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A Real-Time  COVID-19 Clinical Trials Registry

A Real-Time  COVID-19 Clinical Trials Registry | Virus World |

Given the accelerated rate at which trial information and findings are emerging, an urgent need exists to track clinical trials, avoid unnecessary duplication of efforts, and understand what trials are being done and where. In response, we have developed a COVID-19 clinical trials registry to collate all trials.


Data are pulled from the International Clinical Trials Registry Platform, including those from the Chinese Clinical Trial Registry,, Clinical Research Information Service - Republic of Korea, EU Clinical Trials Register, ISRCTN, Iranian Registry of Clinical Trials, Japan Primary Registries Network, and German Clinical Trials Register. Both automated and manual searches are done to ensure minimisation of duplicated entries and for appropriateness to the research questions. Identified studies are then manually reviewed by two separate reviewers before being entered into the registry.


Concurrently, we have developed artificial intelligence (AI)-based methods for data searches to identify potential clinical studies not captured in trial registries. These methods provide estimates of the likelihood of importance of a study being included in our database, such that the study can then be reviewed manually for inclusion. Use of AI-based methods saves 50–80% of the time required to manually review all entries without loss of accuracy.  Finally, we will use content aggregator services, such as LitCovid, to ensure our data acquisition strategy is complete. With this three-step process, the probability of missing important publications is greatly diminished and so the resulting data are representative of global COVID-19 research efforts.


Published in The Lancet (April 24, 2020)


Clinical Trial Registry Site:

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Virus World
Virus World provides a daily blog of the latest news in the Virology field and the COVID-19 pandemic. News on new antiviral drugs, vaccines, diagnostic tests, viral outbreaks, novel viruses and milestone discoveries are curated by expert virologists. Highlighted news include trending and most cited scientific articles in these fields with links to the original publications. Stay up-to-date with the most exciting discoveries in the virus world and the last therapies for COVID-19 without spending hours browsing news and scientific publications.
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RetroVirox Launches Cell-Based Coronavirus Assays for Evaluation of COVID-19 Vaccines and Therapeutics

RetroVirox Launches Cell-Based Coronavirus Assays for Evaluation of COVID-19 Vaccines and Therapeutics | Virus World |

March 17, 2020 - San Diego. RetroVirox has launched a menu of cell-based antiviral services to evaluate experimental therapies and vaccines against coronaviruses, including SARS-CoV-2. Starting today the company will offer in vitro testing with SARS-CoV-2 pseudoviruses to evaluate entry inhibitors against the novel coronavirus causative agent of COVID-19. The  assay utilizes  pseudoviruses coated with the viral spike (S) protein of SARS-CoV-2 to recapitulate the mode of entry of the novel coronavirus. The assay can be used for the following purposes:


  • To determine the neutralizing activity of therapeutic antibodies and antisera
  • To test experimental COVID-19 vaccines using antisera from inoculated animals or humans
  • To evaluate small-molecule and other entry inhibitors targeting the S viral protein, the ACE-2 viral receptor, or host proteases and other targets involved in SARS-CoV-2 viral entry


 RetroVirox also performs in vitro assay against several milder forms of seasonal human coronaviruses (hCoV), including the strains OC43, and 229E. Additional Information about the coronavirus assays offered at RetroVirox is available here. Request additional information by email at

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Asymptomatic COVID-19 Cases May be More Common Than Suspected

Asymptomatic COVID-19 Cases May be More Common Than Suspected | Virus World |

New estimates of the number of asymptomatic people with the coronavirus suggest that "silent" COVID-19 is much more prevalent than once thought, according to two studies published Wednesday. The first study, published in JAMA Network Open, found that 42 percent of cases from a group of people in Wuhan, China, were asymptomatic. The second study, published in Thorax, found much higher rates of asymptomatic individuals: 81 percent of cases on a cruise to Antarctica.


The first study, published in JAMA Network Open, found that 42 percent of cases from a group of people in Wuhan, China, were asymptomatic. The second study, published in Thorax, found much higher rates of asymptomatic individuals: 81 percent of cases on a cruise to Antarctica. Meanwhile, the second study, from Australian researchers, looked at 217 people on a cruise bound for Antarctica. The ship set sail in mid-March, just after the World Health Organization declared the coronavirus a pandemic. The first fever on board was reported eight days into the voyage. Over the following two weeks, eight people had to be evacuated from the ship because they fell ill. All of the 217 people who remained on board were tested for COVID-19. More than half (59 percent) tested positive, but just 19 percent of those patients had symptoms. The other 81 percent were symptom-free...


There was one positive finding, however, from the study in China: Asymptomatic individuals may not spread the virus for as long as symptomatic patients do. The patients without symptoms shed the virus for about eight days, compared with 19 days among those who did have symptoms, the researchers, from Zhongnan Hospital of Wuhan University, found.


Original Studies Published in JAMA (May 27, 2020):


and Thorax (May 27, 2020):

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Merck Takes 3 Major Shots at COVID-19: Themis, IAVI and Ridgeback Bio

Merck Takes 3 Major Shots at COVID-19: Themis, IAVI and Ridgeback Bio | Virus World |

Merck has largely stayed out of the COVID-19 battle, but exploded into it with three major deals and collaborations today. First, Merck is buying Austria-based Themis, a vaccines and immune-modulation therapies company focused on infectious diseases and cancer. Merck hasn’t disclosed financial details, except that it is a cash deal to buy all outstanding Themis shares.


Themis has a pipeline of vaccine candidates and immune-modulatory therapies that it has built using its measles virus vector platform. The vector was originally developed by researchers at the Institut Pasteur and licensed exclusively to Themis for specific viral indications. In March, the company joined a consortium with the Institut Pasteur and The Center for Vaccine Research at the University of Pittsburgh, which is supported by monies from the Coalition for Epidemic Preparedness Innovations (CEPI), to develop a vaccine candidate against COVID-19. “Building on the pioneering work of the Institute Pasteur, the Themis team has established specialized expertise that complements Merck’s own capabilities in the discovery, development, manufacturing and global distribution of vaccines,” said Roger M. Perlmutter, president, Merck Research Laboratories. “We are eager to combine our strengths both to develop an effective COVID-19 vaccine in the near term and to build a pandemic preparedness capability directed toward emerging agents that pose a future epidemic threat.”


Secondly, Merck is collaborating with IAVI, a nonprofit scientific research organization focused on global health challenges. They are partnering to develop a vaccine against COVID-19. The vaccine candidate uses the recombinant vesicular stomatitis virus (rVSV) technology that was used for Merck’s Ebola Zaire virus vaccine, ERVEBO. Merck has also entered an agreement with the Biomedical Advanced Research and Development Authority (BARDA), part of the office of the Assistant Secretary for Preparedness and Response within the U.S. Department of Health and Human Services (HSS)....

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Remdesivir for the Treatment of Covid-19 - Preliminary Report NIAID Trial

Remdesivir for the Treatment of Covid-19 - Preliminary Report NIAID Trial | Virus World |

 Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious.  


We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection- control purposes only.


A total of 1063 patients underwent randomization. The data and safety monitoring board recommended early unblinding of the results on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group. Pre- liminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received pla- cebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001). The Kaplan- Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04). Serious adverse events were reported for 114 of the 541 patients in the remdesivir group who underwent randomization (21.1%) and 141 of the 522 patients in the placebo group who un- derwent randomization (27.0%).


Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACCT-1 number, NCT04280705.)


Published in New England J. Med. (May 22, 2020):

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Macaques Show Protective Immunity Against SARS-CoV-2 After Infection or After Vaccine 

Macaques Show Protective Immunity Against SARS-CoV-2 After Infection or After Vaccine  | Virus World |

Two new studies in macaques offer hope that humans could develop protective immunity against SARS-CoV-2, either as the result of a natural infection or by way of a vaccine. While there are differences between SARS-CoV-2 infection in macaques and humans, these findings - some of the first to show that non-human primates can develop protective immunity to SARS-CoV-2 - are promising in light of the ongoing efforts around the world to develop a vaccine and antibody treatments for COVID-19. An understanding of protective immunity to SARS-CoV-2 is critical for vaccine and public health strategies. A key unanswered question is whether infection with SARS-CoV-2 results in protective immunity against re-exposure; there is currently no data on whether humans are protected from re-exposure in this way. 


Earlier this year, research investigating cynomolgus macaques found these animals to be promising models for testing COVID-19 therapeutics. Here, in two new studies in rhesus macaques, researchers explored whether initial exposure to SARS-CoV-2 protected against reinfection and whether vaccination protected against infection, respectively. In a macaque model of SARS-CoV-2 infection they developed, and which recapitulated certain aspects of human SARS-CoV-2 infection, Abishek Chandrashekar, Ralph Baric, Dan Barouch and colleagues tested whether 9 adult animals who had cleared the virus were immune to viral re-challenge 35 days later. All 9 animals showed little to no symptoms after re-challenge and exhibited immune responses that protected against the second infection (given at the same doses as the first). Additional research will be required to define the durability of natural immunity shown here, the authors note. "Rigorous clinical studies will be required to determine whether SARS-CoV-2 infection effectively protects against SARS-CoV-2 re-exposure in humans," they say....


Original Studies  Published in Science (May 20, 2020):

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Long-Acting Injectable Cabotegravir is Highly Effective to Prevent HIV infection in Cisgender Men and Transgender Women

Long-Acting Injectable Cabotegravir is Highly Effective to Prevent HIV infection in Cisgender Men and Transgender Women | Virus World |

HPTN 083 is the first study to compare the efficacy of CAB LA to daily oral TDF/FTC for HIV PrEP. HPTN 083 enrolled 4,570 cisgender men who have sex with men (MSM) and transgender women (TGW) who have sex with men at 43 sites in Argentina, Brazil, Peru, United States, South Africa, Thailand and Vietnam. For many people, taking a daily pill can be challenging. The development of safe and effective long acting alternative agents for HIV PrEP would increase HIV prevention choices and help those who find taking a daily pill challenging. Some people also may find periodic injections to be a more discreet form of HIV PrEP than daily pills and may prefer CAB LA for that reason.


Participants were assigned randomly (by chance) to either the CAB or oral TDF/FTC group. Neither the participants nor the study team knows who was in which group. Participants in each group received both injections and oral tablets – each participant received one active drug and one placebo (no active drug) in order to maintain the blinded nature of the study. Participants were randomized to one of two study arms and included three steps: Step 1 consisted of 5 weeks of daily oral CAB and a TDF/FTC placebo or 5 weeks of daily oral TDF/FTC and an oral CAB placebo; Step 2 consisted of 148 weeks of intramuscular CAB LA 600 mg every 8 weeks plus daily oral TDF/FTC placebo or 148 weeks of daily oral TDF/FTC plus an intramuscular CAB LA placebo every 8 weeks ; and Step 3 consisted of an open-label daily oral TDF/FTC for 48 weeks after participants completed Step 2.


On May 14, 2020 a Data and Safety Monitoring Board (DSMB) reviewed HPTN 083 study data and recommended that the blinded part of the study be stopped early for successfully meeting its specified objectives. The study results showed that CAB LA, administered every eight weeks, provided high efficacy compared to TDF/FTC. A total of 50 incident HIV infections occurred in HPTN 083, with 38 incident HIV infections in the TDF/FTC arm (incidence rate 1.21%) and 12 incident HIV infections in the CAB arm (incidence rate 0.38%): in other words, approximately three times the number of incident HIV infections were in the TDF/FTC arm than in the CAB arm. The study sponsor, the U.S. National Institute of Allergy and Infectious Diseases (NIAID), approved the decision to stop the blinded part of the study.

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Nasal Gene Expression of ACE-2 in Children and Adults

Nasal Gene Expression of ACE-2 in Children and Adults | Virus World |

This study compares angiotensin-converting enzyme 2 (ACE2) gene expression, which has been associated with SARS-CoV-2 cell entry, in the nasal epithelium of children vs adults. 


We conducted a retrospective examination of nasal epithelium from individuals aged 4 to 60 years encountered within the Mount Sinai Health System, New York, New York, during 2015-2018. Samples were collected from individuals with and without asthma for research on nasal biomarkers of asthma. The study was approved by the Mount Sinai institutional review board. Written informed consent was obtained from participants (or their parents for minors). Nasal epithelium was collected using a cytology brush that was immediately placed in RNA stabilization fluid and stored at −80 °C. RNA was isolated within 6 months. RNA samples were checked for quality and sequenced as a single batch in 2018. Sequence data processing included sequence alignment and normalization of gene expression counts across genes and samples....


The results from this study show age-dependent expression of ACE2 in nasal epithelium, the first point of contact for SARS-CoV-2 and the human body. Covariate-adjusted models showed that the positive association between ACE2 gene expression and age was independent of sex and asthma. Lower ACE2 expression in children relative to adults may help explain why COVID-19 is less prevalent in children. A limitation of this study is that the sample did not include individuals older than 60 years.


Published in JAMA (May 20, 2020):


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Vaccine Experts Say Moderna's Covid-19 Data Leave Big Questions

Vaccine Experts Say Moderna's Covid-19 Data Leave Big Questions | Virus World |

While Moderna blitzed the media, it revealed very little information — and most of what it did disclose were words, not data.  Heavy hearts soared Monday with news that Moderna’s Covid-19 vaccine candidate — the frontrunner in the American market — seemed to be generating an immune response in Phase 1 trial subjects. The company’s stock valuation also surged, hitting $29 billion, an astonishing feat for a company that currently sells zero products. But was there good reason for so much enthusiasm? Several vaccine experts asked by STAT concluded that, based on the information made available by the Cambridge, Mass.-based company, there’s really no way to know how impressive — or not — the vaccine may be. While Moderna blitzed the media, it revealed very little information — and most of what it did disclose were words, not data. That’s important: If you ask scientists to read a journal article, they will scour data tables, not corporate statements. With science, numbers speak much louder than words.


Even the figures the company did release don’t mean much on their own, because critical information — effectively the key to interpreting them — was withheld. Experts suggest we ought to take the early readout with a big grain of salt. Here are a few reasons why. The National Institute for Allergy and Infectious Diseases has partnered with Moderna on this vaccine. Scientists at NIAID made the vaccine’s construct, or prototype, and the agency is running the Phase 1 trial. This week’s Moderna readout came from the earliest of data from the NIAID-led Phase 1. NIAID doesn’t hide its light under a bushel. The institute generally trumpets its findings, often offering director Anthony Fauci — who, fair enough, is pretty busy these days — or other senior personnel for interviews. But NIAID did not put out a press release Monday and declined to provide comment on Moderna’s announcement.


The company’s statement led with the fact that all 45 subjects (in this analysis) who received doses of 25 micrograms (two doses each), 100 micrograms (two doses each), or a 250 micrograms (one dose) developed binding antibodies. Later, the statement indicated that eight volunteers — four each from the 25-microgram and 100-microgram arms — developed neutralizing antibodies. Of the two types, these are the ones you’d really want to see. We don’t know results from the other 37 trial participants...

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Child Vaccinations Plummet 63 Percent, a New Hurdle for N.Y.C. Schools 

Child Vaccinations Plummet 63 Percent, a New Hurdle for N.Y.C. Schools  | Virus World |

Parents have hesitated to take children to doctors’ offices, but students will have to meet immunization requirements to attend school in the fall. Reopening schools, pre-K and day care centers safely this fall was always going to be a crucial part of resuming normal life in New York City, and a herculean challenge for the nation’s largest school system. On Wednesday, Mayor Bill de Blasio raised alarms about an unexpected new hurdle: plummeting rates of childhood vaccinations as anxious parents have kept their children home — and away from doctors’ offices.


During the height of the pandemic, from March 23 to May 9, the number of vaccine doses administered to children dropped 63 percent compared with the same time last year, and by 91 percent for children older than 2, according to the city health department. The city is tentatively planning to reopen its 1,800 public schools in September, along with hundreds of day care sites. But children will not be able to start school and relieve their parents of home schooling and child care duties without shots to protect them against illnesses like measles and chickenpox.


In a typical year, about 98 percent of the city’s public school students are fully vaccinated. “The pieces unfortunately start to fit together in a way that should cause parents real concern,” Mr. de Blasio said in his daily news briefing. Unvaccinated children, he said, could be “at greater threat of contracting a disease that could then put them at a greater threat of contracting Covid.” That is especially urgent now, since New York is seeing a rare but alarming trend of children falling ill with what is being called pediatric multisystem inflammatory syndrome, which appears to be related to the coronavirus and can cause serious illness...

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US Lockdown Protests May Have Spread Virus Widely, Cellphone Data Suggests 

US Lockdown Protests May Have Spread Virus Widely, Cellphone Data Suggests  | Virus World |

Devices associated with protesters travelled up to hundreds of miles after rallies where few precautions were taken. Cellphone location data suggests that demonstrators at anti-lockdown protests – some of which have been connected with Covid-19 cases – are often traveling hundreds of miles to events, returning to all parts of their states, and even crossing into neighboring ones. The data, provided to the Guardian by the progressive campaign group the Committee to Protect Medicare, raises the prospect that the protests will play a role in spreading the coronavirus epidemic to areas which have, so far, experienced relatively few infections. The anonymized location data was captured from opt-in cellphone apps, and data scientists at the firm VoteMap used it to determine the movements of devices present at protests in late April and early May in five states: Michigan, Wisconsin, Illinois, Colorado and Florida.


They then created visualizations that tracked the movements of those devices up to 48 hours after the conclusion of protests. The visualizations only show movements within states, due to the queries analysts made in creating them. But the data scientist Jeremy Fair, executive-vice president of VoteMap, says that many of the devices that are seen to reach state borders are seen to continue across them in the underlying raw data. One visualization shows that in Lansing, Michigan, after a 30 April protest in which armed protesters stormed the capitol building and state police were forced to physically block access to Governor Gretchen Whitmer, devices which had been present at the protest site can be seen returning to all parts of the state, from Detroit to remote towns in the state’s north.

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Cross-Neutralization of SARS-CoV-2 by a Human Monoclonal SARS-CoV Antibody

Cross-Neutralization of SARS-CoV-2 by a Human Monoclonal SARS-CoV Antibody | Virus World |

SARS-CoV-2 is a newly emerged coronavirus responsible for the current COVID-19 pandemic that has resulted in more than 3.7 million infections and 260,000 deaths as of 6 May 202o. Vaccine and therapeutic discovery efforts are paramount to curb the pandemic spread of this zoonotic virus. The SARS-CoV-2 spike (S) glycoprotein promotes entry into host cells and is the main target of neutralizing antibodies.


Here we describe multiple monoclonal antibodies targeting SARS-CoV-2 S identified from memory B cells of an individual who was infected with SARS-CoV in 2003. One antibody, named S309, potently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 by engaging the S receptor-binding domain. Using cryo-electron microscopy and binding assays, we show that S309 recognizes a glycan-containing epitope that is conserved within the sarbecovirus subgenus, without competing with receptor attachment.


Antibody cocktails including S309 along with other antibodies identified here further enhanced SARS-CoV-2 neutralization and may limit the emergence of neutralization-escape mutants. These results pave the way for using S309- and S309-containing antibody cocktails for prophylaxis in individuals at high risk of exposure or as a post-exposure therapy to limit or treat severe disease.


Published in Nature (May 18, 2020):

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The Coronavirus’ Rampage Through the Body

The Coronavirus’ Rampage Through the Body | Virus World |

This video explains how SARS-CoV-2, the virus that causes COVID-19, can severely damage lungs, but in serious cases it doesn’t stop there. Clinicians have observed body-wide damage due to the coronavirus. As researchers begin to better understand the pathology of the disease, new treatments can be deployed to help save lives.

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T Cells Found in COVID-19 Patients ‘Bode Well’ for Long-Term Immunity

T Cells Found in COVID-19 Patients ‘Bode Well’ for Long-Term Immunity | Virus World |

New findings suggest past infections may offer some protection against the novel coronavirus. Immune warriors known as T cells help us fight some viruses, but their importance for battling SARS-CoV-2, the virus that causes COVID-19, has been unclear. Now, two studies reveal infected people harbor T cells that target the virus—and may help them recover. Both studies also found some people never infected with SARS-CoV-2 have these cellular defenses, most likely because they were previously infected with other coronaviruses.


“This is encouraging data,” says virologist Angela Rasmussen of Columbia University. Although the studies don’t clarify whether people who clear a SARS-CoV-2 infection can ward off the virus in the future, both identified strong T cell responses to it, which “bodes well for the development of long-term protective immunity,” Rasmussen says. The findings could also help researchers create better vaccines. The more than 100 COVID-19 vaccines in development mainly focus on another immune response: antibodies. These proteins are made by B cells and ideally latch onto SARS-CoV-2 and prevent it from entering cells. T cells, in contrast, thwart infections in two different ways. Helper T cells spur B cells and other immune defenders into action, whereas killer T cells target and destroy infected cells. The severity of disease can depend on the strength of these T cell responses.


Using bioinformatics tools, a team led by Shane Crotty and Alessandro Sette, immunologists at the La Jolla Institute for Immunology, predicted which viral protein pieces would provoke the most powerful T cell responses. They then exposed immune cells from 10 patients who had recovered from mild cases of COVID-19 to these viral snippets. All of the patients carried helper T cells that recognized the SARS-CoV-2 spike protein, which enables the virus to infiltrate our cells. They also harbored helper T cells that react to other SARS-CoV-2 proteins. And the team detected virus-specific killer T cells in 70% of the subjects, they report today in Cell. “The immune system sees this virus and mounts an effective immune response,” Sette says. 

The results jibe with those of a study posted as a preprint on medRxiv on 22 April by immunologist Andreas Thiel of the Charité University Hospital in Berlin and colleagues. They identified helper T cells targeting the spike protein in 15 out of 18 patients hospitalized with COVID-19. ..


Original Publication in Cell (May 14, 2020):

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Reducing Transmission of SARS-CoV-2

Reducing Transmission of SARS-CoV-2 | Virus World |

Respiratory infections occur through the transmission of virus-containing droplets (>5 to 10 μm) and aerosols (≤5 μm) exhaled from infected individuals during breathing, speaking, coughing, and sneezing. Traditional respiratory disease control measures are designed to reduce transmission by droplets produced in the sneezes and coughs of infected individuals. However, a large proportion of the spread of coronavirus disease 2019 (COVID-19) appears to be occurring through airborne transmission of aerosols produced by asymptomatic individuals during breathing and speaking (13). Aerosols can accumulate, remain infectious in indoor air for hours, and be easily inhaled deep into the lungs. For society to resume, measures designed to reduce aerosol transmission must be implemented, including universal masking and regular, widespread testing to identify and isolate infected asymptomatic individuals.


Humans produce respiratory droplets ranging from 0.1 to 1000 μm. A competition between droplet size, inertia, gravity, and evaporation determines how far emitted droplets and aerosols will travel in air (45). Respiratory droplets will undergo gravitational settling faster than they evaporate, contaminating surfaces and leading to contact transmission. Smaller aerosols (≤5 μm) will evaporate faster than they can settle, are buoyant, and thus can be affected by air currents, which can transport them over longer distances. Thus, there are two major respiratory virus transmission pathways: contact (direct or indirect between people and with contaminated surfaces) and airborne inhalation.


In addition to contributing to the extent of dispersal and mode of transmission, respiratory droplet size has been shown to affect the severity of disease. For example, influenza virus is more commonly contained in aerosols with sizes below 1 μm (submicron), which lead to more severe infection (4). In the case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is possible that submicron virus-containing aerosols are being transferred deep into the alveolar region of the lungs, where immune responses seem to be temporarily bypassed. SARS-CoV-2 has been shown to replicate three times faster than SARS-CoV-1 and thus can rapidly spread to the pharynx from which it can be shed before the innate immune response becomes activated and produces symptoms (6)....

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Do COVID-19 Patients Carry SARS-CoV-2 in Their Blood?

Do COVID-19 Patients Carry SARS-CoV-2 in Their Blood? | Virus World |

Laboratory diagnosis of SARS-CoV-2 infection (the cause of COVID-19) uses PCR to detect viral RNA (vRNA) in respiratory samples. SARS-CoV-2 RNA has also been detected in other sample types, but there is limited understanding of the clinical or laboratory significance of its detection in blood. Methods: We undertook a systematic literature review to assimilate the evidence for the frequency of vRNA in blood, and to identify associated clinical characteristics. 


We performed RT-PCR in serum samples from a UK clinical cohort of acute and convalescent COVID-19 cases (n=212), together with convalescent plasma samples collected by NHS Blood and Transplant (NHSBT) (n=212 additional samples). To determine whether PCR-positive blood samples could pose an infection risk, we attempted virus isolation from a subset of RNA-positive samples. 


We identified 28 relevant studies, reporting SARS-CoV-2 RNA in 0-76% of blood samples; pooled estimate 10% (95%CI 5-18%). Among serum samples from our clinical cohort, 27/212 (12.7%) had SARS-CoV-2 RNA detected by RT-PCR. RNA detection occurred in samples up to day 20 post symptom onset, and was associated with more severe disease (multivariable odds ratio 7.5). Across clinical and convalescent samples collected ≥28 days post symptom onset, 0/244 (0%, 95%CI 0.0-1.5%) had vRNA detected. Among our PCR-positive samples, cycle threshold (ct) values were high (range 33.5-44.8), suggesting low vRNA copy numbers. PCR-positive sera inoculated into cell culture did not produce any cytopathic effect or yield an increase in detectable SARS-CoV-2 RNA. Conclusions: vRNA was detectable at low viral loads in a minority of serum samples collected in acute infection, but was not associated with infectious SARS-CoV-2 (within the limitations of the assays used). This work helps to inform biosafety precautions for handling blood products from patients with current or previous COVID-19.

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SARS-CoV-2 RNA in Municipal Sewage Predicts Outbreak Seven Days Earlier than COVID-19 Test Results

SARS-CoV-2 RNA in Municipal Sewage Predicts Outbreak Seven Days Earlier than COVID-19 Test Results | Virus World |

We report a time course of SARS-CoV-2 RNA concentrations in primary sewage sludge during the Spring COVID-19 outbreak in a northeastern U.S. metropolitan area.


SARS-CoV-2 RNA was detected in all environmental samples and, when adjusted for the time lag, the virus RNA concentrations were highly correlated with the COVID-19 epidemiological curve (R2=0.99) and local hospital admissions (R2=0.99). SARS-CoV-2 RNA concentrations were a seven-day leading indicator ahead of compiled COVID-19 testing data and led local hospital admissions data by three days. Decisions to implement or relax public health measures and restrictions require timely information on outbreak dynamics in a community....


Our results demonstrate: (1) the utility of SARS-CoV-2 primary sludge monitoring to accurately track outbreaks in a community and (2) primary sludge SARS-CoV-2 RNA concentrations can be a leading indicator over other commonly used epidemiology approaches including summarized COVID-19 test results and hospital admissions.


Preprint available in medRxiv (May 22, 2020):

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Hydroxychloroquine or Chloroquine, Alone or with a Macrolide, Decrease  Survival of  COVID-19 Hospitalized Patients

Hydroxychloroquine or Chloroquine, Alone or with a Macrolide, Decrease  Survival of  COVID-19 Hospitalized Patients | Virus World |

Hydroxychloroquine or chloroquine, often in combination with a second-generation macrolide, are being widely used for treatment of COVID-19, despite no conclusive evidence of their benefit. Although generally safe when used for approved indications such as autoimmune disease or malaria, the safety and benefit of these treatment regimens are poorly evaluated in COVID-19.


We did a multinational registry analysis of the use of hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19. The registry comprised data from 671 hospitals in six continents. We included patients hospitalised between Dec 20, 2019, and April 14, 2020, with a positive laboratory finding for SARS-CoV-2. Patients who received one of the treatments of interest within 48 h of diagnosis were included in one of four treatment groups (chloroquine alone, chloroquine with a macrolide, hydroxychloroquine alone, or hydroxychloroquine with a macrolide), and patients who received none of these treatments formed the control group. Patients for whom one of the treatments of interest was initiated more than 48 h after diagnosis or while they were on mechanical ventilation, as well as patients who received remdesivir, were excluded. The main outcomes of interest were in-hospital mortality and the occurrence of de-novo ventricular arrhythmias (non-sustained or sustained ventricular tachycardia or ventricular fibrillation)....


We were unable to confirm a benefit of hydroxychloroquine or chloroquine, when used alone or with a macrolide, on in-hospital outcomes for COVID-19. Each of these drug regimens was associated with decreased in-hospital survival and an increased frequency of ventricular arrhythmias when used for treatment of COVID-19.


Published in  The Lancet (May 22, 2020):

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Early Study of Covid-19 Vaccine Developed in China Sees Mixed Results

Early Study of Covid-19 Vaccine Developed in China Sees Mixed Results | Virus World |

A Covid-19 vaccine candidate being developed by a Chinese drug maker appeared to induce an immune response in subjects, but also showed some concerning although not unexpected results. Data on the vaccine, made by CanSino Biologics, were published Friday in the Lancet, the first time Phase 1 trial data from any Covid-19 vaccine have been published in a scientific journal. The results are likely to be closely examined, particularly in Canada, which recently announced it would test the vaccine and produce it there if results of the early studies were positive.


The study found that one dose of the vaccine, tested at three different levels, appeared to induce a good immune response in some subjects. But about half of the volunteers — people who already had immunity to the backbone of the vaccine — had a dampened immune response. The vaccine is what’s known as a viral vector vaccine; it uses a live but weakened human cold virus, adenovirus 5, onto which genetic material of the SARS-CoV-2 coronavirus has been fused. The Ad5 virus is effectively a delivery system that teaches the immune system to recognize the coronavirus. But many people have had previous infections with adenovirus 5, raising concerns that the immune system would focus on the Ad5 parts of the vaccine rather than the SARS-Cov-2 part. Many research groups that work on viral-vectored vaccines stopped using Ad5 because of concerns about preexisting immunity, which can run to 70% or higher in some populations.


“This is definitely one of the concerns about using vectored vaccines for which people might already have pre-existing immunity,” said Michael Mina, an infectious diseases epidemiologist at Harvard’s T.H. Chan School of Public Health. “If you already have seen a virus or have some pre-existing immunity to it … you run the risk of having your immune response get skewed and picking up primarily the thing you’re already immune to or that you’ve already seen and not focusing so much on the new aspect, which in this case would be the coronavirus proteins that were placed onto the adenovirus vector,” he said. 


In the study, Chinese scientists reported that while people who had high levels of preexisting immunity to Ad5 responded to the vaccine, the rise in antibodies to the SARS-Cov-2 virus was less robust than among those in the study who had low or no preexisting antibodies to Ad5. They also showed antibodies to the adenovirus itself soared among people who had prior immunity, suggesting their systems views the vaccination as a boost of their Ad5 immunity.....


Studiy Published in The Lancet (May 22, 2020):

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Detection of SARS-CoV-2 in Human Breastmilk

Detection of SARS-CoV-2 in Human Breastmilk | Virus World |

It remains unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be shed into breastmilk and transmitted to a child through breastfeeding. Recent investigations have found no evidence of SARS-CoV-2 in human breastmilk, but sample sizes were small.


We examined milk from two nursing mothers infected with SARS-CoV-2. Both mothers were informed about the study and gave informed consent. Ethical approval for this case study was waived by the Ethics Committee of Ulm University and all samples were anonymised. Clinical data and the timecourse of infection in the two mothers is shown in figure 1. After feeding and nipple disinfection, milk was collected with pumps and stored in sterile containers at 4°C or −20°C until further analysis. We determined viral loads using RT-qPCR for SARS-CoV-2 N and ORF1b-nsp14 genes, in both whole and skimmed milk (obtained after removal of the lipid fraction). 


We detected SARS-CoV-2 RNA in milk samples from Mother 2 for 4 consecutive days. Detection of viral RNA in milk from Mother 2 coincided with mild COVID-19 symptoms and a SARS-CoV-2 positive diagnostic test of the newborn (Newborn 2). Mother 2 had been wearing a surgical mask since the onset of symptoms and followed safety precautions when handling or feeding the neonate (including proper hand and breast disinfection, strict washing, and sterilisation of milk pumps and tubes). However, whether Newborn 2 was infected by breastfeeding or other modes of transmission remains unclear. Further studies of milk samples from lactating women and possible virus transmission via breastfeeding are needed to develop recommendations on whether mothers with COVID-19 should breastfeed.


Published in The Lancet (May 21, 2020):

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Alphabet's Verily Unveiled a Research Study to Establish the Accuracy of Coronavirus Antibody Tests

Alphabet's Verily Unveiled a Research Study to Establish the Accuracy of Coronavirus Antibody Tests | Virus World |

Alphabet's life sciences arm Verily unveiled a coronavirus antibody research study to help determine the accuracy of serology tests— a research initiative aimed at better understanding coronavirus antibody testing. Verily is adapting its existing Project Baseline study to support the antibody research endeavor, the first initiative of which will be to roll out out serology testing to patients who have already taken a nasal swab test from Verily's testing program. For context, Verily erected four coronavirus testing sites across California early last month.


Verily's study could be instrumental in establishing the accuracy of coronavirus antibody tests and will add to its myriad coronavirus-specific healthcare initiatives. There are wide variations in the accuracy of different antibody tests — and Verily's research initiative could help the medical community better understand coronavirus immunity as many states prepare to reopen. For context, a number of vendors have released their own antibody tests amid the pandemic, but only a handful have gained FDA approval for use.


Researchers at UCSF and UC Berkeley have noted that dozens of tests performed reasonably well in determining antibodies within the first two weeks of infection — only to produce a greater number of false positives that exceed the number of infected people in some regions. As some states start to resume normal operations, they may rely on using positive antibody test results as "immunity passports" enabling consumers to return to work — but researchers are still uncertain whether a positive result guarantees immunity. And the discrepancies in test results add another layer of ambiguity, as serology tests have not yet been proven to be a reliable marker in determining whether an individual has coronavirus antibodies...


Verily's announcement (May 18, 2020):

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The Bizarre Saga of a Biotech Frozen in Time in the Covid-19 Vaccine Race

The Bizarre Saga of a Biotech Frozen in Time in the Covid-19 Vaccine Race | Virus World |

Sinovac is working on one of the more closely watched candidate vaccines for the disease, but trading of its shares has been long suspended. Moderna’s work on a vaccine for coronavirus has made its founders into paper billionaires. Gilead Sciences has added $10 billion to its market value since the start of 2020. And a rising tide of Covid-19 speculation has sent one major biotech index to its all-time high.


But Sinovac, a Beijing-headquartered company with a coronavirus vaccine already in human trials, has been entirely left out. Thanks to a yearslong battle for corporate control — involving a secret coup, a poison pill, and an office raid — trading of Sinovac’s shares has been halted since early 2019..

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Did The Oxford Covid Vaccine Work In Monkeys? Not Really

Did The Oxford Covid Vaccine Work In Monkeys? Not Really | Virus World |

The day after data appeared from the vaccine maker Sinovac showed complete protection of rhesus monkeys by their vaccine candidate (whole inactivated SARS-CoV-2 virus particles), scientists from the Jenner Institute in Oxford issued a press release announcing that their vaccine (an adenovirus vector based vaccine that carried the SARS-CoV-2 spike protein) worked to protect rhesus monkeys and that they were moving forward with large scale human safety trials. At the time, the substantiating data was not available. Now it is, in the form of a May 13 BioRxiv preprint. Does the data support the claim?


Not really. All of the vaccinated monkeys treated with the Oxford vaccine became infected when challenged, as judged by recovery of virus genomic RNA from nasal secretions. There was no difference in the amount of viral RNA detected from this site in the vaccinated monkeys as compared to the unvaccinated animals. Which is to say, all vaccinated animals were infected. This observation is in marked contrast to the results reported from Sinovac trial. At the highest dose studied, no virus was recovered from vaccinated monkeys from the throat, lung, or rectum of the vaccinated animals. 


There is a second troubling result of the Oxford paper. The titer of neutralizing antibody, as judged by inhibition of virus replication by successive serum dilutions as reported is extremely low. Typically, neutralizing antibodies in effective vaccines can be diluted by more than a thousand fold and retain activity. In these experiments the serum could be diluted only by 4 to 40 fold before neutralizing activity was lost. Again, by contrast the titer of neutralizing antibodies in the serum of those vaccinated with whole inactivated SARS-CoV-2 was high. What then is the argument for pressing forward with the adenovirus vector SARS-CoV-2 spike protein vaccine? The authors present evidence to the effect that, although the vaccine did not protect the animals from infection, it did moderate the disease....


Preprint of the Study Discussed Available at bioRxiv:

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Why Do some COVID-19 Patients Infect Many Others, Whereas Most Don’t Spread the Virus at All?

Why Do some COVID-19 Patients Infect Many Others, Whereas Most Don’t Spread the Virus at All? | Virus World |

Preventing big clusters of cases would help curb the pandemic, scientists say. When 61 people met for a choir practice in a church in Mount Vernon, Washington, on 10 March, everything seemed normal. For 2.5 hours the chorists sang, snacked on cookies and oranges, and sang some more. But one of them had been suffering for 3 days from what felt like a cold—and turned out to be COVID-19. In the following weeks, 53 choir members got sick, three were hospitalized, and two died, according to a 12 May report by the U.S. Centers for Disease Control and Prevention (CDC) that meticulously reconstructed the tragedy.


Many similar “superspreading events” have occurred in the COVID-19 pandemic. A database by Gwenan Knight and colleagues at the London School of Hygiene & Tropical Medicine (LSHTM) lists an outbreak in a dormitory for migrant workers in Singapore linked to almost 800 cases; 80 infections tied to live music venues in Osaka, Japan; and a cluster of 65 cases resulting from Zumba classes in South Korea. Clusters have also occurred aboard ships and at nursing homes, meatpacking plants, ski resorts, churches, restaurants, hospitals, and prisons. Sometimes a single person infects dozens of people, whereas other clusters unfold across several generations of spread, in multiple venues. Other infectious diseases also spread in clusters, and with close to 5 million reported COVID-19 cases worldwide, some big outbreaks were to be expected. But SARS-CoV-2, like two of its cousins, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), seems especially prone to attacking groups of tightly connected people while sparing others. It’s an encouraging finding, scientists say, because it suggests that restricting gatherings where superspreading is likely to occur will have a major impact on transmission, and that other restrictions—on outdoor activity, for example—might be eased....


That’s why in addition to R, scientists use a value called the dispersion factor (k), which describes how much a disease clusters. The lower k is, the more transmission comes from a small number of people. In a seminal 2005 Nature paper, Lloyd-Smith and co-authors estimated that SARS—in which superspreading played a major role—had a k of 0.16. The estimated k for MERS, which emerged in 2012, is about 0.25. In the flu pandemic of 1918, in contrast, the value was about one, indicating that clusters played less of a role.

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Coronavirus Vaccine Trial by Moderna Shows Promising Early Results

Coronavirus Vaccine Trial by Moderna Shows Promising Early Results | Virus World |

The company said its preliminary test in 8 healthy volunteers was safe. It is on an accelerated timetable to begin a larger human trial soon. The first coronavirus vaccine to be tested in people appears to be safe and able to stimulate an immune response against the virus, its manufacturer, Moderna announced on Monday. The findings are based on results from the first eight people who each received two doses of the vaccine, starting in March.


Those people, healthy volunteers, made antibodies that were then tested in human cells in the lab, and were able to stop the virus from replicating — the key requirement for an effective vaccine. The levels of those so-called neutralizing antibodies matched the levels found in patients who had recovered after contracting the virus in the community. The company has said that it is proceeding on an accelerated timetable, with the second phase involving 600 people to begin soon, and a third phase to begin in July involving thousands of healthy people. The Food and Drug Administration gave Moderna the go-ahead for the second phase earlier this month.


If those trials go well, a vaccine could become available for widespread use by the end of this year or early 2021, Dr. Tal Zaks, Moderna’s chief medical officer, said in an interview. How many doses might be ready is not clear, but Dr. Zaks said, “We’re doing our best to make it as many millions as possible.”..


Official Moderna's Press Release:

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Tracking Covid-19 Cases in the US

Tracking Covid-19 Cases in the US | Virus World |

As of May 2020, at least 17 U.S. states have shown an increase in daily cases in the last week.

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Trial Begins to See if Dogs Can 'Sniff Out' Coronavirus

Trial Begins to See if Dogs Can 'Sniff Out' Coronavirus | Virus World |

The dogs are already trained to detect odours of cancers, malaria and Parkinson's disease. The first phase of the trial will be led by the London School of Hygiene & Tropical Medicine, along with the charity and Durham University.  It has been backed with £500,000 of government funding. Innovation minister Lord Bethell said he hoped the dogs could provide "speedy results" as part of the government's wider testing strategy.


The trial will explore whether the "Covid dogs" - made up of Labradors and cocker spaniels - can spot the virus in humans from odour samples before symptoms appear. It will establish whether so-called bio-detection dogs, which could each screen up to 250 people per hour, could be used as a new early warning measure to detect Covid-19 in the future. The first phase will involve NHS staff in London hospitals collecting odour samples from those infected with coronavirus and those who are uninfected. Samples of breath and body odour could come from a number of sources, including used face masks....

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