Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection

Reynolds, Catherine J.; Swadling, Leo; Gibbons, Joseph M.; Pade, Corinna; Jensen, Melanie P; Diniz, Mariana O.; Schmidt, Nathalie M.; Butler, David K.; Amin, Oliver E.; Bailey, Sasha N. L.; Murray, Sam M.; Pieper, Franziska P.; Taylor, Stephen; Jones, Jessica; Jones, Meleri; Lee, Wing-Yiu Jason; Rosenheim, Joshua; Chandran, Aneesh; Joy, George; Genova, Cecilia Di; Temperton, Nigel; Lambourne, Jonathan; Cutiño-Moguel, Teresa; Andiapen, Mervyn; Fontana, Marianna; Smit, Angelique; Semper, Amanda; O’Brien, Ben; Chain, Benjamin M.; Brooks, Tim; Manisty, Charlotte; Treibel, Thomas A.; Moon, James; Investigators, COVIDsortium; Noursadeghi, Mahdad; Altmann, Daniel M.; Maini, Mala K.; McKnight, Áine; Boyton, Rosemary J.

doi:10.1126/sciimmunol.abf3698

Cited by 207 publications

(255 citation statements)

References 61 publications

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“…By contrast, responses to FEC pools were comparable in magnitude to the cumulative SARS-CoV-2-specific T cell responses detected in the HIV negative donors, likely reflecting the lower CMV seropositivity in the HIV negative group compared to the HIV positive group (54.28% CMV seropositive versus 97.87% CMV seropositive, respectively) ( Fig.2d). In line with previous studies we observed a wide breadth and range of cumulative SARS-CoV-2 T cell frequencies, with over 90% of donors in each group showing a response ( Fig.2e, f) 30,[39][40] . However, the proportion of HIV positive and negative donors with T cell responses to individual SARS-CoV-2 pools within given ranges varied, with a higher percentage of HIV positive donors having low level responses (Fig.2g).…”

Section: Sars-cov-2 Multi-specific T Cell Responsessupporting

confidence: 92%

“…These data suggest that, despite effective ART, incomplete immune reconstitution may potentially impact on the magnitude of T cell responses to SARS-CoV-2. Previous observations have demonstrated an association between SARS-CoV-2-specific T cells, age and gender, with T cell immunity to Spike increasing with age and male gender in some studies 30 . Despite an older age and male predominance in our HIV cohort we did not detect any association between ELISpot responses to Spike and donor age ( Supplementary Fig.2f, g).…”

Section: Sars-cov-2 Multi-specific T Cell Responsesmentioning

confidence: 91%

“…In most cases the magnitude of humoral responses is complemented by multi-specific T cell responses and appears to be dependent on the severity and protracted course of COVID-19 disease 18,27,29 . However, humoral and cellular immune responses are not always correlative, with T cell immunity being induced even in the absence of detectable antibodies during mild COVID-19 disease 18,[30][31] and predicted to be more enduring from experience with other coronaviruses [32][33] . Notably, older individuals more often display poorly coordinated immune adaptive responses to SARS-CoV-2 associated with worse disease outcome 18,34 .…”

Section: Introductionmentioning

confidence: 99%

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Characterization of humoral and SARS-CoV-2 specific T cell responses in people living with HIV

Alrubayyi

Gea‐Mallorquí

Touizer

et al. 2021

Preprint

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There is an urgent need to understand the nature of immune responses against SARS-CoV-2, to inform risk-mitigation strategies for people living with HIV (PLWH). We show that the majority of PLWH, controlled on ART, mount a functional adaptive immune response to SARS-CoV-2. Humoral and SARS-CoV-2-specific T cell responses are comparable between HIV-positive and negative subjects and persist 5-7 months following predominately mild COVID-19 disease. T cell responses against Spike, Membrane and Nucleocapsid are the most prominent, with SARS-CoV-2-specific CD4 T cells outnumbering CD8 T cells. We further show that the overall magnitude of SARS-CoV-2-specific T cell responses relates to the size of the naive CD4 T cell pool and the CD4:CD8 ratio in PLWH, in whom disparate antibody and T cell responses are observed. These findings suggest that inadequate immune reconstitution on ART, could hinder immune responses to SARS-CoV-2 with implications for the individual management and vaccine effectiveness in PLWH.

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Section: Sars-cov-2 Multi-specific T Cell Responsessupporting

confidence: 92%

Section: Sars-cov-2 Multi-specific T Cell Responsesmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

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Characterization of humoral and SARS-CoV-2 specific T cell responses in people living with HIV

Alrubayyi

Gea‐Mallorquí

Touizer

et al. 2021

Preprint

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“…We included a total of 169 blood RNA samples from 96 participants in a nested case-control study (Fig. S1) derived from an observational healthcare worker cohort (26–28) . Of these, 114 samples (including 16 convalescent samples collected 6 months after infection) were obtained from 41 incident cases with SARS-CoV-2 infection, and 55 samples from uninfected controls.…”

Section: Resultsmentioning

confidence: 99%

Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV-2 infection

Rosenheim

Bell

et al. 2021

Preprint

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We hypothesised that host-response biomarkers of viral infections may contribute to early identification of SARS-CoV-2 infected individuals, critical to breaking chains of transmission. We identified 20 candidate blood transcriptomic signatures of viral infection by systematic review and evaluated their ability to detect SARS-CoV-2 infection, compared to the gold-standard of virus PCR tests, among a prospective cohort of 400 hospital staff subjected to weekly testing when fit to attend work. The transcriptional signatures had limited overlap, but were mostly co-correlated as components of type 1 interferon responses. We reconstructed each signature score in blood RNA sequencing data from 41 individuals over sequential weeks spanning a first positive SARS-CoV-2 PCR, and after 6-month convalescence. A single blood transcript for IFI27 provided the highest accuracy for discriminating individuals at the time of their first positive viral PCR result from uninfected controls, with area under the receiver operating characteristic curve (AUROC) of 0.95 (95% confidence interval 0.91–0.99), sensitivity 0.84 (0.7–0.93) and specificity 0.95 (0.85–0.98) at a predefined test threshold. The test performed equally well in individuals with and without symptoms, correlated with viral load, and identified incident infections one week before the first positive viral PCR with sensitivity 0.4 (0.17–0.69) and specificity 0.95 (0.85–0.98). Our findings strongly support further urgent evaluation and development of blood IFI27 transcripts as a biomarker for early phase SARS-CoV-2 infection, for screening individuals such as contacts of index cases, in order to facilitate early case isolation and early antiviral treatments as they emerge.

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“…Some of us have recently reported a UK HCW cohort in which about 10% of previously infected HCW carried very low or absent neutralizing antibody levels at 4-months and would presumably be vulnerable to reinfection. 37 Sekine et al described a potent memory T cell response, similar to those desirable in the context of successful vaccines and that confer long-term immunity, independent of the absence or presence of circulating antibodies. Approximately twice as many people showed T-cell immunity compared to those in which they detected antibodies.…”

Section: Discussionmentioning

confidence: 98%

Recurrent COVID-19 including evidence of reinfection and enhanced severity in thirty Brazilian healthcare workers

Santos

Filho

Silva

et al. 2021

Journal of Infection

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111

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Background: There is growing concern about individuals reported to suffer repeat COVID-19 disease episodes, these in a small number of cases characterised as de novo infections with distinct sequences, indicative of insufficient protective immunity even in the short term. Methods: Observational case series and case-control studies reporting 33 cases of recurrent, symptomatic, qRT-PCR positive COVID-19. Recurrent disease was defined as symptomatic recurrence after symptom-free clinical recovery, with release from isolation > 14 days from the beginning of symptoms confirmed by qRT-PCR. The case control study-design compared this group of patients with a control group of 62 patients randomly selected from the same COVID-19 database. Results: Of 33 recurrent COVID-19 patients, 26 were female and 30 were HCW. Mean time to recurrence was 50.5 days which was associated with being a HCW (OR 36.4 (p < 0.0 0 01)), and blood type A (OR 4.8 (p = 0.002)). SARS-CoV-2 antibodies were signifcantly lower in recurrent patients after initial COVID-19 (2.4 ± 0.610; p < 0.0 0 01) and after recurrence (6.4 ± 11.34; p = 0.007). Virus genome sequencing identified reinfection by a different isolate in one patient. Conclusions: This is the first detailed case series showing COVID-19 recurrence with qRT-PCR positivity. For one individual detection of phylogenetically distinct genomic sequences in the first and second episodes confirmed bona fide renfection, but in most cases the data do not formally distinguish between reinfection and re-emergence of a chronic infection reservoir. These episodes were significantly associated with reduced Ab response during initial disease and argue the need for ongoing vigilance without an assumption of protection after a first episode.

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Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection

Cited by 207 publications

References 61 publications

Characterization of humoral and SARS-CoV-2 specific T cell responses in people living with HIV

Characterization of humoral and SARS-CoV-2 specific T cell responses in people living with HIV

Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV-2 infection

Recurrent COVID-19 including evidence of reinfection and enhanced severity in thirty Brazilian healthcare workers

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