PNAS: Eurasian Avian-like H1N1 Swine Influenza Virus With Pandemic Potential In China

#15,349

Although avian influenza viruses generally score highest on the pandemic threat scale (see CDC Adds 3 Novel Flu Viruses To IRAT List) - mostly because they tend to produce a greater lethality in humans - swine influenza viruses start out with an important evolutionary advantage; they are already adapted to a mammalian host. 

And as we've discussed often over the past few years (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?), the progression of human influenza pandemics over the past 130 years has been H2, H3, H1, H2, H3, H1, H1 . . . .

Simply put, novel H1, H2, and H3 flu viruses appear to have fewer barriers to overcome in order to jump to humans - and while they may not prove as virulent as H5 & H7 avian subtypes - that puts them at or near the top of our pandemic threats list.

Every summer for the past decade, we've seen anywhere from a handful to several hundred swine-origin influenza cases turning up in humans, primarily connected with state and local agricultural fairs.  Less well documented, we've also gotten reports of swine-origin influenza jumping to humans in Europe and Asia. 

Credit CDC FLuView

Although North American H1, H2, and H3 swine-origin flu viruses are high on our list of pandemic threats, in late 2015 Chen Hualan, director of China's National Avian Influenza Reference Laboratory, was the lead author on a paper that pegged a new, rising swine flu threat in China (see PNAS: The Pandemic Potential Of Eurasian Avian-like H1N1 (EAH1N1) Swine Influenza).

EAH1N1 was a reassortant virus, with elements from H1N1 avian influenza, human H1N1pdm, and swine-origin influenza viruses.  Despite sharing the same subtype designation as a currently circulating seasonal strain, it was genetically different enough to pose a genuine public health threat. 

In the `Significance' section the authors boiled it down to this:

Here, we found that, after long-term evolution in pigs, the EAH1N1 SIVs have obtained the traits to cause a human influenza pandemic.

In an interview, published by Xinhuanet, lead author Chen Hualan stated: 

"Based on scientific analysis and comprehensive comparison of the main animal flu viruses: H1N1, H3N2, H5N1, H7N9, H9N2 and EAH1N1, we found the EAH1N1 is the one most likely to cause next human flu pandemic. We should attach great importance to the EAH1N1."

Since then, EAH1N1 has become a been a frequent topic of discussion and study. 

Six months later, in Sci Rpts: Transmission & Pathogenicity Of Novel Swine Flu Reassortant Viruses we looked at a study where pigs were experimentally infected with one of these Eurasian-Avian H1N1 swine influenza viruses and the 2009 H1N1pdm virus.

Researchers generated 55 novel reassortant viruses spread across 17 genotypes, demonstrating not only how readily EAH1N1 SIV can reassort with human H1N1pdm in a swine host, but also finding:

`Most of reassortant viruses were more pathogenic and contagious than the parental EA viruses in mice and guinea pigs'. 

Later that same year, in EID Journal: Reassortant EAH1N1 Virus Infection In A Child - Hunan China, 2016, we reviewed the case report on a 30-month old child from Hunan Province, who was infected with one of these reassortant EAH1N1 - H1N1pdm viruses.     

In 2017 we looked at J. Virology: A Single Amino Acid Change Alters Transmissability Of EAH1N1 In Guinea Pigs, while in 2018 we saw Emerg. Microbes & Infect.: Effect Of D701N Substitution In PB2 Of EAH1N1 Swine Flu Viruses which described the growing diversity of novel novel H1N1 and H3N2 flu viruses (including EA H1N1) in China's pig population.

In 2019, we saw a number of studies on EAH1H1, including one that documented the virus in farmed mink in China (see Vet. MicroB.: Eurasian Avian-Like Swine Influenza A (H1N1) Virus from Mink in China).

Since ferrets - which are close relatives of mink - are commonly used in influenza research because their respiratory systems are similar to humans, the ability of this virus to jump to and spread easily in mink is yet another red flag.  

While China holds real-time surveillance information on domestic swine-origin influenza infections close to the vest, a smattering of scientific papers over the past 5 years have increasingly painted EAH1N1 as a potential pandemic threat.   

All of which brings us to a new study, published (alas, behind a paywall) in PNAS, that does little to lower concerns, as they found a greater than 10% seroprevalence for the EAH1N1 among swine workers tested, suggesting that EAH1N1 is gaining human infectivity. 

I'll have more after the break.

RESEARCH ARTICLE

Prevalent Eurasian avian-like H1N1 swine influenza virus with 2009 pandemic viral genes facilitating human infection

Honglei Sun, Yihong Xiao, View ORCID ProfileJiyu Liu, Dayan Wang, Fangtao Li, Chenxi Wang, Chong Li, Junda Zhu, Jingwei Song, Haoran Sun, View ORCID ProfileZhimin Jiang, Litao Liu, Xin Zhang, Kai Wei, Dongjun Hou, Juan Pu, Yipeng Sun, Qi Tong, Yuhai Bi, Kin-Chow Chang, Sidang Liu, View ORCID ProfileGeorge F. Gao, and Jinhua Liu

PNAS first published June 29, 2020 https://doi.org/10.1073/pnas.1921186117
Add to Cart ($10)

Contributed by George F. Gao, April 28, 2020 (sent for review December 9, 2019; reviewed by Ian H. Brown and Xiu-Feng Henry Wan)

This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.

Abstract

Pigs are considered as important hosts or “mixing vessels” for the generation of pandemic influenza viruses. Systematic surveillance of influenza viruses in pigs is essential for early warning and preparedness for the next potential pandemic. Here, we report on an influenza virus surveillance of pigs from 2011 to 2018 in China, and identify a recently emerged genotype 4 (G4) reassortant Eurasian avian-like (EA) H1N1 virus, which bears 2009 pandemic (pdm/09) and triple-reassortant (TR)-derived internal genes and has been predominant in swine populations since 2016.

Similar to pdm/09 virus, G4 viruses bind to human-type receptors, produce much higher progeny virus in human airway epithelial cells, and show efficient infectivity and aerosol transmission in ferrets. Moreover, low antigenic cross-reactivity of human influenza vaccine strains with G4 reassortant EA H1N1 virus indicates that preexisting population immunity does not provide protection against G4 viruses.

Further serological surveillance among occupational exposure population showed that 10.4% (35/338) of swine workers were positive for G4 EA H1N1 virus, especially for participants 18 y to 35 y old, who had 20.5% (9/44) seropositive rates, indicating that the predominant G4 EA H1N1 virus has acquired increased human infectivity. Such infectivity greatly enhances the opportunity for virus adaptation in humans and raises concerns for the possible generation of pandemic viruses.

          (Continue . . . .)

Although we are getting better at identifying potential threats, the two previous pandemics of the last dozen years came out of left field, with absolutely no warning.  Sure, we knew about swine-variant viruses prior to 2009, but no one saw the 2009 H1N1 swine-origin pandemic coming. 

The same can be said for COVID-19.  

We've looked at several bat coronavirus pandemic contenders over the years (see PNAS: SARS-like WIV1-CoV Poised For Human Emergence), but no one strain really stood out, and the SARS-CoV-2 virus that finally did emerge wasn't on that list.

Although EAH1N1 has all of the earmarks of a legitimate pandemic threat, the same was said of H5N1 in 2008 and H7N9 in 2016, and both - at least temporarily - are on the back burner today.  

While it would be great if we could identify the next pandemic threat before it strikes, it is arguably more important to be ready for whatever comes next.  And as COVID-19 has proven, it doesn't necessarily have to be an influenza pandemic. 

As it is, I'm not convinced we are ready to deal with a severe fall wave of COVID-19, much less a new pandemic threat. But ready or not, the next great global health crisis is inevitable, and likely closer in time than we think. 

Whether it originates from EA H1H1 - or comes from totally out of left field -  we need to be a lot better prepared the next time.  

Because as difficult as COVID-19 has been, it is far from being the worst case scenario. 

mSphere: Environmental Contamination From Asymptomatic COVID-19 Patients & Nature: Face Touching Study

How to Wear Face Cover -CDC

#15,348

Yesterday, in EID Journal: Prolonged Infectivity of SARS-CoV-2 in Fomites, we looked at the viability of our pandemic coronavirus on inanimate objects, whose infectivity was remarkably preserved in the presence of proteins, such as those found in human respiratory fluids.

Today, we have two related reports

Briefly, the first - published today in the journal Nature - looks at the frequency of our unconscious touching of our hair, face, neck, and shoulders (HFNS).

In yesterday's blog, I mentioned an older study (see AJIC Face touching: A frequent habit that has implications for hand hygiene) which showed that when in public, we touch our face/mouth/nose frequently; often 20+ times an hour.

 

This first study, based on the analysis of over 75 hours of video surveillance at a Chinese graduate student office, found - among other things - that the subjects spent a remarkable 9% of their time touching their own hair, face, neck, and shoulders (HFNS).

It's a fascinating report, and while limited to a 5-day observation period and to a cohort who knew they were being observed (see APIC: The Impact Of The Hawthorne Effect On Hand Hygiene Audits), it provides a wealth of behavioral information with infection control implications.

Follow the link to read the study in its entirety. 

Most self-touches are with the nondominant hand

Nan Zhang, Wei Jia, Peihua Wang, Marco-Felipe King, Pak-To Chan & Yuguo Li 

Scientific Reports volume 10, Article number: 10457 (2020) Cite this article

Self-touch may promote the transfer of microorganisms between body parts or surfaces to mucosa. In overt videography of a post-graduate office, students spent 9% of their time touching their own hair, face, neck, and shoulders (HFNS). These data were collected from 274,000 s of surveillance video in a Chinese graduate student office. The non-dominant hand contributed to 66.1% of HFNS-touches.

Most importantly, mucous membranes were touched, on average, 34.3 (SE = 2.4) times per hour, which the non-dominant hand contributed to 240% more than the dominant hand.

Gender had no significant effect on touch frequency, but a significant effect on duration per touch. The duration per touch on the HFNS was fitted with a log–log linear distribution. Touch behaviour analysis included surface combinations and a probability matrix for sequential touches of 20 sub-surfaces. These findings may partly explain the observed variation in the literature regarding the microbiome community distribution on human skin, supporting the importance of indirect contact transmission route in some respiratory disease transmission and providing data for risk analysis of infection spread and control. 

(SNIP)

From our study, washing the nondominant hand is more important because of the higher frequency of touching the mucous membranes. In addition, not only the airborne and large droplet routes, but also the fomite route, can be effectively reduced by wearing surgical masks. The eyes, nostrils and lips are three mucous membranes on the face. Only 6.6% of touches of the mucous membranes were on the eyes, which means 93.4% of viral transfer could be blocked by wearing a surgical mask.

(Continue . . . )

 

Today's second study, published this past week in mSphere, looks at the environmental contamination due to the shedding of SARS-CoV-2 from asymptomatic and mild cases in a non-ICU negative-pressure isolation ward in China. 

If this sounds vaguely familiar, roughly six weeks ago, in EID Journal: Detection of SARS-CoV-2 on Surfaces in Quarantine Rooms, we looked at the extensive contamination of a hotel room occupied overnight by two presymptomatic COVID-19 cases, also in China. 

First the link and abstract to this study (which you'll want to read in its entirety), then I'll return with a postscript. 

Asymptomatic COVID-19 Patients Can Contaminate Their Surroundings: an Environment Sampling Study

Li Wei, Ji Lin, Xiaofei Duan, Wenzhi Huang, Xiaojun Lu, Juan Zhou, Zhiyong Zong

Katherine McMahon, Editor

DOI: 10.1128/mSphere.00442-20

ABSTRACT

The contamination of patients’ surroundings by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains understudied. We sampled the surroundings and the air of six negative-pressure non-intensive care unit (non-ICU) rooms in a designated isolation ward in Chengdu, China, that were occupied by 13 laboratory-confirmed coronavirus disease 2019 (COVID-19) patients who had returned from overseas travel, including 2 asymptomatic patients.

A total of 44 of 112 (39.3%) surface samples were positive for SARS-CoV-2 as detected by real-time PCR, suggesting extensive contamination, although all of the air samples were negative.

In particular, in a single room occupied by an asymptomatic patient, four sites were SARS-CoV-2 positive, highlighting that asymptomatic COVID-19 patients do contaminate their surroundings and impose risks for others with close contact. Placement of COVID-19 patients in rooms with negative pressure may bring a false feeling of safety, and the importance of rigorous environment cleaning should be emphasized.

IMPORTANCE Although it has been well recognized that the virus SARS-CoV-2, the causative agent of COVID-19, can be acquired by exposure to fomites, surprisingly, the contamination of patients’ surroundings by SARS-CoV-2 is largely unknown, as there have been few studies. We performed an environmental sampling study for 13 laboratory-confirmed COVID-19 patients and found extensive contamination of patients’ surroundings.

In particular, we found that asymptomatic COVID-19 patients contaminated their surroundings and therefore imposed risks for other people. Environment cleaning should be emphasized in negative-pressure rooms. The findings may be useful to guide infection control practice to protect health care workers

(Continue . . . )

While it seems probable that symptomatic COVID-19 cases shed far more virus and are better able contaminate their surroundings than asymptomatic or presymptomatic carriers, they are also more more easily identified and avoided than `stealth' carriers of SARS-CoV-2. 

How much of an impact that asymptomatic shedding of the virus has on the spread of COVID-19 has yet to be quantified, but the evidence for its contribution continues to mount.

EID Journal: Persistence of SARS-CoV-2 in Aerosol Suspensions

EID Journal: Asymptomatic or Presymptomatic Transmission Of SARS-CoV-2

MMWR: Asymptomatic & Presymptomatic SARS-CoV-2 Infections in Residents of a LTCF

Presymptomatic Transmission of SARS-CoV-2 — Singapore, January 23–March 16, 2020

Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany

When you combine the shedding studies (of both symptomatic & asymptomatic) cases with the fomite contamination and environmental persistence studies, it isn't hard to understand why cases are suddenly surging in Florida, Texas, California and many other states where social distancing rules have recently been relaxed. 

While stealth transmission is undeniably harder to protect against, it can be done.  

Social distancing, scrupulous hand hygiene, wearing face covers, and avoiding touching your face are all things that can reduce the risk of picking up the virus from individuals, the air, or from contaminated surfaces. 

Granted, following this advice rigorously isn't easy, particularly in the summer. Masks and face covers are hot and uncomfortable, and after months of social isolation people want to mingle and have fun.

 

But we are currently seeing what comes from a month of not doing these things in a pandemic.

 

In Florida, that has meant more than a 10-fold increase in daily cases in the past 30 days (see chart below), which corresponds to the relaxation of social distancing rules starting on Memorial Day weekend. 

Florida COVID-19 Dashboard June 29th

  

While going back to a `lockdown' is both socially and economically unacceptable, we need to do a much better job of preventing COVID-19 transmission, even if it is inconvenient.  

Because if we allow these trends continue for very much longer, hospitals will start to become overwhelmed, deaths will inexorably rise, and any hopes for a quick economic recovery will vanish.

 

Making the future course of this pandemic literally in - and arguably on - our hands. 

EID Journal: Prolonged Infectivity of SARS-CoV-2 in Fomites

#15,347

Fomites are any surface or object that can become contaminated with viral, fungal, or bacterial pathogens and that can then later contaminate - and possibly infect - anyone who touches or handles them.  

Important, because research (see AJIC Face touching: A frequent habit that has implications for hand hygiene) has shown that when in public, we touch our face/mouth/nose frequently; often 20+ times an hour.

Common fomites include the turnstile at the subway, the touch screen on your bank’s ATM, the door handle to your office's microwave, the change the cashier gives you at the checkout lane, and the handle of your shopping cart . . . the list is endless.

In 2014's ICAAC Video: How Quickly A Virus Can Spread In A Building, we looked at an experiment on fomite transmission, which they described as:

Using tracer viruses, researchers found that contamination of just a single doorknob or table top results in the spread of viruses throughout office buildings, hotels, and health care facilities. Within 2 to 4 hours, the virus could be detected on 40 to 60 percent of workers and visitors in the facilities and commonly touched objects. Simple use of common disinfectant wipes reduced virus spread by 80 to 99 percent. 

We revisited this topic again in 2018, in  Study: Simulated Influenza A Transmission In An Office Environment, that found:

Influenza A transmission in a graduate student office is simulated via long-range airborne, fomite, and close contact routes based on realistic data of human behaviours. The long-range airborne, fomite and close contact routes contribute to 54.3%, 4.2% and 44.5% of influenza A infections, respectively. 

For the fomite route, 59.8%, 38.1% and 2.1% of viruses are transmitted to the hands of students from private surfaces around the infected students, the students themselves and other susceptible students, respectively. The private surfaces of infected students are highly contaminated. 

Past studies have focused primarily on influenza, but in 2015's IDWeek: Persistence Of MERS-CoV On Hospital Environmental Surfaces, we looked at the widespread MERS coronavirus contamination found in South Korean hospitals during their multi-hospital epidemic 5 years ago.

A more recent study (see EID Journal: Aerosol and Surface Distribution of SARS-CoV-2 in Hospital Wards, Wuhan, China) found extensive surface contamination in and around a ward treating COVID-19 cases, although the viability of the viruses was not tested. 

Despite all of this research, how much of COVID-19's transmission actually comes from contact with contaminated fomites remains unknown.  The CDC's COVID-19 Transmission webpage states:

The virus is thought to spread mainly from person-to-person. 

• Between people who are in close contact with one another (within about 6 feet).
• Through respiratory droplets produced when an infected person coughs, sneezes, or talks.
• These droplets can land in the mouths or noses of people who are nearby or possibly be inhaled into the lungs.
• COVID-19 may be spread by people who are not showing symptoms.

But they also grant that: 

The virus may be spread in other ways

It may be possible that a person can get COVID-19 by touching a surface or object that has the virus on it and then touching their own mouth, nose, or possibly their eyes. This is not thought to be the main way the virus spreads, but we are still learning more about how this virus spreads.

One of the big unknowns is how long the SARS-CoV-2 virus remains viable (and infectious) on different types of surfaces, and under different environmental conditions (temperature, humidity, UV rays, etc.). 

Six weeks ago, in DHS: Decay Rate Calculator For SARS-CoV-2 we looked at simple, but limited tool to calculate the half-life of the virus on non-porous materials under various temperatures and humidities.

All of which brings us to a new study, published this week in the EID Journal, that looks at the persistence of SARS-COV-2 on surfaces - and finds that those that are mixed with proteins (such as found in respiratory fluids) are particularly long lived.  

First some excerpts from the research letter, then I'll return with a postscript:

Research Letter

Prolonged Infectivity of SARS-CoV-2 in Fomites

Boris Pastorino, Franck Touret, Magali Gilles, Xavier de Lamballerie, and Rémi N. Charrel 

Author affiliations: Unité des Virus Émergents, Marseille, France.

Abstract

We spotted severe acute respiratory syndrome coronavirus 2 on polystyrene plastic, aluminum, and glass for 96 hours with and without bovine serum albumin (3 g/L). We observed a steady infectivity (<1 log10 drop) on plastic, a 3.5 log10 decrease on glass, and a 6 log10 drop on aluminum. The presence of proteins noticeably prolonged infectivity.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide, demonstrating a great potential for direct and indirect transmission between humans. Coronaviruses can keep their infectivity in fomites and thus can remain infectious on dry surfaces for hours (1,2). However, limited data are available for SARS-CoV-2 (1). Specifically, there are no data about the role of interfering substances such as proteins on SARS-CoV-2 infectivity in the environment.

We evaluated the stability and infectivity of SARS-CoV-2 deposited on polystyrene plastic, aluminum, and glass for 96 hours at 45%–55% relative humidity (recommended for indoor living spaces by the American Society of Heating, Refrigeration and Air Conditioning Engineers) and 19°C –21°C temperature range using a 106 50% tissue culture infectivity dose (TCID50)/mL inoculum.

(SNIP)

Our data showed that SARS-CoV-2 infectivity was remarkably preserved in the presence of proteins, regardless of the type of surface. A final concentration of 11.4 g/L of proteins, as used in our study, closely mimics that of respiratory fluids, which possess protein concentrations of a similar order of magnitude. However, the respiratory body fluids are complex media including not only proteins, but also enzymes and mucins (present in mucus) that may have a negative effect on virus infectivity. Regarding viral load measurement, the reason for avoiding the use of molecular techniques such as reverse transcription PCR is that despite that they allow quantification of RNA copies and determination of RNA decay, they cannot measure residual infectivity on various surfaces.

The protective effect of proteins had already been described for pandemic SARS-CoV or suggested for influenza A(H1N1) virus, but with less notable effects (4,6). As illustrated in other virus models (7), interfering substances such as proteins influenced the resistance of SARS-CoV-2 to drying and thus its persistence in the environment.

In conclusion, we showed that a moderate protein concentration in droplets markedly increased the infectivity of SARS-CoV-2, suggesting that a protein-rich medium like airway secretions could protect the virus when it is expelled and may enhance its persistence and transmission by contaminated fomites.

Accordingly, it is plausible that fomites infected with SARS-CoV-2 play a key role in the indirect transmission of coronavirus disease (COVID-19). This finding supports surface cleaning as a necessary action that should be enforced and repeated becuase it may play a key role in halting SARS-CoV-2 transmission and mitigating the COVID-19 pandemic.

Dr. Pastorino is research engineer with a PhD in virology. His primary research interests are biosafety aspects of Biosafety Level 3 viruses in the context of preparedness and response against epidemics.

Although we tend to think of an infected person touching a surface in order to contaminate it, research has shown that coughing, sneezing, and even talking can aerosolize the virus, or project large virus-laden droplets, both types which will eventually settle out of the air and onto surfaces. 

There are also mechanical ways to aerosolize, and potentially spread, the virus.  Earlier this month, in EID Journal: More Toilet Plume Research In A Time Of COVID-19 and again in Another Toilet Plume Study To Ponder, we looked at the potential for flush toilets to spread the virus. 

While exact role that contaminated fomites play in the COVID-19 pandemic remains unquantified, the available evidence suggests it plays a non-trivial role, making the CDC's guidance on fomites (see Extended Guidance for Cleaning and Disinfecting (Homes, Schools, Businesses, etc.) and hand hygiene, nothing to sneeze at. 

 

180 Days Later

 

AFD Blog on 12/30/2019

 

#15,346

One hundred and eighty mornings ago I awoke (at 2am) 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 48 hours I'd written 6 blogs on the topic, and FluTrackers had amassed scores of reports. But despite our early concerns, none of us could have predicted how dramatically the world was about to change. 

And that is the crux of the matter. Obscure events, often occurring in far off places, can have a huge global impact.  Next time, it could be a new avian flu subtype emerging in Egypt, or perhaps an arenavirus jumping from rodents to humans in South America, or a swine influenza virus circulating in pigs in the American Midwest bridging the species barrier.  

The CDC maintains an IRAT List of 19 influenza viruses with pandemic potential, 16 of which have been added in the past 9 years (see CDC Adds 3 Novel Flu Viruses To IRAT List). This list contains - while not all encompassing - 15 avian viruses, 3 swine variant viruses, and 1 canine virus.

Although social distancing may limit opportunities for some of these viruses to jump to humans while COVID-19 rages, there are no guarantees that we won't see another major infectious disease crisis before our current pandemic has ended.  

Meanwhile the COVID-19 pandemic continues to defy early expectations. Exactly what that portends for this fall and winter remains uncertain, but its economic, societal, and public health impacts are only likely to grow in the months ahead. 

To this we can add a predicted overly active Atlantic Hurricane season, the potential for other natural disasters (earthquakes, wildfires, floods, etc.) both here and around the world, continued uncertainties in the global supply chain (see CIDRAP: Growing Drug Shortages Due To COVID-19), high unemployment and our pernicious and unresolved global economic crisis.

It's no wonder our collective stress levels are through the roof. 

While I can't predict which shoe will be the next to drop, the world is too big of a place not to provide a constant supply of new threats. Most will be local, some will be regional, and a few may become global. 

The only certainty is . . . the more they pile up, the less effectively governments and relief agencies around the world will be to respond.

The takeaway from the last six months is now - perhaps more than at any time in our lifetimes - we need to be building individual, family, and community resilience. And for most families, that means being prepared to deal with the unexpected. 

In recent years preparedness has gotten a bit of a bad name. The popular image of a prepper - promulgated by the media - is that of a nut out gathering squirrels, as they anxiously await doomsday.

While that archetype undoubtedly exists, most `preppers' - like myself - gear up to deal with more reasonable, and more survivable, scenarios like hurricanes, floods, blizzards, and yes, even pandemics.  

 

And personally, over the past 3 years, I'm 2 for 4 on that short list. 

Long time readers of this blog know that I  - like FEMA and Ready.gov - heavily promote personal and family preparedness year round. And given the challenges facing the world right now - and what may come in the months ahead - investing in some family preparedness this summer may be cheap insurance. 

While where you live, and your local threat environment, may dictate some changes, my general goals for personal and family preparedness include:

• A battery operated NWS Emergency Radio to find out what was going on, and to get vital instructions from emergency officials
• A decent first-aid kit, so that you can treat injuries
• Enough non-perishable food and water on hand to feed and hydrate your family (including pets) for the duration (10 to 14 days minimum)
• A way to provide light when the grid is down.
• A way to cook safely without electricity
• A way to purify or filter water
• A way to stay cool (fans) or warm when the power is out.
• A small supply of cash to use in case credit/debit machines are not working
• An emergency plan, including meeting places, emergency out-of-state contact numbers, a disaster buddy, and in case you must evacuate, a bug-out bag
• Spare supply of essential prescription medicines that you or your family may need
• A way to entertain yourself, or your kids, during a prolonged blackout

 

Nearly six weeks ago, in Why Preparing For This Year's Hurricane Season Will Be `Different', we looked at some of the challenges of preparing for a hurricane, or any other disaster, during a pandemic.  

While store shelves are better stocked today, it wouldn't take more than a whiff of a new threat - like an approaching storm - to see them wiped clean again.  And queuing up with hundreds of other shoppers during a pandemic in order to prepare for a new threat is a recipe for infection. 

A week ago, a Bankrate poll was released which asked Americans' what their biggest financial regret was.   

Survey: Americans’ biggest coronavirus financial regret is not having enough emergency savings

The coronavirus pandemic has hit Americans hard, and a new Bankrate survey says Americans’ top financial regret is not having enough emergency savings to withstand the crisis.

 

The survey shows that of Americans with financial regrets, the biggest regret is a lack of emergency savings, which was noted by 23 percent of respondents. But when it comes to their biggest financial priority going forward, Americans are focused on paying down debt (22 percent), followed by saving more for emergencies (17 percent).

          (Continue . . . )

Despite a long history of periodic recessions - and two economic crashes in living memory - they hadn't prepared for an economic downturn. They assumed that today would be pretty much the same as yesterday, and that tomorrow would be the same as today. 

Preppers, on the other hand, expect - and prepare for - the unexpected. 

Now is the time, while store shelves are reasonably stocked, and the economy has opened a little, to ask yourself what your biggest regret would be a year from now if we get blindsided by another disaster or  crisis during this pandemic - or if COVID-19's 2nd wave proves to be much larger than the first. 

What can you do today to mitigate the hardships - or to protect your family - during the uncertain  months ahead? 

Do you have an emergency plan or a first aid kit?  Is your pantry lean, or can you and your family get by for a few weeks without visiting a grocery store?   Can you stay cool in the summer, and warm in the winter, if the power is out for days or weeks?   Do you have a disaster buddy?

Looking back over the past 6 months, it's hard imagine what the next 180 days may bring. Hopefully better times. But hope is not a plan. 

While you can't plan for every contingency, and most of us are on a very tight budget, anything you can do in advance to prepare for the next disaster or crisis will be money well spent. But the operative words are `in advance'. 

Some recent preparedness blogs you may have missed include:

My New (And Improved) Solar Battery Project (for CPAP)

My New Solar Power System (Updated For 2020)

 

The Natural Disaster Most People Don't Think About

What Other Threats May Come

CDC: Updated COVID-19 Checklist For Older Persons

Hurricane Preparedness Week: Day 7 - Complete A Written Plan

 

The Lancet: Yet Another Study On Neurological Manifestations In Severe COVID-19 Patients

#15,345

Although many people still regard COVID-19 as primarily a respiratory disease, the evidence suggests - at least among those severely ill - that neurological, cardiovascular, and hematological complications are not uncommon.  

Some of the non-neurological complications we've explored include:

WHO Scientific Brief: Multisystem Inflammatory Syndrome in Children & Adolescents with COVID-19

EID Journal: Two Reports On Thrombotic Events In COVID-19 Patients

EID Journal: Pulmonary Embolism and Increased Levels of d-Dimer in COVID-19 Patients

Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young

Increasingly, however, we are seeing reports of neurological manifestations, and even permanent damage, among COVID-19 patients. 

Last April, in JAMA: Neurologic Manifestations Of Patients With Severe Coronavirus Disease, we examined a report from China that more than 1/3rd of a study group of 214 patients hospitalized with COVID-19 in Wuhan City showed signs of neurological involvement.

Neurological manifestations ranged from relatively mild (headaches, dizziness, anosmia, mild confusion, etc.) to more profound (seizures, stupor, loss of consciousness, etc.) to potentially fatal (ischemic stroke, cerebral hemorrhage, muscle injury (rhabdomyolysis), etc.). 

Not quite 3 weeks ago, in PrePrint: Cytokine Release Syndrome-Associated Encephalopathy in Patients with COVID-19, we saw a preprint (not-yet-peer-reviewed) article describing 5 COVID-19 patients admitted to a renal unit at the Strasbourg University Hospital, all presenting with neurological symptoms and blood markers suggestive of a Cytokine Release Syndrome (CRS),

And earlier this week, in The Lancet: COVID-19: Can We Learn From Encephalitis Lethargica?, we looked at growing concerns over long-lasting neurological sequelae among recovered COVID cases. 

Although I haven't covered them all, more studies have recently emerged that document a neurological component to severe COVID-19 disease, including:

COVID ‐19: A Global Threat to the Nervous System

Igor J. Koralnik MD. Kenneth L. Tyler MD

First published:07 June 2020

https://doi.org/10.1002/ana.25807

Neurologic manifestations in hospitalized patients with COVID-19: The ALBACOVID registry
Carlos Manuel Romero-Sanchez, MD et al.
First published June 1, 2020,

DOI: https://doi.org/10.1212/WNL.0000000000009937

Brain MRI Findings in Severe COVID-19: A Retrospective Observational Study

Prof Stéphane Kremer* , François Lersy*, Prof Jérome de Sèze, Prof Jean-Christophe Ferré, Adel Maamar, Béatrice Carsin-Nicol, Prof Olivier Collange, … See all authors

Published Online:Jun 16 2020 https://doi.org/10.1148/radiol.2020202222

To this growing list we can add a new study, published yesterday in The Lancet Psychiatry, that describes 153 COVID-19 cases treated in UK hospitals which found a wide range of neurological and psychiatric complications affecting both younger and elderly patients. 

First a link and a small snippet: 

Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study

Aravinthan Varatharaj, MRCP, Naomi Thomas, MRCPCH, Mark A Ellul, MRCP, Nicholas W S Davies, PhD, Thomas A Pollak, MRCP, Elizabeth L Tenorio, PhD et al.

Published: June 25, 2020

DOI:https://doi.org/10.1016/S2215-0366(20)30287-X

(Excerpt)

Complete clinical datasets were available for 125 (82%) of 153 patients. 77 (62%) of 125 patients presented with a cerebrovascular event, of whom 57 (74%) had an ischaemic stroke, nine (12%) an intracerebral haemorrhage, and one (1%) CNS vasculitis. 39 (31%) of 125 patients presented with altered mental status, comprising nine (23%) patients with unspecified encephalopathy and seven (18%) patients with encephalitis.

The remaining 23 (59%) patients with altered mental status fulfilled the clinical case definitions for psychiatric diagnoses as classified by the notifying psychiatrist or neuropsychiatrist, and 21 (92%) of these were new diagnoses. Ten (43%) of 23 patients with neuropsychiatric disorders had new-onset psychosis, six (26%) had a neurocognitive (dementia-like) syndrome, and four (17%) had an affective disorder. 18 (49%) of 37 patients with altered mental status were younger than 60 years and 19 (51%) were older than 60 years, whereas 13 (18%) of 74 patients with cerebrovascular events were younger than 60 years versus 61 (82%) patients older than 60 years.

          (Continue . . . )

While dramatic, these findings need to be interpreted cautiously. 

It is unknown what proportion of these neurological problems can be directly attributed to the SARS-CoV-2 virus, what portion were caused by the body's immune response to infection, and how many may have been caused by the stress of being hospitalized, by treatments (isolation, ventilators, drugs, etc.) received, or by previous diagnosed psychiatric conditions.

A 2013 NEJM study by researchers at Vanderbilt University - called Long-Term Cognitive Impairment after Critical Illness - famously found that a large percentage of ICU patients experience some form of dementia or psychosis - both during their hospital stay - and often lingering after their release (see STAT News Hospitals struggle to address terrifying and long-lasting ‘ICU delirium’).

A number of experts have weighed in on yesterday's Lancet study, and their comments can be found on the Science Media Center (SMC).

JUNE 25, 2020

Expert reaction to study looking at brain complications in hospitalised patients with severe COVID-19

Research, published in The Lancet Psychiatry, looked at brain complications in hospitalised patients with severe COVID-19.

While the vast majority of people who contract COVID-19 will recover without serious illness or sequelae, for an unlucky subset, this disease can produce profound, lasting, and sometimes fatal complications. 

Scripps Research: Study Suggests Some Flu Viruses May Be Less Susceptible To A `Universal' Flu Vaccine

Credit NIAID

#15,344

For as along as I've been blogging on infectious diseases, there have been optimistic predictions that we are only 5 years away from having the holy grail of vaccinology; a universal flu vaccine. 

Since I get a flu shot every year, I'm understandably hopeful this can be accomplished. But despite a full court press by the NIH - and many other scientific institutions over the past 15 years - we appear to be still 5 or more years away from having a `universal' flu vaccine. 

A universal flu vaccine is often described in the popular press as being a `one time (or every few years) shot' that would convey nearly full protection against all flu sub-types.   While ideal, the current goal is a bit more modest. 

A little over two years ago, in  J.I.D.: NIAID's Strategic Plan To Develop A Universal Flu Vaccine, we looked at the National Institute of Allergy and Infectious Diseases' short term goals.  

Credit NIAID

Not quite what most people think of when you say `universal flu vaccine', but still a considerable  improvement over what we have right now.  But even with scaled down expectations, success has been elusive. 

Part of the problem has been that influenza viruses, and our human immune system, don't always react the way we expect them to. 

A long standing assumption is that once you are naturally infected with a specific influenza virus, you will carry lifelong - or at least long-lasting - antibody titers that are protective against that specific virus. 

Similar, but potentially less long-lasting effects are also expected from vaccination. This `acquired immunity' is also expected to extend to antigenically similar viruses, although things get much murkier once even minor changes to the virus are introduced.

In the spring of 2019, in a fascinating research study conducted by researchers at the NIH and NIAID (see C.I.D.: Influenza A Reinfection in Sequential Human Challenge), we saw that this wasn't necessarily so.

 

In that study, researchers exposed a small group of healthy volunteers to a specific H1N1 virus, and recorded their subsequent infections and immune responses.

A year later, they repeated this virus challenge on the same group (n=7) with the exact same virus, expecting their residual immunity would protect them. To their surprise they found that at least 3 - and possibly 5 - of the 7 were reinfected with the exact same flu strain.

While the study cohort was small, the results led the researchers to write in their conclusion:

The data presented in this report demonstrate that sequential infection with the identical influenza A virus can occur and suggest it may not be rare. These data raise questions about immune memory responses in an acute superficial respiratory mucosal infection and their implications in development of broadly protective influenza vaccines. Further investigation of these observations is warranted.

There are other potential stumbling blocks, including ADE (Antibody Dependent Enhancement), and OAS (Original Antigenic Sin), both of which can produce paradoxical, and potentially dangerous immune responses among those who are either vaccinated, or previously exposed to a similar virus.

 

Original Antigenic Sin was coined in 1960 by Thomas Francis, Jr. in his article On the Doctrine of Original Antigenic Sin) that postulates that when the body’s immune system is exposed to and develops an immunological memory to one virus, it may be less able to mount a defense against a subsequent exposure to a second slightly different version of the virus.

OAS has been described in relation to influenza viruses, Dengue Fever, and HIV. You can find a terrific background piece on OAS from 2009 by Robert Roos in my blog entitled CIDRAP On Original Antigenic Sin.

And if mistakenly sending the wrong antibodies into the fray isn’t bad enough, sometimes non-neutralizing antibodies can actually enhance a virus’s ability to enter a host’s cells via a process called ADE or Antibody-dependent enhancement.

Issues surrounding OAS and ADE (Antigenic Dependent Enhancement appear to have played a role in 2017's Dengue vaccine debacle (see Philippines: FDA Withdraws Dengvaxia® Vaccine - Sanofi Quantifies Risk), and may influence the impact of other vectorborne diseases (PLoS Currents: Another In Vitro Study Suggests Previous Dengue Exposure May Exacerbate Zika Severity).

Some recent studies have cautioned that some approaches to making universal flu vaccines may risk inducing an ADE response as well, including 

Antibody-dependent enhancement of influenza disease promoted by increase in hemagglutinin stem flexibility and virus fusion kinetics  - PNAS

The potential danger of suboptimal antibody responses in COVID-19  - Nature

To this impressive list of challenges, we can add another - the ability of some influenza viruses to mutate rapidly and evade the vaccine - as explained by the following study and press release - from the Scripps Research Institute.

Different genetic barriers for resistance to HA stem antibodies in influenza H3 and H1 viruses

Nicholas C. Wu1,*, Andrew J. Thompson2,*, Juhye M. Lee3,4,5, Wen Su6, Britni M. Arlian2, Jia Xie7, Richard A. Lerner7,8, Hui-Ling Yen6, Jesse D. Bloom3,4,9, Ian A. Wilson1,8,†

Science 19 Jun 2020:
Vol. 368, Issue 6497, pp. 1335-1340
DOI: 10.1126/science.aaz5143

The study is sadly behind a paywall, but we have press release giving us many of the pertinent details.  I'll have a short postscript when you return. 

Flu mutation study suggests universal flu vaccine may be even more challenging than expected

Many flu strains may be capable of mutating to escape universal-vaccine antibodies.

June 23, 2020

LA JOLLA, CA—Some common strains of influenza have the potential to mutate to evade broad-acting antibodies that could be elicited by a universal flu vaccine, according to a study led by scientists at Scripps Research. The findings highlight the challenges involved in designing such a vaccine, and should be useful in guiding its development.

In the study, published in Science, the researchers found evidence that one of the most common flu subtypes, H3N2, can mutate relatively easily to escape two antibodies that were thought to block nearly all flu strains. Conversely, they found it is much more difficult for another common subtype, H1N1, to escape from the same broadly neutralizing antibodies.

One of the main goals of current influenza research is to develop a universal vaccine that induces broadly neutralizing antibodies, also known as “bnAbs,” to give people long-term protection from the flu.

“These results show that in designing a universal flu vaccine or a universal flu treatment using bnAbs, we need to figure out how to make it more difficult for the virus to escape via resistance mutations,” says the study’s senior author Ian Wilson, DPhil, Hansen Professor of Structural Biology and Chair of the Department of Integrative Structural and Computational Biology at Scripps Research.

The promise of a universal vaccine

Influenza causes millions of cases of illness around the world every year and at least several hundred thousand fatalities. Flu viruses have long posed a challenge for vaccine designers because they can mutate rapidly and vary considerably from strain to strain.

The mix of strains circulating in the population tends to change every flu season, and existing flu vaccines can induce immunity against only a narrow range of recently circulating strains. Thus, current vaccines provide only partial and temporary, season-by-season protection.

Nevertheless, scientists have been working toward developing a universal flu vaccine that could provide long-term protection by inducing an immune response that includes bnAbs. Over the past decade, several research groups, including Wilson’s, have discovered these multi-strain neutralizing antibodies in recovering flu patients, and have analyzed their properties. But to what extent circulating flu viruses can simply mutate to escape these bnAbs has not been fully explored.

In the study, first-authored by postdoctoral research associate Nicholas Wu, PhD, and staff scientist Andrew Thompson, PhD, the team examined whether an H3N2 flu virus could escape neutralization by two of the more promising flu bnAbs that have been discovered so far.

Known as CR9114 and FI6v3, these antibodies bind to a critical region on the virus structure called the hemagglutinin stem, which doesn’t vary much from strain to strain. Because of their broad activity against different flu strains, they’ve been envisioned as antibodies that a universal flu vaccine should be designed to elicit, and also as ingredients in a future therapy to treat serious flu infections.

Using genetic mutations to methodically alter one amino acid building-block of the protein after another at the stem site where the bnAbs bind, Wu and colleagues found many single and double mutations that can allow H3N2 flu to escape the antibodies’ infection-blocking effect.

The team also found a few instances of these “resistance mutations” in a database of gene sequences from circulating flu strains, suggesting that the mutations already happen occasionally in a small subset of ordinary flu viruses. 

Escape skills vary by flu strain 

Although experiments and analyses suggested that H3N2 viruses are broadly capable of developing resistance mutations, the same was not true for H1N1 viruses. The researchers tested several H1N1 viruses and found that none seemed able to mutate and escape, except for rare mutations with weak escape effects. The H3N2 and H1N1 subtypes account for most of the flu strains circulating in humans.

The researchers used structural biology techniques to show how differences in the hemagglutinin stem structure allow H3N2 flu viruses to develop resistance mutations to the two stem-binding antibodies more easily than H1N1 viruses.

“If it’s relatively easy for H3N2 to escape those bnAbs, which are the prototype antibodies that a universal flu vaccine should induce, then we probably need to think more carefully and rigorously about the design of that universal flu vaccine against certain influenza subtypes,” Wu says. “The good news is that a universal flu vaccine should at least work well against the H1N1 subtype.”

The researchers now plan to conduct similar studies with other flu subtypes and bnAbs. They say that in principle, a vaccine eliciting multiple bnAbs that attack different sites on flu viruses or are more accommodating to changes in the virus could help mitigate the problem of resistance mutations.

“Different genetic barriers for resistance to HA stem antibodies in influenza H3 and H1 viruses” was authored by Nicholas Wu, Andrew Thompson, Juhye Lee, Wen Su, Britni Arlian, Jia Xie, Richard Lerner, Hui-Ling Yen, Jesse Bloom, and Ian Wilson.

Support for the research was provided by the Bill and Melinda Gates Foundation (OPP1170236), and the National Institutes of Health (K99 AI139445, F30 AI136326, R01 AI127893, R56 AI127371, R01 AI114730).

(Continue . . . ) 

Not surprisingly, it is H3N2 - the longest running - and arguably fastest mutating, and most agile seasonal flu subtype to emerge in modern times (see The Enigmatic, Problematic H3N2 Influenza Virus) that poses the greatest challenge. 

H3N2 first appeared 52 years ago (1968) as a pandemic strain, and supplanted the short-lived H2N2 virus (which sparked the 1957 pandemic). It then survived challenges by the return of H1N1  - after a 20 year absence - in 1977, and similarly managed to hold on when the 2009 H1N1 pandemic strain emerged.

While long in the tooth, H3N2 is a survivor - in large part because there are so many genetically distinct, yet biologically `fit' -  clades circulating around the world. 

While the challenges to creating a universal flu vaccine are many and varied, the dividends from creating a `universal' flu vaccine are potentially huge.  If developed, it might even stave off - or blunt - the next influenza pandemic. 

It would really help a lot, though, if H3N2 would begin acting its age and retire.