Functional SARS-CoV-2-Specific Immune Memory Persists after Mild COVID-19

Rodda, Lauren B.; Netland, Jason; Shehata, Laila; Pruner, Kurt B.; Morawski, Peter A.; Thouvenel, Christopher D.; Takehara, Kennidy K; Eggenberger, Julie; Hemann, Emily A.; Waterman, Hayley R.; Fahning, Mitchell L.; Chen, Yu; Hale, Malika; Rathe, Jennifer A.; Stokes, Caleb; Wrenn, Samuel; Fiala, Brooke; Carter, Lauren; Hamerman, Jessica A.; King, Neil P.; Gale, Michael; Campbell, Daniel; Rawlings, David J.; Pepper, Marion

doi:10.1016/j.cell.2020.11.029

Cited by 602 publications

(616 citation statements)

References 71 publications

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“…In contrast, polyfunctional SARS-CoV-2 antigen–specific CD4 + and CD8 + memory T cells were elevated at the same time points. The persistence of antigen-specific memory T cells is directly correlated with and parallels the B cell compartment ( Rodda et al, 2021 ; Dan et al, 2020 Preprint ; Gaebler et al, 2020 Preprint ). Despite decreasing serum levels of anti–SARS-CoV-2 neutralizing antibodies, the memory B cell compartment continues to evolve over the first 6 mo after infection, including increased levels of somatic mutations and increasing resistance to escape mutations in the receptor-binding domain (RBD; Gaebler et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…For example, individuals infected with Middle East respiratory syndrome remain immune for 1–3 yr, while protection from seasonal coronaviruses is short-lived ( Wu et al, 2007 ; Edridge et al, 2020 ; Tang et al, 2011 ). Although there is increasing evidence that cellular immunity plays a major role in resolution of COVID-19, little is known about the persistence of cellular immunity to SARS-CoV-2 ( Rodda et al, 2021 ; Rydyznski Moderbacher et al, 2020 ). This is a particularly important issue when considering an individual’s ability to resist a second exposure to the virus.…”

Section: Introductionmentioning

confidence: 99%

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Persistent cellular immunity to SARS-CoV-2 infection

Breton

Mendoza

Hägglöf

et al. 2021

Journal of Experimental Medicine

130

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SARS-CoV-2 is responsible for an ongoing pandemic that has affected millions of individuals around the globe. To gain further understanding of the immune response in recovered individuals, we measured T cell responses in paired samples obtained an average of 1.3 and 6.1 mo after infection from 41 individuals. The data indicate that recovered individuals show persistent polyfunctional SARS-CoV-2 antigen–specific memory that could contribute to rapid recall responses. Recovered individuals also show enduring alterations in relative overall numbers of CD4+ and CD8+ memory T cells, including expression of activation/exhaustion markers, and cell division.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Persistent cellular immunity to SARS-CoV-2 infection

Breton

Mendoza

Hägglöf

et al. 2021

Journal of Experimental Medicine

130

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“…Despite these observations on the decrease of NAbs in patients with mild COVID-19, it is important to note that they do not preclude the protective role of an anamnestic antibody response in previously exposed subjects, nor that of the long-term cellular immunity [5].…”

mentioning

confidence: 94%

Six-month antibody response to SARS-CoV-2 in healthcare workers assessed by virus neutralisation and commercial assays

Bal

Trabaud

Fassier

et al. 2020

Preprint

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We conducted a prospective study in healthcare workers (n=296) of the University Hospital of Lyon, France. Serum samples (n=296) collected six months after disease onset were tested using three commercial assays: the Wantai Ab assay detecting total antibodies against the receptor binding domain (RBD) of the S protein, the bioMerieux Vidas assay detecting IgG to the RBD and the Abbott Architect assay detecting IgG to the N protein. The neutralising antibody (NAb) titre was also determined for all samples with a virus neutralisation assay (VNA) using live virus. The positivity rate was 100% with the Wantai assay, 84.8% with the bioMerieux assay and 55.4% with the Abbott assay. Only 51% of HCWs were positive for the presence of NAb. Less than 10 % of HCWs had a NAb titre greater than 80. At a neutralising titre of 80, the area under the curves [IC 95%] was 0.71 [0.62-0.81], 0.75 [0.65-0.85] and 0.95 [0.92-0.97] for Wantai, Abbott and Vidas respectively. The data presented herein suggest that commercial assays detecting antibodies against the N protein must not be used in long-term seroprevalence surveys while the Wantai assay could be useful for this purpose. VNA should remain the gold standard to assess the protective antibody response, but some commercial assays could be used as first-line screening of long-term presence of NAb.

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“…On the basis of these findings, we focused on correlates of clinical outcomes in convalescent plasma donors that could be inferred through cell-based assays. Recent studies have correlated B cell responses in some individuals with immunity and protection [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, clinical outcome correlations suggest that extrafollicular B cell activation and subsequent plasmablast generation are detrimental to host survival and COVID-19 symptom resolution. Memory B cells are also generated following SARS-CoV-2 infection [ 4 ]. B memory cells are found as multiple subsets, including canonical CD27 + class-switched memory B cells, but also activated CD24-negative and “innate-like” natural CD27 + IgD + IgM + subsets.…”

Section: Introductionmentioning

confidence: 99%

Switched and unswitched memory B cells detected during SARS-CoV-2 convalescence correlate with limited symptom duration

et al. 2021

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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of the pandemic human respiratory illness COVID-19, is a global health emergency. While severe acute disease has been linked to an expansion of antibody-secreting plasmablasts, we sought to identify B cell responses that correlated with positive clinical outcomes in convalescent patients. We characterized the peripheral blood B cell immunophenotype and plasma antibody responses in 40 recovered non-hospitalized COVID-19 subjects that were enrolled as donors in a convalescent plasma treatment study. We observed a significant negative correlation between the frequency of peripheral blood memory B cells and the duration of symptoms for convalescent subjects. Memory B cell subsets in convalescent subjects were composed of classical CD24+ class-switched memory B cells, but also activated CD24-negative and natural unswitched CD27+ IgD+ IgM+ subsets. Memory B cell frequency was significantly correlated with both IgG1 and IgM responses to the SARS-CoV-2 spike protein receptor binding domain (RBD) in most seropositive subjects. IgM+ memory, but not switched memory, directly correlated with virus-specific antibody responses, and remained stable over 3 months. Our findings suggest that the frequency of memory B cells is a critical indicator of disease resolution, and that IgM+ memory B cells may play an important role in SARS-CoV-2 immunity.

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Functional SARS-CoV-2-Specific Immune Memory Persists after Mild COVID-19

Cited by 602 publications

References 71 publications

Persistent cellular immunity to SARS-CoV-2 infection

Persistent cellular immunity to SARS-CoV-2 infection

Six-month antibody response to SARS-CoV-2 in healthcare workers assessed by virus neutralisation and commercial assays

Switched and unswitched memory B cells detected during SARS-CoV-2 convalescence correlate with limited symptom duration

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