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SARS-CoV-2 seropositivity in African women living with HIV and their infants

BMC Infectious Diseases volume 24, Article number: 693 (2024) Cite this article

Abstract

Background

SARS-CoV-2 seropositivity data in women living with HIV (WLHIV), their infants and associated factors in this subpopulation remain limited. We retrospectively measured SARS-CoV-2 seropositivity from 07/2020-11/2021 among WLHIV and their children in the PROMOTE observational cohort in Uganda, Malawi, and Zimbabwe prior to widespread SARS-CoV-2 vaccination in those countries.

Methods

Plasma stored during 3 waves of the COVID-19 pandemic in East/Southern Africa were tested for SARS-CoV-2 specific IgG antibodies (Ab) using serological assays that detect adaptive immune responses to SARS-CoV-2 spike protein. (EUROIMMUN, Mountain Lakes, New Jersey and Roche Diagnostics, Indianapolis, IN). Modified-Poisson regression models were used to calculate prevalence rate ratios (PRR) and 95% confidence intervals (CI) to identify sociodemographic and clinical risk factors.

Results

PROMOTE samples from 918 mothers and 1237 children were analysed. Overall, maternal SARS-CoV-2 seropositivity was 60.1% (95% CI: 56.9 -63.3) and 41.5% (95%CI: 38.8 – 44.2) for children. Non-breastfeeding mothers had a 31% higher risk of SARS-CoV-2 seropositivity compared to breastfeeding mothers (aPRR=1.31, 95%CI: 1.08-1.59). WLHIV with undetectable viral load had a 10% increased risk of SARS-CoV-2 seropositivity (aPRR=1.10, 95%CI: 0.89-1.37). Moreover, those who were normotensive had 12% increased risk SARS-CoV-2 seropositivity (aPRR= 1.12, 95% CI: 0.68-1.85) compared to women with hypertension. Children between 2 and 5 years had a 19% reduced risk of SARS-CoV-2 seropositivity (aPRR=0.81, 95%CI: 0.64-1.02) when compared to younger children. Mother/infant SARS-CoV-2 serostatuses were discordant in 346/802 (43.1%) families tested: mothers+/children- in 72.3%; mothers-/children+ in 26.3%; child+/sibling+ concordance was 34.6%.

Conclusions

These SARS-CoV-2 seropositivity data indicate that by late 2021, about 60% of mothers and about 40% of children in a cohort of HIV-affected families in eastern/southern Africa had been infected with SARS-CoV-2. More mothers than their infants tested SARS-CoV-2+, likely due to a greater external exposure for mothers linked to daily routines/employment, and school closures. Breastfeeding was protective for mothers, likely because of higher likelihood of staying home with young children, and thus less exposure. Discordant results between children within the same families underscores the need to further understand transmission dynamics within households.

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Background

The World Health Organization (WHO) declared the SARS-CoV-2 outbreak a global pandemic on March 11, 2020, following the emergence of a cluster of pneumonia cases in Wuhan, China in December 2019. The disease was later named COVID-19, whose aetiological agent was identified as a novel coronavirus (SARS-CoV-2) [1]. By May 2023, an estimated 765 million people had been infected by SARS-CoV-2 globally, with 8 million deaths recorded, a combined 174 000 of these in 47 African countries [2]. COVID-19 statistics in resource-limited settings is largely collated from national testing programs driven by clinical symptoms and thus may underestimate true spread of the disease. Consequently, there is a paucity of SARS-CoV-2 seropositivity data in the African region and most importantly among people living with HIV (PLWH) who may be at a higher risk of COVID-19 complications/mortality due to underlying compromised immunity.

Current data do not suggest higher SARS-CoV-2 infection rates among PLWH [3,4,5,6] which corroborates findings from an earlier study of blood donor samples in Uganda which reported significantly lower seropositivity to S antibody among HIV-seropositive individuals. Furthermore, some studies assessing COVID-19 severity among PLWH showed no clear evidence of poorer outcomes [7]. However, emerging data is reporting higher risk of morbidity [4] and mortality [8,9,10,11] among some HIV-SARS-CoV-2 co-infected patients, particularly those with low CD4 cell counts and unsuppressed HIV viraemia [12, 13]. Some studies have also postulated that use of some antiretroviral drugs may offer protection against severe outcomes among HIV/SARSCoV-2 co-infected patients [3, 14, 15]. In resource-limited settings with high background endemic infections, PLWH may be at greater risk of severe disease given the high prevalence of TB and malaria that may exacerbate both HIV and COVID-19 co-morbidities [16].

COVID-19 vulnerability has been linked to social and structural determinants like poverty, population density, and lack of access to health services, generating a syndemia of social and health related challenges [17]. In this regard, PLWH share many structural factors for heightened SARS-CoV-2 acquisition and severity of the co-infection. PLWH have been shown to have a higher predisposition to respiratory infections due to compromised immunity when compared to the general population [18].

Data on population-level exposure and immunity to SARS-CoV-2 are fundamental in understanding transmission dynamics, assess population level susceptibility, and inform public health responses. Notably, estimating the proportion of the population that has been infected, particularly in resource-constrained settings, is compounded by asymptomatic or subclinical infections, inadequate testing capacity, and challenges in collecting routine surveillance data [19]. Seropositivity surveys can overcome these issues by identifying antibody responses that reflect prior SARS-CoV-2 exposure.

The PEPFAR-PROMOTE study was a longitudinal five-year follow-up roll over protocol that enrolled mothers living with HIV and their HIV exposed children previously enrolled in the IMPAACT PROMISE perinatal clinical trial from eight high enrolling African sites in the PROMISE trial (NCT01061151/NCT01253538, 2010/02/02). The PROMOTE study which began in 2016 enrolled 3771 mothers and children across the eight sites in Malawi, Uganda, Zimbabwe, and South Africa. The aims of the PROMOTE study were to follow-up on maternal and child health and survival over five years of PROMOTE follow up; assess factors that affect their morbidity and mortality; maternal adherence over time to lifetime ART, longer term complications related to the HIV disease progression, ART, and co-infections among mothers living with HIV; as well as health, survival, growth, and developmental outcomes among their HIV exposed but uninfected children [20]. In the current study, we retrospectively conducted a SARS-CoV-2 seropositivity descriptive study to determine sociodemographic and clinical risk factors, maternal and pregnancy outcomes among Women Living with HIV (WLHIV) and their infants enrolled in the PEPFAR-PROMOTE observational cohort in Uganda, Malawi, and Zimbabwe. For the seropositivity surveillance analyses, data from 918 mothers and 1237 children from these sites (Malawi (Blantyre), Uganda and Zimbabwe) were included.

Methods

Study design and participants

We conducted a retrospective, cross-sectional survey to estimate SARS-CoV-2 antibody prevalence within the PEPFAR-PROMOTE observational cohort study in the midst of the COVID-19 pandemic in Eastern and Southern Africa; and before widespread COVID-19 vaccine immunisations in Malawi, Uganda, and Zimbabwe were available. The most recent or study exit visit sample was tested for each participant. All PROMOTE study participants exited the study between July 2020 and November 2021. All sites are in urban/semi-urban settings; and all women enrolled in PROMOTE were on lifelong antiretroviral therapy (ART) that conform with each country's national guidelines as the prevailing standard of care and are not provided by the study [20].

Study procedures

In the PROMOTE study, maternal follow-up evaluations were conducted every six months to collect data on medical history, ART use and adherence, physical examination, laboratory test results, and new events occurring between visits. The laboratory evaluations included viral load (HIV RNA PCR) testing every six months and complete blood count (CBC), CD4+ cell count, and serum chemistry (ALT, creatinine, and creatinine clearance) every 12 months. Blood was collected at scheduled six-monthly visits and processed plasma was stored at -80°C at the participating laboratories. In this sub-study, only samples collected at the latest visit for each participant were tested for SARS-CoV-2 antibodies and included in the analysis.

Laboratory methods

Available stored plasma samples from 918 mothers and 1237 children enrolled during PEPFAR-PROMOTE study collected between July 2020 and November 2021 were included in this analysis. For Malawi and Zimbabwe cohorts, plasma was tested using the EUROIMMUN Anti-SARS-CoV-2 ELISA (IgG) antibody assay following kit-specific instructions (EUROIMMUN, Mountain Lakes, New Jersey). The EUROIMMUN Anti-SARS-CoV-2 ELISA (IgG) is an enzyme-linked immunosorbent assay intended for the qualitative detection of IgG class antibodies to SARS-CoV-2 to the Spike-1 protein.

For the Uganda cohort, plasma samples were tested with the Roche SARS-CoV-2 IgG antibody test kits, according to the package insert using the anti-SARS-CoV-2 immunoassay (Roche Diagnostics, Indianapolis, IN) for the qualitative detection of antibodies to SARS-CoV-2. The assay uses a recombinant protein representing the nucleocapsid (N) antigen for the determination of antibodies against SARS-CoV-2. The test is used as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection. The samples were also tested according to the package insert using the anti-SARS-CoV-2 S electrochemiluminescence immunoassay (Roche Diagnostics) for qualitative and semi-quantitative detection of antibodies to SARS-CoV-2 spike (S) protein receptor binding domain (RBD) in human serum and plasma.

Statistical analysis

Maternal and infant overall SARS-CoV-2 antibody prevalence and 95% confidence intervals (CI) were calculated and reported. The confidence intervals were calculated using the score test method [21]. We utilised modified-Poisson regression models to calculate prevalence rate ratios (PRR) and 95% confidence intervals (CI) to identify marginal and conditional sociodemographic and clinical risk factors associated with SARS-CoV-2 seropositivity. Each univariable model included country. Each multivariable model included country and maternal risk factors including maternal age, employment status, marital status, level of education, availability of tap water at home, the distance between clinic and home, whether women have hypertension or not, whether they are breastfeeding or not, ART regimen and viral load. Children risk factors included country and age of the infant. SAS version 9.4 (SAS Institute, Cary, NC) was used for analyses.

Ethical considerations

The PROMOTE study was approved by all relevant institutional review boards (IRBs) and women signed a written informed consent form to enrol and be followed-up with their children for five years and to provide study samples as part of their every six-month evaluation. Only samples from participants who provided consent for testing on stored samples were included in this analysis.

Results

The study analysed samples from a total of 2155 participants (918 mothers and 1237 children) from 3 countries (Zimbabwe – 925, Malawi – 649 and Uganda-581) collected between July 2020 and November 2021 (Fig 1). Out of a total of 1237 children included in the study, 19 (1.54%) were living with HIV (Zimbabwe – 7, Malawi – 6 and Uganda - 6) The baseline characteristics were comparable between participants testing positive (+) and negative (-) for SARS-CoV-2 Ab (Table 1)

Fig. 1
figure 1

Flowchart for participants in seropositivity of SARS-CoV-2 antibodies study in three African countries between July 2020 and November 2021

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Table 1 A & B: SARS-CoV-2 antibody seropositivity for mothers (A) and their children (B) across different characteristics and distribution of variables across the two groups
Full size table

Overall, maternal SARS-CoV-2 seropositivity was 60.1% (95% CI: 56.9 -63.3) and 41.5% (95% CI: 38.8 – 44.2) for children. Country-specific SARS-CoV-2 seropositivity ranged between 46.5% to 69.8% among women and between 21.7% and 48.5% among children. Figure 2A-C shows the rates of SARS-CoV-2 antibody seropositivity over time and the periods during which COVID-19 vaccination was launched for each country.

Fig. 2
figure 2

SARS-CoV-2 antibody seropositivity estimates over time for Malawi, Uganda, and Zimbabwe. A Shows SARS-CoV-2 antibody seropositivity rates over time for mothers and their children relative to COVID-19 trends over time in Malawi. Arrow depicts the period during which national COVID-19 vaccine program was launched. Rectangular boundary represents the study sampling period. B Shows SARS-CoV-2 antibody positivity rates over time for mothers and their Children relative to COVID-19 trends over time in Uganda. Arrow depicts the period during which national COVID-19 vaccine program was launched. Rectangular boundary represents the study sampling period. C Shows SARS-CoV-2 antibody positivity rates over time for mothers and their Children relative to COVID-19 trends over time in Zimbabwe. Arrow depicts the period during which national COVID-19 vaccine program was launched. Rectangular boundary represents the study sampling period

Full size image

Mothers who were not breastfeeding prior to sample collection were associated with a 31% (aPRR=1.31, 95%CI: 1.08-1.59) increased risk of SARS-CoV-2 seropositivity compared to those who were breastfeeding. Mothers with undetectable viral load had a 10% increased risk of SARS-CoV-2 seropositivity (aPRR=1.10, 95%CI: 0.89-1.37). Moreover, those who were not hypertensive had 12% increased risk SARS-CoV-2 seropositivity (aPRR= 1.12, 95% CI: 0.68-1.85) compared to those with hypertension (Table 2).

Table 2 Maternal factors associated with SARS-CoV-2 seropositivity
Full size table

Children between 2 and 5 years had a 19% reduced risk of SARS-CoV-2 seropositivity (aPRR=0.81, 95%CI: 0.64-1.02) when compared to younger children. Mother/infant SARS-CoV-2 serostatuses were discordant in 346/802 (43.1%) families tested: mothers+/children- in 72.3%; mothers-/children+ in 26.3%; child+/sibling+ concordance was 34.6%.

Discussion

Our data show that by November 2021, about 60% of mothers and about 40% of children in a cohort of HIV-affected families in eastern/southern Africa had been infected with SARS-CoV-2. The highest SARS-CoV-2 antibody seropositivity rates stood at 69.8% and 48.5% for WLHIV and children who were enrolled in the PROMOTE study in Zimbabwe respectively. In Malawi, we report 61.1% and 46.8% SARS-CoV-2 in WLHIV and their children at the end of October 2021. The seropositivity rates in our study are much higher than the 53% seropositivity estimate reported from a sample of blood donors which suggests higher rates of SARS-Cov-2 infection among WLHIV relative to the general population over this period [22]. For Uganda, our study shows much lower SARS-CoV-2 antibody seropositivity rates of 46.5% in WLHIV and 21.7% in children. The SARS-CoV-2 seropositivity rates in the Ugandan PROMOTE cohort were much lower than the 67.7% reported from another cohort during the same period [23]. The lower antibody seropositivity rates in Uganda may be attributable to a number of factors strict implementation of non-pharmaceutical Interventions such as hand washing, social distancing, wearing masks, prolonged school closures and partly due to the later emergence of COVID in that country. The Ugandan legislative framework enacted laws that resulted in implementation of broad public health measures restricting movement of vehicles, vessels, and aircraft,closure of international borders (except for cargo); closure of education facilities; closure of places of prayers; curfew, and mandatory wearing of facial masks [24]. Striking similarities in infection rates between Malawi and Zimbabwe for both mothers and children may be related to overlapping cultural and socio-behavioural norms between the two countries and similar timing of the pandemic emerging in both countries.

Our study was conducted when COVID-19 vaccination coverage was still extremely low in all 3 countries. The Zimbabwean Government rolled out COVID-19 vaccination in February 2021 with priority being given to health care workers. By the end of October 2021, only 10% of the Zimbabwean population had been vaccinated [25]. The PROMOTE study recruited participants mainly from informal dwellings and peri-urban areas who did not have ready access to COVID-19 vaccination until late 2021 and thus the vaccination rates are likely to be much lower in this group during the time that our study was conducted. COVID-19 vaccination program in Malawi was launched on 11 March 2021,however, the Government`s heavy reliance on COVAX for vaccine supply hugely constrained its rollout; and there were only small, sporadic shipments of AstraZeneca, Johnson & Johnson, and Pfizer vaccines. As a result, the COVID-19 vaccine coverage only reached 3% by November 2021. COVID-19 vaccination rates in Uganda were low with only 2% of the population being vaccinated at the end of August 2021 [25]. These data show that although COVID-19 vaccination started during a period that overlaps with our study, vaccination rates were extremely low and unlikely to affect the SARS-CoV-2 serostatus data generated. Additionally, for Uganda, testing was also done using recombinant protein representing the nucleocapsid (N) antigen which was able to confirm COVID-19 infection as opposed to seropositivity due only to spike protein related to receipt of vaccine.

Risk factor analysis in our study was meant to gain an understanding of whether preexisting conditions, medication for chronic illnesses and sociobehavioral changes may have modified risk of contracting COVID-19. In the African context, we reckon that breastfeeding women were likely to have stayed home with their breastfeeding children due to perceived risk to the infants, consequentially lessening exposure and rates of infection. WLHIV constantly need to visit health care facilities to replenish their medication, and this had potential to increase risk of infection in this sub population. We think understanding these dynamics is important to assess vulnerability of different groups in pandemic situations and thus any knowledge gleaned from current studies could be key in informing future public health approaches. Our results showed a comparable risk of SARS-CoV-2 antibody seropositivity among WLHIV who were on DTG and PI based regimens when compared to those on EFV. This finding is supported by findings from previously published studies which reported no differences in SARS-CoV-2 prevalence between PLWHIV on different ART regimens, suggesting ART does not offer differential protection against SARS-CoV-2 infection [26,27,28]. However, a study by Del Amo et al reported lower risk of infection and related hospitalisation in patients receiving TDF/FTC than those receiving other regimens suggesting the ART regimen has an impact on risk of SARS-CoV-2 infection [3].

Risk factors for post-acute sequelae of SARS-CoV-2 infection (PASC) have generated interest, with recent evidence showing that vaccination reduces but does not exclude the risk of PASC or “long COVID” [29]. Considering concerns about higher COVID-19 [30], increased frequency of autoimmune conditions [31], other medical comorbidities, and sub-optimal vaccine responses among PLWH, further research is urgently needed to ascertain longer-term COVID-19 outcomes among PLWH on different ART regimens.

The current study showed slightly higher SARS-CoV-2 prevalence in children below the age of two years and those above the age of five years compared to the age groups between two and five years. These results partly corroborate findings from a study by Huete-Pérez et al that reported higher SARS-CoV-2 rates in children below 5 years when compared to older counterparts in Nicaragua [32]. The high rates of infection in the age groups below two years and those above 5 years maybe be due to the children above 5 years attending school and interacting with peers outside the home during the pandemic. The mother/infant SARS-CoV-2 antibody results which show that more mothers were infected than their infants may explain the higher seropositivity for children below two years of age who spent a significant amount of time with their mothers for care. This also provides an insight into complex household transmission dynamics that require further investigation. One likely explanation for higher rates of seropositivity in mothers could be the greater need for them to undertake daily routines outside the home, such as going to work, against a background of school closures during the pandemic and increasing risk of infection through out of the home interactions. The strengths of our study include the relatively large sample size and robust demographic and clinical data generated during execution of the PEPFAR PROMOTE study. Furthermore, we used a testing methodology which has been rigorously validated on thousands of samples with high accuracy and precision.

Our study has some limitations. Most participants included in our analysis were on highly active antiretroviral therapy and suppressed HIV viral load for prolonged periods. The women in our study have been in research settings for a long time and have received excellent health services and health education about infection prevention. Therefore, these findings may not be generalizable to WLHIV in the general population who may not be as empowered or able to access regular health care services. Furthermore, our data are derived from three countries that experienced COVID-19 peaks at different times. Our study also employed two different validated SARS-CoV-2 antibody assays across the 3 countries, with Uganda using an assay that is different from the one used in Zimbabwe and Malawi. Variability in kit sensitivity may cause slight differences in positivity rates, making data comparison across countries less reliable. Our study did not perform additional testing to differentiate whether the detected antibodies in children below the age of 2 years were due to infection or passive transmission from the infected mothers. A recent study reported a significant correlation between SARS-CoV-2 IgG antibodies in maternal and cord blood, suggesting that indeed these antibodies can be transferred from mother to child [33].

Conclusions

We found evidence of a high rate of SARS-CoV-2 infections in Southern and Eastern Africa following the second wave infection that occurred between July and November 2021. These SARS-CoV-2 serostatus data indicate that by late 2021, more than half of mothers and more than a third of children in a cohort of HIV-affected families in eastern/southern Africa had been infected with SARS-CoV-2. Breastfeeding women may have modified social behavioural routines that may modify their risk of contracting disease in a pandemic situation. The data also provides evidence that ART regimen does not alter risk of SARS-CoV-2 seropositivity further strengthening data that suggests that ART offers no protection against COVID-19.

Availability of data and materials

De-identified participant data results will be shared upon reasonable request within one year of study publication upon submission of a data request form to the corresponding author (amatubu@uz-ctrc.org). All data sharing guidelines of the sponsors will be followed. Approval of the data request form (provided by the corresponding author) and signing of a data access agreement form will be required

References

  1. Chan JF, Yuan S, Kok KH, To KK, Chu H, Yang J, Xing F, Liu J, Yip CC, Poon RW, Tsoi HW, Lo SK, Chan KH, Poon VK, Chan WM, Ip JD, Cai JP, Cheng VC, Chen H, Hui CK, Yuen KY. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet. 2020;395(10223):514–23. https://doi.org/10.1016/S0140-6736(20)30154-9. (Epub 2020 Jan 24. PMID: 31986261; PMCID: PMC7159286).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. WHO coronavirus (COVID-19) dashboard. https://covid19.who.intDate. Accessed 17 May 2023.

  3. Del Amo J, Polo R, Moreno S, Díaz A, Martínez E, Arribas JR, Jarrín I, Hernán MA, The Spanish HIV/COVID-19 Collaboration. Incidence and Severity of COVID-19 in HIV-positive persons receiving antiretroviral therapy: a cohort study. Ann Intern Med. 2020;173(7):536–41. https://doi.org/10.7326/M20-3689. Epub 2020 Jun 26. PMID: 32589451; PMCID: PMC7394316.

    Article  PubMed  Google Scholar 

  4. Tesoriero JM, Swain CE, Pierce JL, Zamboni L, Wu M, Holtgrave DR, Gonzalez CJ, Udo T, Morne JE, Hart-Malloy R, Rajulu DT, Leung SJ, Rosenberg ES. COVID-19 Outcomes Among Persons Living With or Without Diagnosed HIV Infection in New York State. JAMA Netw Open. 2021;4(2):e2037069. https://doi.org/10.1001/jamanetworkopen.2020.37069. 

  5. Vizcarra P, Pérez-Elías MJ, Quereda C, Moreno A, Vivancos MJ, Dronda F, Casado JL; COVID-19 ID Team. Description of COVID-19 in HIV-infected individuals: a single-centre, prospective cohort. Lancet HIV. 2020;7(8):e554–64. https://doi.org/10.1016/S2352-3018(20)30164-8.

  6. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan. China Lancet. 2020;395(10223):497–506. https://doi.org/10.1016/S0140-6736(20)30183-5. (Epub 2020 Jan 24. Erratum in: Lancet. 2020 Jan 30;: PMID: 31986264; PMCID: PMC7159299).

    Article  CAS  PubMed  Google Scholar 

  7. Cooper TJ, Woodward BL, Alom S, Harky A. Coronavirus disease 2019 (COVID-19) outcomes in HIV/AIDS patients: a systematic review. HIV Med. 2020;21(9):567–77. https://doi.org/10.1111/hiv.12911. (Epub 2020 Jul 15. PMID: 32671970; PMCID: PMC7405326).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Bhaskaran K, Rentsch CT, MacKenna B, Schultze A, Mehrkar A, Bates CJ, Eggo RM, Morton CE, Bacon SCJ, Inglesby P, Douglas IJ, Walker AJ, McDonald HI, Cockburn J, Williamson EJ, Evans D, Forbes HJ, Curtis HJ, Hulme WJ, Parry J, Hester F, Harper S, Evans SJW, Smeeth L, Goldacre B. HIV infection and COVID-19 death: a population-based cohort analysis of UK primary care data and linked national death registrations within the OpenSAFELY platform. Lancet HIV. 2021;8(1):e24–32. https://doi.org/10.1016/S2352-3018(20)30305-2. (Epub 2020 Dec 11. PMID: 33316211; PMCID: PMC7773630).

    Article  CAS  PubMed  Google Scholar 

  9. Western Cape Department of Health in collaboration with the National Institute for Communicable Diseases, South Africa. Risk Factors for Coronavirus Disease 2019 (COVID-19) Death in a Population Cohort Study from the Western Cape Province, South Africa. Clin Infect Dis. 2021;73(7):e2005–15. https://doi.org/10.1093/cid/ciaa1198. Erratum in: Clin Infect Dis. 2022 Apr 9;74(7):1321. https://doi.org/10.1093/cid/ciab803.

  10. Bertagnolio S, Thwin SS, Silva R, Nagarajan S, Jassat W, Fowler R, Haniffa R, Reveiz L, Ford N, Doherty M, Diaz J. Clinical features of, and risk factors for, severe or fatal COVID-19 among people living with HIV admitted to hospital: analysis of data from the WHO Global Clinical Platform of COVID-19. Lancet HIV. 2022;9(7):e486–95. https://doi.org/10.1016/S2352-3018(22)00097-2. (Epub 2022 May 10. PMID: 35561704; PMCID: PMC9090268).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Geretti AM, Stockdale AJ, Kelly SH, Cevik M, Collins S, Waters L, Villa G, Docherty A, Harrison EM, Turtle L, Openshaw PJM, Baillie JK, Sabin CA, Semple MG. Outcomes of Coronavirus Disease 2019 (COVID-19) Related Hospitalization Among People With Human Immunodeficiency Virus (HIV) in the ISARIC World Health Organization (WHO) Clinical Characterization Protocol (UK): A Prospective Observational Study. Clin Infect Dis. 2021;73(7):e2095–106. https://doi.org/10.1093/cid/ciaa1605. (PMID:33095853;PMCID:PMC7665382).

    Article  CAS  PubMed  Google Scholar 

  12. Dandachi D, Geiger G, Montgomery MW, Karmen-Tuohy S, Golzy M, Antar AAR, Llibre JM, Camazine M, Díaz-De Santiago A, Carlucci PM, Zacharioudakis IM, Rahimian J, Wanjalla CN, Slim J, Arinze F, Kratz AMP, Jones JL, Patel SM, Kitchell E, Francis A, Ray M, Koren DE, Baddley JW, Hill B, Sax PE, Chow J. Characteristics, comorbidities, and outcomes in a multicenter registry of patients with human immunodeficiency virus and coronavirus disease 2019. Clin Infect Dis. 2021;73(7):e1964–72. https://doi.org/10.1093/cid/ciaa1339. (PMID:32905581;PMCID:PMC7499544).

    Article  CAS  PubMed  Google Scholar 

  13. Hoffmann C, Casado JL, Härter G, Vizcarra P, Moreno A, Cattaneo D, Meraviglia P, Spinner CD, Schabaz F, Grunwald S, Gervasoni C. Immune deficiency is a risk factor for severe COVID-19 in people living with HIV. HIV Med. 2021;22(5):372–8. https://doi.org/10.1111/hiv.13037. (Epub 2020 Dec 27 PMID: 33368966).

    Article  CAS  PubMed  Google Scholar 

  14. Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, Song B, Cai Y, Wei M, Li X, Xia J, Chen N, Xiang J, Yu T, Bai T, Xie X, Zhang L, Li C, Yuan Y, Chen H, Li H, Huang H, Tu S, Gong F, Liu Y, Wei Y, Dong C, Zhou F, Gu X, Xu J, Liu Z, Zhang Y, Li H, Shang L, Wang K, Li K, Zhou X, Dong X, Qu Z, Lu S, Hu X, Ruan S, Luo S, Wu J, Peng L, Cheng F, Pan L, Zou J, Jia C, Wang J, Liu X, Wang S, Wu X, Ge Q, He J, Zhan H, Qiu F, Guo L, Huang C, Jaki T, Hayden FG, Horby PW, Zhang D, Wang C. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020;382(19):1787–99. https://doi.org/10.1056/NEJMoa2001282. (Epub 2020 Mar 18. PMID: 32187464; PMCID: PMC7121492).

    Article  PubMed  Google Scholar 

  15. Zanella I, Zizioli D, Castelli F, Quiros-Roldan E. Tenofovir, Another Inexpensive, Well-Known and Widely Available Old Drug Repurposed for SARS-COV-2 Infection. Pharmaceuticals (Basel). 2021;14(5):454. https://doi.org/10.3390/ph14050454. 

  16. Ambrosioni J, Blanco JL, Reyes-Urueña JM, Davies MA, Sued O, Marcos MA, Martínez E, Bertagnolio S, Alcamí J, Miro JM. Overview of SARS-CoV-2 infection in adults living with HIV. Lancet HIV. 2021;8(5):e294–305. https://doi.org/10.1016/S2352-3018(21)00070-9. PMID: 33915101; PMCID: PMC8075775.

  17. Sachs JD, Horton R, Bagenal J, Ben Amor Y, Karadag Caman O, Lafortune G. The Lancet COVID-19 Commission. Lancet. 2020;396(10249):454–5. https://doi.org/10.1016/S0140-6736(20)31494-X.

  18. Chang CC, Crane M, Zhou J, Mina M, Post JJ, Cameron BA, Lloyd AR, Jaworowski A, French MA, Lewin SR. HIV and co-infections. Immunol Rev. 2013;254(1):114–42. https://doi.org/10.1111/imr.12063. (PMID:23772618;PMCID:PMC3697435).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Arora RK, Joseph A, Van Wyk J, Rocco S, Atmaja A, May E, Yan T, Bobrovitz N, Chevrier J, Cheng MP, Williamson T, Buckeridge DL. SeroTracker: a global SARS-CoV-2 seropositivity dashboard. Lancet Infect Dis. 2021;21(4):e75–6. https://doi.org/10.1016/S1473-3099(20)30631-9. (Epub 2020 Aug 4. PMID: 32763195; PMCID: PMC7402646).

    Article  CAS  PubMed  Google Scholar 

  20. Taha TE, Yende-Zuma N, Aizire J, Chipato T, Wambuzi Ogwang L, Makanani B, Chinula L, Nyati MM, Hanley S, Brummel SS, Fowler MG. The multi-country PROMOTE HIV antiretroviral treatment observational cohort in Sub-Saharan Africa: Objectives, design, and baseline findings. PLoS One. 2018;13(12):e0208805. https://doi.org/10.1371/journal.pone.0208805.

  21. Agresti A, Coull Brent A. Approximate is Better than “Exact” for Interval Estimation of Binomial Proportions. Am Stat. 1998;52(2):119–26. https://doi.org/10.1080/00031305.1998.10480550.

    Article  Google Scholar 

  22. Bloch EM, Kyeyune D, White JL, Ddungu H, Ashokkumar S, Habtehyimer F, Baker O, Kasirye R, Patel EU, Grabowski MK, Musisi E, Moses K, Hume HA, Lubega I, Shrestha R, Motevalli M, Fernandez RE, Reynolds SJ, Redd AD, Wambongo Musana H, Dhabangi A, Ouma J, Eroju P, de Lange T, Fowler MG, Musoke P, Stramer SL, Whitby D, Zimmerman PA, McCullough J, Sachithanandham J, Pekosz A, Goodrich R, Quinn TC, Ness PM, Laeyendecker O, Tobian AAR. SARS-CoV-2 seroprevalence among blood donors in Uganda: 2019–2022. Transfusion. 2023;63(7):1354–65. https://doi.org/10.1111/trf.17449. (Epub 2023 Jun 16. PMID: 37255467; PMCID: PMC10525030).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Briggs J, Takahashi S, Nayebare P, et al. Seroprevalence of Antibodies to SARS-CoV-2 in Rural Households in Eastern Uganda, 2020-2022. JAMA Netw Open. 2023;6(2):e2255978. https://doi.org/10.1001/jamanetworkopen.2022.55978. 

  24. Achan MI, Nabukenya I, Mitanda S, et al. COVID-19 and the law in Uganda: a case study on development and application of the public health act from 2020 to 2021. BMC Public Health. 2023;23:761. https://doi.org/10.1186/s12889-023-15555-5.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Lines K, Dzimadzi S, Lubega E, Mudimu-Matsangaise P, Rao V, Sebbanja JA, Zidana H, Mitlin D. COVID-19 vaccine rollout: data from informal settlements in Harare, Kampala Lilongwe and Mumbai. Environ Urban. 2023;35(1):49–73. https://doi.org/10.1177/09562478221149876.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Byrd KM, Beckwith CG, Garland JM, Johnson JE, Aung S, Cu-Uvin S, et al. SARS-CoV-2 and HIV coinfection: clinical experience from Rhode Island, United States. J Int AIDS Soc. 2020;23(7):e25573. https://doi.org/10.1002/jia2.25573. (PMID: 32657527).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Inciarte A, Gonzalez-Cordon A, Rojas J, Torres B, de Lazzari E, de la Mora L, et al. Clinical characteristics, risk factors, and incidence of symptomatic coronavirus disease 2019 in a large cohort of adults living with HIV: a single-center, prospective observational study. AIDS. 2020;34(12):1775–80. https://doi.org/10.1097/QAD.0000000000002643. (PMID: 32773471).

    Article  CAS  PubMed  Google Scholar 

  28. Shalev N, Scherer M, LaSota ED, Antoniou P, Yin MT, Zucker J, Sobieszczyk ME. Clinical Characteristics and Outcomes in People Living With Human Immunodeficiency Virus Hospitalized for Coronavirus Disease 2019. Clin Infect Dis. 2020;71(16):2294–7. https://doi.org/10.1093/cid/ciaa635.

  29. Antonelli M, Penfold RS, Merino J, Sudre CH, Molteni E, Berry S, Canas LS, Graham MS, Klaser K, Modat M, Murray B, Kerfoot E, Chen L, Deng J, Österdahl MF, Cheetham NJ, Drew DA, Nguyen LH, Pujol JC, Hu C, Selvachandran S, Polidori L, May A, Wolf J, Chan AT, Hammers A, Duncan EL, Spector TD, Ourselin S, Steves CJ. Risk factors and disease profile of post-vaccination SARS-CoV-2 infection in UK users of the COVID Symptom Study app: a prospective, community-based, nested, case-control study. Lancet Infect Dis. 2022;22(1):43–55. https://doi.org/10.1016/S1473-3099(21)00460-6. (Epub 2021 Sep 1. PMID: 34480857; PMCID: PMC8409907).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Brown LB, Spinelli MA, Gandhi M. The interplay between HIV and COVID-19: summary of the data and responses to date. Curr Opin HIV AIDS. 2021;16(1):63–73. https://doi.org/10.1097/COH.0000000000000659. (PMID:33186229;PMCID:PMC7735216).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Rutishauser RL, Hartogensis W, Deguit CD, Krone M, Hoh R, Hecht FM, Pilcher CD, Bacchetti P, Deeks SG, Hunt PW, McCune JM. Early and Delayed Antiretroviral Therapy Results in Comparable Reductions in CD8+ T Cell Exhaustion Marker Expression. AIDS Res Hum Retroviruses. 2017;33(7):658–67. https://doi.org/10.1089/AID.2016.0324.

  32. Huete-Pérez JA, Ernst KC, Cabezas-Robelo C, Páiz-Medina L, Silva S, Huete A. Prevalence and risk factors for SARS-CoV-2 infection in children with and without symptoms seeking care in Managua, Nicaragua: results of a cross-sectional survey. BMJ Open. 2021;11(9):e051836. https://doi.org/10.1136/bmjopen-2021-051836. (PMID:34548362;PMCID:PMC8457995).

    Article  PubMed  Google Scholar 

  33. Song D, Prahl M, Gaw SL, Narasimhan S, Rai D, Huang A, Flores C, Lin CY, Jigmeddagva U, Wu AHB, Warrier L, Levan J, Nguyen CBT, Callaway P, Farrington L, Acevedo GR, Gonzalez VJ, Vaaben A, Nguyen P, Atmosfera E, Marleau C, Anderson C, Misra S, Stemmle M, Cortes M, McAuley J, Metz N, Patel R, Nudelman M, Abraham S, Byrne J, Jegatheesan P. Passive and active immunity in infants born to mothers with SARS-CoV-2 infection during pregnancy: Prospective cohort study. medRxiv [Preprint]. 2021:2021.05.01.21255871. https://doi.org/10.1101/2021.05.01.21255871. Update in: BMJ Open. 2021 Jul 7;11(7): e053036. PMID: 33972953; PMCID: PMC8109203.

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Acknowledgements

We thank the women and children who participated in the PROMOTE study at each of the research sites. We acknowledge the research teams at the following sites: MU-JHU, Kampala, Uganda; UNC Project Clinical Research Site, Blantyre, Malawi; University of Zimbabwe Clinical Trials Research Centre. The PROMOTE study was funded by the President’s Emergency Plan for AIDS Relief (PEPFAR) through DAIDS/NIAID/NIH grants to each of the following Clinical Trials Units (CTUs): JHU-Uganda CTU Makerere University-Johns Hopkins University (MU-JHU) Research Collaboration, grant # UM1 AI069530-11; The Johns Hopkins University-Blantyre Clinical Trials Unit, grant # UM1AI069518-12; University of Zimbabwe - Clinical Trials Research Centre, grant # 5UM1AI069436-12; and CAPRISA Clinical Trials Unit for AIDS/Tuberculosis Prevention and Treatment, grant # 5UM1 AI069469.

Funding

The Euro immune and Roche SARS-CoV-2 kits used in the study and subsequent training on kit use were donations from Dr. Tobian and Dr. Brooks Jackson. The testing performed in Uganda for the study was funded by a University of Iowa gift fund.

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Authors and Affiliations

  1. University of Zimbabwe Clinical Trials Research Centre, Harare, Zimbabwe

    Taguma A. Matubu & Lynda Stranix-Chibanda

  2. Biostatistics Research Unit, South African Medical Research Council, Durban, South Africa

    Nonhlanhla Yende-Zuma

  3. Centre for the AIDS Programme of Research in South Africa (CAPRISA), Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa

    Nonhlanhla Yende-Zuma

  4. Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Sean S. Brummel

  5. Faculty of Medicine and Health Sciences, Child and Adolescent Health Unit, University of Zimbabwe, Harare, Zimbabwe

    Lynda Stranix-Chibanda

  6. Makerere University-Johns Hopkins University (MU-JHU) Research Collaboration, Kampala, Uganda

    Lillian Wambuzi Ogwang & Patience Atuhaire

  7. Johns Hopkins Bloomberg School of Public Health, Blantyre, Malawi

    Sufia Dadabhai, Jim Aizire & Taha E. Taha

  8. Kamuzu University of Health Sciences-Johns Hopkins Research Project, Blantyre, Malawi

    Felluna Chauwa & Luis Gadama

  9. University of Iowa, Iowa City, Iowa, USA

    JBrooks Jackson

  10. Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Reinaldo E. Fernandez, Aaron A. R. Tobian & Mary Glenn Fowler

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  1. Taguma A. Matubu
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Contributions

All authors contributed to the study conception and design and writing of the manuscript. Material preparation, data collection and analysis were performed by TAM, NYZ, SSB, LSC, LWO, SD, PA, FC, LG, RF, JA, JBJ, AT, TET and MGF. The first draft of the manuscript was written by TAM and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Taguma A. Matubu.

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Ethics approval and consent to participate

This study only included stored samples from participants who had given consent for use of samples for future research. The study was approved by the Medical Research Council of Zimbabwe (MRCZ/E/306).

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Not applicable.

Competing interests

I declare that the authors have no competing interests or any other such interests that might be deemed to have an influence on the results and/or discussion presented in this manuscript.

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Matubu, T.A., Yende-Zuma, N., Brummel, S.S. et al. SARS-CoV-2 seropositivity in African women living with HIV and their infants. BMC Infect Dis 24, 693 (2024). https://doi.org/10.1186/s12879-024-09591-8

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BMC Infectious Diseases

ISSN: 1471-2334

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