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Research Letters

Severe acute respiratory syndrome coronavirus-2 antibody prevalence in people with and without HIV in rural Western Kenya, January to March 2020

Crowell, Trevor A.a,b; Daud, Ibrahim I.c; Maswai, Jonaha,c; Owuoth, Johnd,e; Sing’oei, Valentined,e; Imbach, Michellea,b; Dear, Nicolea,b; Sawe, Fredc,d; Eller, Leigh Annea,b; Polyak, Christina S.a,b; Ake, Julie A.a

Author Information
doi: 10.1097/QAD.0000000000003054

Abstract

The global pandemic of coronavirus disease-19 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has overwhelmed national health systems in many countries. Although the African continent was predicted to be particularly vulnerable, African populations appear to have thus far evaded widespread morbidity and mortality because of COVID-19 [1]. Kenya's first identified COVID-19 case was a 27-year-old woman who traveled from the United States to Nairobi. Her diagnosis on 12 March 2020 immediately prompted nationwide mitigation efforts. Still, the infection spread from her to other airline passengers and, within 2 weeks, COVID-19 infections had been confirmed in five counties including and surrounding Nairobi and Mombasa [2]. This timeline for geographic spread suggested that the local outbreak emanated from arriving travelers at two major ports of entry. However, data from other countries suggest that SARS-CoV-2 was circulating weeks or months before initial cases were detected [3–5]. We retrospectively tested stored serum specimens from people with and without HIV in Western Kenya for evidence of potential SARS-CoV-2 circulation or cross-reactivity before the first Kenyan case was reported in March 2020.

The ongoing African Cohort Study (AFRICOS) enrolls adults with and without HIV in an approximately 5 : 1 ratio in four countries [6]. Seven hospital-based clinics in Kisumu and Kericho, Kenya, provided samples for these analyses. Cohort procedures include 6-monthly medical history-taking, physical examination, and laboratory assessments that include CD4+ T-cell count and HIV RNA quantification for people with HIV (PWH) [7]. At each visit, participants are asked about symptoms in the preceding week. Medical records and laboratory studies are reviewed to identify comorbidities, including some potentially associated with adverse COVID-19 outcomes [6].

Because of the emerging COVID-19 outbreak, study visits were paused on 19 March 2020 [8]. For these analyses, stored serum from 1 January 2020 through 19 March 2020 was retrospectively tested using the Platelia SARS-CoV-2 Total Ab assay (Bio-Rad Laboratories, Hercules, California, USA) to qualitatively detect anti-SARS-CoV-2 nucleocapsid IgM, IgA, and/or IgG. Samples with signal-to-cutoff ratio (S/CO) at least 0.8 on initial testing were retested in duplicate; one or two retest results with S/CO at least 1.0 was considered positive. For each participant with detectable antibodies, stored serum from the preceding study visit (as early as June 2019) was also tested.

A total of 582 participants underwent retrospective testing, including 508 (87.3%) PWH and 327 (56.2%) women. Participants had a median age of 43.3 (interquartile range 35.7–51.6) years. Nineteen (3.3%) had detectable SARS-CoV-2 antibodies (Table 1), including seven who also had a positive test at their preceding visit and 12 who did not (Supplemental Figure, https://links.lww.com/QAD/C264). The prevalence of detectable SARS-CoV-2 antibodies was similar between participants with and without HIV (3.1% vs. 4%, P = 0.68).

Table 1 - Characteristics of participants with detectable severe acute respiratory syndrome coronavirus-2 antibodies prior to coronavirus disease 2019-related pause of African Cohort Study visits in rural Western Kenya.
ID Date Age (years) Sex HIV status CD4+ (cells/μl) HIV RNA (copies/ml) BMI Symptomsa Comorbid conditionsb Comparison to prior visit
1 January 2020 46 M No HIV 20.8 None None Serofast
2 January 2020 66 M With HIV 548 Undetectable 18.0 Cough None Seroconverted
3 January 2020 47 F With HIV 490 Undetectable 18.6 None None Serofast
4 January 2020 50 M With HIV 458 Missing 19.7 None None Seroconverted
5 January 2020 69 M With HIV 418 Undetectable 22.6 None Elevated BP Serofast
6 January 2020 50 M With HIV 194 Undetectable 26.0 None None Seroconverted
7 January 2020 55 F No HIV 28.1 None None Seroconverted
8 February 2020 30 F No HIV 28.3 None None Seroconverted
9 February 2020 44 F With HIV 655 123 23.1 None None Serofast
10 February 2020 49 F With HIV 713 Undetectable 23.9 None None Seroconverted
11 February 2020 26 F With HIV 1044 Undetectable 33.0 None None Seroconverted
12 February 2020 34 F With HIV 491 Undetectable 22.6 None None Seroconverted
13 February 2020 55 F With HIV 755 <40 27.0 None None Serofast
14 February 2020 56 F With HIV 316 Undetectable 21.5 None Hyperglycemia Seroconverted
15 February 2020 51 F With HIV 563 Undetectable 23.7 None Elevated BP, liver disease Seroconverted
16 March 2020 50 F With HIV 557 Undetectable 30.4 None None Serofast
17 March 2020 47 F With HIV 341 <40 27.5 None None Seroconverted
18 March 2020 49 M With HIV 370 Undetectable 24.5 None None Serofast
19 March 2020 41 F With HIV 833 Undetectable 30.1 None Elevated BP Seroconverted
Stored serum samples collected from 1 January 2020 through 19 March 2020 from participants at seven sites in Kenya were tested retrospectively using the Platelia SARS-CoV-2 Total Ab assay to detect anti-SARS-CoV-2 IgM, IgA, and/or IgG. Of 582 participants tested, 19 had detectable antibodies against SARS-CoV-2, with participant and testing characteristics summarized above. For each participant with detectable antibodies, serologic testing was also performed on stored serum from the immediately preceding study visit to evaluate for interval seroconversion, with a negative or equivocal prior test interpreted as ‘seroconverted’ (12 participants) and a positive prior test interpreted as ‘serofast’ (7 participants; see Supplemental Figure, https://links.lww.com/QAD/C264).
aSolicited symptoms at each visit included any of the following in the preceding week: fever, cough, shortness of breath, arthralgias, myalgias, nausea, vomiting, diarrhea.
bComorbid conditions included any of the following: cancer, renal insufficiency, respiratory disease, heart conditions, sickle cell disease, hyperglycemia, asthma, elevated blood pressure, neurologic conditions, immunocompromised state, pregnancy, tobacco smoking. BP, blood pressure.

Our sites in rural Western Kenya are far removed from the urban centers of Nairobi and Mombasa where SARS-CoV-2 was believed to have been introduced into Kenya. However, these sites are near substantial infrastructure development projects, such as highway construction backed by Chinese government and commercial entities. Some of the earliest known cases of COVID-19 in Africa were imported by manufacturing workers who traveled from China to Egypt [9], and it is possible that SARS-CoV-2 could have reached the otherwise remote region of our study similarly via construction workers. Expectedly, the seroprevalence estimates in this study were lower than those reported from African settings later in the pandemic, including a 4.3% seroprevalence among Kenyan blood donors in June 2020 that increased to 9.1% by September 2020 [10].

However, it is likely that some or all of the positive assays in our study were because of cross-reactivity from preexisting antibodies or causes other than SARS-CoV-2, particularly among participants who were serofast from previous visits that substantially predated the emerging COVID-19 pandemic. Although small studies showed no cross-reactivity between the Platelia assay and common alpha or beta coronaviruses (package insert, Bio-Rad Laboratories 16008597, 2020/06), variations in assay performance based on target antigen and study population limit the ability to compare data across studies and to assert that all positive assays in our study represented true SARS-CoV-2 infections [11]. Recent work has suggested that serologic cross-reactivity is significantly more common in samples from Africa than other settings, documenting prepandemic cross-reactive antibodies to the SARS-CoV-2 nucleocapsid protein among approximately one out of six samples tested in Tanzania [12].

Participants with detectable SARS-CoV-2 antibody were almost universally asymptomatic, despite some having risk factors for adverse outcomes of infection. Importantly, our study predominantly enrolls PWH and, accordingly, most cases of detectable SARS-CoV-2 antibodies were observed amongst PWH. The absence of any severe clinical cases of COVID-19 among these individuals is consistent with a growing body of literature that well controlled HIV is not a risk factor for adverse outcomes of SARS-CoV-2 infection [13]. If participants in our study did have asymptomatic infection, then such cases could have contributed to early undetected spread of the pandemic in Kenya. If such participants had preexisting cross-reactive antibodies, then partial immunity to SARS-CoV-2 could potentially explain the lower than predicted morbidity and mortality due to COVID-19 in Africa.

In conclusion, we present serologic data indicating either cross-reactivity or asymptomatic infections that predated the first reported COVID-19 cases in Kenya. Further research is needed to distinguish the two possible explanations for detectable SARS-CoV-2 antibodies in our study. This finding improves our understanding of early COVID-19 epidemiology and may help to predict its future course in Africa, thereby informing resource allocation and COVID-19 response policy.

Acknowledgements

AFRICOS Study Group and Implementing Sites: The study team would like to thank the study participants, local implementing partners, and hospital leadership at Kayunga District Hospital, Kericho District Hospital, AC Litein Mission Hospital, Kapkatet District Hospital, Tenwek Mission Hospital, Kapsabet District Hospital, Nandi Hills District Hospital, and Kisumu West District Hospital.

We would also like to thank the AFRICOS Study Group – from the US Military HIV Research Program Headquarters Group: Danielle Bartolanzo, Alexus Reynolds, Katherine Song, Mark Milazzo, Leilani Francisco, Steven Schech, Badryah Omar, Tsedal Mebrahtu, Elizabeth Lee, Kimberly Bohince, Ajay Parikh, Jaclyn Hern, Emma Duff, Kara Lombardi, Michelle Imbach, and Leigh Anne Eller; from the AFRICOS Uganda Group: Hannah Kibuuka, Michael Semwogerere, Prossy Naluyima, Godfrey Zziwa, Allan Tindikahwa, Claire Nakazzi Bagenda, Hilda Mutebe, Cate Kafeero, Enos Baghendaghe, William Lwebuge, Freddie Ssentogo, Hellen Birungi, Josephine Tegamanyi, Paul Wangiri, Christine Nabanoba, Phiona Namulondo, Richard Tumusiime, Ezra Musingye, Christina Nanteza, Joseph Wandege, Michael Waiswa, Evelyn Najjuma, Olive Maggaga, Isaac Kato Kenoly, and Barbara Mukanza; from the AFRICOS South Rift Valley, Kenya Group: Jonah Maswai, Rither Langat, Aaron Ngeno, Lucy Korir, Raphael Langat, Francis Opiyo, Alex Kasembeli, Christopher Ochieng, Japhet Towett, Jane Kimetto, Brighton Omondi, Mary Leelgo, Michael Obonyo, Linner Rotich, Enock Tonui, Ella Chelangat, Joan Kapkiai, Salome Wangare, Zeddy Bett Kesi, Janet Ngeno, Edwin Langat, Kennedy Labosso, Joshua Rotich, Leonard Cheruiyot, Enock Changwony, Mike Bii, Ezekiel Chumba, Susan Ontango, Danson Gitonga, Samuel Kiprotich, Bornes Ngtech, Grace Engoke, Irene Metet, Alice Airo, and Ignatius Kiptoo; from the AFRICOS Kisumu, Kenya Group: John Owuoth, Valentine Sing’oei, Winne Rehema, Solomon Otieno, Celine Ogari, Elkanah Modi, Oscar Adimo, Charles Okwaro, Christine Lando, Margaret Onyango, Iddah Aoko, Kennedy Obambo, Joseph Meyo, and George Suja; from the AFRICOS Abuja, Nigeria Group: Michael Iroezindu, Yakubu Adamu, Nnamdi Azuakola, Mfreke Asuquo, Abdulwasiu Bolaji Tiamiyu, Afoke Kokogho, Samirah Sani Mohammed, Ifeanyi Okoye, Sunday Odeyemi, Aminu Suleiman, Lawrence C. Umeji, Onome Enas, Miriam Ayogu, Ijeoma Chigbu-Ukaegbu, Wilson Adai, Felicia Anayochukwu Odo, Rabi Abdu, Roseline Akiga, Helen Nwandu, Chisara Sylvestina Okolo, Ogundele Taiwo, Otene Oche Ben, Nicholas Innocent Eigege, Tony Ibrahim Musa, Juliet Chibuzor Joseph, Ndubuisi C. Okeke; from the AFRICOS Lagos, Nigeria Group: Zahra Parker, Nkechinyere Elizabeth Harrison, Uzoamaka Concilia Agbaim, Olutunde Ademola Adegbite, Ugochukwu Linus Asogwa, Adewale Adelakun, Chioma Ekeocha, Victoria Idi, Rachel Eluwa, Jumoke Titilayo Nwalozie, Igiri Faith, Blessing Irekpitan Wilson, Jacinta Elemere, Nkiru Nnadi, Francis Falaju Idowu, Ndubuisi Rosemary, Amaka Natalie Uzeogwu, Theresa Owanza Obende, Ifeoma Lauretta Obilor, Doris Emekaili, Edward Akinwale, and Inalegwu Ochai; from the AFRICOS Mbeya, Tanzania Group: Lucas Maganga, Emmanuel Bahemana, Samoel Khamadi, John Njegite, Connie Lueer, Abisai Kisinda, Jaquiline Mwamwaja, Faraja Mbwayu, Gloria David, Mtasi Mwaipopo, Reginald Gervas, Dorothy Mkondoo, Nancy Somi, Paschal Kiliba, Ephrasia Mwalongo, Gwamaka Mwaisanga, Johnisius Msigwa, Hawa Mfumbulwa, Peter Edwin, Willyhelmina Olomi.

Funding: This work was supported by the Military Infectious Disease Research Program and the President's Emergency Plan for AIDS Relief via cooperative agreements between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the U.S. Department of Defense [W81XWH-11–2–0174, W81XWH-18–2–0040].

Ethical Assurance: The African Cohort Study was approved by institutional review boards of the Walter Reed Army Institute of Research Silver Spring, MD, USA; Makerere University School of Public Health, Kampala, Uganda; Kenya Medical Research Institute, Nairobi, Kenya; Tanzania National Institute of Medical Research, Mbeya, Tanzania; and Nigerian Ministry of Defence, Abuja, Nigeria. All participants provided written informed consent prior to enrollment.

Disclaimer: The views expressed are those of the authors and should not be construed to represent the positions of the U.S. Army or the Department of Defense or the Department of Health and Human Services. The investigators have adhered to the policies for protection of human subjects as prescribed in AR-70.

Conflicts of interest

There are no conflicts of interest.

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