SARS-CoV-2 and the ocular surface: test accuracy and viral load.

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.

Neurological symptoms and comorbidity profile of hospitalized patients with COVID-19.

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.

Polymeric nanoparticles and nanomicelles of hydroxychloroquine co-loaded with azithromycin potentiate anti-SARS-CoV-2 effect.

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.

INQUÉRITO SOROLÓGICO DE COVID-19 EM UM PRESÍDIO NA ERA PRÉ-VACINA

Introdução Inquéritos sorológicos são instrumentos importantes para determinação de magnitude da resposta imune na população. Na Covid-19, muitos estudos de soroprevalência foram realizados pelo mundo com o objetivo de entender a produção de anticorpos nos pacientes sintomáticos e assintomáticos. Objetivo Determinar o número de indivíduos com teste sorológico positivo em um Presídio no Estado de MG. Método Trata-se de um estudo transversal em março de 2021, momento no qual a vacinação estava restrita aos idosos e profissionais de saúde, onde foi realizado um inquérito sorológico em um Presídio no Estado de Minas Gerais. Todos os participantes da pesquisa foram testados em um único dia com teste imunocromatográfico da Abbott IgG. O trabalho foi aprovado pelo Comitê de Ética em Pesquisa com CAAE 40144920.6.0000.5114. A análise dos dados foi realizada através do teste não paramétrico Qui-Quadrado com correção de Yates, aplicado com o objetivo de verificar a existência de diferença significativa entre os grupos pesquisados. Resultados Foram avaliados 93 indivíduos (92% sexo masculino), dos quais 17% eram funcionários da unidade;72% cumpriam pena sob o regime fechado e 11% cumpriam pena sob o regime semiaberto. A tabela 1 apresenta os valores encontrados e esperados. Sorologia Negativo Positivo Total % P-value Funcionário Observado 14 2 16 17% 0.3484 Esperado 13,4 2,6 16,0 Regime fechado Observado 54 13 67 72% Esperado 56,2 10,8 67,0 Regime semi-aberto Observado 10 0 10 11% Esperado 8,4 1,6 10,0 Total Observado 78 15 93 100% Esperado 78,0 15,0 93,0 Tabela 1 - Resultados dos testes sorológicos aplicados por grupo de estudo. Conclusão Os dados apresentados no estudo demonstraram que o resultado do teste de sorologia (negativo ou positivo) independe do grau de isolamento social adotado pelos indivíduos, uma vez que não foi observada diferença entre os funcionários do presídio e os detentos em regime semiaberto. De forma interessante, nível significativo de diferença (números de testes positivos) foi observada para os indivíduos mantidos em regime fechado no sistema prisional.

COMO AS VARIANTES DE SARS-COV-2 IMPACTARAM AS CIRURGIAS ELETIVAS E DE EMERGÊNCIA?

Introdução A pandemia da COVID-19 trouxe inúmeros desafios ao sistema de saúde em todo o mundo. O aumento dos casos de SARS-CoV-2 impactou o gerenciamento de procedimentos cirúrgicos. À medida que o cenário se tornava mais favorável, foi possível a retomada das cirurgias eletivas e de emergência de forma progressiva. Portanto, para evitar infecção hospitalar e garantir um procedimento seguro, a detecção de SARS-CoV-2 tornou-se obrigatória em todos os pacientes antes da cirurgia, de acordo com a demanda de atendimento de cada unidade. Objetivo Nesse sentido, nosso objetivo foi compreender a dinâmica das taxas de positividade de SARS-CoV-2 frente às Variantes de Preocupação (VOCs) e o impacto nas taxas de suspensão de cirurgias em um hospital de São Paulo, Brasil. Método De julho de 2020 a março de 2022, investigamos todos os pacientes pré-operatórios assintomáticos que seriam admitidos para cirurgia eletiva ou de emergência. Para cada paciente foi coletado swab nasofaríngeo 48 horas a 72 horas antes da cirurgia;foi realizado um RT-qPCR (Kit GeneFinder;OSANG Healthcare) para detectar SARS-CoV-2. O Ct foi considerado como inferência da carga viral. Para entender o impacto do SARS-CoV-2 em cirurgias canceladas e adiadas, estabelecemos diferentes fases da pandemia com base na linhagem/variante circulante predominante em São Paulo, Brasil. Resultados Incluímos 4.644 testes de pacientes pré-operatórios de 0 a 103 anos (mediana 48;IQR 27-63). A positividade geral foi de 3,6%. Em seguida, analisamos as taxas em diferentes fases. A maior taxa de suspensão da cirurgia (12,5%) ocorreu no período em que predominava a VOC Omicron. Não observamos diferença significativa quanto às variantes e às cargas virais. Conclusão Nossos achados destacam que a Omicron aumentou significativamente as taxas de positividade nos pacientes assintomáticos rastreados que foram testados antes do procedimento cirúrgico. Em todos os períodos observamos amostras com valor de Ct que apresenta risco de infecção. A maioria dos casos de Omicron são leves e moderados, porém o padrão de transmissibilidade dessa variante ainda impacta a prestação de serviços de saúde. Como os testes pré-operatórios para vírus respiratórios não eram solicitados antes da pandemia, a previsão do impacto em cirurgias em um cenário com variantes mais transmissíveis ou circulação de outro vírus continua sendo um desafio. Intervenções futuras para controle de infecção e proteção de pacientes e cirurgiões são necessárias para a regularidade do sistema de saúde. Ag. Financiadora FAPESP. Nr. Processo 2020/11719-0.

OCORRÊNCIA DE CASOS POSITIVOS DE SARS-COV-2 DURANTE A ONDA DE ÔMICRON EM UM HOSPITAL PÚBLICO DE SÃO PAULO

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.

Evaluation of the Panbio™ COVID-19 ag rapid test at an emergency room in a hospital in São Paulo, Brazil.

BACKGROUND: The performance characteristics of the Panbio™ COVID-19 Ag test was evaluated at an emergency room setting against RT-PCR, considered the gold-standard for the detection of SARS-CoV-2, in São Paulo, Brazil. The study aimed to determine the sensitivity, specificity, Positive Percent Agreement (PPA), and Negative Percent Agreement (NPA) as compared to RT-PCR. METHODS: Specimens from 127 suspected patients were tested by both the Panbio™ COVID-19 Ag test and by RT-PCR. RESULTS: In relation to RT-PCR using Ct values ≤ 40 as the upper limit for positivity, the Panbio™ COVID-19 Ag test showed an overall sensitivity of 84.3% (95% CI 75‒93.8%) and 98.2% (95% CI 96‒98.8%) overall specificity. For Ct values ≤ 25 (n = 37), the Panbio™ COVID-19 Ag test showed 97% sensitivity. DISCUSSION: The concordance between the Panbio™ COVID-19 Ag test and RT-PCR was 97% at Ct values below 25 but decreased at higher Ct values. For disease control, it is very important to identify infected individuals who present COVID-19 symptoms and also those who are suspected of infection due to contact with infected individuals. CONCLUSION: The Panbio™ COVID-19 Ag test is suitable for use as a diagnostic test for rapid screening of patients presenting COVID-19 symptoms, or those suspected of being infected, prior to being admitted to hospital.

Household transmission of COVID-19 according to index case: children, parents, and healthcare workers.

The first SARS-CoV-2 intrafamilial transmission was investigated in China. We evaluated the dynamics of SARS-CoV-2 transmission in 242 individuals from 60 family clusters, including 30 healthcare workers (HCW) and 30 patients, in São Paulo city. Sixty index cases with COVID-19 were selected, being 30 HCW index cases from Hospital São Paulo (HSP) and its 93 household contacts and 30 index case patients from Hospital Infantil Sabará (HIS) and its 89 household contacts. Asymptomatic and symptomatic individuals participating were tested for COVID-19. The secondary attack rates in the family clusters of HCW and HIS patients were 37.63% and 68.54%, respectively. Considering all households, the transmission from adults to children was 55.4%, while the transmission from children to children was 37.5%. Children were more infected if the index case was an adult, suggesting that children were less competent to transmit. The average time for a household to be COVID-19 positive was 4 and 3 days for HCW and HIS patients. Although HCW have a higher risk of infection and social vulnerability, the secondary attack rate was lower than that observed for HIS patients, possibly because HCW are more aware of transmission risks than the general community.

Corrigendum to "Nitazoxanide superiority to placebo to treat moderate COVID-19 - A Pilot prove of concept randomized double-blind clinical trial." [EClinicalMedicine 37 (2021) 100981].

[This corrects the article DOI: 10.1016/j.eclinm.2021.100981.].

Evaluation of the Panbio™ COVID-19 ag rapid test at an emergency room in a hospital in São Paulo, Brazil

Background The performance characteristics of the Panbio™ COVID-19 Ag test was evaluated at an emergency room setting against RT-PCR, considered the gold-standard for the detection of SARS-CoV-2, in São Paulo, Brazil. The study aimed to determine the sensitivity, specificity, Positive Percent Agreement (PPA), and Negative Percent Agreement (NPA) as compared to RT-PCR. Methods Specimens from 127 suspected patients were tested by both the Panbio™ COVID-19 Ag test and by RT-PCR. Results In relation to RT-PCR using Ct values ≤ 40 as the upper limit for positivity, the Panbio™ COVID-19 Ag test showed an overall sensitivity of 84.3% (95% CI 75%‒93.8%) and 98.2% (95% CI 96%‒98.8%) overall specificity. For Ct values ≤ 25 (n = 37), the Panbio™ COVID-19 Ag test showed 97% sensitivity and a specificity of 73.3%. Discussion The concordance between the Panbio™ COVID-19 Ag test and RT-PCR was 97% at Ct values below 25 but decreased at higher Ct values. For disease control, it is very important to identify infected individuals who present COVID-19 symptoms and also those who are suspected of infection due to contact with infected individuals. Conclusion The Panbio™ COVID-19 Ag test is suitable for use as a diagnostic test for rapid screening of patients presenting COVID-19 symptoms, or those suspected of being infected, prior to being admitted to hospital.

The Role of Serology Testing in the Context of Immunization Policies for COVID-19 in Latin American Countries.

This review aims to explore the role and value of serology testing in the context of COVID-19 immunization policies in Latin American countries and the barriers and challenges to the adequate use and uptake of this tool. It builds on a review of the academic literature, evidence, and existing policies, and includes a multistage process of discussion and feedback by a group of five experts. Regional and country-level evidence and resources from five focus countries-Argentina, Brazil, Chile, Colombia, and Mexico-were collected and analyzed. This review contains an overview of (1) the impact of the SARS-CoV-2 pandemic, the variants of concern and current testing strategies, (2) the introduction of COVID-19 vaccination, (3) the potential use of serology testing to support immunization initiatives, (4) the current frameworks for the use of serology testing in the region, and (5) the barriers and challenges to implementing serology testing in the context of COVID-19 immunization policies, including a discussion on the potential actions required to address these barriers and facilitate the uptake of this strategy in the region. Stakeholders can use elements of this document to guide timely decision-making, raise awareness, and inspire further studies.

The clinical course of hospitalized moderately ill COVID-19 patients is mirrored by routine hematologic tests and influenced by renal transplantation.

Several studies of patients with COVID-19 have evaluated biological markers for predicting outcomes, most of them retrospectively and with a wide scope of clinical severity. We followed a prospective cohort of patients admitted in hospital wards with moderate COVID-19 disease, including those with a history of kidney transplantation, and examined the ability of changes in routine hematologic laboratory parameters to predict and mirror the patients' clinical course regarding the severity of their condition (classified as critical vs. non-critical) and in-hospital mortality or hospital discharge. Among the 68 patients, 20 (29%) were kidney transplanted patients (KT), and they had much higher mortality than non-kidney transplanted patients in this cohort (40% X 8.3%). Lymphocytes, neutrophils and neutrophils/lymphocytes ratio (NLR) at admission and platelets as well as the red blood cells parameters hemoglobin, hematocrit, and RDW by the time of hospital discharge or death clearly differentiated patients progressing to critical disease and those with clinical recovery. Patients with deteriorating clinical courses presented elevated and similar NLRs during the first week of hospitalization. However, they were dramatically different at hospital discharge, with a decrease in the survivors (NLR around 5.5) and sustained elevation in non-survivors (NLR around 21). Platelets also could distinguish survivors from non-survivors among the critical patients. In conclusion, routine hematologic tests are useful to monitor the clinical course of COVID-19 patients admitted with moderate disease. Unexpectedly, changes in hematologic tests, including lymphopenia, were not predictive of complicated outcomes among KT recipients.

Impact of COVID-19 on corneal esthesiometry.

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.