Treatment of asymptomatic bacteriuria in the first 2 months after kidney transplant: A controlled clinical trial.

BACKGROUND: The incidence of urinary tract infections (UTIs) in the first 2 months postrenal transplantation (pRT) is very high. We evaluate the efficacy of asymptomatic bacteriuria (AB) screening and treatment on the incidence of UTI in the first 2 months pRT METHODS: We conducted a randomized controlled clinical trial. A urine culture was obtained in all patients on the day of the bladder catheter removal, on week three, and before removal of the ureteral catheter. The intervention group received treatment for AB. The control group did not receive treatment. The primary outcomes were the cumulative incidence of UTI and/or graft pyelonephritis and the time to the first episode of UTI and/or graft pyelonephritis RESULTS: Eighty patients were randomized, 40 in each group, and the median follow-up was 63 days (IQR 54-70). The average age was 29.8 years and 33.7% (n = 27) were women. The incidences of UTI (n = 10, 25 % vs. n = 4, 10%, p = .07) and pyelonephritis (n = 6, 15% vs. n = 1, 2.5%, p = .04) were greater in the intervention group, as also shown in the survival analysis: UTI (HR2.8, 95% CI 0.8-9.1, p = .07) and pyelonephritis (HR 6.5, 95% CI 0.8-54.7, p = .08), respectively. The most commonly isolated bacterium was Escherichia coli (n = 28, 59.5%), and over half were E. coli with extended-spectrum beta-lactamases (n = 15). A major limitation was not obtaining the calculated sample size due to a delay in patient recruitment resulting from the COVID-19 pandemic CONCLUSION: Treatment of AB in the first 2 months pRT does not decrease the incidence of UTI or graft pyelonephritis and may actually increase their frequency. Routine treatment of AB during the first months after renal transplantation should not be a standard procedure.

Validation of a Methodology for the Detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Saliva by Real-Time RT-PCR (preprint)

Background: In January 2021, the city of Concepción in Chile suffered a second wave of COVID-19, while in early April 2021, all of Chile was facing the same situation. This generated the need to modify and validate a methodology for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in saliva, thereby expanding the capacity and versatility of testing.Methods: People who came to the health center in Concepción city to perform a test of real-time reverse transcription polymerase chain reaction (RT-PCR) from a nasopharyngeal swab (NPS) specimen were invited to participate in this study. A total of 131 participants agreed to sign an informed consent and provide saliva and NPS specimens to validate a methodology in terms of sensitivity, specificity, and statistical analysis of the Ct values from RT-PCR.Findings: Calculations pertaining to the 127 participants who were ultimately included in the analysis were the following: sensitivity at 94·34% (95% CI: 84·34%-98·82%) and specificity at 98·65% (95% CI: 92·70%-99·97%). The saliva specimen showed a very similar performance to NPS as demonstrated with the diagnostic parameters.Interpretations: This RT-PCR methodology from the saliva specimen is a highly sensitive and specific alternative as compared to the reference methodology, which uses an NPS specimen. This modified and validated methodology is intended for use in the in vitro diagnosis of SARS-CoV-2, which provides health authorities in Chile and local laboratories with a real alternative for RT-PCR from NPS.Funding Information: Health Public Institute of Chile.Declaration of Interests: All authors declare no competing interests.Ethics Approval Statement: The study had the authorization of the Scientific Ethics Committee of the Health Service of Concepción, Chile Number 20-01-02. Parents or legal guardians for volunteers under the age of 18 signed the informed consent.

Unfavorable Hydroxychloroquine COVID-19 Research Associated with Authors Having a History of Political Party Donations (preprint)

OBJECTIVE: To explore the degree to which political bias in medicine and study authors could explain the stark variation in Hydroxychloroquine (HCQ)/Chloroquine (CQ) study favorability in the US compared to the rest of the world.SETTING: United States and Worldwide.PARTICIPANTS: COVID-19/SARS-CoV-2 preprint and published papers between January 1, 2020 and July 26, 2020 with the terms Hydroxychloroquine and/or Chloroquine; 267 met study criteria, of which 68 originated from the US. 68 control studies were randomly selected from the same time period to serve as a control subset for baseline COVID-19 publication trends and author characteristics, not related to HCQ/CQ.MAIN OUTCOME MEASURES: HCQ/CQ study result favorability, with each recorded as favorable, unfavorable, or neutral. First and last main authors of each US study were entered into FollowTheMoney.org Website, to extract any history of political party donation, and to which political party.RESULTS: Of all US studies (68 total), 39/68 (57.4%) were unfavorable, with only 7/68 (10.3%) of US studies yielding favorable results. This was compared to 199 non-US studies, in with 66/199 (33.2%) were unfavorable, 69/199 (34.7%) favorable, and 64/199 (32.2%) neutral. Studies with at least one US main author were 20.4% (SE 0.053, P<0.05) more likely to report unfavorable results than non-US studies. US Studies with at least one main author donating to any political party were 25.6% (SE 0.085, p<0.01) more likely to have unfavorable results. US studies with at least one author donating to the Democratic party were 20.4% (SE 0.045, p<0.05) more likely to have unfavorable results. Of the US HCQ/CQ papers with listed main author donors, a significantly higher proportion donated to the Democratic party (88.2% (15/17)) than for time-matched COVID-19 non-HCQ/CQ controls (40% (8/20)); p<0.05. Furthermore, US study editorial reviews were largely unfavorable or neutral (95.5%, 21/22), with any listed history of donation all coming from a main author of Democratic party donation record (100%, 7/7). CONCLUSIONS: HCQ/CQ study outcomes from US-based research were quite unfavorable as compared to the rest of the world, amplifying the impact of US author political party donations on unfavorable study results. The intense media exposure in this US election year has polarized our society and may be injecting various forms of bias into medical research, including from the study authors themselves. We thereby suggest the addition of “political disclosures” to the already required “financial disclosures” for scientific research submissions going forth.

Spatial Distribution of COVID-19 in Honduras at the Early Phase of the Pandemic Using Geographic Information Systems (GIS) (preprint)

The epidemic of Coronavirus Disease 2019 (COVID-19) have affected all the regions of the world, nevertheless, in some countries there is a lack of studies on its main clinical and epidemiological features. We analyzed the incidence, incidence rates, and evolution of COVID-19 cases in Honduras from February 18-April 24, 2020.Methods: Using daily epidemiological data from surveillance about COVID-19 in Honduras, we calculated the rates of incidence (cases/100,000 population), and developed at national, departmental, and municipal levels GIS-based maps.Results: February 18 - April 24, 2020, a sum of 3,169 suspected COVID-19 cases have been assessed by RT-PCR, 533 (16.8%) of them were positive, for an incidence rate of 5.73 cases/100,000 pop. The highest peak was reached on March 31 (48 cases). The department with the highest number of cases and incidence rate was Cortes (383 cases, 71.9% of the total, 21.45 cases/100,000 pop). Discussion: The pattern and evolution of COVID-19 epidemic in Honduras has been particularly focused in the major urban areas, San Pedro Sula and Tegucigalpa, the capital city. Studies using geographical information systems linked with clinical disease characteristics are necessary to attain accurate epidemiological data for public health systems. Such information is also useful for assessment of the evolution of the pandemic and monitoring interventions.

Blocking of the CD80/86 axis as a therapeutic approach to prevent progression to more severe forms of COVID-19 (preprint)

In its more severe forms, COVID-19 progresses towards an excessive immune response, leading to the systemic overexpression of proinflammatory cytokines like IL6, mostly from the infected lungs. This cytokine storm can cause multiple organ damage and death. Consequently, there is a pressing need to identify therapies to treat and prevent severe symptoms during COVID-19. Based on previous clinical evidence, we hypothesized that inhibiting T cell co-stimulation by blocking CD80/86 could be an effective therapeutic strategy against progression to severe proinflammatory states. To support this hypothesis, we performed an analysis integrating blood transcriptional data we generated from rheumatoid arthritis patients treated with abatacept -- a CD80/86 co-stimulation inhibitor -- with the pathological features associated with COVID-19, particularly in its more severe forms. We have found that many of the biological processes that have been consistently associated with COVID-19 pathology are reversed by CD80/86 co-stimulation inhibition, including the downregulation of IL6 production. Also, analysis of previous transcriptional data from blood of SARS-CoV-infected patients showed that the response to abatacept has a very high level of antagonism to that elicited by COVID-19. Finally, analyzing a recent single cell RNA-seq dataset from bronchoalveolar lavage fluid cells from COVID-19 patients, we found a significant correlation along the main elements of the C80/86 axis: CD86+/80+ antigen presenting cells, activated CD4+ T cells and IL6 production. Our in-silico study provides additional support to the hypothesis that blocking of the CD80/CD86 signaling axis may be protective of the excessive proinflammatory state associated with COVID-19 in the lungs.

SARS-CoV-2 receptor and entry genes are expressed by sustentacular cells in the human olfactory neuroepithelium (preprint)

Various reports indicate an association between COVID-19 and anosmia, suggesting an infection of the olfactory sensory epithelium, and thus a possible direct virus access to the brain. To test this hypothesis, we generated RNA-seq libraries from human olfactory neuroepithelia, in which we found substantial expression of the genes coding for the virus receptor angiotensin-converting enzyme-2 (ACE2), and for the virus internalization enhancer TMPRSS2. We analyzed a human olfactory single-cell RNA-seq dataset and determined that sustentacular cells, which maintain the integrity of olfactory sensory neurons, express ACE2 and TMPRSS2. We then observed that the ACE2 protein was highly expressed in a subset of sustentacular cells in human and mouse olfactory tissues. Finally, we found ACE2 transcripts in specific brain cell types, both in mice and humans. Sustentacular cells thus represent a potential entry door for SARS-CoV-2 in a neuronal sensory system that is in direct connection with the brain.