Immunogenicity of a Third Dose of BNT162b2 Vaccine among Lung Transplant Recipients-A Prospective Cohort Study.

Two doses of mRNA SARS-CoV-2 vaccines elicit an attenuated humoral immune response among immunocompromised patients. Our study aimed to assess the immunogenicity of a third dose of the BNT162b2 vaccine among lung transplant recipients (LTRs). We prospectively evaluated the humoral response by measuring anti-spike SARS-CoV-2 and neutralizing antibodies in 139 vaccinated LTRs ~4-6 weeks following the third vaccine dose. The t-cell response was evaluated by IFNγ assay. The primary outcome was the seropositivity rate following the third vaccine dose. Secondary outcomes included: positive neutralizing antibody and cellular immune response rate, adverse events, and COVID-19 infections. Results were compared to a control group of 41 healthcare workers. Among LTRs, 42.4% had a seropositive antibody titer, and 17.2% had a positive t-cell response. Seropositivity was associated with younger age (t = 3.736, p < 0.001), higher GFR (t = 2.355, p = 0.011), and longer duration from transplantation (t = -1.992, p = 0.024). Antibody titer positively correlated with neutralizing antibodies (r = 0.955, p < 0.001). The current study may suggest the enhancement of immunogenicity by using booster doses. Since monoclonal antibodies have limited effectiveness against prevalent sub-variants and LTRs are prone to severe COVID-19 morbidity, vaccination remains crucial for this vulnerable population.

Elevated Serum Amyloid A Levels Contribute to Increased Platelet Adhesion in COVID-19 Patients.

Coronavirus disease-19 (COVID-19) patients are prone to thrombotic complications that may increase morbidity and mortality. These complications are thought to be driven by endothelial activation and tissue damage promoted by the systemic hyperinflammation associated with COVID-19. However, the exact mechanisms contributing to these complications are still unknown. To identify additional mechanisms contributing to the aberrant clotting observed in COVID-19 patients, we analyzed platelets from COVID-19 patients compared to those from controls using mass spectrometry. We identified increased serum amyloid A (SAA) levels, an acute-phase protein, on COVID-19 patients' platelets. In addition, using an in vitro adhesion assay, we showed that healthy platelets adhered more strongly to wells coated with COVID-19 patient serum than to wells coated with control serum. Furthermore, inhibitors of integrin aIIbß3 receptors, a mediator of platelet-SAA binding, reduced platelet adhesion to recombinant SAA and to wells coated with COVID-19 patient serum. Our results suggest that SAA may contribute to the increased platelet adhesion observed in serum from COVID-19 patients. Thus, reducing SAA levels by decreasing inflammation or inhibiting SAA platelet-binding activity might be a valid approach to abrogate COVID-19-associated thrombotic complications.

Secondary bacterial infection in COVID-19 patients is a stronger predictor for death compared to influenza patients.

Secondary bacterial infections are a potentially fatal complication of influenza infection. We aimed to define the impact of secondary bacterial infections on the clinical course and mortality in coronavirus disease 2019 (COVID-19) patients by comparison with influenza patients. COVID-19 (n = 642) and influenza (n = 742) patients, admitted to a large tertiary center in Israel and for whom blood or sputum culture had been taken were selected for this study. Bacterial culture results, clinical parameters, and death rates were compared. COVID-19 patients had higher rates of bacterial infections than influenza patients (12.6% vs. 8.7%). Notably, the time from admission to bacterial growth was longer in COVID-19 compared to influenza patients (4 (1-8) vs. 1 (1-3) days). Late infections (> 48 h after admission) with gram-positive bacteria were more common in COVID-19 patients (28% vs. 9.5%). Secondary infection was associated with a higher risk of death in both patient groups 2.7-fold (1.22-5.83) for COVID-19, and 3.09-fold (1.11-7.38) for Influenza). The association with death remained significant upon adjustment to age and clinical parameters in COVID-19 but not in influenza infection. Secondary bacterial infection is a notable complication associated with worse outcomes in COVID-19 than influenza patients. Careful surveillance and prompt antibiotic treatment may benefit selected patients.

A real-life setting evaluation of the effect of remdesivir on viral load in COVID-19 patients admitted to a large tertiary centre in Israel.

OBJECTIVES: The effectiveness of remdesivir, a Food and Drug Administration-approved drug for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has been repeatedly questioned during the current coronavirus disease 2019 (COVID-19) pandemic. Most of the recently reported studies were randomized controlled multicentre clinical trials. Our goal was to test the efficiency of remdesivir in reducing nasopharyngeal viral load and hospitalization length in a real-life setting in patients admitted to a large tertiary centre in Israel. METHODS: A total of 142 COVID-19 patients found to have at least three reported SARS-CoV-2 quantitative RT-PCR tests during hospitalization were selected for this study. Of these, 29 patients received remdesivir, while the remaining non-treated 113 patients served as controls. RESULTS: Among the tested parameters, the control and remdesivir groups differed significantly only in the intubation rates. Remdesivir treatment did not significantly affect nasopharyngeal viral load, as determined by comparing the differences between the first and last cycle threshold values of the SARS-CoV-2 quantitative RT-PCR tests performed during hospitalization (cycle threshold 7.07 ± 6.85 vs. 7.08 ± 7.27, p 0.977 in the control and treated groups, respectively). Remdesivir treatment shortened hospitalization length by less than a day compared with non-treated controls and by 3.1 days when non-intubated patients from both groups were compared. These differences, however, were not statistically significant, possibly because of the small size of the remdesivir group. DISCUSSION: Remdesivir was not associated with nasopharyngeal viral load changes, but our study had a significant disease severity baseline imbalance and was not powered to detect viral load or clinical differences.

Abnormal liver tests in patients with SARS-CoV-2 or influenza - prognostic similarities and temporal disparities.

BACKGROUND & AIMS: Abnormal liver tests are common in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but a possible direct role of the virus in liver injury and its association with short-term outcomes are controversial. Therefore, we aimed to compare the pattern of abnormal liver tests in patients with SARS-CoV-2 with those of patients infected with influenza, a non-hepatotropic respiratory virus, and their association with worse outcomes during hospitalisation. METHODS: We performed a retrospective cohort study of 1,737 hospitalised patients (865 with influenza and 872 with SARS-CoV-2) in a tertiary medical centre. We defined abnormal liver tests as alanine transaminase or aspartate transaminase ≥40 IU/ml at any time-point during hospitalisation. RESULTS: Abnormal liver tests were mild to moderate in most patients regardless of infection type, but the majority of patients with influenza had a transaminase peak earlier during hospitalisation compared with patients with SARS-CoV-2. Abnormal liver tests correlated with markers of severe disease in either influenza or SARS-CoV-2 infections, and were associated with death, occurring mainly in patients with severe liver test abnormalities (>200 IU/L) (38.7% and 60% of patients with influenza or SARS-CoV-2, respectively). In multivariate analysis, controlling for age, sex, lymphopaenia, and C-reactive protein, liver test abnormalities remained significantly associated with death for influenza (odds ratio 4.344; 95% CI 2.218-8.508) and SARS-CoV-2 (odds ratio 3.898; 95% CI 2.203-6.896). These results were confirmed upon propensity score matching. CONCLUSIONS: Abnormal liver tests during hospitalisation with SARS-CoV-2 or influenza infections are common, may differ in their time course, and reflect disease severity. They are associated with worse outcomes, mainly in patients with severe liver test abnormalities, regardless of infection type. LAY SUMMARY: Coronavirus disease 2019 (COVID-19) is a serious global health pandemic, the causative agent of which is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Abnormal liver tests are common among SARS-CoV-2 infected patients and are often associated with worse outcomes. Herein, we compare the pattern of abnormal liver tests and their association with disease severity between 2 major non-hepatotropic respiratory viruses: SARS-CoV-2 and influenza. We show that abnormal liver tests are common in both infections, may slightly differ in their kinetics, and are associated with worse outcomes, especially in patients with severe liver test abnormalities. These results strongly suggest that abnormal liver tests in SARS-CoV-2 patients reflect disease severity, rather than a virus-mediated direct liver injury, and should be closely followed in admitted patients.

Modeling Social Distancing Strategies to Prevent SARS-CoV-2 Spread in Israel: A Cost-Effectiveness Analysis.

OBJECTIVES: While highly effective in preventing SARS-CoV-2 spread, national lockdowns come with an enormous economic price. Few countries have adopted an alternative "testing, tracing, and isolation" approach to selectively isolate people at high exposure risk, thereby minimizing the economic impact. To assist policy makers, we performed a cost-effectiveness analysis of these 2 strategies. METHODS: A modified Susceptible, Exposed, Infectious, Recovered, and Deceased (SEIRD) model was employed to assess the situation in Israel, a small country with ∼9 million people. The incremental cost-effectiveness ratio (ICER) of these strategies as well as the expected number of infected individuals and deaths were calculated. RESULTS: A nationwide lockdown is expected to save, on average, 274 (median 124, interquartile range: 71-221) lives compared to the "testing, tracing, and isolation" approach. However, the ICER will be, on average, $45 104 156 (median $49.6 million, interquartile range: 22.7-220.1) to prevent 1 case of death. CONCLUSION: A national lockdown has a moderate advantage in saving lives with tremendous costs and possible overwhelming economic effects. These findings should assist decision makers dealing with additional waves of this pandemic.