Metabolic Reprogramming in SARS-CoV-2 Infection Impacts the Outcome of COVID-19 Patients.

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection triggers inflammatory clinical stages that affect the outcome of patients with coronavirus disease 2019 (COVID-19). Disease severity may be associated with a metabolic imbalance related to amino acids, lipids, and energy-generating pathways. The aim of this study was to characterize the profile of amino acids and acylcarnitines in COVID-19 patients. A multicenter, cross-sectional study was carried out. A total of 453 individuals were classified by disease severity. Levels of 11 amino acids, 31 acylcarnitines, and succinylacetone in serum samples were analyzed by electrospray ionization-triple quadrupole tandem mass spectrometry. Different clusters were observed in partial least squares discriminant analysis, with phenylalanine, alanine, citrulline, proline, and succinylacetone providing the major contribution to the variability in each cluster (variable importance in the projection >1.5). In logistic models adjusted by age, sex, type 2 diabetes mellitus, hypertension, and nutritional status, phenylalanine was associated with critical outcomes (odds ratio=5.3 (95% CI 3.16-9.2) in the severe vs. critical model, with an area under the curve of 0.84 (95% CI 0.77-0.90). In conclusion the metabolic imbalance in COVID-19 patients might affect disease progression. This work shows an association of phenylalanine with critical outcomes in COVID-19 patients, highlighting phenylalanine as a potential metabolic biomarker of disease severity.

ACE and ACE2 Gene Variants Are Associated With Severe Outcomes of COVID-19 in Men.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19) pandemic, affecting more than 219 countries and causing the death of more than 5 million people worldwide. The genetic background represents a factor that predisposes the way the host responds to SARS-CoV-2 infection. In this sense, genetic variants of ACE and ACE2 could explain the observed interindividual variability to COVID-19 outcomes. In order to improve the understanding of how genetic variants of ACE and ACE2 are involved in the severity of COVID-19, we included a total of 481 individuals who showed clinical manifestations of COVID-19 and were diagnosed by reverse transcription PCR (RT-PCR). Genomic DNA was extracted from peripheral blood and saliva samples. ACE insertion/deletion polymorphism was evaluated by the high-resolution melting method; ACE single-nucleotide polymorphism (SNP) (rs4344) and ACE2 SNPs (rs2285666 and rs2074192) were genotyped using TaqMan probes. We assessed the association of ACE and ACE2 polymorphisms with disease severity using logistic regression analysis adjusted by age, sex, hypertension, type 2 diabetes, and obesity. The severity of the illness in our study population was divided as 31% mild, 26% severe, and 43% critical illness; additionally, 18% of individuals died, of whom 54% were male. Our results showed in the codominant model a contribution of ACE2 gene rs2285666 T/T genotype to critical outcome [odds ratio (OR) = 1.83; 95%CI = 1.01-3.29; p = 0.04] and to require oxygen supplementation (OR = 1.76; 95%CI = 1.01-3.04; p = 0.04), in addition to a strong association of the T allele of this variant to develop critical illness in male individuals (OR = 1.81; 95%CI = 1.10-2.98; p = 0.02). We suggest that the T allele of rs2285666 represents a risk factor for severe and critical outcomes of COVID-19, especially for men, regardless of age, hypertension, obesity, and type 2 diabetes.

Outpatient prescription patterns of COVID-19 drugs in the metropolitan area of Mexico City.

BACKGROUND: We aimed to describe the use of drugs with apparent efficacy in ambulatory patients with confirmed COVID-19 and the relationship of Google Trends searches with prescriptions and the total number of COVID-19 cases in Mexico City. METHODS: Between March 2020 and February 2021, we surveyed 350 patients confirmed to have COVID-19 across 3 hospitals in Mexico City for their ambulatory prescriptions. We analysed the correlation between prescription patterns of 4 drugs with apparent efficacy against COVID-19, Google Trends searches for these drugs, and the overall number of confirmed COVID-19 cases in Mexico City. RESULTS: We included 350 patients, of whom 59% were women with a median age of 38 years (interquartile range, 29-51), and 72% had a bachelor's degree or higher. There were ambulatory medical prescriptions in 172 (49%) patients, and self-prescriptions were reported in 99 (28%) patients. The prescription rate was high for hydroxychloroquine/azithromycin (19%) and dexamethasone (25%). There was a decrease in the prescription of hydroxychloroquine (P < 0.001) and a strong positive correlation between hydroxychloroquine (r = 0.66; 95% confidence interval, 0.11-0.90; P = 0.02) prescription and online searches for hydroxychloroquine. There was a strong positive correlation between online searches for azithromycin, dexamethasone, ivermectin, and vitamin D and the number of confirmed COVID-19 cases. CONCLUSIONS: During the COVID-19 pandemic, there was a high proportion of prescriptions for hydroxychloroquine/azithromycin and dexamethasone despite their unproven efficacy. Analysis of Google Trends showed a strong correlation between the overall number of confirmed COVID-19 cases and searches for such drugs, suggesting a higher rate of prescriptions. Analysis of online searches could thus help to actively survey public health behaviours in the future.