012, respectively). Moreover, there were significant differences in prothrombin time, D-dimer, and fibrinogen levels between the mild group and the severe group (p = 0.029, 0.006, and <0.001, respectively), and in lactate dehydrogenase and troponin (p < 0.001 and p = 0.007, respectively). SARS-CoV-2 RNA load and lymphocyte count, CD4+ T lymphocyte count, and CD8+ T lymphocyte count were linearly negatively correlated (p < 0.001). SARS-CoV-2 RNA load was positively correlated with IL-2R, prothrombin time, lactate dehydrogenase, and hypersensitive troponin T (p = 0.002, p = 0.009, and p < 0.001, respectively). In addition, the time that it took for the nucleic acid test to turn negative was significantly shorter for patients in the mild group than for those in the severe group (Z = -6.713, p < 0.001). In conclusion, relative SARS-CoV-2 RNA load in the nasopharynx is closely related to COVID-19 severity. If the relative RNA load was higher, the lymphocyte count was lower, organ damage was greater, and the time it took for the nucleic acid test to turn negative was longer.


Subject(s)
COVID-19/immunology , Lymphocyte Count , Nasopharynx/virology , RNA, Viral/analysis , Severity of Illness Index , Viral Load , Adolescent , Adult , Aged , CD4 Lymphocyte Count , CD8-Positive T-Lymphocytes/immunology , COVID-19/blood , COVID-19 Nucleic Acid Testing , Female , Humans , Male , Middle Aged , RNA, Viral/genetics , Retrospective Studies , Young Adult
16.
HIV Med ; 22(9): 867-876, 2021 10.
Article in English | MEDLINE | ID: covidwho-1331728

ABSTRACT

OBJECTIVES: We compared the characteristics and clinical outcomes of hospitalized individuals with COVID-19 with [people with HIV (PWH)] and without (non-PWH) HIV co-infection in Spain during the first wave of the pandemic. METHODS: This was a retrospective matched cohort study. People with HIV were identified by reviewing clinical records and laboratory registries of 10 922 patients in active-follow-up within the Spanish HIV Research Network (CoRIS) up to 30 June 2020. Each hospitalized PWH was matched with five non-PWH of the same age and sex randomly selected from COVID-19@Spain, a multicentre cohort of 4035 patients hospitalized with confirmed COVID-19. The main outcome was all-cause in-hospital mortality. RESULTS: Forty-five PWH with PCR-confirmed COVID-19 were identified in CoRIS, 21 of whom were hospitalized. A total of 105 age/sex-matched controls were selected from the COVID-19@Spain cohort. The median age in both groups was 53 (Q1-Q3, 46-56) years, and 90.5% were men. In PWH, 19.1% were injecting drug users, 95.2% were on antiretroviral therapy, 94.4% had HIV-RNA < 50 copies/mL, and the median (Q1-Q3) CD4 count was 595 (349-798) cells/µL. No statistically significant differences were found between PWH and non-PWH in number of comorbidities, presenting signs and symptoms, laboratory parameters, radiology findings and severity scores on admission. Corticosteroids were administered to 33.3% and 27.4% of PWH and non-PWH, respectively (P = 0.580). Deaths during admission were documented in two (9.5%) PWH and 12 (11.4%) non-PWH (P = 0.800). CONCLUSIONS: Our findings suggest that well-controlled HIV infection does not modify the clinical presentation or worsen clinical outcomes of COVID-19 hospitalization.


Subject(s)
COVID-19/epidemiology , Drug Users/statistics & numerical data , HIV Infections/epidemiology , Hospitalization/statistics & numerical data , Adolescent , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Aged, 80 and over , Anti-HIV Agents/therapeutic use , CD4 Lymphocyte Count , COVID-19/drug therapy , COVID-19/mortality , Child , Child, Preschool , Female , HIV Infections/drug therapy , HIV Infections/mortality , Humans , Infant , Infant, Newborn , Male , Middle Aged , Retrospective Studies , Spain/epidemiology , Young Adult
17.
Nat Med ; 27(9): 1530-1535, 2021 09.
Article in English | MEDLINE | ID: covidwho-1327210

ABSTRACT

Heterologous priming with the ChAdOx1 nCoV-19 vector vaccine followed by boosting with a messenger RNA vaccine (BNT162b2 or mRNA-1273) is currently recommended in Germany, although data on immunogenicity and reactogenicity are not available. In this observational study we show that, in healthy adult individuals (n = 96), the heterologous vaccine regimen induced spike-specific IgG, neutralizing antibodies and spike-specific CD4 T cells, the levels of which which were significantly higher than after homologous vector vaccine boost (n = 55) and higher or comparable in magnitude to homologous mRNA vaccine regimens (n = 62). Moreover, spike-specific CD8 T cell levels after heterologous vaccination were significantly higher than after both homologous regimens. Spike-specific T cells were predominantly polyfunctional with largely overlapping cytokine-producing phenotypes in all three regimens. Recipients of both the homologous vector regimen and the heterologous vector/mRNA combination reported greater reactogenicity following the priming vector vaccination, whereas heterologous boosting was well tolerated and comparable to homologous mRNA boosting. Taken together, heterologous vector/mRNA boosting induces strong humoral and cellular immune responses with acceptable reactogenicity profiles.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 Vaccines/immunology , Immunization, Secondary/methods , SARS-CoV-2/immunology , CD4 Lymphocyte Count , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , COVID-19/prevention & control , Humans , Immunogenicity, Vaccine/immunology , Immunoglobulin G/blood , Spike Glycoprotein, Coronavirus/immunology , Vaccination
18.
Nat Med ; 27(9): 1525-1529, 2021 09.
Article in English | MEDLINE | ID: covidwho-1310811

ABSTRACT

Currently approved viral vector-based and mRNA-based vaccine approaches against coronavirus disease 2019 (COVID-19) consider only homologous prime-boost vaccination. After reports of thromboembolic events, several European governments recommended using AstraZeneca's ChAdOx1-nCov-19 (ChAd) only in individuals older than 60 years, leaving millions of already ChAd-primed individuals with the decision to receive either a second shot of ChAd or a heterologous boost with mRNA-based vaccines. However, such combinations have not been tested so far. We used Hannover Medical School's COVID-19 Contact Study cohort of healthcare professionals to monitor ChAd-primed immune responses before and 3 weeks after booster with ChAd (n = 32) or BioNTech/Pfizer's BNT162b2 (n = 55). Although both vaccines boosted prime-induced immunity, BNT162b2 induced significantly higher frequencies of spike-specific CD4+ and CD8+ T cells and, in particular, high titers of neutralizing antibodies against the B.1.1.7, B.1.351 and P.1 variants of concern of severe acute respiratory syndrome coronavirus 2.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , SARS-CoV-2/immunology , CD4 Lymphocyte Count , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Humans , Immunization, Secondary/methods , Immunogenicity, Vaccine/immunology , Spike Glycoprotein, Coronavirus/immunology , Vaccination
19.
AIDS ; 34(12): 1789-1794, 2020 10 01.
Article in English | MEDLINE | ID: covidwho-1301407

ABSTRACT

BACKGROUND: There are limited data describing the presenting characteristics and outcomes among US persons with HIV (PWH) requiring hospitalization for coronavirus disease 2019 (COVID-19). METHODS: We performed a case series of all PWH sequentially admitted with COVID-19 from 8 March 2020 to 23 April 2020 at three hospitals in Atlanta, Georgia. Sociodemographic, clinical and HIV-associated characteristics were collected. RESULTS: Of 530 confirmed COVID-19 cases hospitalized during this period, 20 occurred among PWH (3.8%). The median age was 57 (Q1-Q3, 48-62) years, 65% were men, and 85% were non-Hispanic Black. Presenting median symptom duration was 5 (Q1-Q3, 3-7) days; cough (90%), fever (65%), malaise (60%) and dyspnea (60%) were most common. On admission, 40% of patients required oxygenation support and 65% had an abnormal chest radiograph. Median length of hospitalization was 5 (Q1-Q3, 4-12) days, 30% required intensive care, 15% required intubation, and 15% died. Median CD4 cell count prior to admission was 425 (Q1-Q3, 262-815) cells/µl and 90% of patients had HIV-1 RNA less than 200 copies/ml. Half of the patients had at least five comorbidities; hypertension (70%), dyslipidemia (60%) and diabetes (45%) were most prevalent. All three patients who died had CD4 cell count more than 200, HIV suppression and each had a total of five comorbidities. CONCLUSION: The multisite series in the Southern United States provides characteristics and early outcomes of hospitalized PWH with COVID-19. Nearly all patients had controlled HIV and a high comorbidity burden. Additional study of COVID-19 among PWH is needed to determine the role of age, comorbidities and HIV control in mediating COVID-19 presentation and its sequelae.


Subject(s)
Coronavirus Infections/epidemiology , HIV Infections/epidemiology , Pneumonia, Viral/epidemiology , African Americans/statistics & numerical data , CD4 Lymphocyte Count , COVID-19 , Comorbidity , Coronavirus Infections/ethnology , Coronavirus Infections/therapy , Female , Georgia/epidemiology , HIV Infections/ethnology , HIV Infections/therapy , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/ethnology , Pneumonia, Viral/therapy , Retrospective Studies
20.
Lancet HIV ; 8(8): e474-e485, 2021 08.
Article in English | MEDLINE | ID: covidwho-1275800

ABSTRACT

BACKGROUND: Data on vaccine immunogenicity against SARS-CoV-2 are needed for the 40 million people globally living with HIV who might have less functional immunity and more associated comorbidities than the general population. We aimed to explore safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in people with HIV. METHODS: In this single-arm open-label vaccination substudy within the protocol of the larger phase 2/3 trial COV002, adults aged 18-55 years with HIV were enrolled at two HIV clinics in London, UK. Eligible participants were required to be on antiretroviral therapy (ART), with undetectable plasma HIV viral loads (<50 copies per mL), and CD4 counts of more than 350 cells per µL. A prime-boost regimen of ChAdOx1 nCoV-19, with two doses was given 4-6 weeks apart. The primary outcomes for this substudy were safety and reactogenicity of the vaccine, as determined by serious adverse events and solicited local and systemic reactions. Humoral responses were measured by anti-spike IgG ELISA and antibody-mediated live virus neutralisation. Cell-mediated immune responses were measured by ex-vivo IFN-γ enzyme-linked immunospot assay (ELISpot) and T-cell proliferation. All outcomes were compared with an HIV-uninfected group from the main COV002 study within the same age group and dosing strategy and are reported until day 56 after prime vaccination. Outcomes were analysed in all participants who received both doses and with available samples. The COV002 study is registered with ClinicalTrials.gov, NCT04400838, and is ongoing. FINDINGS: Between Nov 5 and Nov 24, 2020, 54 participants with HIV (all male, median age 42·5 years [IQR 37·2-49·8]) were enrolled and received two doses of ChAdOx1 nCoV-19. Median CD4 count at enrolment was 694·0 cells per µL (IQR 573·5-859·5). No serious adverse events occurred. Local and systemic reactions occurring during the first 7 days after prime vaccination included pain at the injection site (26 [49%] of 53 participants with available data), fatigue (25 [47%]), headache (25 [47%]), malaise (18 [34%]), chills (12 [23%]), muscle ache (19 [36%]), joint pain (five [9%]), and nausea (four [8%]), the frequencies of which were similar to the HIV-negative participants. Anti-spike IgG responses by ELISA peaked at day 42 (median 1440 ELISA units [EUs; IQR 704-2728]; n=50) and were sustained until day 56 (median 941 EUs [531-1445]; n=49). We found no correlation between the magnitude of the anti-spike IgG response at day 56 and CD4 cell count (p=0·93) or age (p=0·48). ELISpot and T-cell proliferative responses peaked at day 14 and 28 after prime dose and were sustained to day 56. Compared with participants without HIV, we found no difference in magnitude or persistence of SARS-CoV-2 spike-specific humoral or cellular responses (p>0·05 for all analyses). INTERPRETATION: In this study of people with HIV, ChAdOx1 nCoV-19 was safe and immunogenic, supporting vaccination for those well controlled on ART. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.


Subject(s)
Antibodies, Viral/blood , COVID-19 Vaccines/immunology , COVID-19/prevention & control , HIV Infections/immunology , SARS-CoV-2/immunology , Adult , CD4 Lymphocyte Count , COVID-19 Vaccines/adverse effects , HIV Infections/drug therapy , Humans , Male , Middle Aged , Vaccination
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