SARS-CoV-2 antibody responses in patients with aggressive haematological malignancies

Muir, Luke; Zheng, Jiexin; Rees-Spear, Chloe; Rosa, Annachiara; Earl, Christopher; Cherepanov, Peter; Gupta, Rajeev; Khwaja, Asim; Jolly, Clare; McCoy, Laura E

doi:10.1101/2020.09.29.20202846

Cited by 5 publications

(13 citation statements)

References 19 publications

(53 reference statements)

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“…Analysis of antibody responses in cancer patients and HV with SARS-CoV-2 infection revealed comparable positivity rates as well as antibody ratios and titers. This is in line with recent ndings in CLL and AML patients (16,17), indicative of functional humoral SARS-CoV-2 immunity in these patients. Similar to previous reports in non-cancer COVID-19 patients (25)(26)(27), a trend to increased anti-S1 IgG ratios was observed in cancer patients with a more severe course of COVID-19.…”

Section: Discussionsupporting

confidence: 92%

“…As of now, data on immune responses and immunity to SARS-CoV-2 in cancer patients are very limited. Two recent studies reported IgG antibody responses in 88% and 67% in acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) patients suffering from COVID-19, respectively (16,17). To date, no data are available on SARS-CoV-2-directed T cell responses in cancer patients.…”

Section: Introductionmentioning

confidence: 99%

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Pre-existing and post-COVID-19 immune responses to SARS-CoV-2 in cancer patients

Bilich

Roerden²,

Maringer

et al. 2021

Preprint

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Cancer patients, in particular patients with hematological malignancies, are at increased risk for critical illness upon COVID-19. We here assessed antibody as well as CD4+ and CD8+ T cell responses in unexposed and SARS-CoV-2-infected cancer patients to characterize SARS-CoV‑2 immunity and to identify immunological parameters contributing to COVID-19 outcome. Unexposed patients with hematological malignancies presented with reduced prevalence of pre-existing SARS-CoV-2 cross-reactive CD4+ T cell responses and signs of T cell exhaustion when compared to solid tumor patients and healthy volunteers. Whereas SARS-CoV-2 antibody responses did not differ between COVID-19 cancer patients and healthy volunteers, intensity, expandability, and diversity of SARS-CoV-2 T cell responses were profoundly reduced in cancer patients, and the latter associated with a severe course of COVID-19. This identifies impaired SARS-CoV-2 T cell immunity as determinant for dismal outcome of COVID-19 in cancer patients.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Pre-existing and post-COVID-19 immune responses to SARS-CoV-2 in cancer patients

Bilich

Roerden²,

Maringer

et al. 2021

Preprint

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“…ELISA was used to screen plasma samples for antibodies against the external Spike antigen, using immobilized recombinant Spike S1 1-530 subunit protein (S1), and against immobilized full-length internal Nucleoprotein (N) antigen to confirm prior infection as previously described (Ng et al 2020; O’Nions et al 2021; Pickering et al 2020) ( Fig. 1A ).…”

Section: Resultsmentioning

confidence: 99%

“…S1A, B ) and as previously described (Pickering et al 2020). The screening assay, followed by titer quantification (based on an in-assay standard curve) (O’Nions et al 2021), demonstrated that 95.8% (23/24) of individuals from the HIV positive group with prior laboratory confirmed COVID-19 and 30.43% (7/23) with suspected disease, during the first wave of the pandemic, had measurable titers for SARS-CoV-2 S1 and N sampled at a median 146 DPSO (DPSO range 46-232) and 181 DPSO (range 131-228), respectively ( Fig. 1A-C ).…”

Section: Resultsmentioning

confidence: 99%

“…This assay is based on a previously described assay (O’Nions et al 2021; Pickering et al 2020; Seow et al 2020). Briefly, 9 columns of a 96-half-well Maxisorp plate (Nalgene, NUNC International, Hereford, UK) were coated overnight at 4°C with 25 μl of S1 or N (gift from Peter Cherepanov, Crick Institute) purified protein at 3 µg/ml in PBS, the remaining 3 columns were coated with 25 μl goat anti-human F(ab)’2 (1:1,000) in PBS to generate an internal standard curve.…”

Section: Methodsmentioning

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

Self Cite

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There is an urgent need to understand the nature of immune responses generated against SARS-CoV-2, to better inform risk-mitigation strategies for people living with HIV (PLWH). Although not all PLWH are considered immunosuppressed, residual cellular immune deficiency and ongoing inflammation could influence COVID-19 disease severity, the evolution and durability of protective memory responses. Here, we performed an integrated analysis, characterizing the nature, breadth and magnitude of SARS-CoV-2-specific immune responses in PLWH, controlled on ART, and HIV negative subjects. Both groups were in the convalescent phase of predominately mild COVID-19 disease. The majority of PLWH mounted SARS-CoV-2 Spike- and Nucleoprotein-specific antibodies with neutralizing activity and SARS-CoV-2-specific T cell responses, as measured by ELISpot, at levels comparable to HIV negative subjects. T cell responses against Spike, Membrane and Nucleocapsid were the most prominent, with SARS-CoV-2-specific CD4 T cells outnumbering CD8 T cells. Notably, the overall magnitude of SARS-CoV-2-specific T cell responses related 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 were observed. Both humoral and cellular responses to SARS-CoV-2 were detected at 5-7 months post-infection, providing evidence of medium-term durability of responses irrespective of HIV serostatus. Incomplete immune reconstitution on ART and a low CD4:CD8 ratio could, however, hamper the development of immunity to SARS-CoV-2 and serve as a useful tool for risk stratification of PLWH. These findings have implications for the individual management and potential effectiveness of vaccination against SARS-CoV-2 in PLWH.

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Neutralizing Antibody Responses After SARS-CoV-2 Infection in End-Stage Kidney Disease and Protection Against Reinfection

Muir

Jaffer

Rees-Spear

et al. 2021

Kidney International Reports

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Patients with end-stage kidney disease (ESKD) represent a vulnerable group with multiple risk factors that are associated with poor outcomes after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Despite established susceptibility to infectious complications and the importance of humoral immunity in protection against SARS-CoV-2, few studies have investigated the humoral immune response to SARS-CoV-2 within this population. Here, we evaluate the seroprevalence of SARS-CoV-2 in patients awaiting renal transplantation and determine whether seroconverted patients with ESKD have durable and functional neutralizing activity against SARS-CoV-2. Serum samples were obtained from 164 patients with ESKD by August 2020. Humoral immune responses were evaluated by SARS-CoV-2 spike S1 subunit and nucleoprotein semiquantitative enzyme-linked immunosorbent assay (ELISA) and SARS-CoV-2 spike pseudotype neutralization assay. All patients with ESKD with reverse-transcriptase polymerase chain reaction (RT-PCR)–confirmed infection (n = 17) except for 1 individual seroconverted against SARS-CoV-2. Overall seroprevalence (anti-S1 and/or anti-N IgG) was 36% and was higher in patients on hemodialysis (44.2%). A total of 35.6% of individuals who seroconverted were asymptomatic. Seroconversion in the absence of a neutralizing antibody (nAb) titer was observed in 12 patients, all of whom were asymptomatic. Repeat measurements at a median of 93 days from baseline sampling revealed that most individuals retained detectable responses although a significant drop in S1, N and nAb titers was observed. Patients with ESKD, including those who develop asymptomatic disease, routinely seroconvert and produce detectable nAb titers against SARS-CoV-2. Although IgG levels wane over time, the neutralizing antibodies remain detectable in most patients, suggesting some level of protection is likely maintained, particularly in those who originally develop stronger responses.

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SARS-CoV-2 antibody responses in patients with aggressive haematological malignancies

Cited by 5 publications

References 19 publications

Pre-existing and post-COVID-19 immune responses to SARS-CoV-2 in cancer patients

Pre-existing and post-COVID-19 immune responses to SARS-CoV-2 in cancer patients

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

Neutralizing Antibody Responses After SARS-CoV-2 Infection in End-Stage Kidney Disease and Protection Against Reinfection

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