SARS‐CoV‐2‐specific humoral and cellular immunity persists through 9 months irrespective of COVID‐19 severity at hospitalisation

Varnaitė, Renata; Christ, Wanda; Chen, Puran; Muvva, Jagadeeswara Rao; Maleki, Kimia T.; García, Marina; Dzidic, Majda; Folkesson, Elin; Skagerberg, Magdalena; Ahlén, Gustaf; Frelin, Lars; Sällberg, Matti; Eriksson, Lars; Rooyackers, Olav; Sönnerborg, Anders; Buggert, Marcus; Björkström, Niklas K.; Strålin, Kristoffer; Klingström, Jonas; Ljunggren, Hans‐Gustaf; Blom, Kim; Gredmark‐Russ, Sara; Akber, Mira; Aleman, Soo; Berglin, Lena; Bergsten, Helena; Björkström, NK; Brighenti, Susanna; Brownlie, Demi; Butrym, Marta; Bj, Chambers; Cornillet, Martin; Cuapio, Angélica; Lozano, I Diaz; Dillner, Lena; Emgård, Johanna; Flodström‐Tullberg, Malin; Färnert, Anna; Gao, Yong; Glans, Hedvig; Gorin, JB; Grip, Jonathan; Haroun-Izquierdo, Alvaro; Henriksson, Elisabet Welin; Hertwig, Laura; Kalsum, Sadaf; Kammann, Tobias; Kokkinou, Efthymia; Kvedaraite, Egle; Loreti, MG; Lourda, Magda; Malmberg, KJ; Marquardt, Nicole; Maucourant, Christopher; Mårtensson, Johan; Michaëlsson, Jakob; Mjösberg, Jenny; Moll, Kirsten; Nauclér, P; Norrby‐Teglund, Anna; Medina, LM Palma; Parrot, Tiphaine; Perez‐Potti, André; Persson, BP; Radler, L.; Ringqvist, Emma; Rivera‐Ballesteros, Olga; Sandberg, J; Sekine, Takuya; Sohlberg, Ebba; Soini, Tea; Svensson, Mattias; Tynell, Janne; Unge, Christian; Kries, Andreas von; Wullimann, David

doi:10.1002/cti2.1306

Cited by 37 publications

(32 citation statements)

References 73 publications

(135 reference statements)

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“…This has also been observed in our results which suggest that the descent of anti-N IgG levels is more pronounced in comparison to the course of anti-S IgG. Additionally, Sandberg et al present similar findings as they conclude that anti-S antibody levels appear to be more stable than those for anti-N ( 9 ).…”

Section: Discussionsupporting

confidence: 90%

“…Our results reveal that in most cases, SARS-CoV-2 S-specific IgG levels remained stable over time and SARS-CoV-2 NCP-specific IgG levels decreased to a stable level within 6–12 months after symptom onset, while their range continuously diminished. Recent studies show that SARS-CoV-2-specific antibody levels after an infection were detectable in the majority of donors over a period of up to 1 year, even though the rate of recession varied ( 9 , 11 , 12 , 26 , 27 ). This supports our findings from the long-term analysis.…”

Section: Discussionmentioning

confidence: 99%

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Long-Lasting Immunity Against SARS-CoV-2: Dream or Reality?

et al. 2021

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Since its declaration as a pandemic in March 2020, SARS-CoV-2 has infected more than 217 million people worldwide and despite mild disease in the majority of the cases, more than 4.5 million cases of COVID-19-associated death have been reported as of September 2021. The question whether recovery from COVID-19 results in prevention of reinfection can be answered with a “no” since cases of reinfections have been reported. The more important question is whether during SARS-CoV-2 infection, a protective immunity is built and maintained afterwards in a way which protects from possibly severe courses of disease in case of a reinfection. A similar question arises with respect to vaccination: as of September 2021, globally, more than 5.2 billion doses of vaccines have been administered. Therefore, it is of utmost importance to study the cellular and humoral immunity toward SARS-CoV-2 in a longitudinal manner. In this study, reconvalescent COVID-19 patients have been followed up for more than 1 year after SARS-CoV-2 infection to characterize in detail the long-term humoral as well as cellular immunity. Both SARS-CoV-2-specific T cells and antibodies could be detected for a period of more than 1 year after infection, indicating that the immune protection established during initial infection is maintained and might possibly protect from severe disease in case of reinfection or infection with novel emerging variants. Moreover, these data demonstrate the opportunity for immunotherapy of hospitalized COVID-19 patients via adoptive transfer of functional antiviral T cells isolated from reconvalescent individuals.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Long-Lasting Immunity Against SARS-CoV-2: Dream or Reality?

et al. 2021

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“…In line with our findings, previous studies also reported retained SARS-CoV-2-specific T cell and antibody responses in prior-infected individuals up to nine months PSO. 36 , 37 , 38 Interestingly, we found that S1-specific T cell responses were not associated with anti-RBD IgG responses, indicating heterogeneity in the durability of humoral and cellular SARS-CoV-2 immunity. Moreover, a previous study showed discordancy between S1 IgG and T cell responses in prior SARS-CoV-2-infected individuals, in which S1 IgG levels increased with age in females while T cell responses increased with age in males.…”

Section: Discussionmentioning

confidence: 72%

SARS-CoV-2 antibody and T cell responses one year after COVID-19 and the booster effect of vaccination: A prospective cohort study

Mak

Koeleman

Vliet

et al. 2022

Journal of Infection

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Objectives : First, to describe SARS-CoV-2 T cell and antibody responses in a prospective cohort of healthcare workers that suffered from mild to moderate COVID-19 approximately one year ago. Second, to assess COVID-19 vaccine-induced immune responses in these prior-infected individuals. Methods : SARS-CoV-2-specific T cell and anti-SARS-CoV-2-Spike-RBD immunoglobulin G (IgG) responses in blood were determined before COVID-19 vaccination with mRNA-1273, BNT162b2, Ad26.CoV2-S or ChAdOx1-S, two weeks after first vaccination, and after second vaccination. Results : 55 prior SARS-CoV-2 infected and seroconverted individuals were included. S1-specific T cell responses and anti-RBD IgG were detectable one year post SARS-CoV-2 infection: 24 spot-forming cells per 10 6 peripheral blood mononuclear cells (SFCs/10 6 PBMCs) after S1 stimulation and anti-RBD IgG concentration of 74 (IQR 36-158) IU/mL. Responses after the first and second vaccination were comparable with S1-specfic T cell responses of 198 (IQR 137-359) and 180 (IQR 103-347) SFCs/10 6 PBMCs, and IgG concentrations of 6792 (IQR 3386-15180) and 6326 (IQR 2336-13440) IU/mL, respectively. These responses retained up to four months after vaccination. Conclusions : Both T cell and IgG responses against SARS-CoV-2 persist for up to one year after COVID-19. A second COVID-19 vaccination in prior-infected individuals did not further increase immune responses in comparison to one vaccination.

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“…Thus far, no differences have been observed in serum anti-spike antibody titers, in vitro serum neutralizing activity, or percentages of spike-specific memory B cells between non-severe and severe COVID-19 patients in the months after infection [ 18 ]. It remains to be determined whether the durability of B cell memory differs between individuals who experienced non-severe or severe disease.…”

Section: Discussionmentioning

confidence: 99%

“…In conclusion, we have shown that the memory B cell response against SARS-CoV-2 spike protein develops differently in patients with non-severe disease compared those with severe disease, with more spike-specific B cells that express a B-cell marker profile associated with durable immunity, characterized by expression of T-bet and FcRL5 in individuals who recovered from non-severe COVID-19. Although antibody titers or percentage of spike-specific memory B cells up to one year are similar or higher in individuals who recovered from severe disease as compared to non-severe cases [ 8 , 18 ], the increased percentage of B cells associated with long-lived immunity in non-severe COVID-19 patients may have consequences for long-term immunity against SARS-CoV-2 re-infection or severity of the resulting disease. T-bet + spike-specific B cells nearly disappeared from the circulation five months post-symptom onset, consistent with loss of these cells from the periphery or migration into tissues.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 spike-specific memory B cells express higher levels of T-bet and FcRL5 after non-severe COVID-19 as compared to severe disease

et al. 2021

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SARS-CoV-2 infection elicits a robust B cell response, resulting in the generation of long-lived plasma cells and memory B cells. Here, we aimed to determine the effect of COVID-19 severity on the memory B cell response and characterize changes in the memory B cell compartment between recovery and five months post-symptom onset. Using high-parameter spectral flow cytometry, we analyzed the phenotype of memory B cells with reactivity against the SARS-CoV-2 spike protein or the spike receptor binding domain (RBD) in recovered individuals who had been hospitalized with non-severe (n = 8) or severe (n = 5) COVID-19. One month after symptom onset, a substantial proportion of spike-specific IgG+ B cells showed an activated phenotype. In individuals who experienced non-severe disease, spike-specific IgG+ B cells showed increased expression of markers associated with durable B cell memory, including T-bet and FcRL5, as compared to individuals who experienced severe disease. While the frequency of T-bet+ spike-specific IgG+ B cells differed between the two groups, these cells predominantly showed an activated switched memory B cell phenotype in both groups. Five months post-symptom onset, the majority of spike-specific memory B cells had a resting phenotype and the percentage of spike-specific T-bet+ IgG+ memory B cells decreased to baseline levels. Collectively, our results highlight subtle differences in the B cells response after non-severe and severe COVID-19 and suggest that the memory B cell response elicited during non-severe COVID-19 may be of higher quality than the response after severe disease.

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SARS‐CoV‐2‐specific humoral and cellular immunity persists through 9 months irrespective of COVID‐19 severity at hospitalisation

Abstract: See the Acknowledgments section for all the members of The Karolinska COVID-19 Study Group.

Cited by 37 publications

References 73 publications

Long-Lasting Immunity Against SARS-CoV-2: Dream or Reality?

Long-Lasting Immunity Against SARS-CoV-2: Dream or Reality?

SARS-CoV-2 antibody and T cell responses one year after COVID-19 and the booster effect of vaccination: A prospective cohort study

SARS-CoV-2 spike-specific memory B cells express higher levels of T-bet and FcRL5 after non-severe COVID-19 as compared to severe disease

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