The extent of infectious SARS-CoV-2 shedding in an Argentinean cohort.

BACKGROUND: To analyze the infectious extent of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) in different settings where prevention strategies are critical to limit infection spread, we evaluated SARS-COV-2 viability to guide public health policies regarding isolation criteria and infection control. METHODS: We attempted viral isolation in 82 nasopharyngeal swabs from 72 patients with confirmed SARS-COV-2 infection. Study population was divided into four groups: (i) Patients during the first week of symptoms; (ii) Patients with prolonged positive PCR; (iii) Healthcare workers from a hospital participating of an outbreak investigation, with SARS-COV-2 infection confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) and (iv) Recipients of convalescent immune plasma (CIP).Vero Cl76 cell-line (ATCC CRL-587) was used in assays for virus isolation. Plasma samples of CIP recipients were also tested with plaque-reduction neutralization test. RESULTS: We obtained infectious SARS-COV-2 isolates from 15/84 nasopharyngeal swabs. The virus could not be isolated from upper respiratory tract samples collected 10-day after onset of symptoms (AOS) in patients with mild-moderate disease. CONCLUSION: The knowledge of the extent of SARS-CoV-2 infectivity AOS is relevant for effective prevention measures. This allows to discuss criteria for end isolation despite persistence of positive PCR and improve timing for hospital discharge with consequent availability of critical beds.

First report of antiviral activity of nordihydroguaiaretic acid against Fort Sherman virus (Orthobunyavirus).

The genus Orthobunyavirus are a group of viruses within arbovirus, with a zoonotic cycle, some of which could lead to human infection. A characteristic of these viruses is their lack of antiviral treatment or vaccine for its prevention. The objective of this work was to study the in vitro antiviral activity of nordihydroguaiaretic acid (NDGA), the most important active compound of Larrea divaricata Cav. (Zigophyllaceae), against Fort Sherman virus (FSV) as a model of Orthobunyavirus genus. At the same time, the effect of NDGA as a lipolytic agent on the cell cycle of this viral model was assessed. The method of reducing plaque forming units on LLC-MK2 cells was used to detect the action of NDGA on CbaAr426 and SFCrEq231 isolates of FSV. NDGA did not show virucidal effect, but it had antiviral activity with a similar inhibition in both isolates, which was dose dependent. It was established that the NDGA has a better inhibition 1-h post-internalization (p.i.), showing a different behavior in each isolate, which was dependent upon the time p.i. Since virus multiplication is dependent on host cell lipid metabolism, the antiviral effect of NDGA has been previously related to its ability to disturb the lipid metabolism, probably by interfering with the 5-lipoxigenase (5-LOX) and the sterol regulatory element-binding proteins (SREBP) pathway. We determined by using caffeic acid, a 5-LOX inhibitor, that the inhibition of this enzyme negatively affected the FSV replication; and by means of resveratrol, a SREBP1 inhibitor, it was showed that the negative regulation of this pathway only had action on the SFCrEq231 reduction. In addition, it was proved that the NDGA acts intracellularly, since it showed the ability to incorporate into LLC-MK2 cells. The information provided in this work converts the NDGA into a compound with antiviral activity in vitro against FSV (Orthobunyavirus), which can be subjected to structural modifications in the future to improve the activity.

Activity Patterns of St. Louis Encephalitis and West Nile Viruses in Free Ranging Birds during a Human Encephalitis Outbreak in Argentina.

St. Louis encephalitis virus (SLEV) (Flavivirus) is a reemerging arbovirus in the southern cone of South America. In 2005, an outbreak of SLEV in central Argentina resulted in 47 human cases with 9 deaths. In Argentina, the ecology of SLEV is poorly understood. Because certain birds are the primary amplifiers in North America, we hypothesized that birds amplify SLEV in Argentina as well. We compared avian SLEV seroprevalence in a variety of ecosystems in and around Córdoba city from 2004 (before the epidemic) and 2005 (during the epidemic). We also explored spatial patterns to better understand the local ecology of SLEV transmission. Because West Nile virus (WNV) was also detected in Argentina in 2005, all analyses were also conducted for WNV. A total of 980 birds were sampled for detection of SLEV and WNV neutralizing antibodies. SLEV seroprevalence in birds increased 11-fold from 2004 to 2005. Our study demonstrated that a high proportion (99.3%) of local birds were susceptible to SLEV infection immediately prior to the 2005 outbreak, indicating that the vertebrate host population was primed to amplify SLEV. SLEV was found distributed in a variety of environments throughout the city of Córdoba. However, the force of viral transmission varied among sites. Fine scale differences in populations of vectors and vertebrate hosts would explain this variation. In summary, we showed that in 2005, both SLEV and to a lesser extent WNV circulated in the avian population. Eared Dove, Picui Ground-Dove and Great Kiskadee are strong candidates to amplify SLEV because of their exposure to the pathogen at the population level, and their widespread abundance. For the same reasons, Rufous Hornero may be an important maintenance host for WNV in central Argentina. Competence studies and vector feeding studies are needed to confirm these relationships.

Immunoglobulin G subclasses in antibody responses to St. Louis encephalitis virus infections.

The aim of this study was to recognize the specific antiviral response patterns of IgG1, IgG2, IgG3 and IgG4 subclasses, elicited during St. Louis encephalitis virus (SLEV) infection in humans. Eighty-five samples of human sera from 44 patients with SLEV infection were obtained between days 1 and 365 or later, after onset of the disease. These samples were processed by immunofluorescence assay for detection of IgG1-, IgG2-, IgG3- and IgG4-specific antibodies. We demonstrate the presence of all isotypes of IgG for more than a year in patients infected with SLEV. However; isotype IgG1 was present at the highest titers, with a peak between days 8 and 30 after onset of the disease.