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1.
Viruses ; 14(6)2022 05 27.
Article in English | MEDLINE | ID: covidwho-1911611

ABSTRACT

Globally, most Human Immunodeficiency Virus type 1 (HIV) transmission occurs through vaginal-penile sex (heterosexual transmission). The local immune environment at the site of HIV exposure is an important determinant of whether exposure during sex will lead to productive infection, and the vaginal and penile immune milieus are each critically shaped by the local microbiome. However, there are key differences in the microbial drivers of inflammation and immune quiescence at these tissue sites. In both, a high abundance of anaerobic taxa (e.g., Prevotella) is associated with an increased local density of HIV target cells and an increased risk of acquiring HIV through sex. However, the taxa that have been associated to date with increased risk in the vagina and penis are not identical. Just as importantly, the microbiota associated with comparatively less inflammation and HIV risk-i.e., the optimal microbiota-are very different at the two sites. In the vagina, Lactobacillus spp. are immunoregulatory and may protect against HIV acquisition, whereas on the penis, "skin type" flora such as Corynebacterium are associated with reduced inflammation. Compared to its vaginal counterpart, much less is known about the dynamics of the penile microbiome, the ability of clinical interventions to alter the penile microbiome, or the impact of natural/induced microbiome alterations on penile immunology and HIV risk.


Subject(s)
HIV Infections , HIV-1 , Female , Humans , Inflammation , Male , Penis , Vagina/microbiology
2.
J Virol ; 96(13): e0050922, 2022 07 13.
Article in English | MEDLINE | ID: covidwho-1891737

ABSTRACT

Cell-mediated immunity is critical for long-term protection against most viral infections, including coronaviruses. We studied 23 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected survivors over a 1-year post-symptom onset (PSO) interval by ex vivo cytokine enzyme-linked immunosorbent spot assay (ELISpot) assay. All subjects demonstrated SARS-CoV-2-specific gamma interferon (IFN-γ), interleukin 2 (IL-2), and granzyme B (GzmB) T cell responses at presentation, with greater frequencies in severe disease. Cytokines, mainly produced by CD4+ T cells, targeted all structural proteins (nucleocapsid, membrane, and spike) except envelope, with GzmB and IL-2 greater than IFN-γ. Mathematical modeling predicted that (i) cytokine responses peaked at 6 days for IFN-γ, 36 days for IL-2, and 7 days for GzmB, (ii) severe illness was associated with reduced IFN-γ and GzmB but increased IL-2 production rates, and (iii) males displayed greater production of IFN-γ, whereas females produced more GzmB. Ex vivo responses declined over time, with persistence of IL-2 in 86% and of IFN-γ and GzmB in 70% of subjects at a median of 336 days PSO. The average half-life of SARS-CoV-2-specific cytokine-producing cells was modeled to be 139 days (~4.6 months). Potent T cell proliferative responses persisted throughout observation, were CD4 dominant, and were capable of producing all 3 cytokines. Several immunodominant CD4 and CD8 epitopes identified in this study were shared by seasonal coronaviruses or SARS-CoV-1 in the nucleocapsid and membrane regions. Both SARS-CoV-2-specific CD4+ and CD8+ T cell clones were able to kill target cells, though CD8 tended to be more potent. IMPORTANCE Our findings highlight the relative importance of SARS-CoV-2-specific GzmB-producing T cell responses in SARS-CoV-2 control and shared CD4 and CD8 immunodominant epitopes in seasonal coronaviruses or SARS-CoV-1, and they indicate robust persistence of T cell memory at least 1 year after infection. Our findings should inform future strategies to induce T cell vaccines against SARS-CoV-2 and other coronaviruses.


Subject(s)
COVID-19 , Cytokines , Immunity , SARS-CoV-2 , CD4-Positive T-Lymphocytes , CD8-Positive T-Lymphocytes , COVID-19/immunology , COVID-19 Vaccines , Cytokines/immunology , Female , Humans , Immunologic Memory , Interferon-gamma/metabolism , Interleukin-2/immunology , Male , Severity of Illness Index , Time Factors
3.
JAMA Netw Open ; 5(2): e2146798, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1694847

ABSTRACT

Importance: The incidence of infection during SARS-CoV-2 viral waves, the factors associated with infection, and the durability of antibody responses to infection among Canadian adults remain undocumented. Objective: To assess the cumulative incidence of SARS-CoV-2 infection during the first 2 viral waves in Canada by measuring seropositivity among adults. Design, Setting, and Participants: The Action to Beat Coronavirus study conducted 2 rounds of an online survey about COVID-19 experience and analyzed immunoglobulin G levels based on participant-collected dried blood spots (DBS) to assess the cumulative incidence of SARS-CoV-2 infection during the first and second viral waves in Canada. A sample of 19 994 Canadian adults (aged ≥18 years) was recruited from established members of the Angus Reid Forum, a public polling organization. The study comprised 2 phases (phase 1 from May 1 to September 30, 2020, and phase 2 from December 1, 2020, to March 31, 2021) that generally corresponded to the first (April 1 to July 31, 2020) and second (October 1, 2020, to March 1, 2021) viral waves. Main Outcomes and Measures: SARS-CoV-2 immunoglobulin G seropositivity (using a chemiluminescence assay) by major geographic and demographic variables and correlation with COVID-19 symptom reporting. Results: Among 19 994 adults who completed the online questionnaire in phase 1, the mean (SD) age was 50.9 (15.4) years, and 10 522 participants (51.9%) were female; 2948 participants (14.5%) had self-identified racial and ethnic minority group status, and 1578 participants (8.2%) were self-identified Indigenous Canadians. Among participants in phase 1, 8967 had DBS testing. In phase 2, 14 621 adults completed online questionnaires, and 7102 of those had DBS testing. Of 19 994 adults who completed the online survey in phase 1, fewer had an educational level of some college or less (4747 individuals [33.1%]) compared with the general population in Canada (45.0%). Survey respondents were otherwise representative of the general population, including in prevalence of known risk factors associated with SARS-CoV-2 infection. The cumulative incidence of SARS-CoV-2 infection among unvaccinated adults increased from 1.9% in phase 1 to 6.5% in phase 2. The seropositivity pattern was demographically and geographically heterogeneous during phase 1 but more homogeneous by phase 2 (with a cumulative incidence ranging from 6.4% to 7.0% in most regions). The exception was the Atlantic region, in which cumulative incidence reached only 3.3% (odds ratio [OR] vs Ontario, 0.46; 95% CI, 0.21-1.02). A total of 47 of 188 adults (25.3%) reporting COVID-19 symptoms during phase 2 were seropositive, and the OR of seropositivity for COVID-19 symptoms was 6.15 (95% CI, 2.02-18.69). In phase 2, 94 of 444 seropositive adults (22.2%) reported having no symptoms. Of 134 seropositive adults in phase 1 who were retested in phase 2, 111 individuals (81.8%) remained seropositive. Participants who had a history of diabetes (OR, 0.58; 95% CI, 0.38-0.90) had lower odds of having detectable antibodies in phase 2. Conclusions and Relevance: The Action to Beat Coronavirus study found that the incidence of SARS-CoV-2 infection in Canada was modest until March 2021, and this incidence was lower than the levels of population immunity required to substantially reduce transmission of the virus. Ongoing vaccination efforts remain central to reducing viral transmission and mortality. Assessment of future infection-induced and vaccine-induced immunity is practicable through the use of serial online surveys and participant-collected DBS.


Subject(s)
COVID-19 Serological Testing/statistics & numerical data , COVID-19/epidemiology , Immunoglobulin G/blood , Adolescent , Adult , Aged , COVID-19/immunology , Canada/epidemiology , Female , Humans , Incidence , Male , Middle Aged , Pandemics , SARS-CoV-2 , Surveys and Questionnaires
4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-322524

ABSTRACT

Background: The prevalence of infection in Canada’s COVID-19 viral waves, the predictors of infection, and the durability of antibody responses to infection remain undocumented.Methods: We organized serial online surveys of a representative group of Canadian adults about their COVID experience in the first (n=19 994;April-July 2020) and second viral wave (n=14 621;October 2020-March 2021). We paired these with IgG analysis of SARS-CoV-2 seroprevalence in self-collected dried blood spots after the first (n=8967) and second (n=7102) waves.Findings: Canada’s cumulative seroprevalence of SARS-CoV-2 among unvaccinated adults rose from ~2% after the first wave to 7% after the second. The seropositivity pattern was heterogeneous demographically and geographically during the first wave, but more homogeneous by the second (except in the four Atlantic Provinces, cumulative seroprevalence ~3%). Seroprevalence among visible minorities rose sharply from about 2% to >8% from the first to second wave. About a quarter of those reporting COVID symptoms during the second wave were seropositive, and in both waves the odds ratio (OR) of seropositivity for COVID symptoms exceeded six. About one-fifth of seropositives reported no symptoms. Of 134 seropositive adults in the first wave who were retested after the second, 83% (111) remained seropositive at least seven months later. Current smokers and people with a history of diabetes had lower ORs of infection. We calculated the absolute numbers of seropositive adults nationwide, which nearly quadrupled from 0.57 million to 1.90 million, with the largest increases among older adults. Infection fatality rates fell from 3.7 to 2.6/1000 infections, most notably at older ages.Interpretation: Canada’s COVID pandemic grew substantially between the first and second viral waves. Home-based DBS collection offers a practicable way to document evolving demographic and geographic patterns and to assess the levels and durability of population immunity, including from SARS-CoV-2 vaccination.Funding: Pfizer Global Medical, Unity Health Foundation, and the Canadian COVID-19 Immunity Task Force. Declaration of Interest: None to declare. Ethical Approval: The Ab-C study was approved by the Unity Health Toronto Ethics Review Board.

5.
J Telemed Telecare ; : 1357633X211059688, 2021 Dec 28.
Article in English | MEDLINE | ID: covidwho-1582817

ABSTRACT

INTRODUCTION: In addition to shifting and expanding clinical responsibilities, rapidly evolving information and guidelines during the COVID-19 pandemic has made it difficult for health care workers (HCW) to synthesise and translate COVID-19 information into practice. This study evaluated whether a COVID-19-specific telemedicine education program (ECHO COVID) would impact health care workers' self-efficacy and satisfaction in the management of patients with COVID-19. METHODS: A prospective mixed methods parallel-design study was conducted among ECHO COVID participants using pre-post questionnaires and a focus group discussion. Questionnaire results were examined for changes in health care workers' self-efficacy and satisfaction. Focus group discussion data were analysed to explore health care workers' experience in ECHO COVID and the context of their practice during the COVID-19 pandemic. RESULTS: 239 health care workers registered in ECHO COVID and 114 (47.7%) completed questionnaires and attended at least one ECHO COVID session. Median self-efficacy scores increased from 5 (IQR 4-6) to 6 (IQR 6-6) (p < 0.0001), independent of profession, years in practice, age group, or practice environment. Participants were highly satisfied with ECHO COVID sessions with a median score of 4 (IQR 4-5). Focus group discussion data indicated that health care workers gained knowledge through ECHO COVID and revealed facilitators for ECHO COVID program success, including the transition to virtual care, the practicability of knowledge provided, and a 'perspective from the trenches.' DISCUSSION: This study demonstrated that a telemedicine education program aimed to support health care workers in managing patients with COVID-19 had a positive impact on health care workers' self-efficacy and satisfaction. This impact was specifically mediated by the ECHO COVID program.

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