Impact of COVID-19 RT-PCR testing of asymptomatic health care workers on absenteeism and hospital transmission during the pandemic.

Reducing the transmission of SARS-CoV-2 from asymptomatic and pre-symptomatic patients is critical in controlling the circulation of the virus. This study evaluated the prevalence of RT-PCR positivity in serial tests (every 20 days) in 429 asymptomatic health care workers (HCW) and its impact on absenteeism from May to August 2020. Asymptomatic HCW from a COVID-19 reference hospital in Campinas (1.2 million inhabitants), Brazil, were tested, screened, and placed on leave. A time-series segmented regression of weekly absenteeism rates was used, and cases of infection among hospitalized patients were analyzed. Viral gene sequencing and phylogenetic analysis were performed on samples gathered from professionals who had a positive result. A significant decrease in absenteeism was detected 3-4 weeks after the intervention at a time of increased transmission within the city. The prevalence of RT-PCR positivity among asymptomatic professionals was 17.3%. Phylogenetic analyses of 59 samples detected nine clusters, two of them strongly suggestive of intra-hospital transmission with strains (75% B.1.1.28) circulating in the region during this period. Testing and placing asymptomatic professionals on leave contributed to control strategy for COVID-19 transmission in the hospital environment, and in reducing positivity and absenteeism, which directly influences the quality of care and exposes professionals to an extra load of stress. BACKGROUND: Reducing the transmission of SARS-CoV-2 from asymptomatic and pre-symptomatic patients is critical in controlling the circulation of the virus. METHODS: This study evaluated the prevalence of RT-PCR positivity in serial tests (every 20 days) in 429 asymptomatic health care workers (HCW) and its impact on absenteeism from May to August 2020. Asymptomatic HCW from a COVID-19 reference hospital in Campinas (1.2 million inhabitants), Brazil, were tested, screened, and placed on leave. A time-series segmented regression of weekly absenteeism rates was used, and cases of infection among hospitalized patients were analyzed. Viral gene sequencing and phylogenetic analysis were performed on samples gathered from professionals who had a positive result. RESULTS: A significant decrease in absenteeism was detected 3-4 weeks after the intervention at a time of increased transmission within the city. The prevalence of RT-PCR positivity among asymptomatic professionals was 17.3%. Phylogenetic analyses of 59 samples detected nine clusters, two of them strongly suggestive of intra-hospital transmission with strains (75% B.1.1.28) circulating in the region during this period. CONCLUSIONS: Testing and placing asymptomatic professionals on leave contributed to control strategy for COVID-19 transmission in the hospital environment, and in reducing positivity and absenteeism, which directly influences the quality of care and exposes professionals to an extra load of stress.

Reinfection rate in a cohort of healthcare workers over 2 years of the COVID-19 pandemic.

In this large cohort of healthcare workers, we aimed to estimate the rate of reinfections by SARS-CoV-2 over 2 years of the COVID-19 pandemic. We investigated the proportion of reinfections among all the cases of SARS-CoV-2 infection from March 10, 2020 until March 10, 2022. Reinfection was defined as the appearance of new symptoms that on medical evaluation were suggestive of COVID-19 and confirmed by a positive RT-PCR. Symptoms had to occur more than 90 days after the previous infection. These 2 years were divided into time periods based on the different variants of concern (VOC) in the city of São Paulo. There were 37,729 medical consultations due to COVID-19 at the hospital's Health Workers Services; and 25,750 RT-PCR assays were performed, of which 23% (n = 5865) were positive. Reinfection by SARS-CoV-2 was identified in 5% (n = 284) of symptomatic cases. Most cases of reinfection occurred during the Omicron period (n = 251; 88%), representing a significant increase on the SARS-CoV-2 reinfection rate before and during the Omicron variant period (0.8% vs. 4.3%; p < 0.001). The mean interval between SARS-CoV-2 infections was 429 days (ranged from 122 to 674). The Omicron variant spread faster than Gamma and Delta variant. All SARS-CoV-2 reinfections were mild cases.

Technical performance of a lateral flow immunoassay for detection of anti-SARS-CoV-2 IgG in the outpatient follow-up of non-severe cases and at different times after vaccination: comparison with enzyme and chemiluminescent immunoassays.

This study assessed the technical performance of a rapid lateral flow immunochromatographic assay (LFIA) for the detection of anti-SARS-CoV-2 IgG and compared LFIA results with chemiluminescent immunoassay (CLIA) results and an in-house enzyme immunoassay (EIA). To this end, a total of 216 whole blood or serum samples from three groups were analyzed: the first group was composed of 68 true negative cases corresponding to blood bank donors, healthy young volunteers, and eight pediatric patients diagnosed with other coronavirus infections. The serum samples from these participants were obtained and stored in a pre-COVID-19 period, thus they were not expected to have COVID-19. In the second group of true positive cases, we chose to replace natural cases of COVID-19 by 96 participants who were expected to have produced anti-SARS-CoV-2 IgG antibodies 30-60 days after the vaccine booster dose. The serum samples were collected on the same day that LFIA were tested either by EIA or CLIA. The third study group was composed of 52 participants (12 adults and 40 children) who did or did not have anti-SARS-CoV-2 IgG antibodies due to specific clinical scenarios. The 12 adults had been vaccinated more than seven months before LFIA testing, and the 40 children had non-severe COVID-19 diagnosed using RT-PCR during the acute phase of infection. They were referred for outpatient follow-up and during this period the serum samples were collected and tested by CLIA and LFIA. All tests were performed by the same healthcare operator and there was no variation of LFIA results when tests were performed on finger prick whole blood or serum samples, so that results were grouped for analysis. LFIA's sensitivity in detecting anti-SARS-CoV-2 IgG antibodies was 90%, specificity 97.6%, efficiency 93%, PPV 98.3%, NPV 86.6%, and likelihood ratio for a positive or a negative result were 37.5 and 0.01 respectively. There was a good agreement (Kappa index of 0.677) between LFIA results and serological (EIA or CLIA) results. In conclusion, LFIA analyzed in this study showed a good technical performance and agreement with reference serological assays (EIA or CLIA), therefore it can be recommended for use in the outpatient follow-up of non-severe cases of COVID-19 and to assess anti-SARS-CoV-2 IgG antibody production induced by vaccination and the antibodies decrease over time. However, LFIAs should be confirmed by using reference serological assays whenever possible.

ANÁLISE DA POSITIVIDADE E TÍTULOS DE NEUTRALIZAÇÃO EM PVHIV E CONTROLES NÃO VACINADOS COM IGG POSITIVO PARA SARS-COV-2

Introdução Testes de neutralização têm se tornado a principal referência para avaliar proteção após exposição ao SARS-CoV-2 ou após a vacinação. Alguns estudos sugerem que pessoas que vivem com HIV (PVHIV) têm menor probabilidade de soroconversão após a vacinação para COVID-19, porém a resposta humoral após infecção natural é pouco conhecida. Objetivo Avaliar a positividade e títulos de anticorpos neutralizantes em PVHIV e controles com IgG positivo identificados no Estudo Prevent, realizado antes da implementação das vacinas para COVID-19 no Brasil. Método O Estudo Prevent incluiu PVHIV sob tratamento ARV e contactantes próximos sem diagnóstico de infecção por HIV acompanhados por 120 dias com avaliação clínica semanal e avaliação sorológica (IgM/IgG) ao início (TS1) e final (TS2) do seguimento, entre abril/2020 e janeiro/2021. Todas as amostras com IgG reagente (+) foram submetidas a um teste correlato de anticorpos neutralizantes (TCAN). Resultados Um total de 74 amostras tiveram IgG reagente;entre PVHIV, 9 tiveram TS1+ e TS2 não reagente (NR);14 tiveram TS1+ e TS2+;e 18 tiveram TS1 NR e TS2+. No grupo controle, 6 tiveram TS1+/TS2 NR;5 tiveram TS1+ e TS2+ e apenas 2 tiveram TS1 NR e TS2+. Quanto à avaliação do TCAN, houve positividade em 39/56 (69%;IC95% 56-81) amostras de PVHIV, e em 14/18 (78%;IC95% 52-94) amostras de controles. 21 amostras foram positivas no TS e negativas no TCAN (17 PVHIV e 4 controles) além de 1 amostra TNeutrAc indeterminada após TS positivo (PVHIV). Embora as medianas de porcentagens de neutralização tenham sido mais altas entre controles em relação a PVHIV tanto nas amostras iniciais quanto ao término do estudo, essa diferença não atingiu significância estatística. Conclusão Testes de neutralização para SARS-CoV-2 ainda possuem aplicabilidade e interpretação controversos. Entretanto, até o momento consistem na metodologia mais aceita para avaliar níveis de proteção contra o vírus. Nossos resultados sugerem tendência a resposta neutralizante inferior entre PVHIV comparadas com controles.

Prediction of SARS-CoV-2-positivity from million-scale complete blood counts using machine learning.

Background: The Complete Blood Count (CBC) is a commonly used low-cost test that measures white blood cells, red blood cells, and platelets in a person's blood. It is a useful tool to support medical decisions, as intrinsic variations of each analyte bring relevant insights regarding potential diseases. In this study, we aimed at developing machine learning models for COVID-19 diagnosis through CBCs, unlocking the predictive power of non-linear relationships between multiple blood analytes. Methods: We collected 809,254 CBCs and 1,088,385 RT-PCR tests for SARS-Cov-2, of which 21% (234,466) were positive, from 900,220 unique individuals. To properly screen COVID-19, we also collected 120,807 CBCs of 16,940 individuals who tested positive for other respiratory viruses. We proposed an ensemble procedure that combines machine learning models for different respiratory infections and analyzed the results in both the first and second waves of COVID-19 cases in Brazil. Results: We obtain a high-performance AUROC of 90 + % for validations in both scenarios. We show that models built solely of SARS-Cov-2 data are biased, performing poorly in the presence of infections due to other RNA respiratory viruses. Conclusions: We demonstrate the potential of a novel machine learning approach for COVID-19 diagnosis based on a CBC and show that aggregating information about other respiratory diseases was essential to guarantee robustness in the results. Given its versatile nature, low cost, and speed, we believe that our tool can be particularly useful in a variety of scenarios-both during the pandemic and after.

SARS-CoV-2 and rhinovirus infections: are there differences in clinical presentation, laboratory abnormalities, and outcomes in the pediatric population?

This study aims to assess COVID-19 and other respiratory viruses in pediatric patients. Between April 17 and September 30, 2020, we collected 1,566 respiratory samples from 1,044 symptomatic patients who were younger than 18 years old to assess SARS-CoV-2 infection. Of these, 919 were analyzed for other respiratory pathogens (ORP). Patients with laboratory-confirmed COVID-19 or ORP were included. We evaluated 76 pediatric COVID-19 infections and 157 other respiratory virus infections. Rhinovirus occurred in 132/157 (84%). COVID-19 patients who were significantly older, had more fevers, headaches and pneumonia than those with ORP. The median white blood cell count was lower in patients with SARS-CoV-2 than in those with ORP (6,470 versus 8,170; p=0.02). COVID-19 patients had significantly worse symptoms than those with ORP.

Use and misuse of biomarkers and the role of D-dimer and C-reactive protein in the management of COVID-19: A post-hoc analysis of a prospective cohort study.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is associated with high mortality among hospitalized patients and incurs high costs. Severe acute respiratory syndrome coronavirus 2 infection can trigger both inflammatory and thrombotic processes, and these complications can lead to a poorer prognosis. This study aimed to evaluate the association and temporal trends of D-dimer and C-reactive protein (CRP) levels with the incidence of venous thromboembolism (VTE), hospital mortality, and costs among inpatients with COVID-19. METHODS: Data were extracted from electronic patient records and laboratory databases. Crude and adjusted associations for age, sex, number of comorbidities, Sequential Organ Failure Assessment score at admission, and D-dimer or CRP logistic regression models were used to evaluate associations. RESULTS: Between March and June 2020, COVID-19 was documented in 3,254 inpatients. The D-dimer level ≥4,000 ng/mL fibrinogen equivalent unit (FEU) mortality odds ratio (OR) was 4.48 (adjusted OR: 1.97). The CRP level ≥220 mg/dL OR for death was 7.73 (adjusted OR: 3.93). The D-dimer level ≥4,000 ng/mL FEU VTE OR was 3.96 (adjusted OR: 3.26). The CRP level ≥220 mg/dL OR for VTE was 2.71 (adjusted OR: 1.92). All these analyses were statistically significant (p<0.001). Stratified hospital costs demonstrated a dose-response pattern. Adjusted D-dimer and CRP levels were associated with higher mortality and doubled hospital costs. In the first week, elevated D-dimer levels predicted VTE occurrence and systemic inflammatory harm, while CRP was a hospital mortality predictor. CONCLUSION: D-dimer and CRP levels were associated with higher hospital mortality and a higher incidence of VTE. D-dimer was more strongly associated with VTE, although its discriminative ability was poor, while CRP was a stronger predictor of hospital mortality. Their use outside the usual indications should not be modified and should be discouraged.

Differences in children and adolescents with SARS-CoV-2 infection: a cohort study in a Brazilian tertiary referral hospital.

OBJECTIVES: To compare demographic/clinical/laboratory/treatments and outcomes among children and adolescents with laboratory-confirmed coronavirus disease 2019 (COVID-19). METHODS: This was a cross-sectional study that included patients diagnosed with pediatric COVID-19 (aged <18 years) between April 11, 2020 and April 22, 2021. During this period, 102/5,951 (1.7%) of all admissions occurred in neonates, children, and adolescents. Furthermore, 3,962 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection samples were processed in patients aged <18 years, and laboratory-confirmed COVID-19 occurred in 155 (4%) inpatients and outpatients. Six/155 pediatric patients were excluded from the study. Therefore, the final group included 149 children and adolescents (n=97 inpatients and 52 outpatients) with positive SARS-CoV-2 results. RESULTS: The frequencies of sore throat, anosmia, dysgeusia, headache, myalgia, nausea, lymphopenia, pre-existing chronic conditions, immunosuppressive conditions, and autoimmune diseases were significantly reduced in children and adolescents (p<0.05). Likewise, the frequencies of enoxaparin use (p=0.037), current immunosuppressant use (p=0.008), vasoactive agents (p=0.045), arterial hypotension (p<0.001), and shock (p=0.024) were significantly lower in children than in adolescents. Logistic regression analysis showed that adolescents with laboratory-confirmed COVID-19 had increased odds ratios (ORs) for sore throat (OR 13.054; 95% confidence interval [CI] 2.750-61.977; p=0.001), nausea (OR 8.875; 95% CI 1.660-47.446; p=0.011), and lymphopenia (OR 3.575; 95% CI 1.355-9.430; p=0.010), but also had less hospitalizations (OR 0.355; 95% CI 0.138-0.916; p=0.032). The additional logistic regression analysis on patients with preexisting chronic conditions (n=108) showed that death as an outcome was significantly associated with pediatric severe acute respiratory syndrome (SARS) (OR 22.300; 95% CI 2.341-212.421; p=0.007) and multisystem inflammatory syndrome in children (MIS-C) (OR 11.261; 95% CI 1.189-106. 581; p=0.035). CONCLUSIONS: Half of the laboratory-confirmed COVID-19 cases occurred in adolescents. Individuals belonging to this age group had an acute systemic involvement of SARS-CoV-2 infection. Pediatric SARS and MIS-C were the most important factors associated with the mortality rate in pediatric chronic conditions with COVID-19.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Seroprevalence and Risk Factors Among Oligo/Asymptomatic Healthcare Workers: Estimating the Impact of Community Transmission.

We evaluated the seroprevalence of SARS-CoV-2 and risk factors among 4987 oligo/asymptomatic healthcare workers; seroprevalence was 14% and factors associated with SARS-CoV-2 infection were lower educational level (aOR, 1.93; 95% CI, 1.03-3.60), using public transport to work (aOR, 1.65; 95% CI, 1.07-2.62), and working in cleaning or security (aOR, 2.05; 95% CI, 1.04-4.03).

Critical preparedness and operational response actions directed for the acute and post-acute COVID-19 pandemic in Brazil: the experience of a nationwide outpatient healthcare group.

ABSTRACT: While the new Coronavirus Disease 2019 (COVID-19) pandemic rapidly spread across the world, South America was reached later in relation to Asia, Europe and the United States of America (USA). Brazil concentrates now the largest number of cases in the continent and, as the disease speedily progressed throughout the country, prompt and challenging operational strategies had to be taken by institutions caring for COVID-19 and non-COVID-19 patients in order to assure optimal workflows, triage, and management. Although hospitals in the USA, Europe and Asia have shared their experience on this subject, little has been discussed about such strategies in South America or by the perspective of outpatient centers, which are paramount in the radiology field. This article shares the guidelines adopted early in the pandemic by a nationwide outpatient healthcare center composed by a network of more than 200 patient service centers and nearly 2,000 radiologists in Brazil, discussing operational and patient management strategies, staff protection, changes adopted in the fellowship program, and the effectiveness of such measures.

No association between vitamin D status and COVID-19 infection in São Paulo, Brazil.

In recent years the immunomodulatory actions of vitamin D, a steroid hormone, have been extensively studied. In 2020, due to the COVID-19 pandemic, the question arose as to 25(OH)D status would be related to susceptibility to SARS-CoV-2 infection, since several studies pointed out a higher prevalence and severity of the disease in populations with low levels of 25(OH)D. Thus, we investigated the 25(OH)D levels in adults "Detected" positive for SARS CoV-2 by RT-PCR (reverse transcriptase polymerase chain reaction) test, and in negative controls, "not Detected", using the Fleury Group's examination database, in Sao Paulo, Brazil. Of a total of 14.692 people with recent assessments of 25(OH)D and RT-PCR tests for COVID-19, 2.345 were positive and 11.585 were negative for the infection. The groups did not differ in the percentage of men and women, or in the age distribution. There were no differences in the distribution of 25(OH)D between the two groups (p = 0.08); mean 25(OH)D of 28.8 ± 21.4 ng/mL and 29.6 ± 18.1 ng/mL, respectively. In the specific population studied, clinical, environmental, socioeconomic and cultural factors should have greater relevance than 25(OH)D in determining the susceptibility to COVID-19.

Establishing a mass spectrometry-based system for rapid detection of SARS-CoV-2 in large clinical sample cohorts.

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is pressing public health systems around the world, and large population testing is a key step to control this pandemic disease. Here, we develop a high-throughput targeted proteomics assay to detect SARS-CoV-2 nucleoprotein peptides directly from nasopharyngeal and oropharyngeal swabs. A modified magnetic particle-based proteomics approach implemented on a robotic liquid handler enables fully automated preparation of 96 samples within 4 hours. A TFC-MS system allows multiplexed analysis of 4 samples within 10 min, enabling the processing of more than 500 samples per day. We validate this method qualitatively (Tier 3) and quantitatively (Tier 1) using 985 specimens previously analyzed by real-time RT-PCR, and detect up to 84% of the positive cases with up to 97% specificity. The presented strategy has high sample stability and should be considered as an option for SARS-CoV-2 testing in large populations.

Performance of a qualitative rapid chromatographic immunoassay to diagnose COVID-19 in patients in a middle-income country.

OBJECTIVES: We evaluated a rapid chromatographic immunoassay (IgG/IgM antibodies) and an ELISA assay to diagnose COVID-19 in patient sat two Brazilian hospitals. METHODS: A total of 122 subjects with COVID-19 were included: 106 SARS-COV-2 RT-PCR-positive patients and 16 RT-PCR-negative patients with symptoms and chest computed tomography (CT) consistent with COVID-19. Ninety-six historical blood donation samples were used as controls. Demographic and clinical characteristics were retrieved from electronic records. Sensitivity and specificity were calculated, as were their 95% binomial confidence intervals using the Clopper-Pearson method. All analyses were performed in R version 3.6.3. RESULTS: The sensitivity of the chromatographic immunoassay in all RT-PCR-positive patients, irrespective of the timing of symptom onset, was 85.8% (95% binomial CI 77.7% to 91.9%). This increased with time after symptom onset, and at >14 days was 94.9% (85.9% to 98.9%). The specificity was 100% (96.4% to 100%). 15/16 (94%) RT- PCR-negative cases tested positive. The most frequent comorbidities were hypertension and diabetes mellitus and the most frequent symptoms were fever, cough, and dyspnea. All RT-PCR-negative patients had pneumonia. The most frequent thoracic CT findings were ground glass changes (n = 11, 68%), which were bilateral in 9 (56%) patients, and diffuse reticulonodular infiltrates (n = 5, 31%). CONCLUSIONS: The COVID-19 rapid chromatographic immunoassay evaluated in this study had a high sensitivity and specificity using plasma, particularly after 14 days from symptom onset. ELISA and qualitative rapid chromatographic immunoassays can be used for the diagnosis of RT-PCR-negative patients.

Evolution and epidemic spread of SARS-CoV-2 in Brazil.

Brazil currently has one of the fastest-growing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemics in the world. Because of limited available data, assessments of the impact of nonpharmaceutical interventions (NPIs) on this virus spread remain challenging. Using a mobility-driven transmission model, we show that NPIs reduced the reproduction number from >3 to 1 to 1.6 in São Paulo and Rio de Janeiro. Sequencing of 427 new genomes and analysis of a geographically representative genomic dataset identified >100 international virus introductions in Brazil. We estimate that most (76%) of the Brazilian strains fell in three clades that were introduced from Europe between 22 February and 11 March 2020. During the early epidemic phase, we found that SARS-CoV-2 spread mostly locally and within state borders. After this period, despite sharp decreases in air travel, we estimated multiple exportations from large urban centers that coincided with a 25% increase in average traveled distances in national flights. This study sheds new light on the epidemic transmission and evolutionary trajectories of SARS-CoV-2 lineages in Brazil and provides evidence that current interventions remain insufficient to keep virus transmission under control in this country.

Liver transplant recipients infected with SARS-CoV-2 in the early postoperative period: Lessons from a single center in the epicenter of the pandemic.

The impact of coronavirus disease-19 (COVID-19) in liver recipients remains largely unknown. Most data derive from small retrospective series of patients transplanted years ago. We aimed to report a single-center case series of five consecutive patients in the early postoperative period of deceased-donor liver transplantation who developed nosocomial COVID-19. Two patients presented important respiratory discomfort and eventually died. One was 69 years old and had severe coronary disease. She rapidly worsened after COVID-19 diagnosis on 9th postoperative day. The other was 67 years old with non-alcoholic steatohepatitis, who experienced prolonged postoperative course, complicated with cytomegalovirus infection and kidney failure. He was diagnosed on 36th postoperative day and remained on mechanical ventilation for 20 days, ultimately succumbing of secondary bacterial infection. The third, fourth, and fifth patients were diagnosed on 10th, 11th, and 18th postoperative day, respectively, and presented satisfactory clinical evolution. These last two patients were severely immunosuppressed, since one underwent steroid bolus for acute cellular rejection and another also used anti-thymocyte globulin for treating steroid-resistant rejection. Our novel experience highlights that COVID-19 may negatively impact the postoperative course, especially in elder and obese patients with comorbidities, and draws attention to COVID-19 nosocomial spread in the early postoperative period.