Immune mechanisms associated with sex-based differences in severe COVID-19 clinical outcomes

Arnold, Cosby G.; Libby, Anne M.; Vest, Alexis; Hopkinson, Andrew; Monte, Andrew A.

doi:10.1186/s13293-022-00417-3

Cited by 37 publications

(40 citation statements)

References 46 publications

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“…From a purely epidemiological standpoint, one would expect in general that the most infected group would be those unvaccinated, not wearing masks and less careful because of low risk of a severe illness, with males and females equally likely to become infected [ 20 ]. However, as presented in Figure 1 , based on actual detection rate, that is most certainly not the case.…”

Section: Resultsmentioning

confidence: 99%

Am I Paid Well Enough to Be Diagnosed with COVID-19? Determinants of Gender Differences in Infection Detection Rate among Polish Working Age Population

Walkowiak

2022

JPM

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In comparison to Western European countries, Poland had a relatively lower percentage of its population diagnosed with COVID-19. Moreover, even the detected cases were not showing any pattern consistent with the expected chance of infection and were at best only remotely related to the severity of the illness that is known to increase with age. Instead, the crucial factor in detecting illness was whether the individual was likely to receive adequate compensation for being confined to their home, with employed women being the most likely to be diagnosed. In every Polish sub-region (powiat), in the 25–54 age group, the share of men diagnosed with COVID-19 was lower than that of women, with the missing share ranging from 8% to 36%. Based on the regression model (adjusted R² = 43.9%), there were relevant non-economic factors such as education, vaccination rate and increasing median age that were reducing this gap. However, the key factors, such as the share of population entitled to sick leave derived from employment rate, or the share of the self-employed population who were unlikely to receive adequate compensation, were related to economic incentives. It would seem that gender differences, in reaction to economic stimuli, widened the discrepancies, as the same factors were affecting women as well. While the testing rates in Poland, the lowest of all the EU countries, clearly played a role in creating the environment in which testing was perceived by the general population as somewhat optional, Polish citizens themselves through their actions aggravated the problem further, creating the impression of people receiving inadequate or no compensation for their time of self-isolation. In spite of well-intentioned government efforts to extend compensation to at least some groups, a significant share of the population clearly behaved as if they feared self-isolation more than the actual virus. Therefore, for both compliance and fairness purposes, both the severity of restrictions and the availability of compensation should be reconsidered.

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Section: Resultsmentioning

confidence: 99%

Am I Paid Well Enough to Be Diagnosed with COVID-19? Determinants of Gender Differences in Infection Detection Rate among Polish Working Age Population

Walkowiak

2022

JPM

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“…Sex-based differences in COVID-19 outcomes are mediated by immune response. Females have been found to show some stronger immune responses to a variety of infections, likely due to genetic and hormonal differences in the immune system [38][39][40][41].…”

Section: Discussionmentioning

confidence: 99%

“…Many components of the immune response to viral infection vary by sex. Higher levels of TLR7, an endosomal receptor expressed on dendritic and B cells, which recognizes viral infections and triggers a type I interferon (IFN) response, have been found among women than men, and this provides an advantage in response to COVID-19 [41,42]. Men have weaker T cell response than women and this is associated with worse outcomes in male patients [43].…”

Section: Discussionmentioning

confidence: 99%

“…Men also have increased cytokine concentrations and dysregulated inflammatory response, which would lead to higher complications [40]. The levels of protective SARS-CoV-2 immunoglobulin G (IgG) antibody are higher in female patients compared to male patients with severe infection, and this also contributes to better clinical outcomes [41].…”

Section: Discussionmentioning

confidence: 99%

“…Sex hormones play an important role in immune function and response to viral infections. Among women, higher estrogen levels inhibit the pro-inflammatory innate immune response, enhance T helper 2 and humoral immune response, and exert protective effects on endothelial cell function, reducing the effect of SARS-CoV-2 infections [41,43].…”

Section: Discussionmentioning

confidence: 99%

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Sex Differences in COVID-19 Hospitalization and Hospital Mortality among Patients with COPD in Spain: A Retrospective Cohort Study

Miguel-Díez

López‐de‐Andrés

Jiménez‐García

et al. 2022

Viruses

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(1) Background: We aimed to assess the effect of COPD in the incidence of hospital admissions for COVID-19 and on the in-hospital mortality (IHM) according to sex. (2) Methods: We used national hospital discharge data to select persons aged ≥40 years admitted to a hospital with a diagnosis of COVID-19 in 2020 in Spain. (3) Results: The study population included 218,301 patients. Age-adjusted incidence rates of COVID-19 hospitalizations for men with and without COPD were 10.66 and 9.27 per 1000 persons, respectively (IRR 1.14; 95% CI 1.08–1.20; p < 0.001). The IHM was higher in men than in women regardless of the history of COPD. The COPD was associated with higher IHM among women (OR 1.09; 95% CI 1.01–1.22) but not among men. The COPD men had a 25% higher risk of dying in the hospital with COVID-19 than women with COPD (OR 1.25, 95% CI 1.1–1.42). (4) Conclusions: Sex differences seem to exist in the effect of COPD among patients suffering COVID-19. The history of COPD increased the risk of hospitalization among men but not among women, and COPD was only identified as a risk factor for IHM among women. In any case, we observed that COPD men had a higher mortality than COPD women. Understanding the mechanisms underlying these sex differences could help predict the patient outcomes and inform clinical decision making to facilitate early treatment and disposition decisions.

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Analysis of 52 240 source plasma donors of convalescent COVID‐19 plasma: Sex, ethnicity, and age association with initial antibody levels and rate of dissipation

Schmidt¹,

Peter

Chastain³

et al. 2022

J of Clinical Apheresis

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Background COVID‐19 convalescent plasma (CCP) was approved under emergency authorization to treat critically ill patients with COVID‐19 in the United States in 2020. We explored the demographics of donors contributing plasma for a hyperimmune, plasma‐derived therapy to evaluate factors that may be associated with anti‐SARS‐CoV‐2 antibody response variability and, subsequently, antibody titers. Study Design An electronic search of CCP donors was performed across 282 US plasma donation centers. Donations were screened for nucleocapsid protein‐binding‐IgG using the Abbott SARS‐CoV‐2 IgG assay. Results Overall, 52 240 donors donated 418 046 units of CCP. Donors were of various ethnicities: 43% Caucasian, 34% Hispanic, 17% African American, 2% Native American, 1% Asian, and 3% other. Females had higher initial mean anti‐SARS‐CoV‐2 antibody titers but an overall faster rate of decline ( P < .0001). Initial antibody titers increased with age: individuals aged 55 to 66 years had elevated anti‐SARS‐CoV‐2 titers for longer periods compared with other ages ( P = .0004). African American donors had the lowest initial antibody titers but a slower rate of decline ( P < .0001), while Caucasian ( P = .0088) and Hispanic ( P = .0193) groups had the fastest rates of decline. Most donor antibody levels decreased below the inclusion criteria (≥1.50) within 30 to 100 days of first donation, but donation frequency did not appear to be associated with rate of decline. Conclusion Several factors may be associated with anti‐SARS‐CoV‐2 antibody response including donor age and sex. Evaluating these factors during development of future hyperimmune globulin products may help generation of therapies with optimal efficacy.

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Immune mechanisms associated with sex-based differences in severe COVID-19 clinical outcomes

Cited by 37 publications

References 46 publications

Am I Paid Well Enough to Be Diagnosed with COVID-19? Determinants of Gender Differences in Infection Detection Rate among Polish Working Age Population

Am I Paid Well Enough to Be Diagnosed with COVID-19? Determinants of Gender Differences in Infection Detection Rate among Polish Working Age Population

Sex Differences in COVID-19 Hospitalization and Hospital Mortality among Patients with COPD in Spain: A Retrospective Cohort Study

Analysis of 52 240 source plasma donors of convalescent COVID‐19 plasma: Sex, ethnicity, and age association with initial antibody levels and rate of dissipation

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