ABSTRACT
Glucose-6 phosphate dehydrogenase deficiency (G6PDd) was suggested as a risk factor of severity in patients with COVID-19. In this article, we assessed the influence of G6PDd on the infection, severity, and clinical progression of patients with COVID-19. This prospective cohort study included adult participants ([≥]18 years old) who had clinical and/or radiological COVID-19 findings or positive RT-PCR results. Epidemiological and clinical data were extracted from electronic medical records. G6PD activity was measured in SD Biosensor STANDARD G6PD(R) equipment at admission and one year after discharge. Samples were genotyped for the three most common single nucleotide polymorphisms (SNPs) for G6PDd in the Brazilian Amazon s1050828, rs1050829 and rs5030868, corresponding to G6PD African A-(G202A, A376G), G6PD African A+(A376G) and G6PD Mediterranean(C563T), respectively. Seven hundred fifty-three patients were included, of which 123 (16.3%) were G6PDd. The G6PDd group had a higher mean hemoglobin, and lower values of C-reactive protein and leukocytes at admission. There was no association between G6PDd and COVID-19 severity, considering that the frequency of G6PDd who needed to be hospitalized (1.9%) or demanding invasive mechanical ventilation (16.0%) or died (21.1%) was lower than G6PD normal patients. Only 29 out of 116 (25%) participants carried the African genotype. Out of 30 participants tested as G6PDd during disease, only 11 (36.7%) results agreed one year after discharge. In conclusion, caution must be taken when G6PDd screening in patients with acute COVID-19.
ABSTRACT
INTRODUCTORY PARAGRAPHAs in many other settings, peak excess mortality preceded the officially reported first wave peak of the COVID-19 epidemic in Manaus, Brazil, reflecting delayed case recognition and limited initial access to diagnostic testing. To avoid early information bias, we used detailed age and gender stratified death certificate and hospitalisation data to evaluate the epidemics trajectory and infer the cause of its decline using a stochastic model. Our results are consistent with heterogenous transmission reducing over time due to the development of herd immunity. Relative to a baseline model that assumed homogenous mixing across Manaus, a model that permitted a small, self-isolated population fraction raised the estimated herd-immunity threshold from 28% to 30% and reduced the final attack rate from 86% to 65%. In the latter scenario, a substantial proportion of vulnerable, older individuals remained susceptible to infection. Given uncertainties regarding the distancing behaviours of population subgroups with different social and economic characteristics, and the duration of sterilising or transmission-modifying immunity in exposed individuals, we conclude that the potential for epidemic outbreaks remains, but that future waves of infection are likely to be much less pronounced than that already experienced.
ABSTRACT
COVID-19 is still placing a heavy health and financial burden worldwide. Impairments in patient screening and risk management play 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 instrumental analysis using 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 with 728 patients (369 confirmed COVID-19 and 359 controls) was enrolled from three Brazilian epicentres (Sao Paulo capital, Sao Paulo countryside and Manaus) in the months of April, May, June and July 2020. We were able to elect and identify 21 molecules that are related to the diseases pathophysiology and 26 features to patients health-related outcomes. With specificity >97% and sensitivity >83% from blinded data, this screening approach is understood as a tool with great potential for real-world application.
ABSTRACT
BackgroundThere is no specific antiviral therapy recommended for the disease caused by SARS-CoV-2 (COVID-19). Recent publications have drawn attention to the possible benefit of chloroquine (CQ). Our study aimed to comprehensively evaluate the safety and efficacy of two different CQ dosages in patients with established severe COVID-19. MethodsWe performed a parallel, double-blinded, randomized, phase IIb clinical trial, aiming to assess safety and efficacy of two different CQ dosages as adjunctive therapy of hospitalized patients with SARS in Manaus, Brazilian Amazon. Eligible participants were allocated to receive orally or via nasogastric tube high dose CQ (600mg CQ twice daily for 10 days or total dose 12g); or low dose CQ (450mg for 5 days, twice daily only on the first day, or total dose 2.7g). In addition, all patients received ceftriaxone and azithromycin. This study was registered with ClinicalTrials.gov, number NCT04323527. FindingsOut of a pre-defined 440 patients sample size, 81 patients were enrolled. The high dosage CQ arm presented more QTc>500ms (18.9%), and a trend toward higher lethality (39%) than the lower dosage. Fatality rate until day 13 was 27% (95%CI=17.9-38.2%), overlapping with the CI of historical data from similar patients not using CQ (95%CI=14.5-19.2%). In 27 patients with paired samples, respiratory secretion at day 4 was negative in only six patients (22%). InterpretationPreliminary findings suggest that the higher CQ dosage (10-day regimen) should not be recommended for COVID-19 treatment because of its potential safety hazards. Such results forced us to prematurely halt patient recruitment to this arm. Given the enormous global push for the use of CQ for COVID-19, results such as the ones found in this trial can provide robust evidence for updated COVID-19 patient management recommendations. FundingThis study was funded by the Government of the Amazonas State, Farmanguinhos (Fiocruz), SUFRAMA, CAPES, FAPEAM, and federal funds granted by a coalition of Brazilian senators. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSBefore the CloroCovid-19 trial began, to our knowledge, there were no published reports of robust clinical studies on the safety and/or efficacy of chloroquine (CQ) and/or hydroxychloroquine (HCQ) for the treatment of COVID-19 during the recent 2020 pandemic. We searched PubMed and also MedRxiv.org (pre-print server for health sciences, without peer review), without any language restrictions and including Chinese publications, for studies published between Dec 2019 and April 5, 2020, using the search terms COVID-19, coronavirus, SARS-Cov-2. We found three non-randomized studies with limited sample sizes in which (1) HCQ use led to a decrease in SARS-Cov-2 detected in respiratory secretions five days after treatment, together with azithromycin (France, 36 patients); (2) HCQ use shortened time to clinical recovery (China, 62 patients); and (3) CQ was superior to control treatment in inhibiting the exacerbation of pneumonia, improving lung imaging findings, and promoting virus-negative conversion and shortening the disease course (China, 100 patients). We found no published studies comparing different dosages of CQ/HCQ and their thorough safety assessment. Added value of this studyIn a larger patient population, we found that a higher dosage of CQ for 10 days presented toxicity red flags, particularly affecting QTc prolongation. The limited sample size recruited so far does not allow to show any benefit regarding treatment efficacy, however the higher fatality associated with the higher dosage by day 13 of follow-up resulted in a premature halting of this arm. This is the first double-blinded, randomized clinical trial addressing different dosages of CQ for the treatment of severe patients with COVID-19 in the absence of a control group using placebo. Due to the impossibility of not using the drug recommended at the national level, we used historical data from the literature to infer comparisons for lethality endpoints. Follow-up until day 28 is ongoing with a larger sample size, in which long-term lethality will be better estimated. Implications of all the available evidenceThe preliminary findings from CloroCovid-19 trial suggest that the higher dosage of CQ (12 g total dose over 10 days) in COVID-19 should not be recommended because of safety concerns regarding QTc prolongation and increased lethality, in the Brazilian population, and more often in older patients in use of drugs such as azithromycin and oseltamivir, which also prolong QTc interval. Among patients randomized to the lower dosage group (5 days of treatment, total dose 2.7 g), given the limited number of patients so far enrolled, it is still not possible to estimate a clear benefit of CQ in patients with severe ARDS. Preliminary data on viral clearance in respiratory secretions in our confirmed cases are also indicative of little effect of the drug at high dosage. More studies initiating CQ prior to the onset of the severe phase of the disease are urgently needed.
