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Should we be worried about monkeypox?

7 July 2022 by Gertrud U. Rey

by Gertrud U. Rey

The prevalence of monkeypox cases is continuing to increase around the world, with 7,243 total confirmed global cases as of today. Although this sounds awfully familiar, monkeypox virus is highly unlikely to cause a pandemic like the one we are presently experiencing, for at least two reasons: 1) monkeypox virus is not transmitted as easily as SARS-CoV-2, and 2) we have all the tools needed for quelling local outbreaks, thus hopefully preventing further community spread.

Because monkeypox has been endemic to Central and West Africa for several decades, scientists have had ample time to develop a thorough understanding of the virus and its associated disease. Monkeypox virus belongs to the Poxviridae, a family of viruses that also includes cowpox virus, variola virus (which causes smallpox), and vaccinia virus (the source of the modern smallpox vaccine). The name “monkeypox” resulted from the fact that the virus infects primates and was initially isolated from a laboratory monkey. However, it is actually thought to also circulate in rodents, which occasionally come into contact with humans, who can then further spread it to other humans.

Human-to-human transmission of monkeypox virus is far less efficient than that of SARS-CoV-2, which is commonly spread in the absence of symptoms, whereas monkeypox virus is only thought to be transmitted while an infected person is symptomatic. In addition, SARS-CoV-2 is readily spread when an infected person breathes, sneezes, or coughs around other people. In contrast, monkeypox virus is only transmitted by direct contact with lesion material or inhalation of respiratory droplets during prolonged face-to-face interaction with an infected person. Recent news reports have highlighted clusters of infections among men who have sex with men, leading some to infer that monkeypox is a sexually-transmitted disease. However, there is no evidence to suggest that the virus is present in sexual bodily fluids, therefore, it is not considered to be a sexually-transmitted pathogen. The high incidence of infections in the gay community could be explained by transmission through very close contact, which, by definition, includes sex.

The incubation period for monkeypox virus can range from 5 to 21 days, with an average of one week between infection and onset of symptoms. Initial symptoms usually include fever, swollen lymph nodes, headache, and muscle aches; and these symptoms are followed by a distinctive skin rash consisting of clear fluid-filled vesicles. The vesicles eventually fill with pus and ultimately crust over to give way to a new layer of healthy skin. Early symptoms are similar to those of chickenpox, which is caused by varicella-zoster virus (a herpesvirus, unrelated to poxviruses). However, unlike chickenpox lesions, which can individually exist in different stages of development throughout the course of infection, monkeypox lesions typically appear, progress, and disappear together.

Should the need arise, there are at least two licensed smallpox-specific vaccines that can also prevent monkeypox. ACAM2000 is a replication-competent live-attenuated vaccinia virus developed by Sanofi Pasteur Biologics Co. This vaccine is administered with a traditional bifurcated needle, and although very effective, it is associated with pretty severe side effects, including sore arm, fever, body aches, and occasional myocarditis. MVA-BN (marketed as “Jynneos” in the US) is a highly attenuated replication-incompetent vaccinia virus produced by Bavarian Nordic. MVA-BN/Jynneos is delivered by injection under the skin, is much better tolerated than ACAM2000, and is approved to be used as a monkeypox-specific vaccine. Fortunately, because of the long incubation period, it is possible to be vaccinated shortly after an exposure to monkeypox virus and still be protected from monkeypox disease.

It is unclear how long either of the available vaccines protect a person from disease, and whether individuals who were immunized against smallpox decades ago are protected from monkeypox today. Routine global smallpox vaccination ended in the late 1970s, so it is likely that the current outbreaks are fueled by non-immune people who were born since then, and/or by vaccinated individuals whose immunity has waned. However, even if infections continue to increase in number, it is unlikely that everybody in the general population would need to be vaccinated. Instead, proactively administering the vaccine to contacts and contacts of contacts of an infected person in a strategy termed “ring vaccination” would probably be sufficient to stop spread. That is, the vaccine would be administered in an area in a ring around the outbreak.

There are also several FDA-approved antiviral drugs that could be effective against monkeypox virus infection. Tecovirimat, which can be taken orally, prevents release of newly formed viral particles from infected cells, thus potentially blocking transmission of monkeypox virus. Cidofovir (administered by infusion into the vein) and its derivative brincidofovir (taken orally), disrupt replication of smallpox virus and could thus also be used for treating monkeypox virus infection.  

Considering all these factors, the average person is at low risk of becoming infected with monkeypox virus. Nevertheless, the World Health Organization has declared that there is no room for complacency and is urging governments to take some coordinated action to stop the spread of the virus. Because we have the tools to deal with monkeypox outbreaks and have hopefully learned from the disorganized manner in which the present pandemic was handled initially, a federal preparedness response should be implemented as soon as possible.

[The monkeypox outbreak was previously covered at least on Infectious Disease Puscast episodes 3 and 4; TWiV 902, TWiV 915; and TWiV Special Monkeypox Clinical Update with Dr. Daniel Griffin.]

Filed Under: Basic virology, Gertrud Rey, Information Tagged With: acam2000, antiviral drug, bifurcated needle, bodily fluids, brincidofovir, cidofovir, fluid-filled vesicles, Jynneos, lesion, men who have sex with men, monkeypox, MVA-BN, Poxviridae, ring vaccination, sexually transmitted disease, smallpox, symptoms, tecovirimat, transmission, vaccine, vaccinia, variola

Richard R Ernst Lecture 2022 – Vincent Racaniello

27 May 2022 by Vincent Racaniello

It was my great honor to be selected as the Richard R Ernst Lecturer for 2022.

Following is the text of the email that I received on 25 September 2020 informing me that I had received this award. Note that the committee had already made its decision in December 2019!

The aim of the Richard R. Ernst Lecture is to strengthen the relationship and understanding between the sciences, society, and politics and to raise awareness for the questions and challenges our global society is facing today and will face in the future. The RRE Lecture is a public lecture for a scientifically interested general audience. As part of the event the lecturer will be awarded the Richard R. Ernst Gold Medal. Richard R. Ernst is the 1991 recipient of the Chemistry Nobel prize. Previous recipients of the Gold Medal are:

2009 Prof. Dr. Gottfried Schatz (Biozentrum Basel)
2010 Kofi Annan (Former UN Secretary-General)
2011 Prof. Dr. Ernst Ludwig Winnacker (Secretary General of the Human Frontier Science Program Organization)
2012 Prof. Dr. Sir Roger Penrose (University of Oxford)
2013 Prof. Dr. Ahmed Zewail (Caltech)
2014 Prof. Dr. Kamil Ugurbil (University of Minnesota)
2015 Prof. Dr. Steven Chu (Universities of Berkeley and Stanford)
2017 Prof. Dr. Felicitas Pauss (ETH Zurich und CERN)
2019 Prof. Dr. Emmanuelle Charpentier (MPI for the Science of Pathogens, Berlin)

The ongoing Covid-19 pandemic and the accompanying public discourse have shown more than ever how important the education of the general public about scientific topics and the process of research is. With your series of podcasts, where current research in virology, immunology, microbiology, etc. is discussed with experts in an accessible manner, you provide an invaluable service to the general public and the scientific community.

Watch a recording of the ceremony and my lecture below.

Filed Under: Basic virology, Information Tagged With: COVID-19, pandemic, public discourse, Richard R Ernst, science, science communication, viral, virology, virus, viruses

Paul’s Uncle Doesn’t Want to Get Vaccinated

15 February 2022 by Vincent Racaniello

From the authors of Paul Has Measles, Paul Stays Home, and Paul and the Mosquitos, comes Paul’s Uncle Doesn’t Want to Get Vaccinated, an illustrated book for children about vaccines and vaccine hesitancy.

Uncle Henry doesn’t want to get vaccinated against COVID-19. Paul, Sophie, and Luis are afraid that he will get sick, so they show him a book that explains how vaccines work and why they are so important. Do you think they can convince him?

Paul and the Mosquitoes is written by Susana López, Selene Zárate, and Martha Yocupicio, with illustrations by Eva Lobatón.

A pdf of Paul and the Mosquitos can be downloaded free of charge here.

Filed Under: Information Tagged With: COVID-19, SARS-CoV-2, vaccine, viral, virology, virus

A controlled trial of face masks for COVID-19

9 December 2021 by Vincent Racaniello

It will be some time before a substantial fraction of the human population is immunized to prevent COVID-19. In the meantime, widespread use of face masks can have an impact on disease, a conclusion suggested by results of a trial carried out in Bangladesh.

WHO would not recommend the use of face masks until June 2020 for two reasons: there was no evidence for their effectiveness from controlled trials, and the idea that wearing them would encourage behaviors, such as failing to physically distance, leading to more transmission. Both have been tested in the Bangladeshi trial.

The face mask trial was carried out in rural Bangladesh from November 2020 to April 2021. It enrolled 342,183 adults in 600 villages and consisted of control groups (no mask wearing) and groups that wore either a surgical mask or a cloth mask. Mask wearing was 13.3% in control villages and 42.3% in treatment villages. The primary outcome was symptom seroprevalence, determined by assaying blood samples from those who reported symptoms.

Wearing masks reduced symptomatic seroprevalence in treatment villages (0.68%) compared with control villages (0.76%). The reduction in seroprevalence by mask wearing was 11% overall, and 23% among those between the ages of 50 and 60, and 35% among those over 60 years of age. This reduction corresponds to 1,514 fewer people reporting symptoms, and 105 fewer seropositive. It is not clear why a greater reduction in COVID-19 cases were observed in the elderly. A higher percentage of them might have worn masks, or they might be more susceptible to infections that can be stopped by masks. Surgical masks had a clear impact on development of COVID-19, while the effects seen with cloth masks did not reach statistical significance.

These results do not imply that mask wearing prevents only 10% of COVID-19 cases or deaths. It is likely that near-universal masking could have an even greater impact.

Equally important were the findings that masking increased, rather than decreased, physical distancing: in control villages, 24.1% of observed individuals were physically distanced, compared with 29.2% in treatment villages. An explanation for this result is that wearing a mask may convince people to take the pandemic more seriously.

Also interesting was the observation that in-person reinforcement was the best way to encourage people to wear masks. This reinforcement includes stopping people in public places and reminding them to wear masks. Public messaging, such as text messages, had no effect. This information is important for policy makers who feel that public messaging can be effective.

Finally, there was little reduction in mask-wearing in the 10 weeks after the study ended. After this time mask wearing dropped but was still 10 percentage points higher in treatment regions.

At a cost of $1.50 per person, the use of face masks can have a substantial impact on reducing COVID-19, especially in countries with little access to vaccines.

Filed Under: Basic virology, Information Tagged With: COVID-19, face mask, SARS-CoV-2, viral, virology, virus, viruses

Red blood cells are immune sentinels

12 November 2021 by Vincent Racaniello

Did you know that the innate immune DNA sensor TLR9 is on the membrane of red blood cells? I didn’t know that. To learn about why it’s there, listen to Immune episode #50. In that episode we review evidence that toll-like receptor 9 on the surface of red blood cells binds DNA, leading to uptake by macrophages and innate immune activation.

Filed Under: Immune, Information Tagged With: anemia, DNA, immune, immunology, inflammation, innate immune sensor, red blood cell, sepsis, TLR9

Pills for COVID-19

11 November 2021 by Vincent Racaniello

Multiple vaccines have been developed that have made substantial contributions to controlling the COVID-19 pandemic, but where are the antivirals? Only repurposed drugs have been used and not with much success. That situation seems about to change with the authorization of drugs that target the RNA polymerase (Molnupiravir) and a viral protease (Paxlovid).

Molnupiravir is an orally available pro-drug of the nucleoside analog N4-hydroxycytidine (NHC). The latter is a nucleoside analogue which is incorporated into RNA by the viral RNA-dependent RNA polymerase. Once incorporated into RNA, NHC is recognized as either C or U by the RNA polymerase. As a consequence, many mutations are introduced into the viral genome, causing lethal mutagenesis and inhibition of infectivity. NHC has been shown to block SARS-CoV-2 transmission in ferrets.

Interim results in 775 patients of a phase 3 clinical trial with molnupiravir show that the drug reduced hospitalization or death about 50% compared with placebo in patients with mild to moderate COVID-19: 7.3% of patients who received molnupiravir were either hospitalized or died through Day 29 (28/385), compared with 14.1% of placebo-treated patients (53/377). No deaths were reported in patients who received molnupiravir, as compared to 8 deaths in patients who received placebo, through day 29. The trial required that all patients have laboratory-confirmed COVID-19 with symptom onset within 5 days of assignment to control or drug group. Patients were recruited from multiple countries and included those with risk factors for poor disease. Merck expects to produce 10 million doses of the drug in 2021 and has submitted an application for emergency use authorization (EUA).

Paxlovid is an inhibitor of the 3CL or main protease of SARS-CoV-2, an essential viral enzyme that is required to process precursor proteins into functional products. The drug works by binding to the active site of the protease. Such inhibitors have been successfully developed and are approved for the treatment of AIDS and hepatitis C. Paxlovid inhibits viral reproduction in cell culture and in virus-infected mice when given orally. In a phase I trial in 4 participants, the drug was safe and well tolerated and reached levels greater than needed to inhibit reproduction in cell culture.

Interim analysis of a phase 2/3 randomized, placebo-controlled study of Paxlovid showed that the drug reduced the risk of hospitalization or death by 89%. This study enrolled non-hospitalized patients with COVID-19 who were at risk for severe illness. The patients were treated with Paxlovid within 3 days of symptom onset. Of the patients who received the drug, 3/389 were hospitalized through day 28 (0.8%) compared with 27/385 in the placebo group hospitalized and 7 deaths (7%). Similar results were obtained in a group of patients treated within 5 days of symptom onset. Based on these results, Pfizer plans to submit an application for EUA.

The only antiviral repurposed for SARS-CoV-2 that had any efficacy is remdesivir, whose widespread adoption is limited by the need to administer the drug intravenously. Because they are taken orally, Molnupiravir and Paxlovid should have a far greater impact on the pandemic, especially for people who refuse to be vaccinated. If these drugs had been available before the pandemic – which was certainly possible – it might have been largely prevented.

Filed Under: Basic virology, Information Tagged With: antiviral, coronavirus, COVID-19, Molnupiravir, Paxlovid, protease inhibitor, SARS-CoV-2, viral, virology, virus, viruses

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by Vincent Racaniello

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