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Background: In SARS-CoV-2 infection, cytokines and laboratory biomarkers play a key role in disease progression and their long-term levels have been associated with the outcome of long COVID-19., Objectives: I) study the levels of cytokines, hematological and biochemical biomarkers in the acute and post-acute phases of COVID-19 disease; and II) assess the impact of COVID-19 vaccine doses on fatigue symptoms., Methods: This study is an exploratory cohort nested within a clinical and laboratory follow-up of surviving participants after pre-vaccine acute COVID-19 infection with severe clinical manifestations. We analyzed the inflammatory biomarker profiles of fifty SARS-Cov-2 negative healthy controls from before the COVID-19 pandemic, and eighty patients in the acute phase (Day 1, Day 7 and Day 14), and during 4 months and 2 years after hospitalization., Results: Four months after hospitalization, 91.3% (73/80) of patients exhibited onset of long COVID symptoms, which persisted in 63.7% (51/80) after 2 years. Comparing the baseline values of the cytokines in the controls versus the follow-up times, the cytokines IL-6, IL-8 and IL-10 were high in the acute phase, declining over time after the individual's recovery, while IL-1β showed an inverse variation, remaining high after 2 years. IL-1β, IL-10, and TNF increased over time post-acute infection, indicating a long-term inflammatory response. Vaccination with four doses, compared to three doses, showed a slight protective effect against fatigue symptoms in the male population (IRR 0.48, 95% CI 0.22 - 1.02; p=0.054 ). Neutrophil and leukocyte counts showed a significant reduction 2 years after hospitalization. However, platelet count was the laboratory biomarker that best reflects the prediction of long COVID symptoms up for to 2 years., Conclusion: Although the frequency of long COVID symptoms declines over time after the acute illness, symptoms continue to persist 2 years after hospital discharge. Vaccination with a fourth dose booster appears to significantly influence reduction of symptoms associated with long COVID fatigue among the males. We further identified important laboratory biomarkers for long COVID. Elevated levels of IL-1β, IL-10, and TNF, along with low levels of IL-6, IL-18, and IL-12p70, also offer new insights into the inflammatory state in long COVID., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Maciel, Pinto, Maia Silva, Goulart, Silva, Chaves, Mouta, Sato, Valente, Mwangi, de Melo, Monteiro, Lacerda, Arêas, Sampaio, Costa and Almeida-Val.)

Objective: To determine risk factors for the development of long coronavirus disease 2019 (COVID-19) in healthcare personnel (HCP)., Methods: We conducted a case-control study among HCP who had confirmed symptomatic COVID-19 working in a Brazilian healthcare system between March 1, 2020, and July 15, 2022. Cases were defined as those having long COVID according to the Centers for Disease Control and Prevention definition. Controls were defined as HCP who had documented COVID-19 but did not develop long COVID. Multiple logistic regression was used to assess the association between exposure variables and long COVID during 180 days of follow-up., Results: Of 7,051 HCP diagnosed with COVID-19, 1,933 (27.4%) who developed long COVID were compared to 5,118 (72.6%) who did not. The majority of those with long COVID (51.8%) had 3 or more symptoms. Factors associated with the development of long COVID were female sex (OR, 1.21; 95% CI, 1.05-1.39), age (OR, 1.01; 95% CI, 1.00-1.02), and 2 or more SARS-CoV-2 infections (OR, 1.27; 95% CI, 1.07-1.50). Those infected with the SARS-CoV-2 δ (delta) variant (OR, 0.30; 95% CI, 0.17-0.50) or the SARS-CoV-2 o (omicron) variant (OR, 0.49; 95% CI, 0.30-0.78), and those receiving 4 COVID-19 vaccine doses prior to infection (OR, 0.05; 95% CI, 0.01-0.19) were significantly less likely to develop long COVID., Conclusions: Long COVID can be prevalent among HCP. Acquiring >1 SARS-CoV-2 infection was a major risk factor for long COVID, while maintenance of immunity via vaccination was highly protective.

Background: There is a lack of information on the role of chronic use of hydroxychloroquine during the SARS-CoV-2 outbreak. Our aim was to compare the occurrence of COVID-19 between rheumatic disease patients on hydroxychloroquine with individuals from the same household not taking the drug during the first 8 weeks of community viral transmission in Brazil., Methods: This baseline cross-sectional analysis is part of a 24-week observational multi-center study involving 22 Brazilian academic outpatient centers. All information regarding COVID-19 symptoms, epidemiological, clinical, and demographic data were recorded on a specific web-based platform using telephone calls from physicians and medical students. COVID-19 was defined according to the Brazilian Ministry of Health (BMH) criteria. Mann-Whitney, Chi-square and Exact Fisher tests were used for statistical analysis and two binary Final Logistic Regression Model by Wald test were developed using a backward-stepwise method for the presence of COVID-19., Results: From March 29th to May 17st, 2020, a total of 10,443 participants were enrolled, including 5166 (53.9%) rheumatic disease patients, of whom 82.5% had systemic erythematosus lupus, 7.8% rheumatoid arthritis, 3.7% Sjögren's syndrome and 0.8% systemic sclerosis. In total, 1822 (19.1%) participants reported flu symptoms within the 30 days prior to enrollment, of which 3.1% fulfilled the BMH criteria, but with no significant difference between rheumatic disease patients (4.03%) and controls (3.25%). After adjustments for multiple confounders, the main risk factor significantly associated with a COVID-19 diagnosis was lung disease (OR 1.63; 95% CI 1.03-2.58); and for rheumatic disease patients were diagnosis of systemic sclerosis (OR 2.8; 95% CI 1.19-6.63) and glucocorticoids above 10 mg/ day (OR 2.05; 95% CI 1.31-3.19). In addition, a recent influenza vaccination had a protective effect (OR 0.674; 95% CI 0.46-0.98)., Conclusion: Patients with rheumatic disease on hydroxychloroquine presented a similar occurrence of COVID-19 to household cohabitants, suggesting a lack of any protective role against SARS-CoV-2 infection. Trial registration Brazilian Registry of Clinical Trials (ReBEC; RBR - 9KTWX6)., (© 2021. The Author(s).)

Background: Steroid use for coronavirus disease 2019 (COVID-19) is based on the possible role of these drugs in mitigating the inflammatory response, mainly in the lungs, triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to evaluate the efficacy of methylprednisolone (MP) among hospitalized patients with suspected COVID-19., Methods: A parallel, double-blind, placebo-controlled, randomized, Phase IIb clinical trial was performed with hospitalized patients aged ≥18 years with clinical, epidemiological, and/or radiological suspected COVID-19 at a tertiary care facility in Manaus, Brazil. Patients were randomly allocated (1:1 ratio) to receive either intravenous MP (0.5 mg/kg) or placebo (saline solution) twice daily for 5 days. A modified intention-to-treat (mITT) analysis was conducted. The primary outcome was 28-day mortality., Results: From 18 April to 16 June 2020, 647 patients were screened, 416 were randomized, and 393 were analyzed as mITT, with 194 individuals assigned to MP and 199 to placebo. SARS-CoV-2 infection was confirmed by reverse transcriptase polymerase chain reaction in 81.3%. The mortality rates at Day 28 were not different between groups. A subgroup analysis showed that patients over 60 years old in the MP group had a lower mortality rate at Day 28. Patients in the MP arm tended to need more insulin therapy, and no difference was seen in virus clearance in respiratory secretion until Day 7., Conclusions: The findings of this study suggest that a short course of MP in hospitalized patients with COVID-19 did not reduce mortality in the overall population., Clinical Trials Registration: NCT04343729., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

COVID-19 is still placing a heavy health and financial burden worldwide. Impairment in patient screening and risk management plays a fundamental role on how governments and authorities are directing resources, planning reopening, as well as sanitary countermeasures, especially in regions where poverty is a major component in the equation. An efficient diagnostic method must be highly accurate, while having a cost-effective profile. We combined a machine learning-based algorithm with mass spectrometry to create an expeditious platform that discriminate COVID-19 in plasma samples within minutes, while also providing tools for risk assessment, to assist healthcare professionals in patient management and decision-making. A cross-sectional study enrolled 815 patients (442 COVID-19, 350 controls and 23 COVID-19 suspicious) from three Brazilian epicenters from April to July 2020. We were able to elect and identify 19 molecules related to the disease's pathophysiology and several discriminating features to patient's health-related outcomes. The method applied for COVID-19 diagnosis showed specificity >96% and sensitivity >83%, and specificity >80% and sensitivity >85% during risk assessment, both from blinded data. Our method introduced a new approach for COVID-19 screening, providing the indirect detection of infection through metabolites and contextualizing the findings with the disease's pathophysiology. The pairwise analysis of biomarkers brought robustness to the model developed using machine learning algorithms, transforming this screening approach in a tool with great potential for real-world application.

Background: In SARS-CoV-2 infection, cytokines and laboratory biomarkers play a key role in disease progression and their long-term levels have been associated with the outcome of long COVID-19. Objectives: I) study the levels of cytokines, hematological and biochemical biomarkers in the acute and post-acute phases of COVID-19 disease; and II) assess the impact of COVID-19 vaccine doses on fatigue symptoms. Methods: This study is an exploratory cohort nested within a clinical and laboratory follow-up of surviving participants after pre-vaccine acute COVID-19 infection with severe clinical manifestations. We analyzed the inflammatory biomarker profiles of fifty SARS-Cov-2 negative healthy controls from before the COVID-19 pandemic, and eighty patients in the acute phase (Day 1, Day 7 and Day 14), and during 4 months and 2 years after hospitalization. Results: Four months after hospitalization, 91.3% (73/80) of patients exhibited onset of long COVID symptoms, which persisted in 63.7% (51/80) after 2 years. Comparing the baseline values of the cytokines in the controls versus the follow-up times, the cytokines IL-6, IL-8 and IL-10 were high in the acute phase, declining over time after the individual's recovery, while IL-1β showed an inverse variation, remaining high after 2 years. IL-1β, IL-10, and TNF increased over time post-acute infection, indicating a long-term inflammatory response. Vaccination with four doses, compared to three doses, showed a slight protective effect against fatigue symptoms in the male population (IRR 0.48, 95% CI 0.22 - 1.02; p=0.054). Neutrophil and leukocyte counts showed a significant reduction 2 years after hospitalization. However, platelet count was the laboratory biomarker that best reflects the prediction of long COVID symptoms up for to 2 years. Conclusion: Although the frequency of long COVID symptoms declines over time after the acute illness, symptoms continue to persist 2 years after hospital discharge. Vaccination with a fourth dose booster appears to significantly influence reduction of symptoms associated with long COVID fatigue among the males. We further identified important laboratory biomarkers for long COVID. Elevated levels of IL-1β, IL-10, and TNF, along with low levels of IL-6, IL-18, and IL-12p70, also offer new insights into the inflammatory state in long COVID. [ABSTRACT FROM AUTHOR]

The article explores clinical observations about our randomized METCOVID clinical trial on the efficacy of methylprednisolone (MP) in the adjuvant treatment of coronavirus disease 2019 (COVID-19). As the benefit of MP for 5 days was estimated to be 50%, it is likely that the overall final analysis was not powered to estimate such a difference.