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PURPOSE: This study aimed to evaluate the pre-sence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in the ocular surface of individuals clinically suspected of coronavirus disease 2019 (COVID-19) and determine the accuracy of different approaches of molecular testing on the ocular surface based on the nasopharyngeal positivity status for COVID-19. METHODS: A total of 152 individuals with suspected COVID-19 symptoms who simultaneously underwent nasopharyngeal and two different tear film collection techniques for quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR) were included. Tears were collected and randomized: one eye had the filter strip for the Schirmer test and the contralateral eye had conjunctival swab/cytology in the inferior fornix. All patients underwent slit lamp biomicroscopy. The accuracy of various ocular surface collection techniques used for the detection of SARS-CoV-2 RNA was determined. RESULTS: Of the 152 patients enrolled in the study, 86 (56.6%) had COVID-19 confirmed by nasopharyngeal PCR. Both tear film collection techniques detected viral particles: the Schirmer test was positive in 16.3% (14/86) and the conjunctival swab/cytology in 17.4% (15/86), with no statistically significant differences. No positive ocular tests were found among those with negative nasopharyngeal PCR tests. The overall agreement of the ocular tests was 92.7%, and in combination, the sensitivity would increase to 23.2%. The mean cycle threshold values in the nasopharyngeal, Schirmer, and conjunctival swab/cytology tests were 18.2 ± 5.3, 35.6 ± 1.4, and 36.4 ± 3.9, respectively. Compared with the nasopharyngeal test, the Schirmer (p=0.001) and conjunctival swab/cytology (p<0.001) tests had significantly different Ct values. CONCLUSION: The Schirmer (16.3%) and conjunctival swab (17.4%) tests were comparably capable of detecting SARS-CoV-2 RNA in the ocular surface by RT-PCR accurately based on nasopharyngeal status and demonstrated indistinct sensitivity and specificity. Simultaneous specimen sampling and processing from the nasopharyngeal, Schirmer, and conjunctival swab/cytology tests demonstrated significantly lower viral load in both ocular surface approaches than in the nasopharyngeal test. Ocular manifestations detected by slit lamp biomicroscopy were not associated with ocular RT-PCR positivity.
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BACKGROUND: The neurological manifestations in COVID-19 adversely impact acute illness and post-disease quality of life. Limited data exist regarding the association of neurological symptoms and comorbid individuals. OBJECTIVE: To assess neurological symptoms in hospitalized patients with acute COVID-19 and multicomorbidities. METHODS: Between June 2020 and July 2020, inpatients aged 18 or older, with laboratory-confirmed COVID-19, admitted to the Hospital São Paulo (Federal University of São Paulo), a tertiary referral center for high complexity cases, were questioned about neurological symptoms. The Composite Autonomic Symptom Score 31 (COMPASS-31) questionnaire was used. The data were analyzed as a whole and whether subjective olfactory dysfunction was present or not. RESULTS: The mean age of the sample was 55 ± 15.12 years, and 58 patients were male. The neurological symptoms were mostly xerostomia (71%), ageusia/hypogeusia (50%), orthostatic intolerance (49%), anosmia/hyposmia (44%), myalgia (31%), dizziness (24%), xerophthalmia (20%), impaired consciousness (18%), and headache (16%). Furthermore, 91% of the patients had a premorbidity. The 44 patients with subjective olfactory dysfunction were more likely to have hypertension, diabetes, weakness, shortness of breath, ageusia/hypogeusia, dizziness, orthostatic intolerance, and xerophthalmia. The COMPASS-31 score was higher than that of previously published controls (14.85 ± 12.06 vs. 8.9 ± 8.7). The frequency of orthostatic intolerance was 49% in sample and 63.6% in those with subjective olfactory dysfunction (2.9-fold higher risk compared to those without). CONCLUSION: A total of 80% of inpatients with multimorbidity and acute COVID-19 had neurological symptoms. Chemical sense and autonomic symptoms stood out. Orthostatic intolerance occurred in around two-thirds of the patients with anosmia/hyposmia. Hypertension and diabetes were common, mainly in those with anosmia/hyposmia.
ANTECEDENTES: As manifestações neurológicas na COVID-19 impactam adversamente na enfermidade aguda e na qualidade de vida após a doença. Dados limitados existem em relação a associação de sintomas neurológicos e indivíduos com comorbidades. OBJETIVO: Avaliar os sintomas neurológicos em pacientes de hospitalizados com COVID-19 aguda e múltiplas comorbidades. MéTODOS: Entre junho e julho de 2020, pacientes de hospitais com idade 18 anos ou acima e COVID-19 laboratorialmente confirmada, admitidos no Hospital São Paulo (Universidade Federal de São Paulo), um centro de referência terciário para casos de alta complexidade, foram perguntados sobre sintomas neurológicos. O questionário Pontuação composta de sintoma autonômico (COMPASS-31) foi usado. Os dados foram analisados no geral e se a disfunção olfatória subjetiva estava presente ou não. RESULTADOS: A média de idade da amostra foi 55 ± 15.12 anos. 58 pacientes eram homens. Os sintomas neurológicos foram principalmente xerostomia (71%), ageusia/hipogeusia (50%), intolerância ortostática (49%), anosmia/hiposmia (44%), mialgia (31%), tontura (24%), xeroftalmia (20%), comprometimento na consciência (18%) e cefaleia (16%). Além disso, 91% dos pacientes tinham uma pré-morbidade. Os 44 pacientes com disfunção olfatória tinham maior chance de ter hipertensão, diabetes, fraqueza, falta de ar, ageusia/hipogeusia, tontura, intolerância ortostática e xeroftalmia. A pontuação do COMPASS-31 foi maior do que a de controles previamente publicados (14,85 ± 12,06 vs. 8,9 ± 8,7). A frequência de intolerância ortostática foi 49% na amostra e 63,6% naqueles com disfunção olfatória subjetiva (risco 2.9 vezes maior comparado com os sem). CONCLUSãO: Um total de 80% dos pacientes hospitalizados com múltiplas morbidades e COVID-19 aguda tinham sintomas neurológicos. Os sintomas do sentido químico e autonômicos se destacaram. A intolerância ortostática ocorreu em cerca de dois terços dos pacientes com anosmia/hiposmia. A hipertensão e o diabetes foram comuns, principalmente naqueles com anosmia/hiposmia.
Subject(s)
Ageusia , COVID-19 , Hypertension , Orthostatic Intolerance , Xerophthalmia , Humans , Male , Adult , Middle Aged , Aged , Female , COVID-19/complications , Anosmia/epidemiology , SARS-CoV-2 , Dizziness/epidemiology , Quality of Life , Brazil/epidemiology , Comorbidity , Hypertension/epidemiologyABSTRACT
The outbreak of coronavirus (COVID-19) has put the world in an unprecedented scenario. To reestablish the world routine as promote the effective treatment of this disease, the world is looking for new (and old) drug that can efficiently kill the virus. In this study, we have developed two nanosystems: polymeric nanoparticles and nanomicelles-based on hydroxychloroquine and azithromycin. The nanosystem was fully characterized by AFM and DLS techniques. Also, the nanosystems were radiolabeled with 99mTc and pulmonary applied (installation) in vivo to evaluate the biological behavior. The toxicity of both nanosystem were evaluated in primary cells (FGH). Finally, both nanosystems were evaluated in vitro against the SARS-CoV-2. The results demonstrated that the methodology used to produce the nanomicelles and the nanoparticle was efficient, the characterization showed a nanoparticle with a spherical shape and a medium size of 390 nm and a nanomicelle also with a spherical shape and a medium size of 602 nm. The nanomicelles were more efficient (~ 70%) against SARS-CoV-2 than the nanoparticles. The radiolabeling process with 99mTc was efficient (> 95%) in both nanosystems and the pulmonary application demonstrated to be a viable route for both nanosystems with a local retention time of approximately, 24 h. None of the nanosystems showed cytotoxic effect on FGH cells, even in high doses, corroborating the safety of both nanosystems. Thus, claiming the benefits of the nanotechnology, especially with regard the reduced adverse we believe that the use of nanosystems for COVID-19 treatment can be an optimized choice. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40097-022-00476-3.
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Introdução O vírus pandêmico SARS-CoV-2 evoluiu e variantes de preocupação (VOC) foram substituindo as anteriores até que uma nova VOC denominada Ômicron disseminou-se rapidamente e suplantou a VOC Delta que circulava pelo país desde maio de 2021. Em São Paulo, uma nova onda de casos determinou grande impacto no primeiro trimestre de 2022, gerando milhares de infecções além de internações e óbitos. Objetivo Descrever as características dos pacientes hospitalizados durante a onda da variante Ômicron no complexo do Hospital São Paulo (HSP)–UNIFESP. Método Foram avaliados dados epidemiológicos e clínicos de pacientes confirmados por teste molecular para SARS-COV-2 no período de 01/01/2022 a 30/04/2022. Resultados Foram testados 2286 pacientes, dos quais 435 (19,03%) obtiveram um qRT-PCR positivo, com um total de 55 (12,64%) óbitos. A mediana de idade foi de 51 anos (IIQ: 31-66) entre os pacientes positivos e 69 anos (IIQ: 57-76) entre os pacientes que vieram à óbito. A mediana do valor do CT obtido no ensaio qRT-PCR para o grupo positivo foi de 27 (19-33) e 22 (17-32) entre os casos de óbito. Em janeiro houve maior internação (761) e maior positividade. (36,53%). A positividade foi maior no grupo etário de 70-79 (23,83%) e menor no de 0 a 9 anos (12,88%). A letalidade foi significante em > 60 anos (5,04% x 26,11% p = 0,02) sendo de 37,50% acima de 80 anos. Dentre os infectados 62,76% receberam só 2 doses de vacina. Entre os 301 pacientes elegíveis para o primeiro reforço vacinal (dose 3), 41,86% receberam o reforço. Entre os pacientes que vieram a óbito, apesar da taxa de administração do esquema vacinal básico ter sido superior (83,64%), a adesão à primeira dose de reforço foi ainda menor (36,36%). O segundo reforço vacinal não foi administrado em nenhum dos pacientes elegíveis. Dentre os pacientes que vieram a óbito, a maior parte possuía ao menos 2 comorbidades (69,10%), sendo neoplasia (23, 41,81%), hipertensão Arterial (40%), diabetes mellitus (34,55%) e cardiopatia (29,09%) as mais frequentes. Mesmo com 3 doses de vacina, 12,70% (16/126) dos pacientes foram a óbito, sendo 12 pacientes com mais de 70 anos. Conclusão O surgimento de uma nova variante capaz de evadir a imunidade prévia de uma população, ainda que parcialmente imunizada, determinou internação hospitalar. Indivíduos imunodeprimidos e aqueles acima de 60 anos apresentaram maior risco de óbito, particularmente aqueles maiores de 70 anos, ainda que com 3 doses de vacina.
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[This corrects the article DOI: 10.1016/j.eclinm.2021.100981.].
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Individuals with suspected COVID-19 symptoms (n=202) were tested using nasopharyngeal RT-qPCR. All individuals underwent corneal esthesiometry measurements using the Cochet-Bonnet esthesiometer during their first visit; 50 participants underwent an additional measurement at a mean interval of 32.5 (17.8) days. COVID-19 was confirmed in 101 subjects (50%) using nasopharyngeal PCR. The mean time from symptom onset to disease diagnosis and corneal esthesiometry was 4.2 (2.1) days. Mean corneal esthesiometry findings based on the positive and negative PCR status indicated no statistical difference. This study demonstrated that COVID-19 had no effect on corneal esthesiometry in individuals with acute-phase COVID-19.
Subject(s)
COVID-19 , Cornea , HumansABSTRACT
BACKGROUND: The absence of specific antivirals to treat COVID-19 leads to the repositioning of candidates' drugs. Nitazoxanide (NTZ) has a broad antiviral effect. METHODS: This was a randomized, double-blind pilot clinical trial comparing NTZ 600 mg BID versus Placebo for seven days among 50 individuals (25 each arm) with SARS-COV-2 RT-PCR+ (PCR) that were hospitalized with mild respiratory insufficiency from May 20th, 2020, to September 21st, 2020 (ClinicalTrials.gov NCT04348409). Clinical and virologic endpoints and inflammatory biomarkers were evaluated. A five-point scale for disease severity (SSD) was used. FINDINGS: Two patients died in the NTZ arm compared to 6 in the placebo arm (p = 0.564). NTZ was superior to placebo when considering SSD (p < 0001), the mean time for hospital discharge (6.6 vs. 14 days, p = 0.021), and negative PCR at day 21 (p = 0.035), whereas the placebo group presented more adverse events (p = 0.04). Among adverse events likely related to the study drug, 14 were detected in the NTZ group and 22 in placebo (p = 0.24). Among the 30 adverse events unlikely related, 21 occurred in the placebo group (p = 0.04). A decrease from baseline was higher in the NTZ group for d-Dimer (p = 0.001), US-RCP (p < 0.002), TNF (p < 0.038), IL-6 (p < 0.001), IL-8 (p = 0.014), HLA DR. on CD4+ T lymphocytes (p < 0.05), CD38 in CD4+ and CD8+ T (both p < 0.05), and CD38 and HLA-DR. on CD4+ (p < 0.01). INTERPRETATION: Compared to placebo in clinical and virologic outcomes and improvement of inflammatory outcomes, the superiority of NTZ warrants further investigation of this drug for moderate COVID-19 in larger clinical trials. A higher incidence of adverse events in the placebo arm might be attributed to COVID-19 related symptoms.