Assessment of COVID-19 mRNA vaccination titer and side effects in healthy volunteers

Objectives An effective vaccine against SARS-CoV-2 is essential to mitigate the COVID-19 pandemic. In these several months, a number of groups have started to report humoral responses and side effects after BNT162b2 vaccinations. Although these reports demonstrate the safety and efficacy, further studies are warranted to verify these findings. Here we examined the levels of SARS-CoV-2 antibodies in Japanese healthy volunteers who underwent BNT162b2 vaccine, to assess the humoral responses and side effects. Methods Forty-one healthy volunteers’ samples were used for the measurement of SARS-CoV-2 antibodies with chemiluminescent assays against the Receptor Binding Domain (RBD) of the virus. We also measured the side effects of the vaccination. Results Although the levels of IgM varied, all participants were seronegative for IgM and IgG before vaccination, and both IgM and IgG were significantly increased after the vaccinations. We further analyzed the humoral responses in relation to age, and found that the IgG levels for 14 days and 35 days, and IgM levels for 14 days after vaccination showed clear declining trends with age. Commonly reported side effects in the participants were sore arm/pain (90.0%) after the first dose, and generalized weakness/fatigue (70.0%), fever (57.5%), and sore arm/pain (90.0%) after the second dose. Conclusions BNT162b2 vaccination generates sufficient production of IgG especially after the second dose, though the response decreases age-dependently. The high frequencies of generalized weakness/fatigue, fever, and sore arm/pain were not negligible, especially after the second dose. This may be associated with the age characteristics of the population.

Blood indices and circulating tumor cells for predicting metastasis of hepatocellular carcinoma after liver transplantation

Objectives Liver transplantation (LT) can benefit the long-term survival of hepatocellular carcinoma (HCC) patients. We hypothesized that circulating tumor cell (CTC) levels and subtypes are intimately associated with metastasis status of HCC patients. This study was designed to test that compositive hematological indices including CTC can provide a prediction of post-LT metastasis. Methods Between 2017 and 2018, 37 HCC patients within Hangzhou criteria receiving LT were included for analysis. The 24-month follow-up was mainly conducted by outpatient and telephone. Blood samples were collected, and hematological indices were examined. The outcomes such as PFS, recurrence, metastasis, location of recurrence/metastasis, and number of metastases were recorded. Results The follow-up analysis showed that microvascular invasion (MVI) classification at the baseline is associated with metastasis. Next, α-fetoprotein (AFP) level was another useful indicator of postoperative metastasis, especially at the third or fourth month; the protein induced by vitamin K absence or antagonist-II (PIVKA-II) level three months after LT was significantly higher for those who had later metastasis. The mesenchymal CTC level at the 45th day was increased for in the metastasis group. Using two-ends Logistic regression, the calculated value MP (metastasis predictor, by above factors). Had an AUC of 0.858 in the ROC curve, with a cutoff value of 0.328. Conclusions In conclusion, microvascular invasion, AFP level at the third or fourth month, PIVKA-II level at the third month, and mesenchymal CTC level at day 45 were associated with post-LT metastasis. Using Logistic regression based on above variables, the two-year metastasis can be predicted with satisfactory sensitivity and accuracy.

The neonatal microbiome in utero and beyond: perinatal influences and long-term impacts

The neonatal microbiome offers a valuable model for studying the origins of human health and disease. As the field of metagenomics expands, we also increase our understanding of early life influences on its development. In this review we will describe common techniques used to define and measure the microbiome. We will review in utero influences, normal perinatal development, and known risk factors for abnormal neonatal microbiome development. Finally, we will summarize current evidence that links early life microbial impacts on the development of chronic inflammatory diseases, obesity, and atopy.

Comparison of APACHE II scores and mortality with CRP/albumin, neutrophil/lymphocyte and thrombocyte/lymphocyte ratios in patients admitted to internal medicine and anesthesia reanimation intensive care unit

Objectives This study aimed to evaluate the relationship between C-reactive protein/albumin (CRP/Alb), neutrophil/lymphocyte (NLR), platelet/lymphocyte (PLR) ratios and the Acute Physiology And Chronic Health Evaluation II (APACHE II) score and 28-day mortality among 400 patients admitted to internal medicine and anesthesia reanimation intensive care unit (ICU). Methods This prospective study included a total of 400 patients who were admitted to hospital internal medicine and anesthesia reanimation ICUs. Results The most common reasons for ICU admission were pneumonia (29.3%), gastrointestinal bleeding (10.3%), acute exacerbation of chronic kidney disease (CKD) (10.3%), and acute kidney injury (7.5%). The comparison of the laboratory findings with survival outcomes revealed that among the patients with acute exacerbation of CKD, the median NLR (p=0.043) and median CRP/Alb (p=0.021) were significantly higher in patients who died. For all of the patients, the APACHE II score was positively correlated with CRP (p<0.001) and CRP/Alb (p<0.001), negatively correlated with Alb (p<0.001), positively correlated with the NLR (p<0.001), and positively correlated with the PLR. Conclusions The APACHE II score was significantly correlated with the CRP/Alb ratio, NLR, and PLR. The NLR and CRP/Alb ratio were statistically associated with mortality in patients hospitalized for acute exacerbation of CKD.

Ending diagnostic odyssey using clinical whole-exome sequencing (CWES)

Objectives Most rare diseases are genetic diseases. Due to the diversity of rare diseases and the high likelihood of patients with rare diseases to be undiagnosed or misdiagnosed, it is not unusual that these patients undergo a long diagnostic odyssey before they receive a definitive diagnosis. This situation presents a clear need to set up a dedicated clinical service to end the diagnostic odyssey of patients with rare diseases. Methods Therefore, in 2014, we started an Undiagnosed Diseases Program in Hong Kong with the aim of ending the diagnostic odyssey of patients and families with rare diseases by clinical whole-exome sequencing (CWES), who have not received a definitive diagnosis after extensive investigation. Results In this program, we have shown that genetic diseases diagnosed by CWES were different from that using traditional approaches indicating that CWES is an essential tool to diagnose rare diseases and ending diagnostic odysseys. In addition, we identified several novel genes responsible for monogenic diseases. These include the TOP2B gene for autism spectrum disorder, the DTYMK gene for severe cerebral atrophy, the KIF13A gene for a new mosaic ectodermal syndrome associated with hypomelanosis of Ito, and the CDC25B gene for a new syndrome of cardiomyopathy and endocrinopathy. Conclusions With the incorporation of CWES in an Undiagnosed Diseases Program, we have ended diagnostic odysseys of patients with rare diseases in Hong Kong in the past 7 years. In this program, we have shown that CWES is an essential tool to end diagnostic odysseys. With the declining cost of next-generation sequencers and reagents, CWES set-ups are now affordable for clinical laboratories. Indeed, owing to the increasing availability of CWES and treatment modalities for rare diseases, precedence can be given to both common and rare medical conditions.

Fast forward evolution in real time: the rapid spread of SARS-CoV-2 variant of concern lineage B.1.1.7 in Saxony-Anhalt over a period of 5 months

Objectives Random mutations and recombinations are the main sources for the genetic diversity in SARS-CoV-2, with mutations in the SARS-CoV-2 spike (S) receptor binding motif (RBM) representing a high potential for the emergence of new putative variants under investigation (VUI) or variants of concern (VOC). It is of importance, to measure the different circulating SARS-CoV-2 lineages in order to establish a regional SARS-CoV-2 surveillance program. We established whole genome sequencing (WGS) of circulating SARS-CoV-2 lineages in order to establish a regional SARS-CoV-2 surveillance program. Methods We established a surveillance program for circulating SARS-CoV-2 lineages by performing whole genome sequencing (WGS) in SARS-CoV-2 isolates. Specimens were collected over a period of 5 months from three different sites. Specimens were collected from both patients suffering from COVID-19 and from outpatients without any clinical signs or symptoms; both in a tertiary university hospital, and two private laboratories within an urban area of eastern part Germany. Results Viral WGS from the 364 respiratory specimens with positive SARS-CoV-2 RT-PCR comprised 16 different SARS-CoV-2 lineages. The majority of the obtained sequences (252/364=69%) was assigned to the variant of concern (VOC) Alpha (B.1.1.7). This variant first appeared in February in our samples and quickly became the dominant virus variant. All SNP PCR results could be verified using WGS. Other VOCs found in our cohort were Beta (B.1.351, n=2) and Delta (B.1.617.2, n=1). Conclusions Lineage analysis revealed 16 different virus variants among 364 respiratory samples analyzed by WGS. The number of distinct lineages dramatically decreased over time in leaving only few variants, in particular, the VOC Alpha or B.1.1.7. By closer inspection of point mutations, we found several distinct mutations of the viral spike protein that were reported to increase affinity or enable immune escape. Within a study period of only 5 months, SARS-CoV-2 lineage B.1.1.7 became the dominant lineage in our study population. This study emphasizes the benefit of SARS-CoV-2 testing by WGS. The increasing use of WGS to sequence the entire SARS-CoV-2 genome will reveal additional VUIs and VOCs with the potential to evade the immune system and, thus, will be a promising tool for data mining of relevant information for epidemiological studies. SARS-CoV-2 lineage monitoring using WGS is an important surveillance tool for early detection of upcoming new lineages of concern.

The correlation between the prevalence of gestational diabetes mellitus and maternal age in Southern China

Objectives The present study aimed to survey the prevalence of gestational diabetes mellitus (GDM) in Southern China and further to analyze the correlation between the prevalence of GDM and maternal age. Methods A retrospective cross-sectional study was carried out at the Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, Foshan, China between January and April 2020. Oral glucose tolerance tests (OGTT) was performed, using a 75 g glucose load and venous samples were drawn at 0 h, 1 h and 2 h at 24–28 weeks of gestation. GDM was diagnosed by International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. Results The prevalence of GDM was 14.87% by IADPSG criteria. The incidence of GDM outcome increased and plasma glucose levels remained high among the age subgroups (<20, 20–24, 25–29, 30–34, 35–39, ≥40 years old) in pregnant women. Moreover, the levels of plasma glucose levels after OGTT kept rising among the pregnant women with non-gestational diabetes mellitus (non-GDM). Furthermore, pregnant women were inclined to have abnormal plasma glucose values at 1 h and 2 h than initial fasting plasma glucose (FPG) after OGTT as the age increased. Conclusions Our findings demonstrate that the incidence of GDM outcome and plasma glucose levels increase as the maternal age increase.

Update on endothelial dysfunction in COVID-19: severe disease, long COVID-19 and pediatric characteristics

Objectives To review current literature on the role of endothelial dysfunction in coronavirus disease-2019 (COVID-19) infection in terms of pathophysiology, laboratory features and markers, clinical phenotype in adults and children, as well as long COVID-19. Content We conducted a thorough assessment of the literature and critically analyzed current data, mostly utilizing the PubMed and Medline search engines to find original studies published in the previous decade. Summary and Outlook Accumulating evidence suggests that endothelial dysfunction may be a common denominator of severe COVID-19 in adults and children, as well as long COVID-19, implicating mutual pathophysiological pathways. This narrative review summarizes the up-to-date knowledge of endothelial dysfunction caused by COVID-19, including novel aspects of long COVID-19 and pediatric disease. This knowledge is important in order not only to understand the multisystemic attack of COVID-19, but also to improve patient management and prognosis.