S evere acute respiratory syndrome coronavirus (SARS-CoV) 2, is a readily transmissible zoonotic pathogen and the etiologic agent of the coronavirus disease (COVID-19) pandemic (1). To determine aerosol stability of the virus, we measured the dynamic (short-term) aerosol efficiencies of SARS-CoV-2 and compared its efficiency with those of SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). The Study We analyzed these 3 viruses' dynamic aerosol efficiencies using 3 nebulizers, the Collison 3-jet (C3), Collison 6-jet (C6) (http://www.chtechusa.com), and Aerogen Solo (AS) (https://www.aerogen.com), to generate viral aerosols (Appendix, https://wwwnc. cdc.gov/EID/article/26/9/20-1806-App1.pdf). We performed comparative efficiency experiments once in each of 4 aerobiology laboratories (Tulane Uni
The emergent coronavirus, designated severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a zoonotic pathogen that has demonstrated remarkable transmissibility in the human population and is the etiological agent of a current global pandemic called COVID-19. We measured the dynamic (short-term) aerosol efficiencies of SARS-CoV-2 and compared the efficiencies with two other emerging coronaviruses, SARS-CoV (emerged in 2002) and Middle Eastern respiratory syndrome CoV (MERS-CoV; emerged starting in 2012). We also quantified the long-term persistence of SARS-CoV-2 and its ability to maintain infectivity when suspended in aerosols for up to 16 hours.
With continued expansion of the COVID-19 pandemic, antiviral drugs are desperately needed to treat patients at high risk of life-threatening disease and even to limit spread if administered early during infection. Typically, the fastest route to identifying and licensing a safe and effective antiviral drug is to test those already shown safe in early clinical trials for other infections or diseases. Here, we tested in vitro oleandrin, derived from the Nerium oleander plant and shown previously to have inhibitory activity against several viruses. Using Vero cells, we found that prophylactic oleandrin administration at concentrations down to 0.05 μg/ml exhibited potent antiviral activity against SARS-CoV-2, with an 800-fold reduction in virus production, and a 0.1 μg/ml dose resulted in a greater than 3,000-fold reduction in infectious virus production. The EC50 values were 11.98ng/ml when virus output was measured at 24 hours post-infection, and 7.07ng/ml measured at 48 hours post-infection. Therapeutic (post-infection) treatment up to 24 hours after infection of Vero cells also reduced viral titers, with the 0.1 μg/ml dose causing greater than 100-fold reductions as measured at 48 hours, and the 0.05 μg/ml dose resulting in a 78-fold reduction. The potent prophylactic and therapeutic antiviral activities demonstrated here strongly support the further development of oleandrin to reduce the severity of COVID-19 and potentially also to reduce spread by persons diagnosed early after infection.IMPORTANCECOVID-19, a pandemic disease caused by infection with SARS-CoV-2, has swept around the world to cause millions of infections and hundreds-of-thousands of deaths due to the lack of vaccines and effective therapeutics. We tested oleandrin, derived from the Nerium oleander plant and shown previously to reduce the replication of several viruses, against SARS-CoV-2 infection of Vero cells. When administered both before and after virus infection, nanogram doses of oleandrin significantly inhibited replication by up to 3,000-fold, indicating the potential to prevent disease and virus spread in persons recently exposed to SARS-CoV-2, as well as to prevent severe disease in persons at high risk. These results indicate that oleandrin should be tested in animal models and in humans exposed to infection to determine its medical usefulness in controlling the pandemic.
Background There is a scarcity of information about patients with mild or moderate symptoms during the coronavirus disease 2019 (COVID-19). This is especially true for those who attended and were followed up at primary care settings. Objectives We aim to measure the seroprevalence of antibodies against SARS-CoV-2 infection in a community sample of possible cases and among probable cases followed in primary care. Methods We selected a random sample of 600 individuals stratified by age groups from a total population of 19 899 individuals from a community area in Barcelona. We also invited all the patients that had been followed by General Practitioners (GPs). For both populations, we used COVID-19 rapid lateral flow immunoassays, which qualitatively assess the presence of patient-generated Immunoglobulins G (IgG) and Immunoglobulin M (IgM). Results Three hundred and eleven asymptomatic individuals from the randomly selected sample participated in the study. The mean age was 43.7 years [standard deviation (SD) = 21.79] and 55% were women. Seventeen individuals were seropositive for IgM and/or IgG, resulting in an overall prevalence of 5.47% (95% confidence interval = 3.44–8.58). Six hundred and thirty-four symptomatic patients were followed up by GPs. The mean age was 46.97 years (SD = 20.05) and 57.73% were women. Of these, 244 patients (38.49%) were seropositive. Results of the multivariate logistic regression analysis showed that the odds ratio for a positive test was significantly increased in patients who had fever, ageusia and contact with a patient diagnosed with COVID-19. Conclusions The seroprevalence of antibodies against SARS-CoV-2 among possible cases was lower than expected. Approximately, 40% of the symptomatic patients followed up by GPs during the peak months of the pandemic were positive.
With continued expansion of the coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome 2 (SARS-CoV-2), both antiviral drugs as well as effective vaccines are desperately needed to treat patients at high risk of life-threatening disease. Here, we present in vitro evidence for significant inhibition of SARS-CoV-2 by oleandrin and a defined extract of N. oleander (designated as PBI-06150). Using Vero cells, we found that prophylactic (pre-infection) oleandrin (as either the pure compound or as the active principal ingredient in PBI-06150) administration at concentrations as low as 0.05 µg/ml exhibited potent antiviral activity against SARS-CoV-2, with an 800- fold reduction in virus production, and a 0.1 µg/ml concentration resulted in a greater than 3,000-fold reduction in infectious virus production. The half maximal effective concentration (EC 50 ) values were 11.98 ng/ml when virus output was measured at 24 h post-infection, and 7.07 ng/ml measured at 48 h post-infection. Therapeutic (post-infection) treatment up to 24 h after SARS-CoV-2 infection of Vero cells also reduced viral titers, with 0.1 µg/ml and 0.05 µg/ml concentrations causing greater than 100-fold reduction as measured at 48 h, and the 0.05 µg/ml concentration resulting in a 78-fold reduction. Concentrations of oleandrin up to 10 µg/ml were well tolerated in Vero cells. We also present in vivo evidence of the safety and efficacy of defined N. oleander extract (PBI-06150), which was administered to golden Syrian hamsters in a preparation containing as high as 130 µg/ml of oleandrin. In comparison to administration of control vehicle, PBI-06150 provided a statistically significant reduction of the viral titer in the nasal turbinates (nasal conchae). The potent prophylactic and therapeutic antiviral activities demonstrated here, together with initial evidence of its safety and efficacy in a relevant hamster model of COVID-19, support the further development of oleandrin and/or defined extracts containing this molecule for the treatment of SARS-CoV-2 and associated COVID-19 disease and potentially also for reduction of virus spread by persons diagnosed early after infection.
In order to establish prognostic criteria for patients with hydatid cysts and to identify functional antigenic components of Echinococcus granulosus 87 sera from 36 patients were studied by enzyme-linked immuno-filtration assay (ELIFA) to characterize the four main classes of specific immunoglobulins and to determine compared immunological profiles (CIP) between samples or subjects. This method uses filtration with labelled antibodies to reveal precipitating systems preformed by immuno-electro-diffusion on cellulose acetate strips. IgG antibodies were demonstrated in the arc 5 and in 11 others bands. Specific IgA, IgE and IgM to Echinococcus granulosus was found in 19%, 53% and 69% respectively of patients with hydatids. The presence of IgM and/or IgE antibodies one year after treatment always correlated with disease. Specific IgA was detected more often in patients with pulmonary cysts. Pre- and post-operative monitoring by CIP-ELIFA proved simple and rapid to perform and of decided prognostic value. Two antigens, corresponding to arc 5 and arc X, were frequently associated with the poly-isotypic immune response.
Background During the coronavirus disease 2019 (COVID-19) pandemic little information has been available about patients with mild or moderate symptoms attended and followed in the primary care setting, most of whom had an unknown status for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Objectives We aim to measure the seroprevalence of antibodies against SARS-CoV-2 infection in a community sample of asymptomatic individuals and among symptomatic patients (without confirmed diagnosis) followed in a primary care setting. As a secondary objective, we estimated the proportions of symptomatic patients seeing at an emergency department (ED), hospitalized or dying, and identified the most important clinical symptoms associated with a positive infection. Methods From April 21 to April 24 2020, we selected a random sample of 600 individuals stratified by age groups, from a total population of 19,899 individuals from a community area in Barcelona (study population 1). From April 29 to May 5 2020, we also invited all the patients that had been followed by general practitioners (GPs) (study population 2). We used for both populations COVID-19 Rapid lateral flow immunoassay which qualitatively assesses the presence of patient-generated IgG and IgM in approximately 10-15 minutes. The prevalence (95% confidence intervals [CI]) of infection (past and current) was defined as the proportion of individuals with antibody seropositivity. Odds ratios (ORs) for a positive test result were estimated using logistic regression analysis. Results Three hundred and eleven asymptomatic individuals from the randomly selected sample accepted to participate in the study. The overall mean age was 43.7 years (SD 21.79, range 1-94) and 55% were women. Seventeen individuals were seropositive for IgM and/or IgG, resulting an overall prevalence of 5,47% (95% CI, 3.44-8.58). Six-hundred and thirty-four symptomatic patients were followed by GPs. The overall mean age was 46.97 years (SD 20.05, range 0-92) and 57.73% were women. Of these, 244 patients (38.49%) were seropositive for IgM and/or IgG. During the follow-up period, 27.13% of symptomatic patients attended the ED, 11.83% were hospitalized and about 2% died. Results of the multivariate logistic regression analysis showed that the OR for a positive test was significantly increased in patients who had fever (>38°C), ageusia and contact with a patient diagnosed with COVID-19. Conclusions The seroprevalence of antibodies against SARS-CoV-2 among asymptomatic individuals in the general population was lower than expected. Approximately 40% of the symptomatic patients followed by GPs during the peak months of the pandemic in Barcelona, were positive. Fever (>38°C), anosmia, ageusia and contact with a patient diagnosed with COVID-19 were associated with a positive test result.
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