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1.
Cell Host Microbe ; 30(2): 154-162.e5, 2022 02 09.
Article in English | MEDLINE | ID: covidwho-1708092

ABSTRACT

Characterizing SARS-CoV-2 evolution in specific geographies may help predict properties of the variants that come from these regions. We mapped neutralization of a SARS-CoV-2 strain that evolved over 6 months from ancestral virus in a person with advanced HIV disease in South Africa; this person was infected prior to emergence of the Beta and Delta variants. We longitudinally tracked the evolved virus and tested it against self-plasma and convalescent plasma from ancestral, Beta, and Delta infections. Early virus was similar to ancestral, but it evolved a multitude of mutations found in Omicron and other variants. It showed substantial but incomplete Pfizer BNT162b2 escape, weak neutralization by self-plasma, and despite pre-dating Delta, it also showed extensive escape of Delta infection-elicited neutralization. This example is consistent with the notion that SARS-CoV-2 evolving in individual immune-compromised hosts, including those with advanced HIV disease, may gain immune escape of vaccines and enhanced escape of Delta immunity, and this has implications for vaccine breakthrough and reinfections.


Subject(s)
Antibodies, Neutralizing/blood , HIV Infections/pathology , Immune Evasion/immunology , Immunogenicity, Vaccine/immunology , SARS-CoV-2/immunology , Adult , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19 Vaccines/immunology , Cell Line , Chlorocebus aethiops , Female , HIV-1/immunology , Humans , Immunocompromised Host/immunology , Neutralization Tests , SARS-CoV-2/isolation & purification , South Africa , Vaccination , Vero Cells
2.
Clin Infect Dis ; 2021 Sep 02.
Article in English | MEDLINE | ID: covidwho-1700901

ABSTRACT

BACKGROUND: There is limited understanding of SARS-CoV-2 pathogenesis in African populations with a high burden of infectious disease comorbidities such as HIV. The kinetics, magnitude and duration of virus-specific antibodies and the underlying B cell responses in people living with HIV (PLWH) in sub-Saharan Africa have not been fully characterized. METHODS: We longitudinally followed SARS-CoV-2 infected individuals in Durban, KwaZulu-Natal, South Africa and characterized SARS-CoV-2 receptor binding domain-specific IgM, IgG and IgA antibodies weekly for a month, and then at 3 months post diagnosis. 7/30 (41.7%) were PLWH, 83% (25/30) of which were on ART and with full HIV suppression. Potency of convalescent plasma neutralization was determined using a live virus neutralization assay and antibody secreting cell population frequencies were determined by flow cytometry. RESULTS: Similar seroconversion rates, time to peak antibody titer, peak magnitude and durability of anti-SARS-CoV-2 IgM, IgG, IgA, were observed in HIV uninfected and PLWH with complete HIV suppression on ART. In addition, similar neutralization potency against an isolate of SARS-CoV-2, circulating at the time of sampling in the first wave of SARS-CoV-2 infections in South Africa was observed in both groups. Loss of IgA was significantly associated with age (p=0.023) and a previous diagnosis of TB (p=0.018). CONCLUSIONS: Similar antibody response kinetics and neutralization potency in HIV negative and PLWH on stable ART in an African setting suggests that COVID-19 natural infections may confer comparable antibody immunity in these groups. This provides hope that COVID-19 vaccines will be effective in PLWH on stable ART.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-321510

ABSTRACT

A coordinated system of disease surveillance will be critical to effectively control the coronavirus disease 2019 (Covid-19) pandemic. Such systems enable rapid detection and mapping of epidemics and inform allocation of scarce prevention and intervention resources. Although many lower- and middle-income settings lack infrastructure for optimal disease surveillance, health and demographic surveillance systems (HDSS) provide a unique opportunity for epidemic monitoring. This protocol describes a surveillance program at the Africa Health Research Institute’s Population Intervention Platform site in northern KwaZulu-Natal. The program leverages a longstanding HDSS in a rural, resource-limited setting with very high prevalence of HIV and tuberculosis to perform Covid-19 surveillance. Our primary aims include: describing the epidemiology of the Covid-19 epidemic in rural KwaZulu-Natal;determining the impact of the Covid-19 outbreak and non-pharmaceutical control interventions (NPI) on behaviour and wellbeing;determining the impact of HIV and tuberculosis on Covid-19 susceptibility;and using collected data to support the local public-sector health response. The program involves telephone-based interviews with over 20,000 households every four months, plus a sub-study calling 750 households every two weeks. Each call asks a household representative how the epidemic and NPI are affecting the household and conducts a Covid-19 risk screen for all resident members. Any individuals screening positive are invited to a clinical screen, potential test and referral to necessary care – conducted in-person near their home following careful risk minimization procedures. In this protocol we report the details of our cohort design, questionnaires, data and reporting structures, and standard operating procedures in hopes that our project can inform similar efforts elsewhere.

4.
AIDS ; 35(14): 2391-2393, 2021 11 15.
Article in English | MEDLINE | ID: covidwho-1494132
5.
Elife ; 102021 10 05.
Article in English | MEDLINE | ID: covidwho-1450948

ABSTRACT

There are conflicting reports on the effects of HIV on COVID-19. Here, we analyzed disease severity and immune cell changes during and after SARS-CoV-2 infection in 236 participants from South Africa, of which 39% were people living with HIV (PLWH), during the first and second (Beta dominated) infection waves. The second wave had more PLWH requiring supplemental oxygen relative to HIV-negative participants. Higher disease severity was associated with low CD4 T cell counts and higher neutrophil to lymphocyte ratios (NLR). Yet, CD4 counts recovered and NLR stabilized after SARS-CoV-2 clearance in wave 2 infected PLWH, arguing for an interaction between SARS-CoV-2 and HIV infection leading to low CD4 and high NLR. The first infection wave, where severity in HIV negative and PLWH was similar, still showed some HIV modulation of SARS-CoV-2 immune responses. Therefore, HIV infection can synergize with the SARS-CoV-2 variant to change COVID-19 outcomes.


Subject(s)
COVID-19/complications , COVID-19/immunology , HIV Infections/complications , HIV Infections/immunology , Immunity, Cellular , Severity of Illness Index , Adult , Aged , CD4 Lymphocyte Count , Female , Humans , Male , Middle Aged , SARS-CoV-2 , South Africa
6.
Clin Infect Dis ; 2021 Sep 02.
Article in English | MEDLINE | ID: covidwho-1393221

ABSTRACT

BACKGROUND: There is limited understanding of SARS-CoV-2 pathogenesis in African populations with a high burden of infectious disease comorbidities such as HIV. The kinetics, magnitude and duration of virus-specific antibodies and the underlying B cell responses in people living with HIV (PLWH) in sub-Saharan Africa have not been fully characterized. METHODS: We longitudinally followed SARS-CoV-2 infected individuals in Durban, KwaZulu-Natal, South Africa and characterized SARS-CoV-2 receptor binding domain-specific IgM, IgG and IgA antibodies weekly for a month, and then at 3 months post diagnosis. 7/30 (41.7%) were PLWH, 83% (25/30) of which were on ART and with full HIV suppression. Potency of convalescent plasma neutralization was determined using a live virus neutralization assay and antibody secreting cell population frequencies were determined by flow cytometry. RESULTS: Similar seroconversion rates, time to peak antibody titer, peak magnitude and durability of anti-SARS-CoV-2 IgM, IgG, IgA, were observed in HIV uninfected and PLWH with complete HIV suppression on ART. In addition, similar neutralization potency against an isolate of SARS-CoV-2, circulating at the time of sampling in the first wave of SARS-CoV-2 infections in South Africa was observed in both groups. Loss of IgA was significantly associated with age (p=0.023) and a previous diagnosis of TB (p=0.018). CONCLUSIONS: Similar antibody response kinetics and neutralization potency in HIV negative and PLWH on stable ART in an African setting suggests that COVID-19 natural infections may confer comparable antibody immunity in these groups. This provides hope that COVID-19 vaccines will be effective in PLWH on stable ART.

7.
Lancet Glob Health ; 9(7): e967-e976, 2021 07.
Article in English | MEDLINE | ID: covidwho-1271838

ABSTRACT

BACKGROUND: There has been remarkable progress in the treatment of HIV throughout sub-Saharan Africa, but there are few data on the prevalence and overlap of other significant causes of disease in HIV endemic populations. Our aim was to identify the prevalence and overlap of infectious and non-communicable diseases in such a population in rural South Africa. METHODS: We did a cross-sectional study of eligible adolescents and adults from the Africa Health Research Institute demographic surveillance area in the uMkhanyakude district of KwaZulu-Natal, South Africa. The participants, who were 15 years or older, were invited to participate at a mobile health camp. Medical history for HIV, tuberculosis, hypertension, and diabetes was established through a questionnaire. Blood pressure measurements, chest x-rays, and tests of blood and sputum were taken to estimate the population prevalence and geospatial distribution of HIV, active and lifetime tuberculosis, elevated blood glucose, elevated blood pressure, and combinations of these. FINDINGS: 17 118 adolescents and adults were recruited from May 25, 2018, to Nov 28, 2019, and assessed. Overall, 52·1% (95% CI 51·3-52·9) had at least one active disease. 34·2% (33·5-34·9) had HIV, 1·4% (1·2-1·6) had active tuberculosis, 21·8% (21·2-22·4) had lifetime tuberculosis, 8·5% (8·1-8·9) had elevated blood glucose, and 23·0% (22·4-23·6) had elevated blood pressure. Appropriate treatment and optimal disease control was highest for HIV (78·1%), and lower for elevated blood pressure (42·5%), active tuberculosis (29·6%), and elevated blood glucose (7·1%). Disease prevalence differed notably by sex, across age groups, and geospatially: men had a higher prevalence of active and lifetime tuberculosis, whereas women had a substantially high prevalence of HIV at 30-49 years and an increasing prevalence of multiple and poorly controlled non-communicable diseases when older than 50 years. INTERPRETATION: We found a convergence of infectious and non-communicable disease epidemics in a rural South African population, with HIV well treated relative to all other diseases, but tuberculosis, elevated blood glucose, and elevated blood pressure poorly diagnosed and treated. A public health response that expands the successes of the HIV testing and treatment programme to provide multidisease care targeted to specific populations is required to optimise health in such settings in sub-Saharan Africa. FUNDING: Wellcome Trust, Bill & Melinda Gates Foundation, the South African Department of Science and Innovation, South African Medical Research Council, and South African Population Research Infrastructure Network. TRANSLATION: For the isiZulu translation of the abstract see Supplementary Materials section.


Subject(s)
Diabetes Mellitus/epidemiology , Epidemics , HIV Infections/epidemiology , Hypertension/epidemiology , Rural Health/statistics & numerical data , Tuberculosis/epidemiology , Adolescent , Adult , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Multimorbidity , Prevalence , South Africa/epidemiology
8.
Future Virology ; 15(9):609-609–624, 2020.
Article in English | ProQuest Central | ID: covidwho-1136398

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by SARS coronavirus 2 (SARS-CoV-2), is spreading rapidly with no established effective treatments. While most cases are mild, others experience uncontrolled inflammatory responses with oxidative stress, dysregulation of iron and coagulation as features. Lactoferrin, ovotransferrin and lysozyme are abundant, safe antimicrobials that have wide antiviral as well as immunomodulatory properties. In particular, lactoferrin restores iron homeostasis and inhibits replication of SARS-CoV, which is closely related to SARS-CoV-2. Ovotransferrin has antiviral peptides and activities that are shared with lactoferrin. Both lactoferrin and lysozyme are ‘immune sensing’ as they may stimulate immune responses or resolve inflammation. Mechanisms by which these antimicrobials may treat or prevent COVID-19, as well as sources and forms of these, are reviewed.

9.
Wellcome Open Res ; 5: 109, 2020.
Article in English | MEDLINE | ID: covidwho-1027389

ABSTRACT

A coordinated system of disease surveillance will be critical to effectively control the coronavirus disease 2019 (Covid-19) pandemic. Such systems enable rapid detection and mapping of epidemics and inform allocation of scarce prevention and intervention resources. Although many lower- and middle-income settings lack infrastructure for optimal disease surveillance, health and demographic surveillance systems (HDSS) provide a unique opportunity for epidemic monitoring. This protocol describes a surveillance program at the Africa Health Research Institute's Population Intervention Platform site in northern KwaZulu-Natal. The program leverages a longstanding HDSS in a rural, resource-limited setting with very high prevalence of HIV and tuberculosis to perform Covid-19 surveillance. Our primary aims include: describing the epidemiology of the Covid-19 epidemic in rural KwaZulu-Natal; determining the impact of the Covid-19 outbreak and non-pharmaceutical control interventions (NPI) on behaviour and wellbeing; determining the impact of HIV and tuberculosis on Covid-19 susceptibility; and using collected data to support the local public-sector health response. The program involves telephone-based interviews with over 20,000 households every four months, plus a sub-study calling 750 households every two weeks. Each call asks a household representative how the epidemic and NPI are affecting the household and conducts a Covid-19 risk screen for all resident members. Any individuals screening positive are invited to a clinical screen, potential test and referral to necessary care - conducted in-person near their home following careful risk minimization procedures. In this protocol we report the details of our cohort design, questionnaires, data and reporting structures, and standard operating procedures in hopes that our project can inform similar efforts elsewhere.

10.
ProQuest Central; 2020.
Preprint in English | ProQuest Central | ID: ppcovidwho-2115

ABSTRACT

A coordinated system of disease surveillance will be critical to effectively control the coronavirus disease 2019 (Covid-19) pandemic. Such systems enable rapid detection and mapping of epidemics and inform allocation of scarce prevention and intervention resources. Although many lower- and middle-income settings lack infrastructure for optimal disease surveillance, health and demographic surveillance systems (HDSS) provide a unique opportunity for epidemic monitoring. This protocol describes a surveillance program at the Africa Health Research Institute’s Population Intervention Platform site in northern KwaZulu-Natal. The program leverages a longstanding HDSS in a rural, resource-limited setting with very high prevalence of HIV and tuberculosis to perform Covid-19 surveillance. Our primary aims include: describing the epidemiology of the Covid-19 epidemic in rural KwaZulu-Natal;determining the impact of the Covid-19 outbreak and non-pharmaceutical control interventions (NPI) on behaviour and wellbeing;determining the impact of HIV and tuberculosis on Covid-19 susceptibility;and using collected data to support the local public-sector health response. The program involves telephone-based interviews with over 20,000 households every four months, plus a sub-study calling 750 households every two weeks. Each call asks a household representative how the epidemic and NPare affecting the household and conducts a Covid-19 risk screen for all resident members. Any individuals screening positive are invited to a clinical screen, potential test and referral to necessary care – conducted in-person near their home following careful risk minimization procedures. In this protocol we report the details of our cohort design, questionnaires, data and reporting structures, and standard operating procedures in hopes that our project can inform similar efforts elsewhere.

11.
Wellcome Open Res ; 5:109-109, 2020.
Article in English | MEDLINE | ID: covidwho-721642

ABSTRACT

A coordinated system of disease surveillance will be critical to effectively control the coronavirus disease 2019 (Covid-19) pandemic. Such systems enable rapid detection and mapping of epidemics and inform allocation of scarce prevention and intervention resources. Although many lower- and middle-income settings lack infrastructure for optimal disease surveillance, health and demographic surveillance systems (HDSS) provide a unique opportunity for epidemic monitoring. This protocol describes a surveillance program at the Africa Health Research Institute's Population Intervention Platform site in northern KwaZulu-Natal. The program leverages a longstanding HDSS in a rural, resource-limited setting with very high prevalence of HIV and tuberculosis to perform Covid-19 surveillance. Our primary aims include: describing the epidemiology of the Covid-19 epidemic in rural KwaZulu-Natal;determining the impact of the Covid-19 outbreak and non-pharmaceutical control interventions (NPI) on behaviour and wellbeing;determining the impact of HIV and tuberculosis on Covid-19 susceptibility;and using collected data to support the local public-sector health response. The program involves telephone-based interviews with over 20,000 households every four months, plus a sub-study calling 750 households every two weeks. Each call asks a household representative how the epidemic and NPI are affecting the household and conducts a Covid-19 risk screen for all resident members. Any individuals screening positive are invited to a clinical screen, potential test and referral to necessary care - conducted in-person near their home following careful risk minimization procedures. In this protocol we report the details of our cohort design, questionnaires, data and reporting structures, and standard operating procedures in hopes that our project can inform similar efforts elsewhere.

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