Tuesday, November 24, 2020

Denmark: Rise In Humans Infected With Mink Variant COVID-19 in Central Jutland

 

Central Jutland - Credit Wikipedia


#15,579

Even as lockdown restrictions have recently been eased in North Jutland where Denmark reported an outbreak of `mink-variant' COVID-19 - both in humans and farmed mink last month (see SSI Update -Relaxation Of North Jutland Restrictions) - the number of `variant' virus infections in Central Jutland has begun to rise.

Yesterday the Danish government announced new measures to contain the spread of these variant viruses in two municipalities in North Jutland; Holstebro and Ringkøbing-Skjern, which have a combined population of about 100,000.

While the term `mink-variant' is used, that is a broad term that covers at least 5 different mutated strains of the virus, including `cluster 5' which was linked to potentially reduced vaccine effectiveness.  

At last word, this most problematic variant hasn't been reported in Denmark since mid-September. 

Genetic sequencing of new isolates, however, is ongoing. 

The government introduces measures to contain infection with mink variants in Holstebro and Ringkøbing-Skjern municipalities

PRESS RELEASE - The government is launching a number of measures to reduce and contain the infection in Holstebro and Ringkøbing-Skjern municipalities. This is because a high incidence of infection has been found among people related to mink farms and fur series.

The health authorities recommend that special measures be taken in relation to testing, infection detection and self-isolation.

And the residents of the affected municipalities are encouraged to interact with as few people as possible.

The measures will tentatively be valid until and including 3 December 2020.

See the full list of measures here .

A local task force is set up consisting of the Danish Agency for Patient Safety and the local police authorities to handle local initiatives.

On the basis of new data from the health authorities for the spread of infection, sequencing, etc. the Task Force, including the health authorities, has assessed the situation. The task force pays particular attention to: 

  • In the Central Jutland Region, it is in the municipalities of Holstebro and Ringkøbing-Skjern that most people with connections to mink production have been infected with COVID-19.
  • In the Central Jutland Region, 47 cases (26%) and 48 cases (27%) out of a total of 180 cases of COVID-19 in persons associated with mink production have so far occurred in Holstebro and Ringkøbing-Skjern municipalities.
  • Results of the sequencing in the Central Jutland Region show that in weeks 44 and 45, 12% and 9% of all sequenced samples are positive for mink variants, respectively, compared to 3% and 6% of the samples in weeks 42 and 43, respectively.
  • In Holstebro Municipality on 23 November, an incidence per 100,000 inhabitants, of 305, where the number the week before was 276. In Ringkøbing-Skjern Municipality on 23 November, an incidence per. 100,000 inhabitants out of 101 infected, where the number the week before was 108.
The Statens Serum Institut states that it is possible that the proportion of infected with mink variants will increase in Holstebro and Ringkøbing-Skjern municipalities in the coming weeks, due to the sharp increase in the number of newly infected farms and infected people associated with mink farms.

The task force follows developments in the Central Jutland Region closely. Developments in the Region of Southern Denmark but also other parts of the country with mink farming are also monitored. There may therefore be a need for more municipalities to be covered by the measures.
Further information:
Ministry of Health and the Elderly press telephone: 21 32 47 27


For more on the history, and concerns, over `mink variant' COVID-19, you may wish to revisit:


Preprint: Recurrent Mutations in SARS-CoV-2 Genomes Isolated from Mink Point to Rapid Host-Adaptation

EID Journal: SARS-CoV-2 Transmission between Mink (Neovison vison) and Humans, Denmark

ECDC Rapid Risk Assessment: Detection of New SARS-CoV-2 Variants Related to Mink

WHO Statement On SARS-CoV-2 Mink-associated Variant Strain – Denmark

MMWR: ACIP - Ethical Principles for Allocating Initial Supplies of COVID-19 Vaccine In The United States

  

HHS Sample Framework For Vaccine Distribution 

#15,578

While there are still no currently approved COVID-19 vaccines in the United States, early clinical trial data has been encouraging on both safety and effectiveness, and so one or more will likely receive an EUA (Emergency Use Authorization) before the end of the year. 

A tremendous accomplishment, given it has been less than a year since SARS-CoV-2 emerged. But creating a vaccine may end up being the easy part.  Getting two doses into the arms of enough people to significantly impact the spread of the virus my prove the far greater challenge. 

Not only will initial vaccine supplies be limited, there is a huge amount of vaccine skepticism - or downright resistance - among the general population.  A recent Gallup Poll found only 58% of Americans would be willing to take the vaccine - up from 50% two months ago  - but well below the  ideal uptake for the vaccine. 

And this is before the expected full-court press on social media channels by the anti-vaccine brigade, once a vaccine is approved.  

As I pointed out last August in Remembering An Emergency Pandemic Vaccine Program That Went Awry, demand for the 1976 Swine flu Shot was very high until the newspapers began highlighting several (elderly) recipients who died within days of getting the jab.  Their deaths were likely unrelated to the vaccine, but it was a `good' story, and so the papers ran with it. 

Today, between 24-hour cable news networks and scores of social media outlets, any deaths that occur within days or a couple of weeks of receiving a COVID vaccine will probably get a lot of adverse attention. 

Much like what we saw last month in South Korea (see South Korea's Flu Vaccine Investigation) after reports emerged of dozens of deaths (out of millions of flu shot recipients), even though their CDC could find no link to the vaccine.  

When you vaccinate large numbers of an elderly population, a small percentage will die due to other causes within days.  While expected, it is nevertheless a public relations nightmare. 

While early clinical trials suggest these COVID vaccines are safe, they are somewhat notorious for producing brief, and self-limiting side effects in many people, including fever, `flu-like' symptoms, and general malaise.   It reportedly isn't pleasant. 

How this will affect uptake is unknown, but many who opted for the first jab may decide against taking the booster 28 days later.  

And then there is the thorny problem of who to prioritize for the vaccine, when supplies do become available.  Healthcare workers are likely to be at or near the front of the line, but deciding who to vaccinate next is much tougher. 

  • The elderly in nursing homes are at greatest risk of death from COVID - but they are also the frailest cohort - and some percentage will inevitably succumb in the days and weeks after the receiving the shot, potentially eroding confidence in the vaccine.  We also don't know how effective the vaccine will be in the elderly. 
  • Essential workers are - by the very nature of their jobs - at greater risk of viral exposure, and often belong to ethic groups that have been disproportionately impacted by the pandemic. They often have less access to medical services, and arguably have a better chance of spreading the virus than nursing home residents. 

Further down the line will be those over 65 (but not in nursing facilities), and adults under 65.  As we discussed a month ago in A COVID Vaccine Reality Check, pregnant women and children probably won't be offered the jab in the beginning due to a lack of safety data (see CDC: 10 Things Healthcare Professionals Need to Know about U.S. COVID-19 Vaccination Plans).

While the U.S. government has not finalized their plans, yesterday the CDC's MMWR carried a lengthy report from ACIP (The Advisory Committee on Immunization Practices) on the ethical principals that will be used to guide their decision.  

Their four guiding principals and associated criteria are listed as:

Maximize benefits and minimize harms

  • What groups are at highest risk for SARS-CoV-2 infection, COVID-19 disease, hospitalization, and death?
  • What groups are essential to the COVID-19 response?
  • What groups are essential to maintaining critical functions of society?
  • What are the important characteristics of these groups (e.g., size or geographic distribution) that might inform the magnitude of benefit based on the amount of vaccine available or its characteristics? 

Promote justice

  • Does the allocation plan result in fair and equitable access of the vaccine for all groups?
  • How do characteristics of the vaccine and logistical considerations affect fair access for all persons?
  • Does allocation planning include input from groups who are disproportionately affected by COVID-19 or face health inequities resulting from social determinants of health, such as income and health care access? 

Mitigate health inequities

  • Does the plan identify and address barriers to vaccination among any groups who are disproportionately affected by COVID-19 or who face health inequities resulting from social determinants of health, such as income and health care access?
  • Does the allocation plan contribute to a reduction in health disparities in COVID-19 disease and death?
  • What health inequities might inadvertently result from the allocation plan, and what interventions could remove or reduce them?
  • Is there a mechanism for timely assessment of vaccination coverage among groups experiencing disadvantage and the possibility for course correction if inequities are identified? 

Promote transparency

  • How does development of the allocation plan include diverse input, and if possible, public engagement?
  • Are the allocation plan and evidence-based methods publicly available?
  • Is the allocation plan clear about what is known and unknown and about the quality of available evidence?
  • What is the process for revision of allocation plans based on new information?
  • Is there a mechanism to report demographic data elements for vaccine recipients (e.g., age, race/ethnicity, and occupation) to support equitable vaccination coverage? 

Just the logistics required to roll out a 2-jab emergency vaccination campaign to over 300 million Americans next year are staggering, even assuming everything goes right with the vaccine.

Trying to do so fairly and equitably - particularly with limited resources - is an unenviable job. 

I've posted the summary and some excerpts from the MMWR report below, but you'll want to follow the link to read it in its entirety. I'll have a brief postscript when you return.

The Advisory Committee on Immunization Practices’ Ethical Principles for Allocating Initial Supplies of COVID-19 Vaccine — United States, 2020

Early Release / November 23, 2020 / 69

Nancy McClung, PhD1; Mary Chamberland, MD1,2; Kathy Kinlaw, MDiv3; Dayna Bowen Matthew, JD, PhD4; Megan Wallace, DrPH1,5; Beth P. Bell, MD6; Grace M. Lee, MD7; H. Keipp Talbot, MD8; José R. Romero, MD9; Sara E. Oliver, MD1; Kathleen Dooling, MD1 (View author affiliations)View suggested citation

Summary

What is already known about this topic?

During the period when the U.S. supply of COVID-19 vaccines is limited, the Advisory Committee on Immunization Practices (ACIP) will make vaccine allocation recommendations.

What is added by this report?

In addition to scientific data and implementation feasibility, four ethical principles will assist ACIP in formulating recommendations for the initial allocation of COVID-19 vaccine: 1) maximizing benefits and minimizing harms; 2) promoting justice; 3) mitigating health inequities; and 4) promoting transparency.

What are the implications for public health practice?

Ethical principles will aid ACIP in making vaccine allocation recommendations and state, tribal, local, and territorial public health authorities in developing vaccine implementation strategies based on ACIP’s recommendations.

(SNIP)
Discussion

During a pandemic, ethical guidelines can help steer and support decisions around prioritization of limited resources (3,4). Consideration of ethical values and principles has featured prominently in discussions about allocation of COVID-19 vaccines. This consideration is particularly relevant because the COVID-19 pandemic has highlighted long-standing, systemic health and social inequities. Although various frameworks for COVID-19 vaccine allocation demonstrate differences in their structure (e.g., based on varying combinations of different goals, objectives, criteria, and other structural elements) and emphasis (e.g., inclusion of global and national considerations), nearly all reference values and principles similar to those which ACIP considers fundamental (5–8). ACIP viewed the following characteristics as critical for its ethical approach to COVID-19 vaccine allocation when supply is limited: simplicity in structure and definitions; acceptability to stakeholders; and ease of application, both at the national and state, tribal, local, and territorial levels.
 
Allocation of limited vaccine supplies is complicated by efforts to address the multiple goals of a vaccine program, most notably those related to the reduction of morbidity and mortality and the minimization of disruption to society and the economy. If the goals of a pandemic vaccination program are not clearly articulated and prioritized, drawing distinctions between groups that merit consideration for allocation of vaccine when supply is constrained can become difficult. The unanimity in opinion for early vaccination of health care personnel indicates that maintenance of health care capacity has emerged as a high priority in the context of a severe pandemic. This perspective aligns with ethical considerations for pandemic influenza planning (3,4). If vaccine supply remains constrained, it might be necessary to identify subsets of other groups for subsequent early allocation of COVID-19 vaccine.
 
At the national, state, tribal, local, and territorial levels, such decisions should be guided, in part, by ethical principles and consideration of essential questions, with particular consideration of mitigation of health inequities in persons experiencing disproportionate COVID-19 morbidity and mortality. In the setting of a constrained supply, the benefits of vaccination will be delayed for some persons; however, as supply increases, there will eventually be enough vaccine for everyone.
 
In addition to ethical considerations, ACIP’s recommendations regarding receipt of the initial allocations of COVID-19 vaccine during the period of constrained supply will be based on science (e.g., available information about the vaccine’s characteristics such as safety and efficacy in older adults and epidemiologic risk) and feasibility of implementation (e.g., storage and handling requirements). Thus, ACIP’s allocation recommendations will be made in conjunction with specific recommendations for the use of each FDA-authorized or licensed COVID-19 vaccine. Although the ethical principles in this report are fundamental for stewardship of limited vaccine supply, they can also be applied when COVID-19 vaccines are widely available, to ensure equitable and just access for all persons.
           
          (Continue . . . .)


Despite the vaccine-fueled optimism in the markets, and `aspirational' statements by policy makers that everyone who wants a vaccine can likely get one by the spring, we've a long way to go before COVID-19 recedes into a minor seasonal threat.  

Even assuming everything goes extraordinarily well with the vaccine's launch, we still have this winter and spring to get through.   

All of which means that face covers, social distancing, and scrupulous hand hygiene remain our best defense against the virus for the immediate future (see CDC Scientific Brief: Community Use of Cloth Masks to Control the Spread of SARS-CoV-2).

 

Monday, November 23, 2020

Study: Hypertension, Medications, and Risk of Severe COVID‐19

Credit CDC Hypertension

#15,577

Shortly after the emergence of COVID-19 we learned that the causative virus - SARS-CoV-2 - bound to ACE2 receptor cells (see ACE2 Is the SARS-CoV-2 Receptor Required for Cell Entry), which immediately raised concerns over the risks that millions of patients currently receiving ACE Inhibitor or ARB therapy for hypertension might face with this new virus.

Early on, opinions were mixed - with a number of hypothesized downsides - including:
Patients who Take ACEIs and ARBs May Be at Increased Risk of Severe COVID-19
Mar 25, 2020 
At the same time, we saw this opposite take:
ACEI/ARB Treatment May Benefit Patients With COVID-19 and Hypertension
Florence Chaverneff, Ph.D.
Despite this uncertainty, a number of leading journals cautioned against halting ACE or ARB therapy, citing insufficient evidence of harm (see March AHA news release).

In May, the World Health Organization published a scientific brief (see WHO Scientific Brief: COVID-19 & The Use Of ACE Inhibitors or ARBs), that reviewed the (scant) existing literature - and while not exactly a ringing endorsement - found:
 `. .. low-certainty evidence that patients on long-term therapy with ACE inhibitors or ARBs are not at higher risk of poor outcomes from COVID-19.'

Three weeks later, in Meta-Analysis: COVID-19 Mortality Among Patients Taking ACEIs & ARBs For Hypertension, we looked at a meta-analysis published in the AHA journal Hypertension, which found decreased mortality ( among patients with hypertension) who were receiving ACEI or ARB therapy.

While the news since then has been overwhelmingly supportive for the continued use of ACE inhibitors and ARBs during this pandemic, those recommendations have often been based on limited data derived from observational studies.  

We've a new analysis, published two days ago in the Journal of Clinical Hypertension, which provides additional reassurance on the topic, albeit again from an observational study. 

The full open-access study is available at the link below. 

Hypertension, medications, and risk of severe COVID‐19: A Massachusetts community‐based observational study

Ann Z. Bauer ScD ,Rebecca Gore PhD ,Susan R. Sama ScD ,Richard Rosiello MD ,Lawrence Garber MD ,Devi Sundaresan MS ,Anne McDonald RN … See all authors 

First published: 21 November 2020 

https://doi.org/10.1111/jch.1410

Abstract

It remains uncertain whether the hypertension (HT) medications angiotensin‐converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) mitigate or exacerbate SARS‐CoV‐2 infection. We evaluated the association of ACEi and ARB with severe coronavirus disease 19 (COVID‐19) as defined by hospitalization or mortality among individuals diagnosed with COVID‐19. We investigated whether these associations were modified by age, the simultaneous use of the diuretic thiazide, and the health conditions associated with medication use.

In an observational study utilizing data from a Massachusetts group medical practice, we identified 1449 patients with a COVID‐19 diagnosis. In our study, pre‐infection comorbidities including HT, cardiovascular disease, and diabetes were associated with increased risk of severe COVID‐19. Risk was further elevated in patients under age 65 with these comorbidities or cancer. Twenty percent of those with severe COVID‐19 compared to 9% with less severe COVID‐19 used ACEi, 8% and 4%, respectively, used ARB.

In propensity score‐matched analyses, use of neither ACEi (OR = 1.30, 95% CI 0.93 to 1.81) nor ARB (OR = 0.94, 95% CI 0.57 to 1.55) was associated with increased risk of severe COVID‐19. Thiazide use did not modify this relationship. Beta blockers, calcium channel blockers, and anticoagulant medications were not associated with COVID‐19 severity.

In conclusion, cardiovascular‐related comorbidities were associated with severe COVID‐19 outcomes, especially among patients under age 65. We found no substantial increased risk of severe COVID‐19 among patients taking antihypertensive medications. Our findings support recommendations against discontinuing use of renin–angiotensin system (RAS) inhibitors to prevent severe COVID‐19.

          (SNIP)

Discussion
In this analysis of data on COVID‐19 patients from a large group medical practice, we investigated the relationship between pre‐infection treatment with hypertension medications and severe COVID‐19, among all individuals diagnosed with COVID‐19 in a community‐based population in central Massachusetts. Our primary focus was on RAS inhibitors as they may induce elevated expression of ACE2, the cellular receptor of SAR‐CoV‐2, raising concern that these medications might increase the risk of severe sequelae of COVID‐19.
Our findings are consistent with other recent studies which have found no deleterious effect of these or any of five hypertension medication classes with regard to COVID‐19 severity.12-14, 25, 26 Further, we investigated the potential for effect modification by additional use of the diuretic thiazide on the RAS inhibitors and found no such relationship.
Collectively, these findings do not support a change to the current use of these medications in relation to COVID‐19. While this is consistent with the guidance of the professional societies’ recommendations,27 our results are based only on reported use of hypertension medications prior to COVID‐19 diagnosis. We did not have data to investigate the effect on severity of continued or discontinued use of these medications after COVID‐19 diagnosis.
(SNIP)
Our findings do not support the discontinuation of ACEi or ARB in the management of hypertension, as a preventive measure to reduce risk of severe COVID‐19 disease. Other studies should also investigate whether or not hypertension medications were continued during hospitalization. Findings should be confirmed using other populations and study designs including randomized controlled trials.
 
More investigation of pre‐infection risk factors such vitamin D3 level,37 anticoagulant medication use,38 diabetes control,39 blood type,40 MMR, and flu vaccine status,41 in both the general and younger populations, is warranted.
(Continue . . . )

As always, I am not a doctor and none of this constitutes medical advice. Always consult your doctor before changing or stopping your medications.  


France: MOA Reports COVID-19 Outbreak In Mink Farm - Eure-et-Loire region

 

Credit Wikipedia 

#15,776

In last Friday's Blog Preprint: Recurrent Mutations in SARS-CoV-2 Genomes Isolated from Mink Point to Rapid Host-Adaptation - and the day before that in EID Journal: SARS-CoV-2 Transmission between Mink (Neovison vison) and Humans, Denmark -we looked at the propensity for mink to become infected by SARS-CoV-2 - the virus that causes COVID-19 - and recent concerns over mutated stains emerging in Mink farms and jumping back into humans in Denmark.

As mink are notoriously susceptible to both human and novel influenza viruses (see blogs below), their susceptibility to SARS-CoV-2 comes as little surprise.   

Nature: Semiaquatic Mammals As Intermediate Hosts For Avian Influenza 

Vet. MicroB.: Eurasian Avian-Like Swine Influenza A (H1N1) Virus from Mink in China
H9N2 Adaptation In Minks 

Since late spring we've seen reports of COVID-19 burning through mink farm in the Netherlands, Spain, Denmark, Sweden, Italy, Greece and the United States, which has resulted in the culling of millions of animals.  

Yesterday, the French Ministry of Agriculture announced the detection of COVID-19 at at at least one mink farm in the Eure-et-Loire region of northern France, and the testing of additional farms.  

None of the farm personnel have tested positive for the virus, and there is no indication that the problematic mutated strain found in Denmark was present. Tests, however, are ongoing.    

This (translated) statement from the MOA.

Surveillance of SARS-COV-2 in mink farms: a contaminated farm
  
22/11/2020
COMMUNICATED

Covid-19 infection spreads in mink farms in some European Union member states, mainly in Denmark, with the recent discovery of a variant virus, but also in the Netherlands and more recently in Sweden and in Greece - isolated cases have been detected in Italy and Spain. Cases are also reported in the United States of America.

France has in turn detected American mink contaminated by Covid-19.

Following the alerts notified by the Dutch health authorities last April, specific surveillance systems were put in place and biosecurity measures were reinforced in all mink farms in France from May. At the same time, the services of the Ministry of Health were alerted.

Analyzes have been carried out since mid-November as part of a scientific program led by ANSES to define the health status of the 4 French mink farms vis-à-vis the SARS-COV-2 virus.

At this stage, these analyzes revealed that the virus was circulating on a farm in Eure-et-Loir. As soon as they learned of these results, the Ministers concerned immediately ordered the slaughter of all 1000 animals still present on the farm and the elimination of products from these animals, in order to protect public health against the Covid-19.
Another breeding is unharmed. Analyzes are still underway in the last two farms and results are expected later this week. If results prove to be positive in one of these two farms, the same slaughtering measures as in the first concerned farm would be applied.

The results of the analyzes carried out on the breeders of the 4 farms were all negative. Reinforced surveillance has been put in place for 4 people in connection with the contaminated farm and new analyzes are underway.

The virus sequencing analysis will be known by the end of the week and should make it possible to exclude any contamination by the SARS-COV-2 variant.

Surveillance and enhanced biosecurity measures are maintained in the other three farms.

The ministers recall the importance of barrier gestures to fight against the spread of Covid-19: the aim is to protect mink from possible contamination from farm staff, but also, as a precaution, to avoid contact between infected animals and farm staff.
  

While COVID-19 is believed to have originated in bats - much as both SARS  & MERS - it isn't known whether the virus jumped directly to humans, or went through an intermediate host before jumping to humans. 

Even though COVID-19 is already well established in humans, it still matters that we find out how the virus jumped to humans - and identify any other animal reservoirs of the virus - where it could potentially mutate and jump back into humans. 

Raccoon dogs in China (which are neither raccoons or dogs, but are foxes), have been suggested as a plausible intermediate host for COVID-19 (see EID Journal: Susceptibility of Raccoon Dogs for Experimental SARS-CoV-2 Infection), as have a number of other small mammals. 

While dogs and cats are plausible intermediate hosts SARS-CoV-2 (see J. Clin. Microb: Serological Screening Of Dogs & Cats For Influenza A - Europe  and Seroprevalence of SARS-CoV-2 in Dogs & Cats - Italy), there is currently no evidence to suggest that either play a significant role in spreading COVID-19 to people.




To wrap up, three days ago The Lancet published a comment by one of our favorite researchers - Marion Koopmans, a noted virologist and head of the Erasmus MC Department of Viroscience - who succinctly addresses growing concerns over the existence of one or more alternate SARS-CoV-2 reservoirs, and the need to expand the search beyond just mink. 

Follow the link to read it in its entirety.  Highly recommended. 

COMMENT|ONLINE FIRST

SARS-CoV-2 and the human-animal interface: outbreaks on mink farms

Marion Koopmans

Published:November 20, 2020

 

Sunday, November 22, 2020

CDC Scientific Brief: Community Use of Cloth Masks to Control the Spread of SARS-CoV-2


#15,575

Repeatedly over the past 14+ years we've looked at the likely need for - and scientific rationale for using - cloth masks by the public during a severe respiratory disease outbreak or pandemic.

In 2009's The Man In The Ironed Mask, we looked at the inevitable PPE shortages that would arise during any severe pandemic, and a design - published in the CDC's EID Journal - of a `Simple Respiratory Mask' that could be made at home out of Tee shirt material. 



A year earlier (2008), months before the 2009 H1N1 pandemic emerged, we looked at another study published in PLoS One (see Professional and Home-Made Face Masks Reduce Exposure to Respiratory Infections among the General Population by Marianne van der Sande, Peter Teunis, Rob Sabel) that concluded:

Any type of general mask use is likely to decrease viral exposure and infection risk on a population level, in spite of imperfect fit and imperfect adherence, personal respirators providing most protection. Masks worn by patients may not offer as great a degree of protection against aerosol transmission.

While many studies suggested cloth or homemade masks `might' provide some benefit to the general public, the evidence of their effectiveness has come mainly from countries (particularly in Asia) that encourage mask use - even during regular flu seasons - which tended to have fewer flu cases (see HK CDW: Surgical Masks For Respiratory Protection).

In 2014's Efficacy Of Hand Hygiene Alone Against Influenza Infection, however, we looked at Dr. Allison Aiello's multi-year study at the University of Michigan that compared the effectiveness of handwashing and facemasks (alone, and in combination) at reducing the spread of seasonal influenza in a college dorm setting.

Their results?

Neither face mask use and hand hygiene nor face mask use alone was associated with a significant reduction in the rate of ILI, although combined, they produced a 35% to 51% reduction of infection over the control group.

But not all of the evidence was positive on cloth masks - at least when used by HCWs - as in this 2015 study (see BMJ Open: Protectiveness (Or Lack, Thereof) Of Reusable Cloth Medical Masks ) which compared the efficacy of cloth masks to medical masks in a high risk hospital environment and found them wanting. 

Despite growing evidence of their benefit, the public use of masks during a pandemic has long been dismissed as ineffective or heavily discouraged by most Western nations (see WHO Interim Advice On The Community, Home, Healthcare Use of Masks For nCoV2019 and this infamous Feb 29th tweet by the U.S. Surgeon General).

Over the spring, as COVID-19's spread proved impossible to control, public health's opinion on public mask wearing slowly changed, and now most countries and public health agencies accept what Asian nations have known for years; masks worn by the public can significantly reduce the spread of respiratory diseases during a pandemic. 

No, cloth masks aren't as good as N95s - and probably aren't as good as surgical masks - but they are better than nothing. 

All of which brings us to a recently updated CDC Scientific Brief (first published Nov 10th) on the use of cloth masks by the public during this COVID-19 pandemic. 

Scientific Brief: Community Use of Cloth Masks to Control the Spread of SARS-CoV-2

Updated Nov. 20, 2020
 
Background

SARS-CoV-2 infection is transmitted predominately by respiratory droplets generated when people cough, sneeze, sing, talk, or breathe. CDC recommends community use of masks, specifically non-valved multi-layer cloth masks, to prevent transmission of SARS-CoV-2. Masks are primarily intended to reduce the emission of virus-laden droplets (“source control”), which is especially relevant for asymptomatic or presymptomatic infected wearers who feel well and may be unaware of their infectiousness to others, and who are estimated to account for more than 50% of transmissions.1,2 Masks also help reduce inhalation of these droplets by the wearer (“filtration for personal protection”). The community benefit of masking for SARS-CoV-2 control is due to the combination of these effects; individual prevention benefit increases with increasing numbers of people using masks consistently and correctly.

Source Control to Block Exhaled Virus

Multi-layer cloth masks block release of exhaled respiratory particles into the environment,3-6 along with the microorganisms these particles carry.7,8 Cloth masks not only effectively block most large droplets (i.e., 20-30 microns and larger)9 but they can also block the exhalation of fine droplets and particles (also often referred to as aerosols) smaller than 10 microns ;3,5 which increase in number with the volume of speech10-12 and specific types of phonation.13 Multi-layer cloth masks can both block up to 50-70% of these fine droplets and particles3,14 and limit the forward spread of those that are not captured.5,6,15,16 Upwards of 80% blockage has been achieved in human experiments that have measured blocking of all respiratory droplets,4 with cloth masks in some studies performing on par with surgical masks as barriers for source control.3,9,14
Filtration for Personal Protection

Studies demonstrate that cloth mask materials can also reduce wearers’ exposure to infectious droplets through filtration, including filtration of fine droplets and particles less than 10 microns. The relative filtration effectiveness of various masks has varied widely across studies, in large part due to variation in experimental design and particle sizes analyzed. Multiple layers of cloth with higher thread counts have demonstrated superior performance compared to single layers of cloth with lower thread counts, in some cases filtering nearly 50% of fine particles less than 1 micron .14,17-29 Some materials (e.g., polypropylene) may enhance filtering effectiveness by generating triboelectric charge (a form of static electricity) that enhances capture of charged particles18,30 while others (e.g., silk) may help repel moist droplets31 and reduce fabric wetting and thus maintain breathability and comfort.

Human Studies of Masking and SARS-CoV-2 Transmission

Data regarding the “real-world” effectiveness of community masking are limited to observational and epidemiological studies.
  • An investigation of a high-exposure event, in which 2 symptomatically ill hair stylists interacted for an average of 15 minutes with each of 139 clients during an 8-day period, found that none of the 67 clients who subsequently consented to an interview and testing developed infection. The stylists and all clients universally wore masks in the salon as required by local ordinance and company policy at the time.32
  • In a study of 124 Beijing households with > 1 laboratory-confirmed case of SARS-CoV-2 infection, mask use by the index patient and family contacts before the index patient developed symptoms reduced secondary transmission within the households by 79%.33
  • A retrospective case-control study from Thailand documented that, among more than 1,000 persons interviewed as part of contact tracing investigations, those who reported having always worn a mask during high-risk exposures experienced a greater than 70% reduced risk of acquiring infection compared with persons who did not wear masks under these circumstances.34
  • A study of an outbreak aboard the USS Theodore Roosevelt, an environment notable for congregate living quarters and close working environments, found that use of face coverings on-board was associated with a 70% reduced risk.35
  • Investigations involving infected passengers aboard flights longer than 10 hours strongly suggest that masking prevented in-flight transmissions, as demonstrated by the absence of infection developing in other passengers and crew in the 14 days following exposure.36,37
Seven studies have confirmed the benefit of universal masking in community level analyses: in a unified hospital system,38 a German city,39 a U.S. state,40 a panel of 15 U.S. states and Washington, D.C.,41,42 as well as both Canada43 and the U.S.44 nationally. Each analysis demonstrated that, following directives from organizational and political leadership for universal masking, new infections fell significantly. Two of these studies42,44 and an additional analysis of data from 200 countries that included the U.S.45 also demonstrated reductions in mortality.
An economic analysis using U.S. data found that, given these effects, increasing universal masking by 15% could prevent the need for lockdowns and reduce associated losses of up to $1 trillion or about 5% of gross domestic product.42

Conclusions

Experimental and epidemiological data support community masking to reduce the spread of SARS-CoV-2. The prevention benefit of masking is derived from the combination of source control and personal protection for the mask wearer. The relationship between source control and personal protection is likely complementary and possibly synergistic14, so that individual benefit increases with increasing community mask use. Further research is needed to expand the evidence base for the protective effect of cloth masks and in particular to identify the combinations of materials that maximize both their blocking and filtering effectiveness, as well as fit, comfort, durability, and consumer appeal.
 
Adopting universal masking policies can help avert future lockdowns, especially if combined with other non-pharmaceutical interventions such as social distancing, hand hygiene, and adequate ventilation.

 

Masks alone, even properly fit-tested N95s, can't guarantee 100% protection to the wearer, and should never be viewed as a panacea for a pandemic. 

But when properly worn, and when used as part of a `layered' approach to personal protection (avoiding indoor crowds, good hand hygiene, social distancing, etc.), even cloth masks can help reduce your risk of infection. 

Maybe just a little, maybe a lot more.  We'll know better after this pandemic is over.

But either way, I don't plan to leave my house without one.  

Saturday, November 21, 2020

PNAS: Nipah Virus Dynamics in Bats and Implications for Spillover to Humans


Credit CDC

#15,574

Although many people believe that COVID-19 emerged from out of left field, the truth is we've been watching a number of bat borne viruses - including coronaviruses - for decades, fearing a spillover event such as occurred in China in 2019 (see Curr. Opinion Virology: Viruses In Bats & Potential Spillover To Animals And Humans).

High on our list - which also includes Ebola, Hendra, MERS-CoV and SARS-CoV - is the Nipah virus, which has caused sporadic outbreaks in humans - including human-to-human spread - over the past couple of decades. 

Carried by fruit bats common to S.E. Asia, in 1998 Nipah sparked an outbreak in Malaysia, which spread first from bat to pigs - and then from pigs to humans - eventually infecting at least 265 people, killing 105 (see Lessons from the Nipah virus outbreak in Malaysia).

Since then, we've seen sporadic outbreaks in Bangladesh and India. Unlike COVID-19 - which appears to kill roughly 1% of those infected, human infection with the Nipah virus is fatal between 70% and 90% of the time.  

In addition to bats and humans - other mammals have been infected in the wild (horses, pigs, and dogs) - and many others have been experimentally infected in the lab (including guinea pigs, hamsters, ferrets, squirrel monkeys, and African green monkeys).

In the 2013 paper The pandemic potential of Nipah virus by Stephen P. Luby, the author wrote (bolding mine):
Characteristics of Nipah virus that increase its risk of becoming a global pandemic include: humans are already susceptible; many strains are capable of limited person-to-person transmission; as an RNA virus, it has an exceptionally high rate of mutation: and that if a human-adapted strain were to infect communities in South Asia, high population densities and global interconnectedness would rapidly spread the infection.
While we've not seen truly large community spread of Nipah, the same could have been said about Ebola prior to 2014, when it was deemed `too lethal to spread efficiently'; until is spread across 3 nations in West Africa killing more than 11,000 people

Over the past 20 years Nipah, and other bat-borne viruses, have increasingly become viewed as legitimate pandemic threats.

In Steven Soderbergh's 2011 pandemic thriller `Contagion, technical advisor Ian Lipkin - director of Columbia University’s Center for Infection and Immunity in New York - painstakingly created a fictional MEV-1 pandemic virus based on a mutated Nipah virus.
  •  In 2015's Blue Ribbon Study Panel Report on Biodefense a bi-partisan panel described a fictional biological attack on Washington D.C.  using a genetically engineered Nipah virus as part of their presentation. 
  • Two years ago, in the Johns Hopkins Clade X exercise, a genetically altered Nipah virus (spliced onto a parainfluenza backbone) was the cause of their fictional pandemic.  
  • Also in 2018, in WHO List Of Blueprint Priority Diseases, we saw Nipah and Henipaviral diseases listed among the 8 viral threats in need of urgent accelerated research and development.
    Dr. Ian Lipkin is one of the authors of the following report (edited by Dr. Anthony Fauci), published earlier this month in PNAS, that presents evidence from a 6-year EcoHealth Alliance study that shows that (various strains) of Nipah are more widespread in bats than previously believed, and that the risk of a major spillover must be taken seriously.
    RESEARCH ARTICLE
    Nipah virus dynamics in bats and implications for spillover to humans
    Jonathan H. Epstein, Simon J. Anthony, Ariful Islam, A. Marm Kilpatrick, Shahneaz Ali Khan, Maria D. Balkey, Noam Ross,Ina Smith, Carlos Zambrana-Torrelio,Yun Tao, Ausraful Islam, Phenix Lan Quan,Kevin J. Olival, M. Salah Uddin Khan, Emily S. Gurley, M. Jahangir Hossein, Hume E. Field, Mark D. Fielder, Thomas Briese, Mahmudur Rahman, Christopher C. Broder, Gary Crameri, Lin-Fa Wang, eStephen P. Luby, W. Ian Lipkin, and VPeter Daszak
    PNAS November 17, 2020 117 (46) 29190-29201; first published November 2, 2020; https://doi.org/10.1073/pnas.2000429117
    Significance
    Nipah virus (NiV) is a zoonotic virus and World Health Organization (WHO) priority pathogen that causes near-annual outbreaks in Bangladesh and India with >75% mortality. This work advances our understanding of transmission of NiV in its natural bat reservoir by analyzing data from a 6-y multidisciplinary study of serology, viral phylogenetics, bat ecology, and immunology. We show that outbreaks in Pteropus bats are driven by increased population density, loss of immunity over time, and viral recrudescence, resulting in multiyear interepizootic periods. Incidence is low, but bats carry NiV across Bangladesh and can shed virus at any time of year, highlighting the importance of routes of transmission to the timing and location of human NiV outbreaks.
    Abstract
    Nipah virus (NiV) is an emerging bat-borne zoonotic virus that causes near-annual outbreaks of fatal encephalitis in South Asia—one of the most populous regions on Earth. In Bangladesh, infection occurs when people drink date-palm sap contaminated with bat excreta. Outbreaks are sporadic, and the influence of viral dynamics in bats on their temporal and spatial distribution is poorly understood. We analyzed data on host ecology, molecular epidemiology, serological dynamics, and viral genetics to characterize spatiotemporal patterns of NiV dynamics in its wildlife reservoir, Pteropus medius bats, in Bangladesh.  
    We found that NiV transmission occurred throughout the country and throughout the year. Model results indicated that local transmission dynamics were modulated by density-dependent transmission, acquired immunity that is lost over time, and recrudescence. Increased transmission followed multiyear periods of declining seroprevalence due to bat-population turnover and individual loss of humoral immunity. Individual bats had smaller host ranges than other Pteropus species (spp.), although movement data and the discovery of a Malaysia-clade NiV strain in eastern Bangladesh suggest connectivity with bats east of Bangladesh.  
    These data suggest that discrete multiannual local epizootics in bat populations contribute to the sporadic nature of NiV outbreaks in South Asia. At the same time, the broad spatial and temporal extent of NiV transmission, including the recent outbreak in Kerala, India, highlights the continued risk of spillover to humans wherever they may interact with pteropid bats and the importance of limiting opportunities for spillover throughout Pteropus’s range.
             (Continue . . . . )
     
    Follow the link to read the full, highly detailed, research report.  A less rigorous, but still informative press release from EchoHealth Alliance (below) provides the gist of the findings. 

    Six-Year Study Indicates Nipah Virus More Widespread than Previously Thought


    NEW YORK – November 2, 2020 – In annual outbreaks throughout Bangladesh, Nipah virus kills around 70 percent of the people it infects. The virus, a distant relative of measles, has no vaccine and no proven medical countermeasures. EcoHealth Alliance, a nonprofit working at the intersection of animal, environmental, and human health on a global scale, released Monday the results of a major six-year study to understand how these outbreaks begin and how to prevent them.

    Outbreaks typically occur within what is known as the “Nipah belt,” which stretches along Bangladesh’s western border with India. But EcoHealth Alliance scientists found that bats throughout Bangladesh had relatively similar patterns of Nipah virus infection. The research is published in the journal Proceedings of the National Academy of Sciences of the United States of America.

    "Nipah circulates regularly in large fruit eating bats throughout many parts of Asia, but human outbreaks can only occur where there is a route of transmission from bats to humans," EcoHealth Alliance Vice President for Science and Outreach Dr. Jonathan Epstein said."The problem is, we don’t have a good handle on where else in the world spillover may be happening, which means we’re likely missing outbreaks. Risk is not so much limited by geography as it is by human behavior. This is a virus that spreads from person to person and is lethal in three quarters of those it infects, which is why we have to pay close attention to it and do what we can to prevent outbreaks."

    Nipah outbreaks have been linked to consumption of raw date palm sap, as well as infection through an intermediate host such as domesticated animals such as pigs.

    Of eight bat colonies studied across Bangladesh over a period from 2006 to 2012, researchers from EcoHealth Alliance and its partners found Nipah antibodies present in each location. In one bat colony studied continuously for six years, outbreaks in the bats occurred about every two years, about time it takes for bats to lose herd immunity. Outbreaks in bats can lead to human outbreaks, when there is a route of transmission available. Nipah virus, which in humans leads to brain swelling and often leaves patients in a coma, is already identified as one of the World Health Organization’s highest priority pathogens for vaccine development.

    "Finding that bats carrying Nipah virus can be infected anywhere and at any time of year means we have to pay closer attention in areas where Nipah outbreaks may not have been previously reported, to make sure we’re not missing small outbreaks that could lead to bigger ones, " Dr. Epstein, the paper’s lead author, said.

    The study also found that the strains of Nipah virus that cause human outbreaks reflect the strains carried by local bats, and that there were different strains of Nipah virus in different areas of the country. Genetic differences in the virus may impact disease severity or transmissibility in humans, something Dr. Epstein is currently studying under new funding from the National Institutes of Health.

    Outside of India and Bangladesh, previous outbreaks of Nipah have occurred in Malaysia, Singapore, and the Philippines.

             (Continue . . . )


    While the Nipah outbreaks we've seen have only demonstrated limited human-to-human transmission, each outbreak provides the virus with additional opportunities to better adapt to humans, and potentially increase its threat. 

    Nipah isn't alone in this category. There are many other zoonotic viruses with pandemic potential, including Lassa Fever, Monkeypox, MERS-CoV, novel flu, and Disease X; the one we don't know about yet.

    While it might seem cruel beyond belief for another, possibly even deadlier, virus to emerge in the next few years - the simple truth is - nature doesn't care. Viruses will continue to evolve, and occasionally jump species, because they can. 

    The only thing we can do is make sure we are far better prepared for the next pandemic than we were for this one.  But the clock is ticking.