. 2022 Nov 16;19(1):57.

doi: 10.1186/s12979-022-00310-y.

The oldest unvaccinated Covid-19 survivors in South America

Mateus V de Castro^#¹, Monize V R Silva^#¹, Michel S Naslavsky^{1

2}, Marilia O Scliar^{1

2}, Kelly Nunes^{1

2}, Maria Rita Passos-Bueno^{1

2}, Erick C Castelli^#³, Jhosiene Y Magawa^{4

5

6}, Flávia L Adami⁷, Ana I S Moretti⁴, Vivian L de Oliveira⁴, Silvia B Boscardin⁷, Edecio Cunha-Neto^{5

6}, Jorge Kalil^{4

5}, Emmanuelle Jouanguy^{8

9}, Paul Bastard^{8

9}, Jean-Laurent Casanova^{9

10}, Mauricio Quiñones-Vega^{11

12}, Patricia Sosa-Acosta^{11

12}, Jéssica de S Guedes^{11

12}, Natália P de Almeida^{11

12}, Fábio C S Nogueira^{11

12}, Gilberto B Domont¹¹, Keity S Santos^#^{4

5

6}, Mayana Zatz^{13

14}

Affiliations

¹ Human Genome and Stem Cell Research Center, University of São Paulo, São Paulo, São Paulo, Brazil.
² Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo, São Paulo, São Paulo, Brazil.
³ Department of Pathology, School of Medicine, UNESP - São Paulo State University, Botucatu, São Paulo, Brazil.
⁴ Laboratório de Imunologia, Instituto do Coração (InCor), LIM19, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, (HCFMUSP), São Paulo, Brazil.
⁵ Instituto de Investigação em Imunologia-Instituto Nacional de Ciências e Tecnologia-iii-INCT, São Paulo, Brazil.
⁶ Departamento de Clínica Médica, Disciplina de Imunologia Clínica e Alergia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
⁷ Laboratory of Antigen Targeting to Dendritic Cells, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
⁸ Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.
⁹ Imagine Institute, University of Paris, Paris, France.
¹⁰ St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
¹¹ Proteomics Unit, Department of Biochemistry, Institute of Chemistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
¹² Laboratory of Proteomics (LabProt), Institute of Chemistry, LADETEC, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
¹³ Human Genome and Stem Cell Research Center, University of São Paulo, São Paulo, São Paulo, Brazil. mayazatz@usp.br.
¹⁴ Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo, São Paulo, São Paulo, Brazil. mayazatz@usp.br.

^# Contributed equally.

PMID: 36384671
PMCID: PMC9666972
DOI: 10.1186/s12979-022-00310-y

The oldest unvaccinated Covid-19 survivors in South America

Mateus V de Castro et al. Immun Ageing. 2022.

. 2022 Nov 16;19(1):57.

doi: 10.1186/s12979-022-00310-y.

Authors

Affiliations

¹ Human Genome and Stem Cell Research Center, University of São Paulo, São Paulo, São Paulo, Brazil.
² Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo, São Paulo, São Paulo, Brazil.
³ Department of Pathology, School of Medicine, UNESP - São Paulo State University, Botucatu, São Paulo, Brazil.
⁴ Laboratório de Imunologia, Instituto do Coração (InCor), LIM19, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, (HCFMUSP), São Paulo, Brazil.
⁵ Instituto de Investigação em Imunologia-Instituto Nacional de Ciências e Tecnologia-iii-INCT, São Paulo, Brazil.
⁶ Departamento de Clínica Médica, Disciplina de Imunologia Clínica e Alergia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
⁷ Laboratory of Antigen Targeting to Dendritic Cells, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
⁸ Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.
⁹ Imagine Institute, University of Paris, Paris, France.
¹⁰ St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
¹¹ Proteomics Unit, Department of Biochemistry, Institute of Chemistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
¹² Laboratory of Proteomics (LabProt), Institute of Chemistry, LADETEC, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
¹³ Human Genome and Stem Cell Research Center, University of São Paulo, São Paulo, São Paulo, Brazil. mayazatz@usp.br.
¹⁴ Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo, São Paulo, São Paulo, Brazil. mayazatz@usp.br.

^# Contributed equally.

PMID: 36384671
PMCID: PMC9666972
DOI: 10.1186/s12979-022-00310-y

Erratum in

Correction: The oldest unvaccinated Covid-19 survivors in South America.
de Castro MV, Silva MVR, Naslavsky MS, Scliar MO, Nunes K, Passos-Bueno MR, Castelli EC, Magawa JY, Adami FL, Moretti AIS, de Oliveira VL, Boscardin SB, Cunha-Neto E, Kalil J, Jouanguy E, Bastard P, Casanova JL, Quiñones-Vega M, Sosa-Acosta P, Guedes JS, de Almeida NP, Nogueira FCS, Domont GB, Santos KS, Zatz M. de Castro MV, et al. Immun Ageing. 2022 Dec 7;19(1):61. doi: 10.1186/s12979-022-00319-3. Immun Ageing. 2022. PMID: 36476248 Free PMC article. No abstract available.

Abstract

Background: Although older adults are at a high risk of severe or critical Covid-19, there are many cases of unvaccinated centenarians who had a silent infection or recovered from mild or moderate Covid-19. We studied three Brazilian supercentenarians, older than 110 years, who survived Covid-19 in 2020 before being vaccinated.

Results: Despite their advanced age, humoral immune response analysis showed that these individuals displayed robust levels of IgG and neutralizing antibodies (NAbs) against SARS-CoV-2. Enrichment of plasma proteins and metabolites related to innate immune response and host defense was also observed. None presented autoantibodies (auto-Abs) to type I interferon (IFN). Furthermore, these supercentenarians do not carry rare variants in genes underlying the known inborn errors of immunity, including particular inborn errors of type I IFN.

Conclusion: These observations suggest that their Covid-19 resilience might be a combination of their genetic background and their innate and adaptive immunity.

Keywords: Covid-19; Elderly; SARS-CoV-2; Supercentenarians.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

**Fig. 1**
Supercentenarians present higher titers of IgG to RBDs of seasonal coronaviruses than for SARS-CoV-2 and neutralization titers above 160 (the minimum titer initially established by the FDA for convalescent plasma donors) [35]. The numbers represent the 3 individuals. The graph on top indicates IgG ratios for each RBD and the table above shows VNT for SARS-COV-2. VNT - Virus Neutralization Titers. Antibody levels expressed in ratios are shown for SARS-CoV-2 and the four seasonal coronaviruses. Neutralization titers are expressed in dilution. ID 02 was asymptomatic, and IDs 1 and 3 were symptomatic and recovered from Covid-19

**Fig. 2**
Plasma proteomics and metabolomics analyses of the supercentenarians infected with SARS-CoV-2 compared to healthy elderly subjects (> 95 years-old / non-infected). Volcano plots showing differentially expressed proteins **(A)** and metabolites **(B)**. Red and blue dots represent the up- and down-regulated proteins/metabolites, respectively. Protein-metabolite interaction network was built with the statistically significant proteins with OmicsAnalyst platform **(C)**. Red and blue nodes denote the up- and down-regulated proteins/metabolites, respectively. Circle and diamond node shapes represent metabolites and proteins, respectively

See this image and copyright information in PMC

References

1. WHO Coronavirus (COVID–19) Dashboard. [cited 2022 Jul 11]. Available from: https://covid19.who.int.
1. Chai S, Li Y, Li X, Tan J, Abdelrahim MEA, Xu X. Effect of age of COVID–19 inpatient on the severity of the disease: A meta-analysis. Int J Clin Pract. 2021;75(10):e14640. - PMC - PubMed
1. Hägg S, Jylhävä J, Wang Y, Xu H, Metzner C, Annetorp M. Age, Frailty, and Comorbidity as Prognostic Factors for Short-Term Outcomes in Patients With Coronavirus Disease 2019 in Geriatric Care. J Am Med Dir Assoc. 2020;21(11):1555–9.e2. - PMC - PubMed
1. Thakur B, Dubey P, Benitez J, Torres JP, Reddy S, Shokar N. A systematic review and meta-analysis of geographic differences in comorbidities and associated severity and mortality among individuals with COVID–19. Sci Rep. 2021;20(1):8562. - PMC - PubMed
1. Conheça a faixa etáriadosmortospor covid– 19 no Brasileemma is 4 países.[cited 2022 Jul 26]. Available from: https://www.poder360.com.br/coronavirus/conheca-a-faixa-etaria-dos-morto....

Grants and funding

R01 GM075091/GM/NIGMS NIH HHS/United States

LinkOut - more resources

Full Text Sources
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

The oldest unvaccinated Covid-19 survivors in South America

Affiliations

The oldest unvaccinated Covid-19 survivors in South America

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

Figures

References

Grants and funding

LinkOut - more resources

Full Text Sources

Miscellaneous