Publications

Apart from autopsy, tissue correlates of coronavirus disease 2019 (COVID-19) clinical stage are lacking. In the current study, cutaneous punch biopsy specimens of 15 individuals with severe/critical COVID-19 and six with mild/moderate COVID-19 were examined. Evidence for arterial and venous microthrombi, deposition of C5b-9 and MASP2 (representative of alternative and lectin complement pathways, respectively), and differential expression of interferon type I-driven antiviral protein MxA (myxovirus resistance A) versus SIN3A, a promoter of interferon type I-based proinflammatory signaling, were assessed. Control subjects included nine patients with sepsis-related acute respiratory distress syndrome (ARDS) and/or acute kidney injury (AKI) pre-COVID-19. Microthrombi were detected in 13 (87%) of 15 patients with severe/critical COVID-19 versus zero of six patients with mild/moderate COVID-19 (P < 0.001) and none of the nine patients with pre-COVID-19 ARDS/AKI (P < 0.001). Cells lining the microvasculature staining for spike protein of severe acute respiratory syndrome coronavirus 2, the etiologic agent of COVID-19, also expressed tissue factor. C5b-9 deposition occurred in 13 (87%) of 15 patients with severe/critical COVID-19 versus zero of six patients with mild/moderate COVID-19 (P < 0.001) and none of the nine patients with pre-COVID-19 ARDS/AKI (P < 0.001). MASP2 deposition was also restricted to severe/critical COVID-19 cases. MxA expression occurred in all six mild/moderate versus two (15%) of 13 severe/critical cases (P < 0.001) of COVID-19. In contrast, SIN3A was restricted to severe/critical COVID-19 cases co-localizing with severe acute respiratory syndrome coronavirus 2 spike protein. SIN3A was also elevated in plasma of patients with severe/critical COVID-19 versus control subjects (P ≤ 0.02). In conclusion, the study identified premortem tissue correlates of COVID-19 clinical stage using skin. If validated in a longitudinal cohort, this approach could identify individuals at risk for disease progression and enable targeted interventions.

BACKGROUND AND OBJECTIVES

African American women experience faster telomere shortening (i.e., cellular aging) compared with other racial-gender groups. Prior research demonstrates that race and gender interact to influence culturally specific norms for responding to socially-relevant stress and other stress-coping processes, which may affect healthy aging.

RESEARCH DESIGN AND METHODS

Data are from African American Women's Heart & Health Study participants who consented to DNA extraction (n = 140). Superwoman Schema (SWS) was measured using 5 validated subscales: presenting strength, emotion suppression, resisting vulnerability, motivation to succeed, and obligation to help others. Racial identity was measured using 3 subscales from the Multidimensional Inventory of Black Identity: racial centrality, private regard, and public regard. Relative telomere length (rTL) was measured using DNA extracted from blood samples. Path analysis tested associations and interactions between SWS and racial identity dimensions with rTL.

RESULTS

For SWS, higher resistance to being vulnerable predicted longer telomeres. For racial identity, high private regard predicted longer telomeres while high public regard predicted shorter telomeres. Interactions were found between public regard and 2 SWS dimensions: among women with high public regard, emotion suppression (β = 0.20, p < .05) and motivation to succeed (β = 0.18, p < .05) were associated with longer rTL. The interaction between high centrality and emotion suppression predicted shorter rTL (β = -0.17, p < .05).

DISCUSSION AND IMPLICATIONS

Culturally specific responses to gendered racism and racial identity, developed early in life and shaped over the life course, are important psychosocial determinants of cellular aging among African American women.