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2.
Viruses ; 14(5)2022 05 13.
Article in English | MEDLINE | ID: covidwho-1903475

ABSTRACT

Currently, there are no evidence-based treatment options for long COVID-19, and it is known that SARS-CoV-2 can persist in part of the infected patients, especially those with immunosuppression. Since there is a robust secretion of SARS-CoV-2-specific highly-neutralizing IgA antibodies in breast milk, and because this immunoglobulin plays an essential role against respiratory virus infection in mucosa cells, being, in addition, more potent in neutralizing SARS-CoV-2 than IgG, here we report the clinical course of an NFκB-deficient patient chronically infected with the SARS-CoV-2 Gamma variant, who, after a non-full effective treatment with plasma infusion, received breast milk from a vaccinated mother by oral route as treatment for COVID-19. After such treatment, the symptoms improved, and the patient was systematically tested negative for SARS-CoV-2. Thus, we hypothesize that IgA and IgG secreted antibodies present in breast milk could be useful to treat persistent SARS-CoV-2 infection in immunodeficient patients.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , COVID-19/complications , Eating , Female , Humans , Immunoglobulin A , Immunoglobulin G , Milk, Human , NF-kappa B , RNA, Viral , SARS-CoV-2/genetics
3.
Virulence ; 13(1): 1031-1048, 2022 12.
Article in English | MEDLINE | ID: covidwho-1900978

ABSTRACT

The ongoing COVID-19 pandemic caused a significant loss of human lives and a worldwide decline in quality of life. Treatment of COVID-19 patients is challenging, and specific treatments to reduce COVID-19 aggravation and mortality are still necessary. Here, we describe the discovery of a novel class of epiandrosterone steroidal compounds with cationic amphiphilic properties that present antiviral activity against SARS-CoV-2 in the low micromolar range. Compounds were identified in screening campaigns using a cytopathic effect-based assay in Vero CCL81 cells, followed by hit compound validation and characterization. Compounds LNB167 and LNB169 were selected due to their ability to reduce the levels of infectious viral progeny and viral RNA levels in Vero CCL81, HEK293, and HuH7.5 cell lines. Mechanistic studies in Vero CCL81 cells indicated that LNB167 and LNB169 inhibited the initial phase of viral replication through mechanisms involving modulation of membrane lipids and cholesterol in host cells. Selection of viral variants resistant to steroidal compound treatment revealed single mutations on transmembrane, lipid membrane-interacting Spike and Envelope proteins. Finally, in vivo testing using the hACE2 transgenic mouse model indicated that SARS-CoV-2 infection could not be ameliorated by LNB167 treatment. We conclude that anti-SARS-CoV-2 activities of steroidal compounds LNB167 and LNB169 are likely host-targeted, consistent with the properties of cationic amphiphilic compounds that modulate host cell lipid biology. Although effective in vitro, protective effects were cell-type specific and did not translate to protection in vivo, indicating that subversion of lipid membrane physiology is an important, yet complex mechanism involved in SARS-CoV-2 replication and pathogenesis.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antiviral Agents/pharmacology , COVID-19/drug therapy , Chlorocebus aethiops , HEK293 Cells , Humans , Lipids , Mice , Pandemics , Quality of Life , Vero Cells , Virus Replication
4.
Nat Med ; 28(7): 1476-1485, 2022 07.
Article in English | MEDLINE | ID: covidwho-1830084

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Gamma variant of concern has spread rapidly across Brazil since late 2020, causing substantial infection and death waves. Here we used individual-level patient records after hospitalization with suspected or confirmed coronavirus disease 2019 (COVID-19) between 20 January 2020 and 26 July 2021 to document temporary, sweeping shocks in hospital fatality rates that followed the spread of Gamma across 14 state capitals, during which typically more than half of hospitalized patients aged 70 years and older died. We show that such extensive shocks in COVID-19 in-hospital fatality rates also existed before the detection of Gamma. Using a Bayesian fatality rate model, we found that the geographic and temporal fluctuations in Brazil's COVID-19 in-hospital fatality rates were primarily associated with geographic inequities and shortages in healthcare capacity. We estimate that approximately half of the COVID-19 deaths in hospitals in the 14 cities could have been avoided without pre-pandemic geographic inequities and without pandemic healthcare pressure. Our results suggest that investments in healthcare resources, healthcare optimization and pandemic preparedness are critical to minimize population-wide mortality and morbidity caused by highly transmissible and deadly pathogens such as SARS-CoV-2, especially in low- and middle-income countries.


Subject(s)
COVID-19 , Aged , Aged, 80 and over , Bayes Theorem , Brazil/epidemiology , COVID-19/epidemiology , Hospitals , Humans , SARS-CoV-2
5.
Viruses ; 13(11)2021 10 22.
Article in English | MEDLINE | ID: covidwho-1481018

ABSTRACT

A SARS-CoV-2 B.1.1.7 variant of concern (VOC) has been associated with increased transmissibility, hospitalization, and mortality. This study aimed to explore the factors associated with B.1.1.7 VOC infection in the context of vaccination. On March 2021, we detected SARS-CoV-2 RNA in nasopharyngeal samples from 14 of 22 individuals vaccinated with a single-dose of ChAdOx1 (outbreak A, n = 26), and 22 of 42 of individuals with two doses of the CoronaVac vaccine (outbreak B, n = 52) for breakthrough infection rates for ChAdOx1 of 63.6% and 52.4% for CoronaVac. The outbreaks were caused by two independent clusters of the B.1.1.7 VOC. The serum of PCR-positive symptomatic SARS-CoV-2-infected individuals had ~1.8-3.4-fold more neutralizing capacity against B.1.1.7 compared to the serum of asymptomatic individuals. These data based on exploratory analysis suggest that the B.1.1.7 variant can infect individuals partially immunized with a single dose of an adenovirus-vectored vaccine or fully immunized with two doses of an inactivated vaccine, although the vaccines were able to reduce the risk of severe disease and death caused by this VOC, even in the elderly.


Subject(s)
COVID-19 Vaccines , COVID-19/immunology , COVID-19/virology , SARS-CoV-2/classification , SARS-CoV-2/genetics , Vaccination , Adenoviridae , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/immunology , Brazil/epidemiology , COVID-19/prevention & control , COVID-19 Serological Testing , Cohort Studies , Disease Outbreaks/statistics & numerical data , Female , Genetic Vectors , Humans , Immunoglobulin G/blood , Male , Middle Aged , RNA, Viral , Vaccines, Inactivated , Whole Genome Sequencing , Young Adult
6.
BMJ Glob Health ; 6(4)2021 04.
Article in English | MEDLINE | ID: covidwho-1476465

ABSTRACT

INTRODUCTION: Little evidence exists on the differential health effects of COVID-19 on disadvantaged population groups. Here we characterise the differential risk of hospitalisation and death in São Paulo state, Brazil, and show how vulnerability to COVID-19 is shaped by socioeconomic inequalities. METHODS: We conducted a cross-sectional study using hospitalised severe acute respiratory infections notified from March to August 2020 in the Sistema de Monitoramento Inteligente de São Paulo database. We examined the risk of hospitalisation and death by race and socioeconomic status using multiple data sets for individual-level and spatiotemporal analyses. We explained these inequalities according to differences in daily mobility from mobile phone data, teleworking behaviour and comorbidities. RESULTS: Throughout the study period, patients living in the 40% poorest areas were more likely to die when compared with patients living in the 5% wealthiest areas (OR: 1.60, 95% CI 1.48 to 1.74) and were more likely to be hospitalised between April and July 2020 (OR: 1.08, 95% CI 1.04 to 1.12). Black and Pardo individuals were more likely to be hospitalised when compared with White individuals (OR: 1.41, 95% CI 1.37 to 1.46; OR: 1.26, 95% CI 1.23 to 1.28, respectively), and were more likely to die (OR: 1.13, 95% CI 1.07 to 1.19; 1.07, 95% CI 1.04 to 1.10, respectively) between April and July 2020. Once hospitalised, patients treated in public hospitals were more likely to die than patients in private hospitals (OR: 1.40%, 95% CI 1.34% to 1.46%). Black individuals and those with low education attainment were more likely to have one or more comorbidities, respectively (OR: 1.29, 95% CI 1.19 to 1.39; 1.36, 95% CI 1.27 to 1.45). CONCLUSIONS: Low-income and Black and Pardo communities are more likely to die with COVID-19. This is associated with differential access to quality healthcare, ability to self-isolate and the higher prevalence of comorbidities.


Subject(s)
COVID-19/ethnology , COVID-19/mortality , Hospital Mortality/ethnology , Pneumonia, Viral , Poverty Areas , Residence Characteristics/statistics & numerical data , Adult , Aged , Aged, 80 and over , Brazil/epidemiology , Cross-Sectional Studies , Female , Health Status Disparities , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , SARS-CoV-2 , Seroepidemiologic Studies , Socioeconomic Factors
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