Clinical pathology selected abstracts

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Editor: Deborah Sesok-Pizzini, MD, MBA, chief medical officer, Labcorp Diagnostics, Burlington, NC, and adjunct professor, Department of Clinical Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia.

Analysis of donor antibody titer in a COVID-19 convalescent plasma trial

March 2021—Convalescent plasma, with neutralizing and non-neutralizing anti-viral antibodies, has been used to treat COVID-19 patients. Plasma is collected from people who have recovered from the disease and transfused to those who are infected. Data have shown improvements in patients with severe infections who are transfused with COVID-19 convalescent plasma. The majority of people who have COVID-19 will demonstrate IgM and IgG antibodies within two weeks of symptom onset. These antibodies have specificity toward the receptor-binding domain (RBD) and spike protein viral epitopes that correspond to virus neutralization. The authors conducted a study to investigate the relationship between clinical and serological parameters in convalescent plasma donors and better define the antibody response of patients receiving anti-SARS-CoV-2 convalescent plasma. They conducted a prospective open-label clinical study to determine the feasibility, safety, and immunological impact of administering anti-SARS-CoV-2 convalescent plasma to hospitalized patients who were 18 years or older. Multivariable analysis was used to assess the clinical and serological parameters in 103 confirmed COVID-19 convalescent plasma donors 28 or more days after their symptoms resolved. The authors also analyzed mixed effects regression models with piecewise linear trends to characterize serial antibody responses in 10 convalescent plasma recipients with severe COVID-19. The results showed that donor antibody titers ranged from zero to 1:1:3892 (anti-RBD) and zero to 1:3289 (anti-spike). Of interest, higher anti-RBD and anti-spike titers were significantly associated with increased age, hospitalization for COVID-19 fever, and absence of myalgia. Fatigue was also significantly associated with anti-RBD antibodies. With regard to ABO blood types, AB donors had significantly higher anti-RBD and anti-spike antibodies compared with O donors. The anti-RBD antibody titer increased 31 percent per day during the first three days after transfusion and the anti-spike antibody titer increased 40 percent. The authors concluded that donor characteristics such as advanced age, fever, absence of myalgia, and fatigue are associated with higher convalescent antibody titer to COVID-19. Despite variability in donor antibody titer, 80 percent of convalescent plasma recipients showed a significant increase in antibody levels after transfusion. The authors suggested that more studies are needed to characterize convalescent plasma donor and recipient pairs to improve understanding of the therapeutic mechanism of convalescent plasma therapy.

Madariaga MLL, Guthmiller JJ, Schrantz S, et al. Clinical predictors of donor antibody titre and correlation with recipient antibody response in a COVID-19 convalescent plasma clinical trial. J Intern Med. 2020. https://doi.org/10.1111/joim.13185

Correspondence: Dr. Maria Lucia L. Madariaga at mlmadariaga@uchicago.edu

Association of biomarkers with age at onset of incident CHD in women

Coronary heart disease is a leading factor in premature mortality and morbidity in women younger than 65 and men younger than 55. Identifying those who have a greater risk of premature CHD can help efforts to prevent and manage the disease before it progresses. However, there is little information about the factors associated with premature CHD, particularly in women. Most studies have examined the differences in levels of LDL and HDL cholesterol and triglycerides. Yet there may also be novel biomarkers related to lipoprotein subfractions, inflammation, and metabolic pathways that can help define an early CHD diagnosis. The authors conducted a study in which they investigated the relative risk of more than 50 clinical CHD risk factors and lipid, lipoprotein, inflammatory, and metabolic biomarkers to identify potential novel CHD biomarkers in women. They studied a prospective cohort of 28,024 female U.S. health professionals who were 45 years or older. The women had no known CHD risk factors and participated in the Women’s Health Study. The median follow-up was 21.4 years. The women were grouped by age and examined for CHD onset. The age groups were younger than 55 years, 55 through 64, 65 through 74, and 75 or older. The participants contributed to different age groups over time. Incident CHD was defined as the first myocardial infarction, percutaneous coronary intervention, coronary artery bypass grafting, or CHD death. The results showed that of all the clinical risk factors for women, diabetes had the highest adjusted hazard ratio (aHR) for CHD onset at any age. Other risk factors for study participants younger than 55 years were metabolic syndrome, hypertension, obesity, and smoking. Of the approximately 50 biomarkers examined, lipoprotein insulin resistance had the highest standardized aHR, at 6.40 for women younger than 55 years. The authors found that most risk factors and biomarkers had associations that increased over time with age. A few lipid and lipoprotein biomarkers, such as total HDL particles, did not differ significantly in their association of CHD with increasing age at disease onset. The authors concluded that diabetes, insulin resistance, hypertension, obesity, and smoking are the strongest risk factors for predicting premature CHD in women. They found that of all the lipid, inflammatory, and metabolic biomarkers examined, insulin resistance measured by the lipoprotein insulin resistance (LPIR) score was associated with the highest standardized relative risk of incident CHD.