Wednesday, September 30, 2020

#Natlprep: Whatever Future Threats May Come

 

Note: This is day 30 of National Preparedness Month. Follow this year’s campaign on Twitter by searching for the #NatlPrep #BeReady or #PrepMonth hashtags.

This month, as part of NPM20, I’ll be rerunning some updated preparedness essays, along with some new ones.


#15,478


Thirty-nine weeks ago, in the wee hours of the morning of December 31st, I awoke (at 2 am) and found a Skype message from Sharon Sanders of FluTrackers alerting me to several strange, and admittedly worrisome media reports from China of an unidentified respiratory outbreak in Wuhan City.

Within a few short weeks we would see this event escalate into The Most Predicted Global Crisis of the 21st Century; a severe pandemic. 

In last October's Inaugural Global Health Security Index, the United States - followed by the UK, The Netherlands, Australia, and Canada - were judged to be the best prepared to deal with a severe pandemic.  A least when graded on the curve. 

But despite two decades of warnings (see WHO: On The Inevitability Of The Next Pandemic), and several close calls (H7N9 in 2017, H1N1 in 2009, SARS in 2003, etc.), over the past 9 months the world has proved itself to be spectacularly unprepared to deal with a fast-moving, viral threat. 

Eleven years ago, in Caught With Our Masks Down, I wrote that the demand for PPEs during a serious pandemic would far exceed the available supply. At one time the HHS estimated the nation would need 30 billion masks (27 billion surgical, 5 Billion N95) to deal with a major pandemic (see Time Magazine A New Pandemic Fear: A Shortage of Surgical Masks).

The good news is we were afforded more than a decade to prepare; to procure the basic PPEs needed protect our healthcare workers, first responders, and the general public.

The bad news is, we instead spent billions on sexy, next-gen-high-tech pandemic `solutions' before first investing in the basic supplies and public health infrastructure we would need to deliver any of these solutions during a severe pandemic.

And nine months into COVID-19, healthcare workers are still scrambling for PPEs, and the public are relegated to using a smorgasbord of less effective face covers. 

As challenging as COVID-19 has been, it is far from the `worst-case' pandemic scenario.  It is a relatively low-mortality pandemic, killing something less than 1% of symptomatic cases. Among hospitalized cases, MERS-CoV has an apparent CFR of 35%,  Nipah over 40% and some strains of avian flu are even higher.  

As we now understand all too well - a pandemic isn't just a public health crisis - it can quickly become a global economic disaster, and can pose a genuine national security threat.  The full economic and societal impact of COVID-19 probably won't be known for a decade or more. 

All of this was foretold a hundred times or more, in exercises, books, and reports - including: 

  • Fifteen years ago Dr. Michael Osterholm, director of CIDRAP, presciently likened a severe pandemic to an 18-month global blizzard, where nearly everything is shut down. Many will find themselves without a paycheck, either due to their refusal to work and risk exposure, or because their jobs are simply no longer available (see Baby, it's Cold Outside).
  • In December of 2012 the U.S. National Intelligence Council released a report called "Global Trends 2030: Alternative Worldsthat tried to anticipate the global shifts that will likely occur over the next two decades (see Black Swan Events). Number one on their hit parade? A severe pandemic. 
  • In 2014, the U.S. Director of National Intelligence declared An Influenza Pandemic As A National Security Threatwriting:  No one can predict which pathogen will be the next to spread to humans, or when or where such a development will occur, but humans will continue to be vulnerable to pandemics, most of which will probably originate in animals.

And yet, despite these warnings, governments and leaders of the world kicked the can down the road each year, pledging to address the deficits in our pandemic preparedness `next year', never truly believing the next pandemic would fall on their watch.  

Sadly, we are probably no better prepared to deal with a great (8.0+) earthquake on the San Andreas, Cascadia, or New Madrid fault lines, or a `Carrington level' CME from the sun, than we are for the next severe pandemic. 

Eight years ago, the earth narrowly missed being hit by a massive CME (see NASA: The Solar Super Storm Of 2012) that could have destroyed a large portion of our electrical grid.  

Since then, scientists have discovered that these severe solar storms happen far more often than previously believed (See Destructive Solar Storms Usually Hit Earth Every 25 Years or So, Say Scientists).

The earth in general, and the United States in particular, have been in an earthquake (and volcanic eruption) `drought' for the past century (see #NatlPrep: Half Of All Americans Need An Earthquake Plan).  But all droughts end eventually (see Dr. Lucy Jones: `Imagine America Without Los Angeles’). 

While we can't predict what the next national, regional, or global crisis will be, it is a pretty safe bet that it will come sooner rather than later.  

There are a lot of things we can do as individuals (see #NatlPrep: Prolonged Grid Down Preparedness), or as business owners (see SBA's Disaster Preparedness and Recovery Plan), to prepare for the next great disaster or crisis - but what is truly needed is a commitment by governments around the globe to prioritize emergency preparedness. 

Not just talk the talk, but to walk the walk. 

Here in the United States I'd love to see a Department of National Resilience  (hopefully with a better acronym than DNR)  - with the funding, and foresight, to adequately prepare local communities to deal with whatever future threats may come. One that actively involves local officials, schools, businesses, civic groups, and individuals - not just another Federal alphabet agency filled with career bureaucrats.  

With millions of people out of work, this could even become a jobs program, benefiting both individuals and their communities.

I'm sure there are thousands of retired EMTs, firefighters, and nurses that would make excellent instructors and plenty of others who would love an opportunity to work, and to make a real difference to their community.    
 
The next big crisis is just around the corner.  

We can either meet it as a prepared society, or we can hope for the best, and take our lumps.  Again. 
 

Tuesday, September 29, 2020

C.I.D.: Another SARS-CoV-2 Reinfection Report - 2 HCWs From India

 

#15,477

It was only 5 weeks ago that HKU Med Announced the 1st Documented Reinfection With SARS-CoV-2  in a 33 year-old Hong Kong man who had tested positive for SARS-CoV-2 last spring, and who  tested positive again after recently returning from a trip to Spain. 

Unlike earlier cases - which were often dismissed as `relapses' public health authorities had access to genetic sequencing information of both of this patient's infections, and were able to determine they were due to two genetically distinct viruses. 

Less than twenty-four hours later, two more reports emerged from Europe (see Two More Reports of SARS-CoV-2 Reinfection (Netherlands & Belgium) - followed a week later by another report from Nevada.  While the number of laboratory confirmed reinfections remains small, the availability of genetic sequence data is limited, making such determinations challenging. 

While many of these documented reinfections have presented asymptomatically, or with mild symptoms, this hasn't always been the case.  The Nevada patient's second illness  - mentioned above - was reportedly a significantly worse than the first, and was serious enough to require hospitalization. 

At the same time we've seen numerous reports of rapidly waning antibody titers in recovered COVID-19 patients, which also raises concerns over the duration and extent of protective immunity following infection (and potentially, vaccination)

This has been the topic of numerous blogs over the past few months, including:

Nature Medicine: Seasonal Coronavirus Protective Immunity Is Short-Lasting

EID Journal: Antibody Profiles According to Mild or Severe SARS-CoV-2 Infection

CDC Clarifies: Recovered COVID-19 Cases Are Not Necessarily Immune To Reinfection

Imperial College London: (REACT) SARS-CoV-2 Antibody Prevalence Study - England

COVID-19: From here To Immunity (Take Two)


Last July (see Kings College: Longitudinal Evaluation & Decline of Antibody Responses in SARS-CoV-2 infection), researchers reported that `the magnitude of the nAb response is dependent upon the disease severity', something we'd seen previously with MERS-CoV (see EID Journal: Antibody Response & Disease Severity In HCW MERS Survivors).

They also found a significant percentage of mild cases saw their nAb titers drop to near baseline within 60 days post-infection.
 
It should be noted that nAb titers aren't the only measure of potential post-infection immunity, as the role of T-Cells and other elements of the innate immune system in fighting this virus are poorly understood. 

How common - or clinically significant - reinfection really is among recovered COVID-19 patients is unknown, but it is obviously a concern for vaccinologists who hope to launch a SARS-COV-2 vaccine early next year. 

All of which brings us to another very brief report, published last week in Clinical Infectious Diseases which describes two Health Care Workers (25 M , 28 F) in India who had laboratory confirmed (asymptomatic) SARS-CoV-2 infection last May, and who subsequently tested positive again in mid-August and early September. 

Since all of their infections were asymptomatic, their discovery was somewhat fortuitous, leading the authors to suggest that reinfections are potentially under-reported occurrences.   Follow the link to read the report in full. 

Asymptomatic reinfection in two healthcare workers from India with genetically distinct SARS-CoV-2 

Vivek Gupta, Rahul C Bhoyar, Abhinav Jain, Saurabh Srivastava, Rashmi Upadhayay, Mohamed Imran, Bani Jolly, Mohit Kumar Divakar, Disha Sharma, Paras Sehgal 

Clinical Infectious Diseases, ciaa1451, https://doi.org/10.1093/cid/ciaa1451
Published: 23 September 2020 

 

While it is becoming increasingly apparent that re-infection can occur with SARS-COV-2 - how often that happens - and how much of a real-world impact it may have on the course and duration of our COVID-19 pandemic remains unknown.

For now, these scattered reports of reinfection are more cautionary signs than warning klaxons.

But we are still very early in this pandemic, surveillance for reinfections is spotty at best, and our understanding of the interaction between SARS-COV-2 and the human immune system is far from complete.  

All of which makes reports like these very much worth our attention. 

Monday, September 28, 2020

CHOP Research: COVID-linked MIS-C Associated with Myocardial Injury

 

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While it is true that most children appear to only suffer mild to moderate illness with SAR-CoV-2 infection, as of late July (see MMWR: COVID-19–Associated Multisystem Inflammatory Syndrome in Children — U.S., March–July 2020) more than 600 kids in the United States have been hospitalized with a severe, life-threatening autoimmune response dubbed MIS-C. 

We first saw this condition described in the UK back in April (see PICS: NHS Alert On Possible Severe Pediatric COVID-19 Complication), and while it is referred to as MIS-C in the United States, it is called PIMS-TS in the UK.

The CDC describes the syndrome on their MIS-C website as:

What is MIS-C?

Multisystem inflammatory syndrome in children (MIS-C) is a condition where different body parts can become inflamed, including the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal organs. Children with MIS-C may have a fever and various symptoms, including abdominal (gut) pain, vomiting, diarrhea, neck pain, rash, bloodshot eyes, or feeling extra tired. We do not yet know what causes MIS-C. However, many children with MIS-C had the virus that causes COVID-19, or had been around someone with COVID-19. 

While we've looked at a wide range of reports of long-term sequelae from COVID-19 in `recovered' adults (see PAHO Epi Alert: Complications & Sequelae Of COVID-19), very little is known about the lasting health impacts of MIS-C in children. 

Researchers at Children’s Hospital of Philadelphia (CHOP) reported last week, however,  that they have found subtle, but worrisome, signs of heart damage among recovered pediatric MIS-C patients.  

We've got a press release, a link to the study, and some excerpts from the CHOP blog:

CHOP Researchers Find MIS-C Associated with Myocardial Injury

21-Sep-2020 9:25 AM EDT, by Children's Hospital of Philadelphia 

September 21, 2020— Using sensitive parameters to assess cardiac function, researchers at Children’s Hospital of Philadelphia (CHOP) have found that cardiac involvement in multisystem inflammatory syndrome in children (MIS-C) differs from Kawasaki disease (KD) and is associated with myocardial injury. The findings were published recently in the Journal of the American College of Cardiology.

Thought to be a post-viral hyperinflammatory response related to COVID-19, MIS-C has some clinical overlap with KD, an inflammatory condition that causes rash, fever, and inflammation of the blood vessels in children. However, the two conditions differ in important ways, particularly when it comes to cardiac involvement. By utilizing a cardiac parameter known as strain, which measures subtle changes in cardiac function not detected by conventional echocardiography, the research team was able to show that while the coronary arteries were not typically involved in MIS-C as they are in KD, myocardial injury was more common in MIS-C.

“By using this novel approach for assessing cardiac function, we were able to detect subtle myocardial changes that were not detected by conventional echocardiography,” said senior author Anirban Banerjee, MD, FACC, an attending cardiologist with the Cardiac Center at CHOP. “Long-term follow-up is essential to fully understand this new disease, including cardiac MRI studies to evaluate for myocardial scarring. This is especially true when considering the possible lingering effects of myocardial injury and consequent need for caution in sports participation.” 

In a retrospective study, the researchers compared echocardiographic findings in 28 patients with MIS-C, 20 patients with classic KD, and 20 healthy controls. The research team analyzed echocardiographic parameters, including various measures of strain, during the acute phase in patients with MIS-C and KD and during the subacute phase in the MIS-C patients (approximately 5 days after hospitalization).

While only one case in the MIS-C group presented with coronary artery dilation, cardiac injury and dysfunction were common, occurring in approximately 60% of MIS-C patients. Left ventricular systolic and diastolic function were worse in MIS-C compared to KD, and although systolic dysfunction in MIS-C patients recovered quickly within several days, diastolic dysfunction persisted. In addition to the left ventricle, both the right ventricle and left atrium – sometimes called the “forgotten chambers” of the heart – were significantly affected. Abnormal strain measurements in the latter two chambers correlated strongly with biomarkers of myocardial injury in MIS-C. 

“Larger studies will be needed to fully characterize coronary involvement in MIS-C,” Banerjee said. “Given the results of this study, we recommend following up with MIS-C patients several times over a one-year period, in a pattern similar to patients with Kawasaki disease, even if they look well outwardly.” 

Matsubara et al. “Echocardiographic Findings in Pediatric Multisystem Inflammatory Syndrome Associated with COVID-19 in the United States,” Journal of the American College of Cardiology, online August 31, 2020, doi: 10.1016/j.jacc.2020.08.056

 

Echocardiographic Findings in Pediatric Multisystem Inflammatory Syndrome Associated with COVID-19 in the United States
Daisuke Matsubara 1, Hunter L Kauffman 1, Yan Wang 1, Renzo Calderon-Anyosa 1, Sumekala Nadaraj 1, Matthew D Elias 1, Travus J White 1, Deborah L Torowicz 1, Putri Yubbu 1, Therese M Giglia 1, Alexa N Hogarty 1, Joseph W Rossano 1, Michael D Quartermain 1, Anirban Banerjee 2
 
PMID: 32890666 PMCID: PMC7467656 DOI: 10.1016/j.jacc.2020.08.056 
Condensed abstract: Multisystem inflammatory syndrome in children (MIS-C) is an illness that resembles Kawasaki Disease (KD) or toxic shock, reported in children with a recent history of COVID-19 infection. This study analyzed echocardiographic manifestations of this illness. In our cohort of 28 MIS-C patients, left ventricular systolic and diastolic function were worse than in classic KD. These functional parameters correlated with biomarkers of myocardial injury. However, coronary arteries were typically spared. The strongest predictors of myocardial injury were global longitudinal strain, right ventricular strain, and left atrial strain. During subacute period, there was good recovery of systolic function, but diastolic dysfunction persisted.


Conclusions: Unlike classic KD, coronary arteries may be spared in early MIS-C, however, myocardial injury is common. Even preserved EF patients showed subtle changes in myocardial deformation, suggesting subclinical myocardial injury. During an abbreviated follow-up, there was good recovery of systolic function but persistence of diastolic dysfunction and no coronary aneurysms.


And for some additional background, some excerpts from this CHOP Cornerstone Blog post:

Researchers Detect Subtle Changes in Cardiac Function in Young Patients With MIS-C 
Published on Sep 21, 2020 in Cornerstone Blog

          (Excerpt)

What are the clinical/therapeutic implications of these findings?

Since cardiac involvement is common in MIS-C, physicians may have to treat them in a manner as we would treat other viral myocarditis cases. We noted cardiogenic shock in 85% of our MIS-C patients. In contrast, the incidence of cardiogenic shock is quite rare in classic KD. Physicians should remember that along with conventional echocardiography, evaluation of strain parameters are quite useful in evaluating subtle changes in heart function in MIS-C patients. Long-term effects of myocardial injury will need to be studied, as this may have implications on sports participation in these children.

What are the main messages you hope physicians will take away from this report?

We have several take-home messages for physicians in the front line. First, coronary arteries are relatively spared (4%) in the acute stage of this disease. Second, cardiac injury/dysfunction is common (60%), with subtle myocardial changes detected by echocardiographic strain parameters. Third, systolic dysfunction recovered quickly within several days; however, diastolic dysfunction persisted. Lastly, not only the left ventricle, but the two “forgotten chambers” of the heart (left atrium and right ventricle), were significantly affected. In fact, strain measurements in the latter two chambers correlated strongly with biomarkers of myocardial injury in MIS-C.

         (Continue . . . )

 


Sunday, September 27, 2020

MRC Report #33: Modelling The Allocation & Impact of a COVID-19 Vaccine







 


HHS Sample Framework For Vaccine Distribution 


#15,475


While the opening, and chaotic, first 9 months of the COVID-19 pandemic has focused primarily on hospital capacity, testing, and NPIs (social distancing, masks, etc.) the hope is that sometime in the next few months (one or more) safe and effective COVID vaccines will become available.  

A major milestone to be sure, but to paraphrase Winston Churchill, more like the `end of the beginning than the beginning of the end'. 

Developing a vaccine, and getting into the arms of billions of people, are two decidedly different tasks.  And there is much we don't know about the production capacity, effectiveness, and duration of protection of any vaccine. 

  • The quantity of vaccine that can be produced and delivered in the first 12 months is unknown, but may be limited to two billion doses or less. 
  • It seems likely that most people will need two doses - spaced 21 to 28 days apart - and that not only increases the complexity of any vaccination program, it would also cut the number of people who can be protected in half.
  • If a COVID-19 vaccine is anything like the flu vaccine, older adults - who are in greatest need of protection - may derive the least immunity.
  • And their are growing concerns - based on a small number of reinfections - that vaccine induced immunity may be measured in months, not years
The U.S. government released an 11-page Strategy For Distributing a COVID-19 paper earlier this month which describes the challenges - but only discusses in general terms - how they will go about prioritizing the vaccine when, and if, one  becomes available. 

Decisions on who gets the vaccine first will be announced only after crucial questions over  manufacturing capacity, VE (vaccine effectiveness) in different age cohorts, and safety in children and other vulnerable populations are answered. 

On Friday, the MRC Centre for Global Infectious Disease Analysis at Imperial College London released their 33rd report on COVID-19, this time centered on modelling the allocation and potential impact of a COVID-19 vaccine. 

While all of the above questions remain unanswered, this 21-page report models and evaluates various scenarios, in hopes of covering the likely bases. 

First, the link and summary from the report, followed by a link and excerpts from a Imperial College of London press release.  You'll want to read the paper in its entirety.  I'll have a postscript when you return.  

Report 33 - Modelling the allocation and impact of a COVID-19 vaccine

Date: 25 September 2020

Authors:

Alexandra B Hogan, Peter Winskill, Oliver J Watson, Patrick GT Walker, Charles Whittaker, Marc Baguelin1, David Haw, Alessandra Løchen, Katy A M Gaythorpe,Imperial College COVID-19 Response Team, Farzana Muhib, Peter Smith, Katharina Hauck, Neil M Ferguson, Azra C Ghani1

1Correspondence:a.ghani@imperial.ac.uk

Download the full PDF for Report 33

Download the full PDF for Report 33 supplement

Summary

Several SARS-CoV-2 vaccine candidates are now in late-stage trials, with efficacy and safety results expected by the end of 2020. Even under optimistic scenarios for manufacture and delivery, the doses available in 2021 are likely to be limited.

Here we identify optimal vaccine allocation strategies within and between countries to maximise health (avert deaths) under constraints on dose supply. We extended an existing mathematical model of SARS-CoV-2 transmission across different country settings to model the public health impact of potential vaccines, using a range of target product profiles developed by the World Health Organization. We show that as supply increases, vaccines that reduce or block infection – and thus transmission – in addition to preventing disease have a greater impact than those that prevent disease alone, due to the indirect protection provided to high-risk groups.

We further demonstrate that the health impact of vaccination will depend on the cumulative infection incidence in the population when vaccination begins, the duration of any naturally acquired immunity, the likely trajectory of the epidemic in 2021 and the level of healthcare available to effectively treat those with disease. Within a country, we find that for a limited supply (doses for <20% of the population) the optimal strategy is to target the elderly and other high-risk groups.

However, if a larger supply is available, the optimal strategy switches to targeting key transmitters (i.e. the working age population and potentially children) to indirectly protect the elderly and vulnerable. Given the likely global dose supply in 2021 (2 billion doses with a two-dose vaccine), we find that a strategy in which doses are allocated to countries in proportion to their population size is close to optimal in averting deaths. Such a strategy also aligns with the ethical principles agreed in pandemic preparedness planning.

        (Continue . . . )




COVID-19 vaccine may not need to be fully effective to benefit public health 

by Dr Sabine L. van Elsland, Stephen Johns

25 September 2020

Even an imperfect, partially effective vaccine against COVID-19 could have a substantial public health benefit if rolled out in 2021, a report says.

Researchers from Imperial's COVID-19 Response Team also found that the optimal approach to allocating vaccine doses within a country will require a detailed understanding of the local setting – including relevant risk groups and the stage and spread of the epidemic.

With limited supply, this might involve targeting elderly and other high-risk groups. With larger supply available to a country, a more efficient strategy would be to vaccinate the working-age population.

The researchers found that as supply increases, vaccines that reduce or block infection – and thus transmission – in addition to preventing disease have a substantial greater impact than those that prevent disease alone, due to the indirect protection provided to high-risk groups.
Global allocation

Even under optimistic scenarios for manufacture and delivery, the doses available in 2021 are likely to be limited. In this report, researchers explore the impact of vaccine allocation within countries and between countries to maximise health and avert deaths under constraints on dose supply.

Allocating the limited doses likely to be available in 2021 to countries according to their population size is almost as efficient as more nuanced strategies. Such a strategy also aligns with the ethical principles agreed in pandemic preparedness planning. Defining the “optimal” strategy ahead of time is challenging because it is sensitive to vaccine characteristics that will not be fully known at the time of roll-out.

Global public health value of the vaccine can be maximised by ensuring equitable access: acting collectively in this way during the early stages of vaccine deployment remains the ethical approach to take, even if this is not the most beneficial short-term strategy from a national perspective, according to this report.


After a summer filled with `Forward Looking' & `Aspirational' Vaccine Press Releases, we are starting to get a badly needed reality check on the likely impact of having a COVID-19 vaccine `in early 2021'. 

Hopes that a vaccine will - within a few months - return us back to `normal' are unrealistic, even if everything goes perfectly.  A vaccine will help, certainly, but there is a long road ahead and we may be dealing with COVID-19 for years to come. 

Of course, no one wants to hear this, anymore than they wanted to hear a year ago that a pandemic was inevitable (see Sept 2019's  WHO/World Bank GPMB Pandemic Report : `A World At Risk'and that a coronavirus was a likely threat (see The JHCHS #Event201 (Fictional) CAPS Pandemic Scenario).

But ready or not, the next pandemic virus is probably already out there - residing in a bird, a pig, a camel, or a bat - evolving inexorably towards human adaptation. If we get lucky, it will wait until we are clear of our current COVID threat before it emerges. 

But we need to prepare as if it it could come tomorrow, as there are no guarantees in life. 

Except, of course, that another pandemic will come.  Count on it. 

Saturday, September 26, 2020

NIOSH & FDA Updates On Counterfeit N95 Respirators & Hand Sanitizers

 


#15,474


For now - and for the foreseeable future - our best protection against COVID-19 are NPIs - Non-pharmaceutical Interventions - like social distancing, rigorous hand hygiene, and the wearing of face covers and/or masks (see Two Studies (The Lancet & EID Journal) On The Impact Of NPIs On COVID-19 Spread).

Unfortunately, for months we've seen numerous reports of fake and/or counterfeit N95 respirators flooding the market, which endanger not only the Health Care Workers who wear them, but potentially anyone they come in contact with.

In early June the FDA issued a letter to healthcare providers warning:

Certain Filtering Facepiece Respirators from China May Not Provide Adequate Respiratory Protection

While some Chinese manufacturers appear to be producing reasonably reliable products, others are clearly not. On June 9th the FDA issued a letter listing 66 manufacturers of N95/KN95 masks that are no long authorized by the EUA.

We last visited the NIOSH website in early August, where we saw the names and pictures of dozens of fake and/or counterfeit N95 respirators being sold as `NIOSH Approved', complete with bogus NIOSH certification numbers. 

Since then NIOSH has updated their page, adding newly reported `fake' or substandard N95 respirators to their list. While these masks are arguably `better than nothing', those who use them in high-risk environments need to be aware of their limitations.

Counterfeit Respirators / Misrepresentation of NIOSH-Approval

Updated September 22, 2020

Counterfeit respirators are products that are falsely marketed and sold as being NIOSH-approved and may not be capable of providing appropriate respiratory protection to workers.
When NIOSH becomes aware of counterfeit respirators or those misrepresenting NIOSH approval on the market, we will post them here to alert users, purchasers, and manufacturers.

How to identify a NIOSH-approved respirator:

NIOSH-approved respirators have an approval label on or within the packaging of the respirator (i.e. on the box itself and/or within the users’ instructions). Additionally, an abbreviated approval is on the FFR itself. You can verify the approval number on the NIOSH Certified Equipment List (CEL) or the NIOSH Trusted-Source page to determine if the respirator has been approved by NIOSH. NIOSH-approved FFRs will always have one the following designations: N95, N99, N100, R95, R99, R100, P95, P99, P100.

Signs that a respirator may be counterfeit:
  • No markings at all on the filtering facepiece respirator
  • No approval (TC) number on filtering facepiece respirator or headband
  • No NIOSH markings
  • NIOSH spelled incorrectly
  • Presence of decorative fabric or other decorative add-ons (e.g., sequins)
  • Claims for the of approval for children (NIOSH does not approve any type of respiratory protection for children)
  • Filtering facepiece respirator has ear loops instead of headbands

Additional Tips for Spotting Counterfeit Respirators Before You Buy

 

Of perhaps even greater concern to the general public, scores of brands of hand sanitizer being sold in the United States have been found to contain dangerous levels of methanol (see CDC HAN #00434: Serious Adverse Health Events Associated with Methanol-based Hand Sanitizers).











Methanol (wood alcohol) has a long, and tragic history of being used to fortify bootleg liquor, and when ingested even in small quantities converts to formic acid, which can cause permanent blindness or even death. It has legitimate industrial uses (as solvents, pesticides, and alternative fuel sources), but is not meant to be ingested.

FDA updates on hand sanitizer since our last visit include:







As we go into the winter respiratory season it wouldn't hurt to check any hand sanitizer you have on hand against the list, regardless of where you purchased it. And check back every couple of weeks, since additional brands may be added over time.

Friday, September 25, 2020

WHO Recommended 2021 Southern Hemisphere Flu Vaccine Composition & Impact Of COVID-19 On Selection

Flu Reports Flat-lined Since Late March - Credit WHO 

#15,473

Over the past several months (see here, here, and here) we've looked at the dearth of influenza reported globally since the emergence of COVID-19 last spring, and speculated on how that might adversely affect the selection of virus components for next year's Southern Hemisphere flu vaccine. 

This week the World Health Organization has convened an expert committee to select vaccine strains, and this afternoon they have released their recommendations (see below).

First the announcement, then a look at their statement on how the COVID-19 pandemic has complicated decisions for next year's (and possibly beyond) flu vaccine.

Recommended composition of influenza virus vaccines for use in the 2021 southern hemisphere influenza season
25 September 2020
It is recommended that quadrivalent vaccines for use in the 2021 southern hemisphere influenza season contain the following:
Egg-based Vaccines
an A/Victoria/2570/2019 (H1N1)pdm09-like virus;
an A/Hong Kong/2671/2019 (H3N2)-like virus;
a B/Washington/02/2019 (B/Victoria lineage)-like virus; and
a B/Phuket/3073/2013 (B/Yamagata lineage)-like virus.

Cell- or recombinant-based Vaccines
an A/Wisconsin/588/2019 (H1N1)pdm09-like virus;
an A/Hong Kong/45/2019 (H3N2)-like virus;
a B/Washington/02/2019 (B/Victoria lineage)-like virus; and
a B/Phuket/3073/2013 (B/Yamagata lineage)-like virus.
It is recommended that trivalent influenza vaccines for use in the 2021 southern hemisphere influenza season contain the following:
Egg-based Vaccines

an A/Victoria/2570/2019 (H1N1)pdm09-like virus;
an A/Hong Kong/2671/2019 (H3N2)-like virus; and
a B/Washington/02/2019 (B/Victoria lineage)-like virus.

Cell- or recombinant-based Vaccines

an A/Wisconsin/588/2019 (H1N1)pdm09-like virus;
an A/Hong Kong/45/2019 (H3N2)-like virus; and
a B/Washington/02/2019 (B/Victoria lineage)-like virus.
 
For more information

25 September 2020: Recommended composition of influenza virus vaccines for use in the 2021 southern hemisphere influenza season - full report pdf, 478kb
 
25 September 2020: Frequently Asked Questions pdf, 216kb

From the accompanying Q&A, the following changes have been made to the Southern Hemisphere 2021 flu vaccine recommendations since the last vaccine:

  • For the A(H1N1)pdm09 vaccine virus component, replacement of the A/Brisbane/02/2018-like virus with an A/Victoria/2570/2019-like virus for egg-based production and an A/Wisconsin/588/2019-like virus for cell-based production, is recommended.
  • For the A(H3N2) vaccine virus component, replacement of the A/South Australia/34/2019-like virus with an A/Hong Kong/2671/2019-like virus for egg-based production and an A/Hong Kong/45/2019-like virus for cell-based production, is recommended.
The new recommendations also differ slightly from the current Northern Hemisphere Flu Vaccine:
  • For the A(H1N1)pdm09 vaccine virus component, replacement of the A/Guangdong-Maonan/SWL1536/2019-like virus with an A/Victoria/2570/2019-like virus for egg-based production and replacement of the A/Hawaii/70/2019-like virus with an A/Wisconsin/588/2019-like virus for cell-based production, is recommended.
  • The other viruses recommended for production of trivalent and quadrivalent 2021 southern hemisphere vaccines are the same as recommended for the 2020-2021 northern hemisphere vaccine.
Normally flu experts would have thousands of antigenically characterized flu samples taken over the past 6 months from around the world to base their decisions on, but as we've seen (see WHO Influenza Update #376), virus submissions have been running about 1/100th of normal.

This paucity of flu surveillance data, and its impact on vaccine component selection, is addressed in 3 sections of today's Q&A document. 

15. What impact has the COVID-19 pandemic had on the GISRS influenza
surveillance?

Influenza surveillance was disrupted during the early stages of the COVID-19 pandemic resulting in substantial decreases in the numbers of specimens tested for influenza and subsequent shipments of viruses to WHO CCs of GISRS compared with the corresponding period in previous years. Reporting directly or indirectly to FluNet by some countries was also delayed or stopped. Some countries were less affected and maintained strong influenza
surveillance as demonstrated by the detection of human cases of zoonotic influenza.
In order to address the persistent public health threat from influenza and maintain global influenza surveillance and response capabilities while responding to the COVID-19 pandemic, an interim WHO guidance document was published to prepare GISRS for the upcoming influenza seasons
From June 1 to August 30 of this year, 107 countries, areas, or territories reported data to the global influenza surveillance platform FluNet – 132 countries, areas, or territories reported data over the same period in 2019. In addition, countries are exploring the use of influenza surveillance systems for COVID-19 sentinel surveillance.
16. What impact has the COVID-19 pandemic had on influenza activity?
The COVID-19 pandemic has had a major impact on influenza activity. Between February and March 2020, influenza activity was elevated in most countries in the northern hemisphere consistent with a typical influenza season. Starting in mid-March, influenza activity decreased sharply, concomitant with the spread of SARS-CoV-2. Implementation of travel restrictions, mitigation strategies and social-distancing measures is likely the reason for decreased influenza activity. Correspondingly, very low levels of influenza detection have been reported globally, including from countries in the temperate zone of the southern hemisphere.

17. How has the COVID-19 pandemic impacted the 2021 southern hemisphere influenza vaccine recommendation?

The amount of genetic and antigenic data available from recently circulating viruses has been significantly lower for this southern hemisphere vaccine recommendation meeting than is typical due to the COVID-19 pandemic. Influenza activity had started in several northern hemisphere countries prior to the emergence of the COVID-19 pandemic, providing a source of viruses collected in 2020, mainly from February and March. While the overall numbers were lower, recent viruses from every WHO region were characterized and the recommendations are based on viruses that are likely to be a fair representation of those that may continue to circulate.

Nevertheless, due to the reduced number of recent viruses circulating and available for characterization, there are uncertainties regarding the full extent of genetic and antigenic diversity. It is unknown what impact the low level of influenza activity will have on forthcoming influenza seasons and which influenza virus types and subtypes will begin to circulate widely when social interactions resume. 

Between `viral interference' from SARS-CoV-2, and pandemic inspired social distancing and NPIs (hand hygiene, face covers, etc.), the global `fluscape' has been radically altered since early spring.  Exactly what this might mean for the emergence of novel flu viruses is unknown. 

But the natural evolution of seasonal flu viruses has also been impacted in ways that we can only begin to envision (see COVID-19, The Next Flu Season, And The Temporary Immunity Hypothesis), and for the most part, this is all happening out of our sight. 

Whether seasonal flu returns this winter, next summer - or stays suppressed for a year or longer - we should be prepared for some surprises when it finally does return.  If nothing else, community immunity to influenza will likely diminish the longer this lull continues. 

While COVID-19 is our number one priority today, history suggests that influenza is unlikely to take a back seat for very long. 


Some Early Reports Of Seasonal Flu Vaccine Shortages & Delays


 




Credit CDC PHIL


#15,472


Although developing a safe and effective COVID-19 vaccine in record time is a huge scientific challenge, the logistics of getting it into the arms of billions of people around the world in a timely fashion - in the middle of a pandemic - may prove even more challenging. 

Complicating matters, it isn't known whether first time recipients will need one - or two - shots, or how long protection from the vaccine might last. 

A global vaccination campaign of this scale has never been attempted, and even if things were to go exceedingly well, it is likely to turn into multi-year endeavor. 

The reality is, for many people of the world, a COVID vaccine is likely a year or more away. 

Although it pales in comparison, the closest thing we have today is the yearly seasonal flu vaccination campaign, and even last year - before COVID-19 emerged - we saw shortages and manufacturing delays (see Taiwan CDC Expands Access To Influenza Antivirals Due To Vaccine Delay), with many countries not receiving shipments until November or even early December.

Earlier this year, we saw warnings in the UK that GPs look set to face 'unprecedented' flu vaccine shortages again this year, and that GPs will not receive third of flu vaccine stock from key supplier until November.

Earlier this week, UK High Street pharmacy giant Boots announced a shortage of flu vaccine (see Boots suspends flu jabs amid coronavirus and issues statement to shoppers)stating:


Boots UK Suspends New Bookings for its Flu Vaccination Services

“We know that this year, our customers have been more conscious than ever about protecting the health of themselves and their families, and protecting against flu has been front of mind for many of us.

“As a result, we have seen more people than ever booking early to get their flu vaccinations, and due to the level of demand and limited stock that we have available, we made the decision to pause taking any new bookings for our private and NHS under 65s Flu Vaccination Services earlier this week.

“Since then, we have been closely monitoring our stock levels of the vaccination recommended by the NHS for patients aged 65 and over, and can confirm that today we have also closed for new bookings for these vaccinations too. This is to make sure we can vaccinate the patients who have already booked their appointment with us.”

Boots UK Spokesperson
 


Other countries have reported delays in flu vaccine deliveries, and while the United States appears to have an ample supply, spot shortages are being reported at some pharmacies here as well. 

Minnesota's WCCO-TV reported yesterday ‘Unprecedented Demand’ For Flu Shots Causing Shortage,  while KETV-7 in Omaha, Nebraska reports  High demand for flu vaccine puts strain on distribution companies

Meanwhile, overnight Reuters is reporting:

Some northern hemisphere countries struggling to source more flu vaccines: WHO
25 SEPTEMBER 2020

GENEVA (Reuters) - Some northern hemisphere countries are having trouble obtaining additional flu vaccines amid increased demand, but health workers and the elderly should be prioritised in case of any shortages, the World Health Organization (WHO) said on Friday.

          (Continue . . . )


Right now, these appear to be fairly minor glitches in the vaccine delivery system. But it is still only September, and for most countries, flu vaccinations don't begin in earnest until October.  

We'll have to see how things work out over the next 30 to 60 days. 

Typically, about half of all Americans (160 million) get the flu shot every year, and the vast majority only require a single dose. A COVID-19 vaccination campaign - when it is launched - would require anywhere to two to four times as many vaccinations.

Two months ago, I suggested that this fall's flu vaccination campaign was particularly important because it would be our last, best opportunity to test our vaccine delivery system under genuine pandemic conditions, and to identify - and hopefully eliminate - as many points of failure as possible.

Hopefully, things will run smoothly with this fall's flu vaccine campaign, but even if it doesn't, what we learn from  could be critical for successfully deploying COVID-19 vaccine in 2021 or beyond

 

Thursday, September 24, 2020

Another SARS-CoV-2 D614G Mutation Study


SARS-CoV-2 - Credit NIAID


#15,471

Five months ago, in COVID-19 & The `M' Wordwe looked at the inevitability of seeing multiple mutations in the SARS-CoV-2 virus over time, as it is a single-stranded RNA virus and is therefore subject to `duplication errors' during replication (see Mechanisms of Viral Mutation).

All viruses mutate, some very slowly, and others - like HIV or Influenza - very rapidly. Most mutations convey no biological advantage to the virus, and many are actually detrimental. Only a few are apt to `improve' the fitness of the virus.

But, when viruses make trillions of copies of themselves, every once in awhile a more biologically `fit' virus will emerge; one that can compete with its parental strain, and sometimes even supplant it. 

In early May of this year, in More COVID-19 (SARS-CoV-2) Mutation Reportswe looked at a pre-print paper from researchers at the Los Alamos National Laboratory that described a new and increasingly dominant `European' strain of COVID-19 which they believed had enhanced transmissibility. 

The gist of this report was a new strain (G clade) of SARS-CoV-2 emerged in Europe in February carrying the D614G mutation (among others), and has since overtaken the original Asian strain in many regions of the world due to its enhanced transmissibility. 

The paper was subsequently published in the journal Cell:

Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID19 Virus

In Brief Korber et al. present evidence that there are now more SARS-CoV-2 viruses circulating in the human population globally that have the G614 form of the Spike protein versus the D614 form that was originally identified from the first human cases in Wuhan, China. Follow-up studies show that patients infected with G614 shed more viral nucleic acid compared with those with D614, and G614-bearing viruses show significantly higher infectious titers in vitro than their D614 counterparts.

Although many researchers cautioned that the pronouncement of a more transmissible `G' clade may be premature, over the summer we've seen several other studies that seem to support the theory that the D614G mutation enhances transmissibility. 

In June, in Scripps Research Institute: SARS-CoV-2 and the D614G Mutationwe looked at one such study: 

The D614G mutation in the SARS-CoV-2 spike protein reduces S1 shedding and increases infectivity

Lizhou Zhang1#, Cody B Jackson1#, Huihui Mou1#, Amrita Ojha1, Erumbi S Rangarajan2, Tina Izard2, Michael Farzan1*, Hyeryun Choe1*

The press release follows:
Mutated coronavirus shows significant boost in infectivity
COVID-19-causing viral variant taking over in the United States and Europe now carries more functional, cell-binding spikes.
June 12, 2020

Yesterday a new study was published on the medRxiv pre-print server, which appears to add more weight to the idea that the D614G mutation increases the transmissibility of the SARS-CoV-2 virus. 

Molecular Architecture of Early Dissemination and Massive Second Wave of the SARS-CoV-2 Virus in a Major Metropolitan Area

Scott Wesley Long, Randall J Olsen, Paul A. Christensen, David W Bernard, James J. Davis, Maulik Shukla, Marcus Nguyen, Matthew Ojeda Saavedra, Prasanti Yerramilli, Layne Pruitt, Sishir Subedi, Hung-Che Kuo, Heather Hendrickson, Ghazaleh Eskandari, Hoang A.T. Nguyen, James Hunter Long, Muthiah Kumaraswami, Jule Goike, Daniel Boutz, Jimmy Gollihar, Jason S. McLellan, Chia-Wei Chou, Kamyab Javanmardi, Ilya J. Finkelstein, James Musser

doi: https://doi.org/10.1101/2020.09.22.20199125

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

Preview PDF

Abstract

We sequenced the genomes of 5,085 SARS-CoV-2 strains causing two COVID-19 disease waves in metropolitan Houston, Texas, an ethnically diverse region with seven million residents. The genomes were from viruses recovered in the earliest recognized phase of the pandemic in Houston, and an ongoing massive second wave of infections. The virus was originally introduced into Houston many times independently. 

Virtually all strains in the second wave have a Gly614 amino acid replacement in the spike protein, a polymorphism that has been linked to increased transmission and infectivity. Patients infected with the Gly614 variant strains had significantly higher virus loads in the nasopharynx on initial diagnosis.

We found little evidence of a significant relationship between virus genotypes and altered virulence, stressing the linkage between disease severity, underlying medical conditions, and host genetics. Some regions of the spike protein - the primary target of global vaccine efforts - are replete with amino acid replacements, perhaps indicating the action of selection.

We exploited the genomic data to generate defined single amino acid replacements in the receptor binding domain of spike protein that, importantly, produced decreased recognition by the neutralizing monoclonal antibody CR30022. Our study is the first analysis of the molecular architecture of SARS-CoV-2 in two infection waves in a major metropolitan region. The findings will help us to understand the origin, composition, and trajectory of future infection waves, and the potential effect of the host immune response and therapeutic maneuvers on SARS-CoV-2 evolution.

Continue . . . )


A press release from Houston Methodist hospital provides additional background. I'll have a brief postscript when you return.

HOUSTON METHODIST COVID-19 STUDY SHOWS RAPID SPREAD AND POTENTIAL FOR MUTANT VIRUSES

Infectious disease pathologists sequence more than 5,000 strains of SARS-CoV-2 gene

HOUSTON - September 23, 2020

Media Contact:

Lisa Merkl, 832.667.5916

Molecular analysis of COVID-19’s powerful second wave in Houston – from May 12 to July 7 – shows a mutated virus strain linked to higher transmission and infection rates than the coronavirus strains that caused Houston’s first wave. Gene sequencing results from 5,085 COVID-positive patients tested at Houston Methodist since early March show a virus capable of adapting, surviving and thriving – making it more important than ever for physician scientists to understand its evolution as they work to discover effective vaccines and therapies.

 In the second major gene sequencing study conducted by James M. Musser, M.D., Ph.D., chair of the Department of Pathology and Genomic Medicine at Houston Methodist, and his team of infectious disease pathologists, they found that the two waves affected different types of patients. The study, preprinted under the title “Molecular architecture of early dissemination and massive second wave of the SARS-CoV-2 virus in a major metropolitan area,” provides the first molecular characterization of SARS-CoV-2 strains causing two distinct COVID-19 disease waves, a problem now occurring extensively in many European countries.

Houston’s second wave hit significantly younger patients who had fewer underlying conditions and were more likely to be Hispanic/Latino living in lower income neighborhoods. In addition, virtually all COVID-19 strains studied during the second wave displayed a Gly614 amino acid replacement in spike protein – the part of the virus that mediates invasion into human cells, gives the coronavirus its telltale crown-like appearance and is the major focus of vaccine efforts worldwide. While this mutation has been linked with increased transmission and infectivity, as well as a higher virus load in the nasopharynx, which connects the nasal cavity with the throat, the mutation did not increase disease severity, researchers said.

The findings reinforce researchers’ concerns of the virus gaining momentum through naturally occurring mutations capable of producing mutant viruses that can escape vaccines – dubbed ‘escapians’ – or mutants that can resist drugs and other therapies.

“This extensive virus genome data gathered from Houston’s earliest cases to date, coupled with the growing database we are building at Houston Methodist, will help us identify the origins of new infection spikes and waves,” said Musser, who is corresponding author on the study. “This information can be an especially helpful community resource as schools and colleges re-open and public health constraints are further relaxed.”

Given the urgency of finding effective treatments for COVID-19, the preliminary report is posted to the preprint server medRxiv, and a manuscript is under peer-review at a prominent scientific journal. This preprint is not the final version of the article.

         (Continue . . . )

At this point in time, it is important to note that researchers have not found any evidence that this `mutated' SARS-CoV-2 strain is any deadlier than the older Asian strain, only that it appears more transmissible.  

This mutation may help explain why Europe and North America - where this new strain is dominant - have had a much harder time controlling transmission than have China, Taiwan, Hong Kong and Japan.

Presumably, if this `G' clade gets introduced into Asian countries often enough, it will present similar challenges there.  

Viruses survive, and thrive, based on their ability to mutate and adapt. That is how this (presumably) bat-origin virus jumped species, and sparked COVID pandemic, and that is how this virus will ensure its survival going forward. 

We should expect this virus will continue to evolve, and that it will continue to surprise us along the way.