Severe Acute Respiratory Syndrome Coronavirus 2 Convalescent Plasma Versus Standard Plasma in Coronavirus Disease 2019 Infected Hospitalized Patients in New York: A Double-Blind Randomized Trial.

OBJECTIVES: Four peer-reviewed publications have reported results from randomized controlled trials of convalescent plasma for coronavirus disease 2019 infection; none were conducted in the United States nor used standard plasma as a comparator. To determine if administration of convalescent plasma to patients with coronavirus disease 2019 increases antibodies to severe acute respiratory syndrome coronavirus 2 and improves outcome. DESIGN: Double-blind randomized controlled trial. SETTING: Hospital in New York. PATIENTS: Patients with polymerase chain reaction documented coronavirus disease 2019 infection. INTERVENTIONS: Patients were randomized (4:1) to receive 2 U of convalescent plasma versus standard plasma. Antibodies to severe acute respiratory syndrome coronavirus 2 were measured in plasma units and in trial recipients. MEASUREMENTS AND MAIN RESULTS: Enrollment was terminated after emergency use authorization was granted for convalescent plasma. Seventy-four patients were randomized. At baseline, mean (sd) Acute Physiology and Chronic Health Evaluation II score (23.4 [5.6] and 22.5 [6.6]), percent of patients intubated (19% and 20%), and median (interquartile range) days from symptom onset to randomization of 9 (6-18) and 9 (6-15), were similar in the convalescent plasma versus standard plasma arms, respectively. Convalescent plasma had high neutralizing activity (median [interquartile range] titer 1:526 [1:359-1:786]) and its administration increased antibodies to severe acute respiratory syndrome coronavirus 2 by 14.4%, whereas standard plasma administration led to an 8.6% decrease (p = 0.005). No difference was observed for ventilator-free days through 28 days (primary study endpoint): median (interquartile range) of 28 (2-28) versus 28 (0-28; p = 0.86) for the convalescent plasma and standard plasma groups, respectively. A greater than or equal to 2 point improvement in the World Health Organization scale was achieved by 20% of subjects in both arms (p = 0.99). All-cause mortality through 90 days was numerically lower in the convalescent plasma versus standard plasma groups (27% vs 33%; p = 0.63) but did not achieve statistical significance. A key prespecified subgroup analysis of time to death in patients who were intubated at baseline was statistically significant; however, sample size numbers were small. CONCLUSIONS: Administration of convalescent plasma to hospitalized patients with coronavirus disease 2019 infection increased antibodies to severe acute respiratory syndrome coronavirus disease 2 but was not associated with improved outcome.

Impact of serological and PCR testing requirements on the selection of COVID-19 convalescent plasma donors.

BACKGROUND: Convalescent plasma is undergoing randomized trials as a potential therapeutic option for COVID-19 infection. Little empirical evidence exists regarding the determination of donor eligibility and experiences with donor selection. STUDY DESIGN AND METHODS: This prospective study was conducted at a tertiary care hospital in New York to select plasma donors for a randomized, double-blind, controlled convalescent plasma trial. Clearance for donation required successful completion of an online questionnaire and an in-person screening visit, which included (a) completion of a Donor Health Questionnaire (DHQ), (b) Immunoglobulin G (IgG) antibody testing using an immunochromatographic anti- severe acute respiratory coronavirus 2 (SARS-CoV-2) test, (c) Polymerase chain reaction (PCR) testing if <28 days from symptom resolution, and (d) routine blood bank testing. RESULTS: After receiving 3093 online questionnaires, 521 individuals presented for in-person screening visits, with 40.1% (n = 209) fully qualifying. Subjects (n = 312) failed to progress due to the following reasons: disqualifying answer from DHQ (n = 30, 9.6%), insufficient antibodies (n = 198, 63.5%), persistent positive PCR tests (n = 14, 4.5%), and blood donation testing labs (n = 70, 22.4%). Importantly, 24.6% and 11.1% of potential donors who reported having PCR-diagnosed infection had low or undetectable SARS-CoV-2 antibody levels, respectively. Surprisingly, 62.9% (56/89) of subjects had positive PCR tests 14-27 days after symptom resolution, with 13 individuals continuing to be PCR positive after 27 days. CONCLUSION: It is feasible for a single site to fully qualify a large number of convalescent plasma donors in a short period of time. Among otherwise qualified convalescent plasma donors, we found high rates of low or undetectable antibody levels and many individuals with persistently positive PCR tests.

Association Between Pulsatile Components of Blood Pressure and Severe Tooth Loss in Rural Ecuador: The Three Villages Study.

Background: Arterial hypertension has been associated with severe tooth loss, but differential associations with individual components of blood pressure (BP) have scarcely been investigated. We assessed the independent associations between pulsatile/steady components of BP and severe tooth loss in community-dwelling adults residing in 3 rural Ecuadorian villages. Methods: Individuals aged ≥40 years living in Atahualpa, El Tambo, and Prosperidad were identified during door-to-door surveys. Data collection focused on the number of remaining teeth and measurements of pulsatile/steady components of BP. Multivariate models were fitted to assess independent associations between pulsatile/steady BP components and severe tooth loss, after adjusting for relevant covariates. Results: A total of 1543 individuals were included. Oral exams identified 426 (28%) individuals with severe tooth loss. BP levels ≥140/90 mm Hg were determined in 481 (31%) individuals. The mean pulse pressure (PP) level was 55.3 ± 19 mm Hg. For systolic BP (SBP), the mean level was 133.1 ± 23.5 mm Hg, and for diastolic BP (DBP) it was 77.8 ± 11.5 mm Hg. Univariate models showed significant associations between severe tooth loss and SBP and PP, but not with DBP. However, the significance was taken away in fully adjusted generalized linear models. Age remained as an independent significant covariate in models using SBP and PP. Causal mediation analyses disclosed that percentages of the effect of severe tooth loss mediated by age were 99.5% for SBP and 98.9% for PP. Conclusion: This study shows that age captures most of the effect of the association between pulsatile components of BP and severe tooth loss.

The association between aortic arterial stiffness, carotid intima-media thickness and carotid plaques in community-dwelling older adults: A population-based study.

OBJECTIVE: Information on the associations among arterial stiffness, carotid intima-media thickness (cIMT) and carotid plaques as biomarkers of atherosclerosis is limited in diverse populations. We aimed to assess whether aortic pulse wave velocity (aPWV) - as a surrogate of arterial stiffness - is associated with increased cIMT and the presence of carotid plaques in a cohort of older adults of Amerindian ancestry. METHODS: Atahualpa residents aged ≥60 years (n = 320) underwent aPWV determinations, and carotid ultrasounds for cIMT and plaque assessment. Multivariate models were fitted to assess the independent association between the aPWV, and cIMT and carotid plaques, after adjusting for relevant confounders. Differences in risk factors across these biomarkers were investigated. RESULTS: Mean values of aPWV were 10.3 ± 1.8 m/s, and those of cIMT were 0.91 ± 0.21 mm (24% had a cIMT >1 mm). Carotid plaques were observed in 118 (37%) subjects. In univariate analyses, risk factors associated with an increased aPWV included age, female gender, poor physical activity and high blood pressure. An increased cIMT was associated with age, male gender, a poor diet, high blood pressure and severe tooth loss. The presence of carotid plaques was associated with increasing age, poor physical activity and high blood pressure. Multivariate models showed a significant association between aPWV and cIMT (ß: 0.028; 95% C.I.: 0.001-0.056; p = 0.047) but not between aPWV and carotid plaques (OR: 1.14; 95% C.I.: 0.83-1.56; p = 0.423). CONCLUSIONS: This study shows an independent association between aPWV and cIMT but not with carotid plaques. These biomarkers may indicate distinct phenotypes for atherosclerosis.

Cerebral small vessel disease score and atherosclerosis burden - A population study in community-dwelling older adults.

OBJECTIVE: Cerebral small vessel disease (cSVD) and large artery atherosclerosis (LAA) are related to different pathogenetic mechanisms. However, relationships between single biomarkers of cSVD and LAA affecting isolated vascular beds have been reported. Using the Atahualpa Project cohort, we aimed to assess the association between cSVD score categories and LAA burden in community-dwelling older adults. PATIENTS AND METHODS: Atahualpa individuals aged ≥60 years undergoing assessment of the cSVD score and LAA in the peripheral, carotid extracranial, and intracranial vascular beds (n = 333) were included. Multivariate models were fitted to assess independent associations between the cSVD score and LAA burden. RESULTS: The cSVD score was 0 points in 62 % individuals, 1 point in 19 %, 2 points in 13 %, and 3-4 points in 7 %. LAA involved the extracranial carotid bed in 43 % individuals, the intracranial bed in 36 %, and the peripheral bed in 20 %. One vascular bed was involved in 111 (33 %) individuals, two beds in 75 (23 %), and three beds in 23 (7 %). The remaining 124 (37 %) had no atherosclerosis. Ordinal logistic regression models showed progressively greater associations between higher categories of cSVD score and the odds of having more beds involved with LAA. Multinomial logistic regression models showed associations between categories of cSVD score and LAA burden, but only when two or three vascular beds were involved. CONCLUSION: This study demonstrates robust associations between the cSVD score and LAA, which become evident at the upper end of the spectrum of cSVD score (3-4 points) and LAA burden (2-3 vascular beds involved).

Cardiovascular Health Status Among Community-Dwelling Ecuadorian Natives Living in Neighboring Rural Communities: The Three Villages Study.

Knowledge of cardiovascular health (CVH) status in rural communities is essential to implement cost-effective strategies aimed to address the growing burden of cardiovascular diseases in these settings. Here, we report on the CVH status and health metrics of 1508 community-dwellers aged ≥ 40 years in three neighboring rural villages of Coastal Ecuador (Atahualpa, El Tambo, and Prosperidad). According to the American Heart Association, a poor CVH status is designated when at least one cardiovascular health metric is in the poor range. About 70% of individuals in the villages studied had a poor CVH status, with no overall differences across villages. However, the relative prevalence of poor health metrics varied. Using Atahualpa as the referent village, a multinomial logistic regression model showed that El Tambo residents were more often smokers and had a worse diet, while Prosperidad residents had more high blood pressure but better fasting glucose levels. Probabilities of having poor health metrics were lower in Atahualpa than in El Tambo (p < 0.001), but not better than in Prosperidad (p = 0.097). Predictive estimates of having poor health metrics were significantly higher in El Tambo than in Atahualpa or in Prosperidad. This comparative study demonstrates that the CVH status of rural populations of coastal Ecuador is basically similar. However, individual health metrics in the poor range were found to vary across villages. While the three villages are generally comparable, interventions should be tailored according to local priorities. The same may occur in other rural communities, but more studies are needed to confirm our findings.