The Role of NS1 Protein in the Diagnosis of Flavivirus Infections.

Nonstructural protein 1 (NS1) is a glycoprotein among the flavivirus genus. It is found in both membrane-associated and soluble secreted forms, has an essential role in viral replication, and modulates the host immune response. NS1 is secreted from infected cells within hours after viral infection, and thus immunodetection of NS1 can be used for early serum diagnosis of dengue fever infections instead of real-time (RT)-PCR. This method is fast, simple, and affordable, and its availability could provide an easy point-of-care testing solution for developing countries. Early studies show that detecting NS1 in cerebrospinal fluid (CSF) samples is possible and can improve the surveillance of patients with dengue-associated neurological diseases. NS1 can be detected postmortem in tissue specimens. It can also be identified using noninvasive methods in urine, saliva, and dried blood spots, extending the availability and effective detection period. Recently, an enzyme-linked immunosorbent assay (ELISA) assay for detecting antibodies directed against Zika virus NS1 has been developed and used for diagnosing Zika infection. This NS1-based assay was significantly more specific than envelope protein-based assays, suggesting that similar assays might be more specific for other flaviviruses as well. This review summarizes the knowledge on flaviviruses' NS1's potential role in antigen and antibody diagnosis.

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.

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.