T-cell responses to MERS coronavirus infection in people with occupational exposure to dromedary camels in Nigeria: an observational cohort study

Abstract

Background: Middle East respiratory syndrome (MERS) remains of global public health concern. Dromedary camels are the source of zoonotic infection. Over 70% of MERS coronavirus (MERS-CoV)-infected dromedaries are found in Africa but no zoonotic disease has been reported in Africa. We aimed to understand whether individuals with exposure to dromedaries in Africa had been infected by MERS-CoV.

Methods: Workers slaughtering dromedaries in an abattoir in Kano, Nigeria, were compared with abattoir workers without direct dromedary contact, non-abattoir workers from Kano, and controls from Guangzhou, China. Exposure to dromedaries was ascertained using a questionnaire. Serum and peripheral blood mononuclear cells (PBMCs) were tested for MERS-CoV specific neutralising antibody and T-cell responses.

Findings: None of the participants from Nigeria or Guangdong were MERS-CoV seropositive. 18 (30%) of 61 abattoir workers with exposure to dromedaries, but none of 20 abattoir workers without exposure (p=0·0042), ten non-abattoir workers or 24 controls from Guangzhou (p=0·0002) had evidence of MERS-CoV-specific CD4₊ or CD8₊ T cells in PBMC. T-cell responses to other endemic human coronaviruses (229E, OC43, HKU-1, and NL-63) were observed in all groups with no association with dromedary exposure. Drinking both unpasteurised camel milk and camel urine was significantly and negatively associated with T-cell positivity (odds ratio 0·07, 95% CI 0·01-0·54).

Interpretation: Zoonotic infection of dromedary-exposed individuals is taking place in Nigeria and suggests that the extent of MERS-CoV infections in Africa is underestimated. MERS-CoV could therefore adapt to human transmission in Africa rather than the Arabian Peninsula, where attention is currently focused.

Funding: The National Science and Technology Major Project, National Institutes of Health.

Figure 1

MERS-CoV-specific CD4₊ and CD8₊ T-cell responses in camel workers and controls (A) Frequencies of MERS-CoV-specific CD4+ T cells. (B) Frequencies of MERS-CoV-specific CD8+ T cells. (C) Summary of aggregate CD4+ T-cell responses to all structural peptide pools in different study groups. (D) Summary of aggregate CD8+ T-cell responses to all structural peptide pools in different study groups. (E) CD4+ T-cell responses to MERS-CoV accessory protein-specific peptide pools. (F) Phenotypes of virus-specific CD4+ T cells. (G,H) Phenotypes of virus-specific CD8+ T cells. Abattoir workers with exposure to dromedaries are represented by red symbols, those without exposure to dromedaries by green symbols, non-abattoir workers by light blue symbols, MERS-positive controls by dark blue symbols (open shapes represent asymptomatic patients), and negative controls from Guangzhou by purple symbols. Symbol shape identifies the same individual. IFN=interferon. MERS-CoV= Middle East respiratory syndrome coronavirus. TNF=tumour necrosis factor. **=p<0·01. ***=p<0·001.

Figure 1

MERS-CoV-specific CD4₊ and CD8₊ T-cell responses in camel workers and controls (A) Frequencies of MERS-CoV-specific CD4+ T cells. (B) Frequencies of MERS-CoV-specific CD8+ T cells. (C) Summary of aggregate CD4+ T-cell responses to all structural peptide pools in different study groups. (D) Summary of aggregate CD8+ T-cell responses to all structural peptide pools in different study groups. (E) CD4+ T-cell responses to MERS-CoV accessory protein-specific peptide pools. (F) Phenotypes of virus-specific CD4+ T cells. (G,H) Phenotypes of virus-specific CD8+ T cells. Abattoir workers with exposure to dromedaries are represented by red symbols, those without exposure to dromedaries by green symbols, non-abattoir workers by light blue symbols, MERS-positive controls by dark blue symbols (open shapes represent asymptomatic patients), and negative controls from Guangzhou by purple symbols. Symbol shape identifies the same individual. IFN=interferon. MERS-CoV= Middle East respiratory syndrome coronavirus. TNF=tumour necrosis factor. **=p<0·01. ***=p<0·001.

Figure 2

T-cell responses against endemic human coronaviruses in the study cohort Aggregate CD4+ (A) and CD8+ (B) T-cell responses to the structural peptide pools from human coronaviruses (229E, HKU1, NL63, and OC43). Abattoir workers with exposure to dromedaries are represented by red symbols, those without exposure to dromedaries by green symbols, non-abattoir workers by black symbols, and MERS-positive controls by purple symbols. Symbol shape identifies the same individual. IFN=interferon. TNF=tumour necrosis factor.