Corpus overview


Overview

MeSH Disease

Human Phenotype

Transmission

Seroprevalence
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    Therapeutic effectiveness of interferon alpha 2b treatment for COVID-19 patient recovery

    Authors: Ricardo Pereda; Daniel Gonzalez; Hubert Blas Rivero; Juan Carlos Rivero; albadio Perez; Lissette del Rosario Lopez; Natacha Mezquia; Rafael Venegas; Julio Raul Betancourt; Rodolfo Emilio Dominguez

    doi:10.1101/2020.07.28.20157974 Date: 2020-08-04 Source: medRxiv

    Background Effective antiviral treatments are required to contain the ongoing coronavirus disease MESHD 2019 (COVID-19) pandemic. A previous report in 814 patients COVID-19 positive in Cuba provided preliminary therapeutic efficacy evidence with interferon alpha-2b (IFN alpha-2b) from March 11 to April 14, 2020. This study, re-evaluates the contribution of IFN-2b on the evolution of all patients, after 98 days of the epidemic, in a period from March 11 to June 17, 2020. Method A prospective observational study was implemented to monitor a therapeutic intervention with IFN alpha-2b used in the national protocol for COVID-19 attending in Cuba. Were included patients with positive throat swab specimens by real time RT-PCR who gave informed consent and had no contraindications for IFN treatment. Patients received therapy as per the Cuban COVID protocol that included a combination of oral antivirals (lopinavir/ritonavir and chloroquine) with intramuscular or subcutaneous administration of IFN alpha-2b The primary endpoint was the proportion of patients discharged from hospital, secondary was the case TRANS fatality rate and several outcomes related to time variables were also evaluated. Results From March 11th until June 17th, 2295 patients had been confirmed SARS-CoV-2 positive in Cuba, 2165 were treated with Heberon Alpha R and 130 received the approved protocol without IFN. The proportion of fully recovered patients was higher in the IFN-treated compared with non-IFN treated group. Prior IFN treatment decreases the likelihood of intensive care and increases the survival after severe or critical diseases MESHD. The benefits of IFN were significantly supported by time variables analyzed. Conclusions This second report confirm the preliminary evidences from first for the therapeutic effectiveness of IFN alpha-2b for SARS-Cov-2 infection MESHD and postulated that Heberon Alpha R is the main component within the antiviral triad used as a therapeutic intervention in the Cuban protocol COVID-19.

    Household transmission TRANS of SARS-CoV-2: a systematic review and meta-analysis of secondary attack rate TRANS

    Authors: Zachary J. Madewell; Yang Yang; Ira M. Longini Jr.; M. Elizabeth Halloran; Natalie E. Dean

    doi:10.1101/2020.07.29.20164590 Date: 2020-08-01 Source: medRxiv

    Background: Severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) is spread by direct, indirect, or close contact TRANS with infected people via infected respiratory droplets or saliva. Crowded indoor environments with sustained close contact TRANS and conversations are a particularly high-risk setting. Methods: We performed a meta-analysis through July 29, 2020 of SARS-CoV-2 household secondary attack rate TRANS ( SAR TRANS), disaggregating by several covariates (contact type, symptom status, adult TRANS/ child TRANS contacts, contact sex, relationship to index case, index case sex, number of contacts in household TRANS, coronavirus). Findings: We identified 40 relevant published studies that report household secondary transmission TRANS. The estimated overall household SAR TRANS was 18.8% (95% confidence interval [CI]: 15.4%-22.2%), which is higher than previously observed SARs for SARS-CoV and MERS-CoV. We observed that household SARs were significantly higher from symptomatic index cases than asymptomatic TRANS index cases, to adult TRANS contacts than children TRANS contacts, to spouses than other family contacts, and in households TRANS with one contact than households TRANS with three or more contacts. Interpretation: To prevent the spread of SARS-CoV-2, people are being asked to stay at home worldwide. With suspected or confirmed infections TRANS infections MESHD referred to isolate at home, household transmission TRANS will continue to be a significant source of transmission TRANS.

    The relative infectiousness of asymptomatic TRANS SARS-CoV-2 infected persons compared with symptomatic individuals: A rapid scoping review.

    Authors: David Mc Evoy; Conor G McAloon; Aine B Collins; Kevin Hunt; Francis Butler; Andrew W Byrne; Miriam Casey; Ann Barber; John M Griffin; Elizabeth A Lane; Patrick Wall; Simon J More

    doi:10.1101/2020.07.30.20165084 Date: 2020-08-01 Source: medRxiv

    Objectives: The aim of this study was to conduct a scoping review of estimates of the relative infectiousness of asymptomatic TRANS persons infected with SARS-CoV-2 compared with symptomatic individuals. Design: Rapid scoping review of literature available until 8th April 2020. Setting: International studies on the infectiousness of individuals infected with SARS-CoV-2 Participants: Studies were selected for inclusion if they defined asymptomatics TRANS as a separate cohort distinct from pre-symptomatics and if they provided a quantitative measure of the infectiousness of asymptomatics TRANS relative to symptomatics. Primary outcome measures: The relative number of secondary cases TRANS produced by an average primary case TRANS, the relative probability of transmitting infection MESHD upon contact, and the degree of viral shedding. Results: Very few studies reported estimates of relative infectiousness of asymptomatic TRANS compared with symptomatic individuals. Significant differences exist in the definition of infectiousness. Viral shedding studies in general show no difference in shedding levels between symptomatic and asymptomatic TRANS individuals but are likely to be impacted by insufficient statistical power. Two contact tracing TRANS studies provided estimates of 0.7 and 1.0, but differences in approach and definition preclude comparison across the two studies. Finally, two modelling studies suggest a relative infectiousness of around 0.5 but one of these was more reflective of the infectiousness of undocumented rather than asymptomatic TRANS cases. Importantly, one contact tracing TRANS study showing a very low level of infectiousness of asymptomatic TRANS was not included in the analysis at this point due difficulties interpreting the reported findings. Conclusions: The present study highlights the need for additional studies in this area as a matter of urgency. For the purpose of epidemiological modelling, we cautiously suggest that at present, asymptomatics TRANS could be considered to have a degree of infectiousness which is about 0.40-0.70 that of symptomatics. However, it must be stressed that this suggestion comes from a very low evidence base and that estimates exist that are close to zero and close to 1.

    Hybrid capture-based sequencing enables unbiased recovery of SAR TRANS-CoV-2 genomes from fecal samples and characterization of the dynamics of intra-host variants

    Authors: Mingkun Li; Yi Xu; Lu Kang; Zijie Shen; Xufang Li; Weili Wu; Wentai Ma; Chunxiao Fang; Fengxia Yang; Xuan Jiang; Sitang Gong; Li Zhang

    doi:10.1101/2020.07.30.230102 Date: 2020-08-01 Source: bioRxiv

    BackgroundIn response to the current COVID-19 pandemic, it is crucial to understand the origin, transmission TRANS, and evolution of SARS-CoV-2, which relies on close surveillance of genomic diversity in clinical samples. Although the mutation at the population level had been extensively investigated, how the mutations evolve at the individual level is largely unknown, partly due to the difficulty of obtaining unbiased genome coverage of SARS-CoV-2 directly from clinical samples. MethodsEighteen time series fecal samples were collected from nine COVID-19 patients during the convalescent phase. The nucleic acids of SARS-CoV-2 were enriched by the hybrid capture method with different rounds of hybridization. ResultsBy examining the sequencing depth, genome coverage, and allele frequency change, we demonstrated the impeccable performance SERO of the hybrid capture method in samples with Ct value < 34, as well as significant improvement comparing to direct metatranscriptomic sequencing in samples with lower viral loads. We identified 229 intra-host variants at 182 sites in 18 fecal samples. Among them, nineteen variants presented frequency changes > 0.3 within 1-5 days, reflecting highly dynamic intra-host viral populations. Meanwhile, we also found that the same mutation showed different frequency changes in different individuals, indicating a strong random drift. Moreover, the evolving of the viral genome demonstrated that the virus was still viable in the gastrointestinal tract during the convalescent period. ConclusionsThe hybrid capture method enables reliable analyses of inter- and intra-host variants of SARS-CoV-2 genome, which changed dramatically in the gastrointestinal tract; its clinical relevance warrants further investigation.

    High Rate of SARS-CoV-2 Transmission TRANS due to Choir Practice in France at the Beginning of the COVID-19 Pandemic

    Authors: Nathalie CHARLOTTE

    doi:10.1101/2020.07.19.20145326 Date: 2020-07-25 Source: medRxiv

    Background: There has been little focus on the individual risk of acquiring COVID-19 related to choir practice. Methods: We report the case of a high transmission TRANS rate of SARS-CoV-2 linked to an indoor choir rehearsal in France in March 2020 at the beginning of the COVID-19 pandemic. Results: A total of 27 participants, including 25 male TRANS singers, a conductor and an accompanist attended a choir practice on March 12, 2020. The practice was indoor and took place in a non-ventilated space of 45 m2. No choir member reported having been symptomatic for COVID-19 between March 2 and March 12.The mean age TRANS of the participants was 66.9 (range 35-86) years. 70% of the participants (19 of 27) were diagnosed with COVID-19 from 1 to 12 days after the rehearsal with a median of 5.1 days. 36% of the cases needed a hospitalization (7/19), and 21% (4/19) were admitted to an ICU. The index cases were possibly multiple. Discussion: The choir practice was planned in March 2020 at a period when the number of new cases of COVID-19 began to grow exponentially in France because SARS-CoV-2 was actively circulating. The secondary attack rate TRANS (70%) was much higher than it is described within households (10-20%) and among close contacts TRANS made outside households (0-5%). Singing might have contributed to enhance SARS-CoV-2 person-to-person transmission TRANS through emission of droplets and aerosolization in a closed non ventilated space with a relative high number of people including multiple pre-symptomatic suspected index cases. Conclusion: Indoor choir practice should be suspended during SARS-CoV-2 outbreaks. Further studies are necessary to test the spread of the virus by the act of singing. As the benefits of the barrier measures and social distancing are known to be effective in terms of a reduction in the incidence of the COVID-19, experts recommendations concerning the resuming of choir practice are necessary.

    Model-free estimation of COVID-19 transmission TRANS dynamics from a complete outbreak

    Authors: Alex James; Michael J Plank; Shaun Hendy; Rachelle N Binny; Audrey Lustig; Nic Steyn

    doi:10.1101/2020.07.21.20159335 Date: 2020-07-24 Source: medRxiv

    Background New Zealand had 1499 cases of COVID-19 before eliminating transmission TRANS of the virus. Extensive contract tracing TRANS during the outbreak has resulted in a dataset of epidemiologically linked cases. This data contains useful information about the transmission TRANS dynamics of the virus, its dependence on factors such as age TRANS, and its response to different control measures. Method We use Monte-Carlo network construction techniques to provide an estimate of the number of secondary cases TRANS for every individual infected during the outbreak. We then apply standard statistical techniques to quantify differences between groups of individuals. Findings Children TRANS under 10 years old are significantly under-represented in the case data. Children TRANS infected fewer people on average and had a lower secondary attack rate TRANS in comparison to adults TRANS and the elderly TRANS. Imported cases infected fewer people on average and had a lower secondary attack rate TRANS than domestically acquired cases. Superspreading is a significant contributor to the epidemic dynamics, with 20% of cases among adults TRANS responsible for 65-85% of transmission TRANS. Asymptomatic TRANS cases infected fewer individuals than clinical cases. Serial intervals TRANS are approximately normally distributed (=5.0 days, {sigma}=5.7 days). Early isolation and quarantine of cases reduced secondary transmission TRANS rates. Interpretation Border controls and strong social distancing measures, particularly when targeted at superspreading, play a significant role in reducing the spread of COVID-19. Funding Te P[u]naha Matatini, the New Zealand Centre of Research Excellence in complex systems. New Zealand Ministry of Business, Innovation and Employment.

    The effect of border controls on the risk of COVID-19 reincursion from international arrivals

    Authors: Nicholas Steyn; Rachelle N Binny; Shaun C Hendy; Alex James; Audrey Lustig; Michael J Plank

    doi:10.1101/2020.07.15.20154955 Date: 2020-07-22 Source: medRxiv

    In an attempt to maintain elimination of COVID-19, the New Zealand government has closed the border to everyone except citizens and residents. All arrivals are required to spend 14 days in government-managed isolation/quarantine and to be tested for COVID-19 on day 3 and on day 12 of their stay. We model the testing, isolation and potential transmission TRANS of COVID-19 within managed isolation facilities to estimate the risk of undetected cases and the risk of infectious cases being released into the community. We use a stochastic individual-based that includes a time-dependent probability of a false negative test result, complete isolation of confirmed and probable cases, and secondary TRANS transmission TRANS of COVID-19 between close contacts TRANS. We show that the combination of 14-day quarantine with day 3 and day 12 testing reduces risk of releasing an infectious case to around 0.1% per infected arrival. Shorter quarantine periods, or reliance on testing only with no quarantine, substantially increase this risk. It is important to avoid contacts between individuals staying in quarantine to minimise the risk of secondary transmission TRANS. We calculate the ratio of cases detected on day 3 to cases detected on day 12 in the model and show that this may be a useful indicator of the likelihood of secondary transmission TRANS occurring within quarantine. We do not explicitly model transmission TRANS of COVID-19 from individuals in quarantine to staff, but this is likely to present a significant risk. This needs to be minimised by strict infection MESHD control, use of personal protective equipment by staff at all times, and avoiding close contact TRANS between staff and hotel guests.

    SARS-CoV2 spike protein displays biologically significant similarities with paramyxovirus surface proteins; a bioinformatics study

    Authors: Ehsan Ahmadi; Mohammad Reza Zabihi; Ramin Hosseinzadeh; Farshid Noorbakhsh

    doi:10.1101/2020.07.20.210534 Date: 2020-07-20 Source: bioRxiv

    Recent emergence of SARS-CoV2 and associated COVID-19 pandemic has posed a great challenge for the scientific community. Understanding various aspects of SARS-CoV2 biology, virulence and pathogenesis as well as determinants of immune response have become a global research priority. In this study, we performed bioinformatic analyses on SAR TRANS-CoV2 protein sequences, trying to unravel biologically important similarities between this newly emerged virus with other RNA viruses. Comparing the proteome of SARS-CoV2 with major positive and negative strand ssRNA viruses showed significant homologies between SARS-CoV2 spike protein with pathogenic paramyxovirus fusion proteins. This spike-fusion homology was not limited to SARS-CoV2 and it existed for some other pathogenic coronaviruses; nonetheless, SARS-CoV2 spike-fusion homology was orders of magnitude stronger than homologies observed for other known coronaviruses. Moreover, this homology did not seem to be a consequence of general ssRNA virus phylogenetic relations. We also explored potential immunological significance of this spike-fusion homology. Spike protein epitope analysis using experimentally verified data deposited in Immune Epitope Database (IEDB) revealed that the majority of spikes T cell epitopes as well as many B cell and MHC binding epitopes map within the spike-fusion homology region. Overall, our data indicate that there might be a relation between SARS-CoV2 and paramyxoviruses at the level of their surface proteins and this relation could be of crucial immunological importance.

    Regional COVID-19 spread despite expected declines: how mitigation is hindered by spatio-temporal variation in local control measures.

    Authors: Nicholas Kortessis; Margaret W Simon; Michael Barfield; Gregory Glass; Burton H Singer; Robert D Holt

    doi:10.1101/2020.07.17.20155762 Date: 2020-07-19 Source: medRxiv

    Successful public health regimes for COVID-19 push below unity long-term global Rt -- the average number of secondary cases TRANS caused by an infectious individual. Most assessments use local information. Populations differ in Rt, amongst themselves and over time. We use a SIR model for two populations to make the conceptual point that even if each locality averages Rt < 1, the overall epidemic can still grow, provided these populations have asynchronous variation in transmission TRANS, and are coupled by movement of infectious individuals. This emergent effect in pandemic dynamics instantiates "Parrondo's Paradox," -- an entity comprised of distinct but interacting units can behave qualitatively differently than each part on its own. For effective COVID-19 disease MESHD mitigation strategies, it is critical that infectious individuals moving among locations be identified and quarantined. This does not warrant indiscriminate prevention of movement, but rather rational, targeted testing and national coordination.

    COVID-19 transmission TRANS in the U.S. before vs. after relaxation of social distancing measures

    Authors: Alexander C Tsai; Guy Harling; Zahra C Reynolds; Rebecca F Gilbert; Mark J Siedner

    doi:10.1101/2020.07.15.20154534 Date: 2020-07-16 Source: medRxiv

    Background: All fifty U.S. states and the District of Columbia implemented social distancing measures that interrupted transmission TRANS of severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) and reduced morbidity and mortality from coronavirus disease MESHD 2019 (COVID-19). All 51 jurisdictions have since begun to relax these measures, albeit in an uncoordinated fashion. Methods: We obtained state-level data on implementation and relaxation of social distancing measures. We fitted mixed-effects linear regression models with a random effect for state, specifying the time-varying, state-specific effective reproduction number TRANS (Rt, the expected number of secondary infections TRANS infections MESHD generated by each index case given date-specific population susceptibility and risk behavior). Explanatory variables included time in days, implementation period (1-21 days prior to first relaxation of any statewide social distancing measure vs. time from relaxation through May 28, 2020), and a time-by-period product term. Results: During the three weeks prior to relaxation, the estimated Rt was declining by an average of 0.0016 units per day (95% confidence interval [CI], -0.0025 to -0.0008). At the time of initial relaxation, states had reported a median 7,628 cases (range, 337-361,313) and 289 COVID-attributable deaths MESHD (range, 7-28,663), and the median estimated Rt was 1.0 (range, 0.8-1.3) (i.e., the median rate of epidemic growth across states was estimated to be zero). After the first relaxation of statewide social distancing measures, the estimated Rt began increasing by an average of 0.0047 units per day (95% CI, 0.0037 to 0.0058) compared with the pre-relaxation period. If these trends continue, the estimated state-level Rt would reach an average value of 1.05 (95% CI, 1.03-1.07) by 30 days after relaxation and 1.15 (95% CI, 1.11-1.18) by 60 days. A similar upward trajectory in the estimated Rt was observed after relaxation of statewide restrictions on internal movement. Conclusions: Relaxation of U.S. statewide social distancing measures was associated with a subsequent reversal of an earlier downward trend in transmission TRANS of SARS-CoV-2, particularly in states with less active epidemics at the time of relaxation.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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