Among individuals who have received COVID-19 vaccines, younger people, females, and those who got the second dose of the Moderna COVID-19 vaccine report more side effects from COVID-19 vaccines that may have led to moderate and severe limitations, according to a recent paper (Front Public Health 2022; doi: 10.3389/fpubh.2022.975781).

These observations from self-reported data might be explained by higher mRNA concentration in the Moderna vaccine, according to researchers. They added that increased side effects in these groups may be associated with additional protective immunity and fewer breakthrough infections, as other studies have shown.

In what the researchers believe is the first survey comparing side effects of Pfizer, Moderna, and Johnson & Johnson COVID-19 vaccines, the researchers surveyed 975 participants who attended the 2021 AACC Annual Scientific Meeting. General questions in the web-based Research Electronic Data Capture (REDCap) survey addressed demographics, past and present health conditions, smoking, exercise, and medications. COVID-19-specific questions covered SARS-CoV-2 vaccine status and type, vaccine side effects after each dose, and whether respondents had boosters, previous COVID-19 infections, diagnostic testing, and COVID-19 symptoms and their severity.

Participants were 47.1% male and had a  median age of 50. Pfizer was the most administered vaccine, with receipt reported by 56.4% of respondents, followed by Moderna (32%) and Johnson & Johnson (7.1%). There were not significant differences in vaccine type received by age, health conditions, smoking, exercise, or type or number of prescription medications. Side effects were reported more frequently after the second dose of the Moderna and Pfizer vaccine or the single-dose Johnson & Johnson vaccines. Males were significantly less likely to report side effects, while females were significantly more likely to report injection site reactions, fatigue, headache, muscle pain, chills, and nausea. In multivariate logistic regressions analyses, the second dose of the Moderna vaccine was associated with a significantly higher risk of side effects than both the second dose of Pfizer and the single dose of the Johnson & Johnson vaccine.

The researchers note the study is limited by a participant population that does not represent the U.S. population and by inability to determine whether patients had tested positive for SARS-CoV-2 before or after vaccination.

HIGH SENSITIVITY CRP TESTS NOT NECESSARY FOR SOME PATIENTS

Lower-cost C-reactive protein (CRP) tests for CRP values in lower ranges correlate highly with more expensive high-sensitivity (hs) CRP tests and can replace them to assess low levels of inflammation and evaluate cardiovascular risk, according to a recent retrospective observational cohort study (J Appl Lab Med 2022; doi: doi.org/10.1093/jalm/jfac069).

Because measurements of regular, lower-cost CRP have become very sensitive, with a lower detection limit of 0.3 mg/L, the researchers aimed to compare and explore the association between CRP and hs-CRP.

They retrospectively reviewed data from 607 consecutive patients referred for cardiovascular risk assessment with hs-CRP. The researchers analyzed data from 570 of the patients and assigned them to low-, medium-, and high-risk groups based on hs-CRP cutoffs of less than 1 mg/L, 1−3 mg/L, and more than 3 mg/L, respectively. The researchers assessed correlation between hs-CRP and CRP with the kappa statistic and visualized with a Bland-Altman plot. They also determined association between hs-CRP and occurrence of acute myocardial infarction, stroke, bypass surgery, or percutaneous coronary intervention via Cox regression analysis visualized with Kaplan-Meier curves.

The researchers saw total number reclassification in 8.6% of cases for CRP risk groups, demonstrating agreement of 91.4%. Correlation between CRP and hs-CRP was significant, with P more than 0.001 and Spearman regression of R2 of +0.98. A Bland-Altman plot displayed an average difference of 0.19 mg/L between CRP and hs-CRP. Cardiovascular events were more likely to occur in patients who were older, with hs-CRP more than 3 mg/L and a history of coronary artery disease

Assessing inflammation markers alone may play a secondary role compared with other established cardiovascular risk factors, the researchers said. They noted that elevated CRP appears helpful for determining patients with higher risk and for predicting further cardiovascular events and mortality.

Study limitations include its observational design and the fact that it was conducted at a single center, a tertiary care hospital at which some rare diseases may have been over-represented. Only 18.3% of patients in the study had multiple measurements of hs-CRP, which is preferred for correct risk group classification.

SINGLE-MOLECULE SEQUENCING MAY IMPROVE CANCER LIQUID BIOPSY

Single-molecule sequencing enables long cell-free (cf) DNA detection and direct methylation analysis for cancer patients, presenting new possibilities for liquid biopsy, according to recent research (Clin Chem 2022; doi.org/10.1093/clinchem/hvac086).

While circulating tumor DNA has become an important cancer care tool, previous research on circulating cfDNA has focused on short DNA fragments. Meanwhile, the conventional approach for methylation analysis, bisulfite sequencing, causes DNA degradation and is not ideal for assessing long DNA properties and methylation patterns.

In response, the researchers conducted a proof-of-concept study to determine whether single-molecule sequencing for cancer liquid biopsy via single-molecule real-time (SMRT) sequencing of plasma DNA could enable direct and concurrent assessment of both long cfDNA molecules and their methylation patterns.

For each molecule, the researchers performed fragment size and direct methylation analysis and computed a methylation score for single-molecule methylation patterns in 13 patients with hepatocellular carcinoma (HCC), 13 patients with hepatitis B infection, and 15 healthy controls.

The median percentage of plasma DNA molecules longer than 1 kb was 15.7% in SMRT sequencing results in patients with HCC, which was 350-fold higher than that produced by short-read sequencing.

The longest plasma DNA molecule carrying a mutant allele was 13,585 bp, demonstrating the existence of long tumor-derived cfDNA molecules in cancer patients. The researchers were able to generalize differential sizes to a broader size range of up to 3 kb. Patients with HCC tended to release more liver-derived DNA fragments into plasma compared with HBV carriers or healthy individuals.

The presence of long tumoral cfDNA might lead to a shift in the current focus of cancer liquid biopsy from short cfDNA molecules of 250 bp to 1 kb-long cfDNA molecules, the researchers wrote.