Relationship of SARS-CoV-2–specific CD4 response to COVID-19 severity and impact of HIV-1 and tuberculosis coinfection

Riou, Catherine; Bruyn, Elsa Du; Stek, Cari; Daroowala, Remy; Goliath, René; Abrahams, Fatima; Said-Hartley, Qonita; Allwood, Brian; Hsiao, Marvin; Wilkinson, Katalin A.; Arlehamn, Cecilia S. Lindestam; Sette, Alessandro; Wasserman, Sean; Wilkinson, Robert J.

doi:10.1172/jci149125

Cited by 135 publications

(135 citation statements)

References 72 publications

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“…This effect was more marked in the second wave group and may reflect some degree of immune regulation. During infection, SARS-CoV-2-specific CD4 T cells exhibit high expression of the activation marker PD-1 (Sattler et al, 2020;Riou et al 2021a), which may limit proliferative capacity in those with recent infection. There was a marked increase in the magnitude and proportion of CD8 responses to spike induced de novo after vaccination, compared to infection, with no difference between the three study groups.…”

Section: Discussionmentioning

confidence: 99%

Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant dependent manner

Keeton

Richardson

Moyo-Gwete

et al. 2021

Preprint

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The Johnson and Johnson Ad26.COV2.S single dose vaccine, designed as an emergency response to the pandemic, represents an attractive option for the scale-up of COVID-19 vaccination in resource-limited countries. We examined the effect of prior infection with ancestral (D614G) or Beta variants on Ad26.COV2.S immunogenicity approximately 28 days post-vaccination. We compared healthcare workers who were SARS-CoV-2 naive (n=20), to those infected during the first wave prior to the emergence of Beta (n=20), and those infected in the second wave (n=20), when Beta was the dominant variant. We demonstrate that a priming exposure from infection significantly increased the magnitude of spike binding antibodies, neutralizing antibodies and antibody-dependent cellular cytotoxicity activity (ADCC) against D614G, Beta and Delta variants. The magnitude of antibody boosting was similar in both waves, despite the longer time interval between wave 1 infection and vaccination (7 months), compared to wave 2 (2 months). ADCC and binding cross-reactivity was similar in both waves. However, neutralization cross-reactivity varied by wave, showing that the antibody repertoire was shaped by the spike sequence of the infecting variant. Robust CD4 and CD8 T cell responses to spike of similar or higher magnitude as those elicited by infection were induced after vaccination. In contrast to antibody responses, prior infection was not required for the generation of high magnitude T cell responses, and T cell recognition of the Beta variant was fully preserved. Therefore, Ad26.COV2.S vaccination following prior infection, even >6 months previously, may result in substantially enhanced protection against COVID-19, of particular relevance in settings of high SARS-CoV-2 seroprevalence. Furthermore, the dominant impact of the infecting variant on neutralization breadth after vaccination has important implications for the design of second-generation vaccines based on variants of concern.

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Section: Discussionmentioning

confidence: 99%

Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant dependent manner

Keeton

Richardson

Moyo-Gwete

et al. 2021

Preprint

Self Cite

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“…These data go in line with recent preliminary data suggesting that very rapid induction of CD8 + T cells could be a cause of asymptomatic disease [ 30 ]. A new study found that severe COVID-19 is not preferentially associated with the quantity of the CD4 + T cell response, but rather poor polyfunctionality and proliferative capacity, as well as enhanced immune activation [ 31 ]. An increased immune activation profile has been distinguished in numerous studies, and together with differential Th2, Th17 or Tfh responses to SARS-CoV-2 been associated with distinct disease outcomes [ 32 , 33 ].…”

Section: T Cell Responses In the Acute Phasementioning

confidence: 99%

T cell immunity to SARS-CoV-2

Nießl

Sekine

Buggert

2021

Seminars in Immunology

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“…The late detection of unsuspected tuberculosis in several otherwise typical COVID-19 patients is a cause for concern and increased clinical vigilance. We have documented here and elsewhere 42 that tuberculosis may adversely impact both antibody and T cell responses to SARS-CoV-2. Conversely, the immunological milieu set up in the lung by SARS-CoV-2, to which corticosteroid therapy will add, may have contributed to reactivation of subclinical or latent tuberculosis 44 .…”

Section: Discussionmentioning

confidence: 73%

“…We next determined relationships between disease severity amongst COVID-19 patients, the presence of HIV-1 and/or tuberculosis as co-morbidities, and the level of anti-SARS-CoV-2 nucleocapsid specific antibody levels determined by the Roche Elecsys assay 41 . We have previously reported increased antinucleocapsid antibody levels in COVID-19 patients with more severe disease although no overall association with survival was noted 42 . Although no significant quantitative difference in cut-off index was observed by HIV-1 and or tuberculosis status, 8/15 tuberculosis patients in total and 5/8 with HIV-1 and tuberculosis were below the threshold for positivity (Figure 4A).…”

Section: Sars-cov-2 Specific Antibody Responsementioning

confidence: 89%

Communicable and non-communicable co-morbidities and the presentation of COVID-19 in an African setting of high HIV-1 and tuberculosis prevalence

Bruyn

Stek

Daroowala

et al. 2021

Preprint

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Objectives To describe the presentation and outcome of SARS–CoV2 infection in an African setting of high non–communicable co–morbidity and also HIV–1 and tuberculosis prevalence. Design Case control analysis with cases stratified by HIV–1 and tuberculosis status. Setting A single–centre observational case–control study of adults admitted to a South African hospital with proven SARS–CoV–2 infection or alternative diagnosis. Participants 104 adults with RT–PCR–proven SARS–CoV2 infection of which 55 (52.9%) were male and 31 (29.8%) HIV–1 co–infected. 40 adults (35.7% male, 30.9% HIV–1 co–infected) admitted during the same period with no RT–PCR or serological evidence of SARS–CoV2 infection and assigned alternative diagnoses. Additional in vitro data from prior studies of 72 healthy controls and 118 HIV–1 uninfected and infected persons participants enrolled to a prior study with either immune evidence of tuberculosis sensitization but no symptoms or microbiologically confirmed pulmonary tuberculosis. Results Two or more co–morbidities were present in 57.7% of 104 RT–PCR proven COVID–19 presentations, the commonest being hypertension (48%), type 2 diabetes mellitus (39%), obesity (31%) but also HIV–1 (30%) and active tuberculosis (14%). Amongst patients dually infected by tuberculosis and SARS–CoV–2, clinical features could be dominated by either SARS–CoV–2 or tuberculosis: lymphopenia was exacerbated, and some markers of inflammation (D–dimer and ferritin) elevated in singly SARS–CoV–2 infected patients were even further elevated (p less than 0.05). HIV–1 and SARS–CoV2 co–infection resulted in lower absolute number and proportion of CD4 lymphocytes, with those in the lowest peripheral CD4 percentage strata exhibiting absent or lower antibody responses against SARS–CoV2. Death occurred in 30/104 (29%) of all COVID–19 patients and in 6/15 (40%) of patients with coincident SARS–CoV–2 and tuberculosis. Conclusions In this South African setting, HIV–1 and tuberculosis are common co–morbidities in patients presenting with COVID–19. In environments in which tuberculosis is common, SARS–CoV–2 and tuberculosis may co–exist with clinical presentation being typical of either disease. Clinical suspicion of exacerbation of co–existent tuberculosis accompanying SARS–CoV–2 should be high.

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Relationship of SARS-CoV-2–specific CD4 response to COVID-19 severity and impact of HIV-1 and tuberculosis coinfection

Cited by 135 publications

References 72 publications

Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant dependent manner

Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant dependent manner

T cell immunity to SARS-CoV-2

Communicable and non-communicable co-morbidities and the presentation of COVID-19 in an African setting of high HIV-1 and tuberculosis prevalence

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