A finding of sex similarities rather than differences in COVID-19 outcomes

Shattuck‐Heidorn, Heather; Danielsen, Ann Caroline; Gompers, Annika; Bruch, Joseph Dov; Zhao, Helen; Boulicault, Marion; Marsella, Jamie; Richardson, Sarah S.

doi:10.1038/s41586-021-03644-7

Cited by 30 publications

(20 citation statements)

References 12 publications

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“…Receptors for sex hormones are also expressed in immune cells, and thus, sex hormones play a role in establishing the sex difference in the immune response ( Kim et al, 2020 ). Takahashi assessed immune phenotype in a sample group of COVID-19 patients and concluded that the number of non-classical monocytes and the level of CCL5 were higher in male patients, and activated CD8 T cell numbers were higher in female patients ( Takahashi et al, 2020 ; Shattuck-Heidorn et al, 2021 ). Further research raises questions about whether the differences in immune response in men related to gut microbiota diversity, given an explanation of men’s preexisting higher mortality rates before the pandemic.…”

Section: Discussionmentioning

confidence: 99%

Oral SARS-CoV-2 Spike Protein Recombinant Yeast Candidate Prompts Specific Antibody and Gut Microbiota Reconstruction in Mice

et al. 2022

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A recent study showed that patients with coronavirus disease 2019 (COVID-19) have gastrointestinal symptoms and intestinal flora dysbiosis. Yeast probiotics shape the gut microbiome and improve immune homeostasis. In this study, an oral candidate of yeast-derived spike protein receptor-binding domain (RBD) and fusion peptide displayed on the surface of the yeast cell wall was generated. The toxicity and immune efficacy of oral administration were further performed in Institute of Cancer Research (ICR) mice. No significant difference in body weights, viscera index, and other side effects were detected in the oral-treated group. The detectable RBD-specific immunoglobulin G (IgG) and immunoglobulin A (IgA) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and more complex microbiota were detected from oral administration mice compared with those of the control group. Interestingly, the recombinant yeast was identified in female fetal of the high-dose group. These results revealed that the displaying yeast could fulfill the agent-driven immunoregulation and gut microbiome reconstitution. The findings will shed light on new dimensions against SARS-CoV-2 infection with the synergistic oral agents as promising non-invasive immunization and restoring gut flora.

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Section: Discussionmentioning

confidence: 99%

Oral SARS-CoV-2 Spike Protein Recombinant Yeast Candidate Prompts Specific Antibody and Gut Microbiota Reconstruction in Mice

et al. 2022

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“…Similarly, a reanalysis of a headline-making paper purporting to show sex differences in immune response to COVID-19 demonstrated that the evidence overwhelmingly pointed to null findings of sex similarity. 7 Furthermore, researchers who study sex differences rarely specify how they operationalize sex. All too commonly, researchers assert sex differences based on aggregations of data by physician- or patient-reported “sex” or “gender” without specification and actual analysis of underlying variables that account for these differences, and an a priori study design suitable to doing so.…”

Section: Main Textmentioning

confidence: 99%

Why “sex as a biological variable” conflicts with precision medicine initiatives

DiMarco

Zhao

Boulicault

et al. 2022

Cell Reports Medicine

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“…Further supporting these findings are similar sex-specific effects of age observed following seasonal influenza vaccination in both younger and older adults [17, 46]. While it is important to not over-interpret ‘within-sex’ differences as ‘between-sex’ differences [47], there is considerable value in studying differences within males or feamles [48, 49]. This is particularly true given the uniqueness of the community-dwelling older adult cohort, which represent the ‘oldest’ old subset, and are distinct from the population of long-term care facility residents that has been the focus of much of the SARS-CoV-2 research in older adults.…”

Section: Discussionmentioning

confidence: 68%

Association of frailty, age, and biological sex with SARS-CoV-2 mRNA vaccine-induced immunity in older adults

Shapiro

Park

Aytenfisu

et al. 2022

Preprint

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Background: Male sex and old age are risk factors for severe COVID-19, but the intersection of sex and aging on antibody responses to SARS-CoV-2 vaccines has not been characterized. Methods: Plasma samples were collected from older adults (75-98 years) before and after three doses of SARS-CoV-2 mRNA vaccination, and from younger adults (18-74 years) post-dose two, for comparison. Antibody binding to SARS-CoV-2 antigens (spike protein [S], S-receptor binding domain [S-RBD], and nucleocapsid [N]) and functional activity against S were measured against the vaccine virus and variants of concern (VOC). Results: Vaccination induced greater antibody titers in older females than males, with both age and frailty associated with reduced antibody responses to vaccine antigens in males, but not females. ACE2 binding inhibition declined more than anti-S or anti-S-RBD IgG in the six months following the second dose (28-fold vs. 12- and 11-fold decreases in titer). The third dose restored functional antibody responses and eliminated disparities caused by sex, age, and frailty in older adults. Responses to the VOC were significantly reduced relative to the vaccine virus, with older males having lower titers to the VOC than females. Older adults had lower responses to the vaccine and VOC viruses than younger adults, with disparities being greater in males than females. Conclusion: Older and frail males may be more vulnerable to breakthrough infections due to low antibody responses before receipt of a third vaccine dose. Promoting third dose coverage in older adults, especially males, is crucial to protecting this vulnerable population.

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A finding of sex similarities rather than differences in COVID-19 outcomes

Cited by 30 publications

References 12 publications

Oral SARS-CoV-2 Spike Protein Recombinant Yeast Candidate Prompts Specific Antibody and Gut Microbiota Reconstruction in Mice

Oral SARS-CoV-2 Spike Protein Recombinant Yeast Candidate Prompts Specific Antibody and Gut Microbiota Reconstruction in Mice

Why “sex as a biological variable” conflicts with precision medicine initiatives

Association of frailty, age, and biological sex with SARS-CoV-2 mRNA vaccine-induced immunity in older adults

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