PCOM Library / Hot Topics in Research / Internal Medicine / Archive for "Infectious Disease"

Category: Infectious Disease

Hot Topics – Remdesivir for Compassionate Use in Severe Covid

Jackie Werner Covid-19, Hot Topics in Research, Pharmaceutical Sciences

Grein J, Ohmagari N, Shin D, et al. Compassionate use of remdesivir for patients with severe covid-19. N Engl J Med. 2020;382(24):2327-2336. https://doi.org/10.1056/NEJMoa2007016.

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BACKGROUND

Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, has shown in vitro activity against SARS-CoV-2.

METHODS

We provided remdesivir on a compassionate-use basis to patients hospitalized with Covid-19, the illness caused by infection with SARS-CoV-2. Patients were those with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support. Patients received a 10-day course of remdesivir, consisting of 200 mg administered intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment. This report is based on data from patients who received remdesivir during the period from January 25, 2020, through March 7, 2020, and have clinical data for at least 1 subsequent day.

RESULTS

Of the 61 patients who received at least one dose of remdesivir, data from 8 could not be analyzed (including 7 patients with no post-treatment data and 1 with a dosing error). Of the 53 patients whose data were analyzed, 22 were in the United States, 22 in Europe or Canada, and 9 in Japan. At baseline, 30 patients (57%) were receiving mechanical ventilation and 4 (8%) were receiving extracorporeal membrane oxygenation. During a median follow-up of 18 days, 36 patients (68%) had an improvement in oxygen-support class, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated. A total of 25 patients (47%) were discharged, and 7 patients (13%) died; mortality was 18% (6 of 34) among patients receiving invasive ventilation and 5% (1 of 19) among those not receiving invasive ventilation.

CONCLUSIONS

In this cohort of patients hospitalized for severe Covid-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%). Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy.

Hot Topics: Asymptomatic Covid Carriers May Not Infect

Jackie Werner Covid-19, Hot Topics in Research

Gao M, Yang L, Chen X, et al. A study on infectivity of asymptomatic SARS-CoV-2 carriers. Respir Med. 2020;169:106026. https://doi.org/10.1016/j.rmed.2020.106026.

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Abstract:

Background: An ongoing outbreak of coronavirus disease 2019 (COVID-19) has spread around the world. It is debatable whether asymptomatic COVID-19 virus carriers are contagious. We report here a case of the asymptomatic patient and present clinical characteristics of 455 contacts, which aims to study the infectivity of asymptomatic carriers.

Material and methods: 455 contacts who were exposed to the asymptomatic COVID-19 virus carrier became the subjects of our research. They were divided into three groups: 35 patients, 196 family members and 224 hospital staffs. We extracted their epidemiological information, clinical records, auxiliary examination results and therapeutic schedules.

Results: The median contact time for patients was four days and that for family members was five days. Cardiovascular disease accounted for 25% among original diseases of patients. Apart from hospital staffs, both patients and family members were isolated medically. During the quarantine, seven patients plus one family member appeared new respiratory symptoms, where fever was the most common one. The blood counts in most contacts were within a normal range. All CT images showed no sign of COVID-19 infection. No severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections was detected in 455 contacts by nucleic acid test.

Conclusion: In summary, all the 455 contacts were excluded from SARS-CoV-2 infection and we conclude that the infectivity of some asymptomatic SARS-CoV-2 carriers might be weak.

Hot Topics: Ivermectin Inhibits Covid in Vitro

Jackie Werner Covid-19, Hot Topics in Research, Pharmaceutical Sciences

Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Research. 2020;178:104787. https://doi.org/10.1016/j.antiviral.2020.104787.

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Abstract:

Although several clinical trials are now underway to test possible therapies, the worldwide response to the COVID-19 outbreak has been largely limited to monitoring/containment. We report here that Ivermectin, an FDA-approved anti-parasitic previously shown to have broad-spectrum anti-viral activity in vitro, is an inhibitor of the causative virus (SARS-CoV-2), with a single addition to Vero-hSLAM cells 2 h post infection with SARS-CoV-2 able to effect ~5000-fold reduction in viral RNA at 48 h. Ivermectin therefore warrants further investigation for possible benefits in humans.

Hot Topics: Social Distancing + PPE Prevent Covid Transmission

Jackie Werner Covid-19, Hot Topics in Research

Chu DK, Akl EA, Duda S, et al. Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: A systematic review and meta-analysis. Lancet. 2020;395(10242):1973-1987. https://doi.org/S0140-6736(20)31142-9.

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Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 and is spread personto-person through close contact. We aimed to investigate the effects of physical distance, face masks, and eye
protection on virus transmission in health-care and non-health-care (eg, community) settings.

Methods We did a systematic review and meta-analysis to investigate the optimum distance for avoiding person-toperson virus transmission and to assess the use of face masks and eye protection to prevent transmission of viruses. We obtained data for SARS-CoV-2 and the betacoronaviruses that cause severe acute respiratory syndrome, and Middle East respiratory syndrome from 21 standard WHO-specific and COVID-19-specific sources. We searched these data sources from database inception to May 3, 2020, with no restriction by language, for comparative studies and for contextual factors of acceptability, feasibility, resource use, and equity. We screened records, extracted data, and assessed risk of bias in duplicate. We did frequentist and Bayesian meta-analyses and random-effects metaregressions. We rated the certainty of evidence according to Cochrane methods and the GRADE approach. This study is registered with PROSPERO, CRD42020177047.

Findings Our search identified 172 observational studies across 16 countries and six continents, with no randomised controlled trials and 44 relevant comparative studies in health-care and non-health-care settings (n=25697 patients). Transmission of viruses was lower with physical distancing of 1 m or more, compared with a distance of less than 1 m
(n=10736, pooled adjusted odds ratio [aOR] 0·18, 95% CI 0·09 to 0·38; risk difference [RD] –10·2%, 95% CI –11·5 to –7·5; moderate certainty); protection was increased as distance was lengthened (change in relative risk
[RR] 2·02 per m; pinteraction=0·041; moderate certainty). Face mask use could result in a large reduction in risk of infection (n=2647; aOR 0·15, 95% CI 0·07 to 0·34, RD –14·3%, –15·9 to –10·7; low certainty), with stronger
associations with N95 or similar respirators compared with disposable surgical masks or similar (eg, reusable 12–16-layer cotton masks; pinteraction=0·090; posterior probability >95%, low certainty). Eye protection also was associated with less infection (n=3713; aOR 0·22, 95% CI 0·12 to 0·39, RD –10·6%, 95% CI –12·5 to –7·7; low certainty). Unadjusted studies and subgroup and sensitivity analyses showed similar findings.

Interpretation The findings of this systematic review and meta-analysis support physical distancing of 1 m or more and provide quantitative estimates for models and contact tracing to inform policy. Optimum use of face masks, respirators, and eye protection in public and health-care settings should be informed by these findings and contextual
factors. Robust randomised trials are needed to better inform the evidence for these interventions, but this systematic appraisal of currently best available evidence might inform interim guidance.

Hot Topics: Covid-19 Outbreak Linked to Air Conditioning

Jackie Werner Covid-19, Hot Topics in Research, Infectious Disease

COVID-19 Outbreak Associated with Air Conditioning in Restaurant, Guangzhou, China, 2020

Lu J, Gu J, Li K, Xu C, Su W, Lai Z, et al. COVID-19 outbreak associated with air conditioning in restaurant, Guangzhou, China, 2020. Emerg Infect Dis. 2020 Jul. Accessed 2020 June 3. https://doi.org/10.3201/eid2607.200764

During January 26–February 10, 2020, an outbreak of 2019 novel coronavirus disease in an air-conditioned restaurant in Guangzhou, China, involved 3 family clusters. The airflow direction was consistent with droplet transmission. To prevent the spread of the virus in restaurants, we recommend increasing the distance between tables and improving ventilation.

Hot Topics: Loss of Smell May Mean Less Severe COVID-19

Jackie Werner Hot Topics in Research, Infectious Disease

Self‐reported olfactory loss associates with outpatient clinical course in Covid‐19

Yan CH, Faraji F, Prajapati DP, Ostrander BT, DeConde AS. Self-reported olfactory loss associates with outpatient clinical course in covid-19. Int Forum Allergy Rhinol. 2020. https://doi.org/10.1002/alr.22592.

Background

Rapid spread of the SARS‐CoV‐2 virus has left many health systems around the world overwhelmed, forcing triaging of scarce medical resources. Identifying indicators of hospital admission for Covid‐19 patients early in the disease course could aid the efficient allocation of medical interventions. Self‐reported olfactory impairment has recently been recognized as a hallmark of Covid‐19 and may be an important predictor of clinical outcome.

Methods

A retrospective review of all patients presenting to a San Diego Hospital system with laboratory‐confirmed positive Covid‐19 infection was conducted with evaluation of olfactory and gustatory function and clinical disease course. Univariable and multivariable logistic regression were performed to identify risk factors for hospital admission and anosmia.

Results

A total of 169 patients tested positive for Covid‐19 disease between March 3 and April 8, 2020. Olfactory and gustatory data were obtained for 128/169 (75.7%) subjects of which 26/128 (20.1%) required hospitalization. Admission for Covid‐19 was associated with intact sense of smell and taste, increased age, diabetes, as well as subjective and objective parameters associated with respiratory failure. On adjusted analysis, anosmia was strongly and independently associated with outpatient care (aOR 0.09 95% CI: 0.01‐0.74) while positive findings of pulmonary infiltrates and/or pleural effusion on chest radiograph (aOR 8.01 95% CI: 1.12‐57.49) was strongly and independently associated with admission.

Conclusions

Normosmia is an independent predictor of admission in Covid‐19 cases. Smell loss in Covid‐19 may associate with a milder clinical course.

Hot Topics: Race and Class Affect COVID-19 Risk

Jackie Werner Hot Topics in Research, Infectious Disease, Public Health

Disparities in the Population at Risk of Severe Illness From COVID-19 by Race/Ethnicity and Income

Raifman M, Raifman J. Disparities in the population at risk of severe illness from COVID-19 by race/ethnicity and income. American Journal of Preventive Medicine. 2020. https://doi.org/10.1016/j.amepre.2020.04.003.

Identifying those at heightened risk of severe illness from novel coronavirus disease 2019 (COVID-19) is essential for modeling disease, designing return-to-work criteria, allocating economic assistance, advancing health equity, and limiting morbidity and mortality. The U.S. Centers for Disease Control and Prevention has identified criteria associated with risk of severe complications from COVID-19 infection. Structural inequities have shaped racial, ethnic, and income disparities for many of these criteria. To date, there has been limited analysis of the proportion of the population at risk in the U.S. based on these criteria, or risk factors by race/ethnicity or income. Preliminary national data on cases by race/ethnicity suggest that disparities in hospitalization are already developing. Quantifying disparities in risk is important for allocating resources to prevent, identify, and treat COVID-19-related severe illness and limit diverging outcomes for already vulnerable subgroups.

Hot Topics: Existing Drugs May Fight Coronavirus

Jackie Werner Hot Topics in Research, Infectious Disease

Discovery and development of safe-in-man broad-spectrum antiviral agents

Andersen PI, Ianevski A, Lysvand H, et al. Discovery and development of safe-in-man broad-spectrum antiviral agents. Int J Infect Dis. 2020. https://doi.org/10.1016/j.ijid.2020.02.018

Viral diseases are one of the leading causes of morbidity and mortality in the world. Virus-specific vaccines and antiviral drugs are the most powerful tools to combat viral diseases. However, broad-spectrum antiviral agents (BSAAs, i.e. compounds targeting viruses belonging to two or more viral families) could provide additional protection of general population from emerging and re-emerging viral diseases reinforcing the arsenal of available antiviral options. Here, we reviewed discovery and development of BSAAs and summarized the information on 119 safe-in-man agents in freely accessible database (https://drugvirus.info/). Future and ongoing pre-clinical and clinical studies will increase the number of BSAAs, expand spectrum of their indications, and identify drug combinations for treatment of emerging and re-emerging viral infections as well as co-infections.

Hot Topics: Color-Changing Bandages Treat Infection

Jackie Werner Hot Topics in Research, Infectious Disease

Colorimetric Band-aids for Point-of-Care Sensing and Treating Bacterial Infection

Sun Y, Zhao C, Niu J, Ren J, Qu X. Colorimetric band-aids for point-of-care sensing and treating bacterial infection. ACS Cent Sci. 2020. https://doi.org/10.1021/acscentsci.9b01104.

Sensing bacterial infections and monitoring drug resistance are very important for the selection of treatment options. However, the common methods of sensing resistance are limited by time-consuming, the requirement for professional personnel, and expensive instruments. Moreover, the abuse of antibiotics causes the accelerated process of bacterial resistance. Herein, we construct a portable paper-based band-aid (PBA) which implements a selective antibacterial strategy after sensing of drug resistance. The colors of PBA indicate bacterial infection (yellow) and drug resistance (red), just like a bacterial resistance colorimetric card. On the basis of color, antibiotic-based chemotherapy and Zr-MOF PCN-224-based photodynamic therapy (PDT) are used on site to treat sensitive and resistant strains, respectively. Eventually, it takes 4 h to sense, and the limit of detection is 104 CFU/mL for drug-resistant E. coli. Compared with traditional PDT-based antibacterial strategies, our design can alleviate off-target side effects, maximize therapeutic efficacy, and track the drug resistance in real time with the naked eye. This work develops a new way for the rational use of antibiotics. Given the low cost and easy operation of this point-of-care device, it can be developed for practical applications.

Hot Topics: Neurotoxin Targets Malaria Mosquitos

Jackie Werner Hot Topics in Research, Infectious Disease

A neurotoxin that specifically targets Anopheles mosquitoes

Contreras E, Masuyer G, Qureshi N, et al. A neurotoxin that specifically targets anopheles mosquitoes. Nature Communications. 2019;10(1):2869. https://doi.org/10.1038/s41467-019-10732-w.

Clostridial neurotoxins, including tetanus and botulinum neurotoxins, generally target vertebrates. We show here that this family of toxins has a much broader host spectrum, by identifying PMP1, a clostridial-like neurotoxin that selectively targets anopheline mosquitoes. Isolation of PMP1 from Paraclostridium bifermentans strains collected in anopheline endemic areas on two continents indicates it is widely distributed. The toxin likely evolved from an ancestral form that targets the nervous system of similar organisms, using a common mechanism that disrupts SNARE-mediated exocytosis. It cleaves the mosquito syntaxin and employs a unique receptor recognition strategy. Our research has an important impact on the study of the evolution of clostridial neurotoxins and provides the basis for the use of P. bifermentans strains and PMP1 as innovative, environmentally friendly approaches to reduce malaria through anopheline control.