miR-155: A Potential Biomarker for Predicting Mortality in COVID-19 Patients

COVID-19, a pandemic of severe acute respiratory syndrome caused by Coronavirus 2 (SARS-CoV-2), continues to pose diagnostic and therapeutic challenges due to its unpredictable clinical course. Prognostic biomarkers may improve care by enabling quick identification of patients who can be safely discharged home versus those who may need careful respiratory monitoring and support. MicroRNAs (miRNAs) have risen to prominence as biomarkers for many disease states and as tools to assist in medical decisions. In the present study, we aimed to examine circulating miRNAs in hospitalized COVID-19 patients and to explore their potential as biomarkers for disease severity. We studied, by quantitative PCR, the expressions of miR-21, miR-146a, miR-146b, miR-155, and miR-499 in peripheral blood. We found that mild COVID-19 patients had 2.5-fold less circulating miR-155 than healthy people, and patients with a severe COVID-19 disease had 5-fold less circulating miR-155 than healthy people. In addition, we found that miR-155 is a good predictor of COVID-19 mortality. We suggest that examining miR-155 levels in patients’ blood, upon admission to hospital, will ameliorate the care given to COVID-19 patients

Maternal and Neonatal Immune Responses Following COVID-19 Infection and Vaccinations in Pregnancy

The objective of the study was to compare the maternal and neonatal humoral immune responses among different groups of women, namely those vaccinated by the BNT162b2 vaccine, not vaccinated, and COVID-19-recovered parturient women at the time of delivery. This is a prospective cohort study of pregnant women, divided into four groups: Group A “Recovered”—recovered and not vaccinated. Group B “Second Vaccination”—first and second doses only. Group C “Third Vaccination”—third dose. Group D “No Third Vaccination”—women eligible for the third dose of the vaccine but did not receive it. Maternal and umbilical cord blood were sampled and tested for SARS-CoV-2 IgG antibodies on admittance to labor and immediately postpartum, respectively. Maternal serum SARS-CoV-2 IgG levels were significantly higher among Group C compared to Group B (741.6 (514.5–1069) vs. 333.5 (327–340.2), respectively). Both groups had higher antibody levels compared to Groups A and D (113.5 (61.62–209.1) and 57.99 (32.93–102.1), respectively). Similarly, umbilical cord blood SARS-CoV-2 IgG levels were also highest among Group C compared to the other three groups (1269 (953.4–1690) vs. Group B, 322.6 (305.6–340.5), Group A, 109 (49.01–242.6), and Group D, 103.9 (48.59–222), respectively). In conclusion, pregnant women who were fully vaccinated with three dosages before delivery generated the highest levels of maternal and neonatal SARS-CoV-2 IgG antibodies

The Predictive Value of Serum ACE2 and TMPRSS2 Concentrations in Patients with COVID-19—A Prospective Pilot Study

One of the major challenges for healthcare systems during the Coronavirus-2019 (COVID-19) pandemic was the inability to successfully predict which patients would require mechanical ventilation (MV). Angiotensin-Converting Enzyme 2 (ACE2) and TransMembrane Protease Serine S1 member 2 (TMPRSS2) are enzymes that play crucial roles in SARS-CoV-2 entry into human host cells. However, their predictive value as biomarkers for risk stratification for respiratory deterioration requiring MV has not yet been evaluated. We aimed to evaluate whether serum ACE2 and TMPRSS2 levels are associated with adverse outcomes in COVID-19, and specifically the need for MV. COVID-19 patients admitted to an Israeli tertiary medical center between March--November 2020, were included. Serum samples were obtained shortly after admission (day 0) and again following one week of admission (day 7). ACE2 and TMPRSS2 concentrations were measured with ELISA. Of 72 patients included, 30 (41.6%) ultimately required MV. Serum ACE2 concentrations >7.8 ng/mL at admission were significantly associated with the need for MV (p = 0.036), inotropic support, and renal replacement therapy. In multivariate logistic regression analysis, elevated ACE2 at admission was associated with the need for MV (OR = 7.49; p = 0.014). To conclude, elevated serum ACE2 concentration early in COVID-19 illness correlates with respiratory failure necessitating mechanical ventilation. We suggest that measuring serum ACE2 at admission may be useful for predicting the risk of severe disease

Reduced Neutralization Efficacy against Omicron Variant after Third Boost of BNT162b2 Vaccine among Liver Transplant Recipients

The immune responses of liver transplant (LT) recipients after the third boost of the BNT162b2mRNA vaccine improved. This study evaluates the durability of the immune response of LT recipients after the third boost, its predictors, and the impact of emerging variants. The receptor-binding domain IgG was determined at median times of 22 (first test) and 133 days (second test) after the administration of the third boost. IgG antibody titers > 21.4 BAU/mL were defined as a positive response. The neutralization efficacies of the vaccine against the wild-type, Omicron, and Delta variants were compared in the first test. The 59 LT recipients were of a median age of 61 years (range 25–82); 53.5% were male. Following administration of the third dose, the positive immune response decreased from 81.4% to 76.3% between the first and second tests, respectively, (p p = 0.02) and hemoglobin > 12 g/dL (p = 0.02) as independent predictors of a maintained positive immune response 133 days after the third dose. The geometric mean titers of Omicron neutralization were significantly lower than the wild-type and Delta virus (21, 137, 128, respectively; p < 0.0001). The immune response after the third BNT162b2mRNA vaccine dose decreased significantly in LT recipients. Further studies are required to evaluate the efficacy of the fourth vaccine dose and the durability of the immune response

High Immune Response Rate to the Fourth Boost of the BNT162b2 Vaccine against the Omicron Variants of Concern among Liver Transplant Recipients

The immune response of liver transplant (LT) recipients to a third dose of the BNT162b2 mRNA vaccine significantly waned after four months. We aimed to evaluate the immune response and breakthrough infection rates of a fourth dose against the Omicron variants among LT recipients. LT recipients who had no past or active SARS-CoV-2 infection and received three doses of the BNT162b2mRNA vaccine were included. Of the 73 LT recipients, 50 (68.5%) received a fourth dose. The fourth dose was associated with a significantly higher positive immune response than the third dose. Receptor-binding domain (RBD) IgG and Omicron BA.1 and BA.2 neutralizing antibodies were determined at a median of 132 and 29 days after the third and fourth vaccines. They were 345 binding antibody units per milliliter (BAU/mL) vs. 2118 BAU/mL (p &lt; 0.0001), 10 vs. 87 (p &lt; 0.0001), and 15 vs. 149 (p = 0.001), respectively. Breakthrough infections were documented among nine (18%) LT recipients after the fourth dose and among seven (30.4%) patients following the third dose (p = 0.2); 93.5% of breakthrough infections were mild. The infection rate after the fourth dose was higher among diabetic vs. nondiabetic recipients (33.3% vs. 6.9%, respectively; p = 0.02). Further studies are needed to evaluate additional factors influencing the breakthrough infection rate among LT recipients