UKHSA: All Children In London Will Be Offered A Polio Booster Shot

#16,935

A decade ago the global eradication of polio seemed tantalizingly close, but in 2014 the resurgence of Polio in the Middle East (see WHO: WPV1 (Polio) Risks In Israel Remain Moderate to High)  and in Africa (see WHO: Polio Outbreak In Horn Of Africa), along with the continued threat of infection in the three remaining polio-endemic nations (Afghanistan, Nigeria and Pakistan), led the WHO to declare the spread of polio a PHEIC (Public Health Emergency of International Concern). 

Eight years later, that declaration remains firmly in place, and over the past 6 weeks we've seen two high profile detections of Polioviruses in wastewater systems in two suburban counties adjacent to New York City and in several districts of London. 

Both strongly suggest that a vaccine-derived poliovirus (VDPV) is circulating in these communities, likely introduced by someone who received (or was exposed to someone who recently received) the oral polio which is now only used in a handful of countries. 

Vaccine-derived polioviruses are a rare downside to using the oral polio vaccine (OPV), which has been discontinued in most western countries for the past 20+ years. 

While most people in the United States and the UK are vaccinated and well protected against the disease, there are undoubtedly some who are either unvaccinated, or under-vaccinated, and may be at risk.  

Today the UK's Joint Committee on Vaccination and Immunisation (JCVI) released their recommendations on a polio vaccination strategy for London (LINK), and the UKHSA published the following statement:

All children aged 1 to 9 in London to be offered a dose of polio vaccine

As further poliovirus has been detected in sewage, JCVI recommends that polio vaccine booster doses should be offered to children across London.

From:UK Health Security Agency Published 10 August 2022

Following the discovery of type 2 vaccine-derived poliovirus in sewage in north and east London, the Joint Committee on Vaccination and Immunisation (JCVI) has advised that a targeted inactivated polio vaccine (IPV) booster dose should be offered to all children between the ages of 1 and 9 in all London boroughs.

This will ensure a high level of protection from paralysis and help reduce further spread of the virus.

Nationally the overall risk of paralytic polio is considered low because most people are protected from this by vaccination.

Many countries globally provide an additional dose of polio-containing vaccine as part of their childhood vaccination schedule. The NHS in London will contact parents when it’s their child’s turn to come forward for a booster or catch-up polio dose – parents should take up the offer as soon as possible.

The programme will start with the areas affected, where the poliovirus has been detected and vaccination rates are low. This will be followed by rapid rollout across all boroughs.

This booster dose will be in addition to the NHS childhood vaccination catch-up campaign across London, where childhood vaccination uptake is lower than the rest of the country. It’s important all children aged 1 to 9 – even if up to date with their vaccinations – accept this vaccine when offered to further strengthen their protection against the poliovirus.

Following the findings earlier this year of type 2 poliovirus (PV2) collected from the Beckton sewage treatment works, further upstream sampling undertaken by the UK Health Security Agency (UKHSA) and the Medicines and Healthcare products Regulatory Agency (MHRA) has now identified at least one positive sample of the poliovirus, currently present in parts of the following boroughs:

• Barnet
• Brent
• Camden
• Enfield
• Hackney
• Haringey
• Islington
• Waltham Forest

The sampling has also detected the virus in lower concentrations and frequency in areas adjacent to the Beckton catchment area to the South (immediately below the Thames) and to the east of Beckton. However, it is not clear whether the virus has established itself in these areas or if the detections are due to people from the affected area visiting these neighbouring areas.

The level of poliovirus found and the high genetic diversity among the PV2 isolates suggests that there is some level of virus transmission in these boroughs which may extend to the adjacent areas. This suggests that transmission has gone beyond a close network of a few individuals.

A total of 116 PV2 isolates have been identified in 19 sewage samples collected in London between 8 February and 5 July this year, but most are vaccine-like virus and only a few have sufficient mutations to be classified as vaccine derived poliovirus (VDPV2).

VDPV2 is of greater concern as it behaves more like naturally occurring ‘wild’ polio and may, on rare occasions, lead to cases of paralysis in unvaccinated individuals.

UKHSA is working closely with health agencies in New York and Israel alongside the World Health Organisation to investigate the links between the poliovirus detected in London and recent polio incidents in these 2 other countries.

Dr Vanessa Saliba, Consultant Epidemiologist at UKHSA, said:

No cases of polio have been reported and for the majority of the population, who are fully vaccinated, the risk is low. But we know the areas in London where the poliovirus is being transmitted have some of the lowest vaccination rates. This is why the virus is spreading in these communities and puts those residents not fully vaccinated at greater risk.

Polio is a serious infection that can cause paralysis but nationally the overall risk is considered low because most people are protected by vaccination. The last case of polio in the UK was in 1984, but decades ago before we introduced the polio vaccination programme around 8,000 people would develop paralysis every year.

It is vital parents ensure their children are fully vaccinated for their age. Following JCVI advice all children aged 1 to 9 years in London need to have a dose of polio vaccine now – whether it’s an extra booster dose or just to catch up with their routine vaccinations. It will ensure a high level of protection from paralysis. This may also help stop the virus spreading further.

Jane Clegg, Chief Nurse for the NHS in London said:

While the majority of Londoners are protected from polio, the NHS will shortly be contacting parents of eligible children aged 1 to 9 years old to offer them a top-up dose to ensure they have maximum protection from the virus.

We are already reaching out to parents and carers of children who aren’t up to date with their routine vaccinations, who can book a catch-up appointment with their GP surgery now and for anyone not sure of their child’s vaccination status, they can check their Red Book.

UKHSA, working with MHRA, has already increased sewage surveillance to assess the extent of spread of the virus and are currently sampling 8 sites across London.

A further 15 sites in London will start sewage sampling in mid-August, and 10 to 15 sites will be stood up nationally to determine if poliovirus is spreading outside of London.

PloS One: Early Risk of Acute Myocardial Infarction Following Hospitalization for Severe Influenza

 

#16,934

In a normal year, seasonal flu kills roughly as many Americans as does gun violence, or car accidents. In a bad year - such as we saw in 2017-2018, influenza can kill as many as both of those combined.

The CDC has an `expected range' of seasonal influenza hospitalizations and deaths (see chart above), but over the past dozen years, we've increasingly seen influenza and other respiratory infections linked to a significant increase in heart attacks, strokes, and even Alzheimer's and/or Dementia.

• Two years ago, in CDC: Another Study Linking Severe Influenza To Heart Damage, we looked at a study of 80,000 people hospitalized for influenza, which found that roughly 12% of adults incurred some degree of cardiac injury.

• In 2019, in PLoS One: Transient Depression of Myocardial Function After Influenza Virus Infection, we looked at a study that found transient myocardial function changes among a small group of influenza patients studied.

• In 2018's NEJM: Acute Myocardial Infarction After Laboratory-Confirmed Influenza Infection, we saw a study that found a `significant association ' between recent (lab confirmed) influenza infection and Myocardial Infarction.  

• And in May 2017, in Int. Med. J.: Triggering Of Acute M.I. By Respiratory Infection we looked at research  from the University of Sydney that found the risk of a heart attack is increased 17-fold in the week following a respiratory infection such as influenza or pneumonia.

While the influenza-cardiac link grows stronger with each year, most people consider it primarily a concern for elderly (> 65)  patients, who are more likely to already have some cardiovascular deficits.

The cardiovascular impact of influenza on a younger cohort remains largely unquantified. 

All of which brings us to a new study, published yesterday by researchers in Hong Kong, which looks specifically at long-term cardiac risks of hospitalized influenza patients aged 45 to 64 years.  

While the absolute risk of having an AMI within 12 months of a severe influenza hospitalization was low (0.92%), the relative risk (compared to non-hospitalized controls) was nearly doubled. 

I've only reproduced the abstract, so you'll want to follow the link to read this study in its entirety.  I'll have a bit more when you return.  

Early risk of acute myocardial infarction following hospitalization for severe influenza infection in the middle-aged population of Hong Kong

Ho Yu Cheng , Erik Fung ,Kai Chow Choi, Hui Jing Zou, Sek Ying Chair

Published: August 9, 2022
https://doi.org/10.1371/journal.pone.0272661

Abstract

Introduction

Despite evidence suggesting an association between influenza infection and increased risk of acute myocardial infarction (AMI) in the older adult population (aged 65 years or above), little is known about its near-term risks in middle-aged adults (aged 45 to 64 years). This study aims to estimate the risks of and association between severe influenza infection requiring hospitalization and subsequent AMI within 12 months in middle-aged adults.

Method

This is a retrospective case-control analysis of territorywide registry data of people aged 45 to 64 years admitting from up to 43 public hospitals in Hong Kong during a 20-year period from January 1997 to December 2017. The exposure was defined as severe influenza infection documented as the principal diagnosis using International Classification of Diseases codes and non-exposure as hospitalization for orthopedic surgery. Logistic regression was used to analyze the risk of subsequent hospitalization for AMI within 12 months following the exposure.

Results

Among 30,657 middle-aged adults with an indexed hospitalization, 8,840 (28.8%) had an influenza-associated hospitalization. 81 (0.92%) were subsequently rehospitalized with AMI within 12 months after the indexed hospitalization. Compared with the control group, the risk of subsequent hospitalization for AMI was significantly increased (odds ratio [OR]: 2.54, 95% confidence interval [CI]: 1.64–3.92, p<0.001). The association remained significant even after adjusting for potential confounders (adjusted OR: 1.81, 95% CI: 1.11–2.95, p = 0.02). Patients with a history of hypertension, but not those with diabetes mellitus, dyslipidemia or atrial fibrillation/flutter, were at increased risk (adjusted OR: 5.01, 95% CI: 2.93–8.56, p<0.001).

Conclusion

Subsequent hospitalization for AMI within 12 months following an indexed respiratory hospitalization for severe influenza increased nearly two-fold compared with the non-cardiopulmonary, non-exposure control. Recommendation of influenza vaccination extending to middle-aged adult population may be justified for the small but significant increased near-term risk of AMI.

          (Continue . . . )

This study focused primarily on one outcome - hospitalization for AMI within one year of infection - but there are other sequelae linked to influenza infection, including Neurocognitive Impacts, and a range of childhood and adolescent development disorders (see Of Pregnancy, Flu & Autism) following in utero exposure.  

Despite some less-than-stellar influenza Vaccine Efficiency (VE) numbers - particularly among those in the highest risk groups (65+) - we've seen evidence that vaccination does reduce complications like heart attacks and strokes.

• In 2015, in UNSW: Flu Vaccine Provides Significant Protection Against Heart Attacks,we saw a study that found that if you are over 50 - getting the flu vaccine can cut your risk of a heart attack by up to 45%.

• In 2018, a study appearing the American Heart Association's journal Circulation, found a substantial reduction in deaths among heart failure patients who received a yearly flu shot (see AHA: Study Shows Flu Shots Reduce Deaths From Heart Failure).

• In January 2019, in Chest: Flu Vaccine Reduces Severe Outcomes Among Hospitalized Patients With COPD, researchers found a lower mortality rate, less critical illness, and a 38% reduction in influenza-related hospitalizations in vaccinated vs unvaccinated individuals.

• Also in 2019, in Flu Vaccine May Lower Stroke Risk in Elderly ICU Patients, we saw a study that found influenza vaccinated ICU survivors had a lower 1-year risk of stroke and a lower 1-year risk of death than unvaccinated survivors.

While the flu vaccine doesn't guarantee you'll avoid infection, most years it provides moderately good protection against circulating influenza viruses. And for those who are vaccinated - but still get the flu - they are less likely to have a severe bout.

This from the CDC:

Flu Vaccine Reduces Serious Flu Outcomes

Flu vaccination has been shown to reduce flu illnesses and more serious flu outcomes that can result in hospitalization or even death in older people. For example, a 2017 study showed that flu vaccination reduced deaths, intensive care unit (ICU) admissions, ICU length of stay, and overall duration of hospitalization among hospitalized flu patients; with the greatest benefits being observed among people 65 years of age and older.

Next month I'll roll up my sleeve to get my 17th seasonal flu shot in the past 17 years. While I recognize it probably only provides my age group with 30%-40% protection, given the long list of things that can go wrong during or following flu infection, I'll take whatever advantage I can get. 

I view getting a yearly flu shot like always wearing a seat belt in an automobile. It doesn't guarantee a good outcome in a wreck, but it sure increases your odds of walking away.

And that, to me, is an extra bit of insurance worth having. 

 

FDA Issues EUA Allowing `Dose-sparing' Intradermal Injection Of JYNNEOS Monkeypox Vaccine

British Columbia Institute of Technology (BCIT). 

Download this book for free at http://open.bccampus.ca, 

CC BY 4.0, via Wikimedia Commons

#16,932

The JYNNEOS Monkeypox vaccine - which was approved in 2019 - remains in short supply while demand continues to soar.  While originally designed to be administered as a subcutaneous injection (see package insert below), the FDA has approved a new, dose-sparing intradermal injection which could increase the number of people who can be vaccinated 5-fold. 

The rationale for this change is based on the results of a single 2015 study which showed that 2 fractional doses (1/5th) of JYNNEOS given intradermally, 28 days apart, provided similar protection as that seen from the original route. 

First the announcement from the FDA, after which I'll have a brief postscript. 

Monkeypox Update: FDA Authorizes Emergency Use of JYNNEOS Vaccine to Increase Vaccine Supply
 
For Immediate Release:August 09, 2022

Today, the U.S. Food and Drug Administration issued an emergency use authorization (EUA) for the JYNNEOS vaccine to allow healthcare providers to use the vaccine by intradermal injection for individuals 18 years of age and older who are determined to be at high risk for monkeypox infection. This will increase the total number of doses available for use by up to five-fold. The EUA also allows for use of the vaccine in individuals younger than 18 years of age determined to be at high risk of monkeypox infection; in these individuals JYNNEOS is administered by subcutaneous injection.

“In recent weeks the monkeypox virus has continued to spread at a rate that has made it clear our current vaccine supply will not meet the current demand,” said FDA Commissioner Robert M. Califf, M.D. “The FDA quickly explored other scientifically appropriate options to facilitate access to the vaccine for all impacted individuals. By increasing the number of available doses, more individuals who want to be vaccinated against monkeypox will now have the opportunity to do so.”

JYNNEOS, the Modified Vaccinia Ankara (MVA) vaccine, was approved in 2019 for prevention of smallpox and monkeypox disease in adults 18 years of age and older determined to be at high risk for smallpox or monkeypox infection. JYNNEOS is administered beneath the skin (subcutaneously) as two doses, four weeks (28 days) apart. For individuals 18 years of age and older determined to be at high risk of monkeypox infection, the EUA now allows for a fraction of the JYNNEOS dose to be administered between the layers of the skin (intradermally). Two doses of the vaccine given four weeks (28 days) apart will still be needed. There are no data available to indicate that one dose of JYNNEOS will provide long-lasting protection, which will be needed to control the current monkeypox outbreak.

Data from a 2015 clinical study of the MVA vaccine evaluated a two-dose series given intradermally compared to subcutaneously. Individuals who received the vaccine intradermally received a lower volume (one fifth) than individuals who received the vaccine subcutaneously. The results of this study demonstrated that intradermal administration produced a similar immune response to subcutaneous administration, meaning individuals in both groups responded to vaccination in a similar way. Administration by the intradermal route resulted in more redness, firmness, itchiness and swelling at the injection site, but less pain, and these side effects were manageable. The FDA has determined that the known and potential benefits of JYNNEOS outweigh the known and potential risks for the authorized uses.

To support the FDA’s authorization of two doses of JYNNEOS administered by the subcutaneous route of administration in individuals younger than 18 years of age, the FDA considered the available JYNNEOS safety and immune response data in adults as well as the historical data with use of live vaccinia virus smallpox vaccine in pediatric populations.

JYNNEOS has been tested in individuals with immunocompromising conditions and has been found to be safe and effective in the trials that were performed to support approval. It was initially developed specifically as an alternative for use in immunocompromised individuals in the event of a smallpox outbreak.

On the basis of the determination by the Secretary of the Department of Health and Human Services on Aug. 9, 2022, that there is a public health emergency, or the significant potential for a public health emergency, that has a significant potential to affect national security or the health and security of United States citizens living abroad, and the declaration on Aug. 9, 2022, that circumstances exist justifying the emergency use of vaccines, the FDA may issue an EUA to allow emergency use of unapproved vaccines or unapproved uses of approved vaccines.

The FDA will provide updates as developments occur and will continue to work with federal public health partners and industry to ensure timely access to all available medical countermeasures. More information can be found on the agency’s monkeypox webpage.

For more than a decade researchers have been warning that the risk from Monkeypox was rising, primarily due to our declining immunity to smallpox. Routine vaccination for smallpox - which is believed to have provided about 85% protection against Monkeypox - was discontinued in the 1970s due to the eradication of the disease. 

Today, with few exceptions, only those over the age of 50 are vaccinated.  And the durability of protection afforded by that vaccine after 50+ years is unknown. 

While it isn't known exactly how effective JYNNEOS will be against Monkeypox, the CDC states:

Vaccine Effectiveness

Because Monkeypox virus is closely related to the virus that causes smallpox, the smallpox vaccine can protect people from getting monkeypox. Past data from Africa suggests that the smallpox vaccine is at least 85% effective in preventing monkeypox. The effectiveness of JYNNEOS(TM) against monkeypox was concluded from a clinical study on the immunogenicity of JYNNEOS and efficacy data from animal studies.

Smallpox and monkeypox vaccines are effective at protecting people against monkeypox when given before exposure to monkeypox. Experts also believe that vaccination after a monkeypox exposure may help prevent the disease or make it less severe.

With this FDA announcement, the current supply of JYNNEOS vaccine (est. 400,000 remaining doses) can be stretched to roughly 2 million.  And given the speed at which Monkeypox is spreading, those additional doses will almost certainly be needed.

CDC Nowcast: BA.5 Still Firmly In Control - BA.4.6 Rising In The Midwest

#16,932

BA.5 wrested control from BA.2.12.1 7 weeks ago and has maintained dominance in the United States since then, rising to an estimated 87.1% of cases today.  This represents only a small jump over last week's number (n=85.5%), but nonetheless shows growth. 

BA.4.6, which made the CDC's Nowcast report for the first time last week, continues to slowly climb, albeit primarily in the Midwest, where it now makes up roughly 13.2% of cases. 

In California, and the Pacific Northwest, it is far less impressive - as it makes up less than 2% of cases - while in New York it is running just over 6%. So far, most of its gains have come at the expense of variants other than BA.5, but we'll continue to monitor its progress. 

Thus far, BA.2.75 - which is getting a lot of press - hasn't made enough of an impact in the United States to show up on the weekly Nowcast report, but it remains on our radar as a potential successor to BA.5 later in the year. 

Otherwise, BA.2.12.1 and BA.2 continue to shrink, and BA.4 has slipped slightly over last week. 

While we seem to be in a holding pattern, with BA.5 firmly in control, Omicron has demonstrated its unique ability to swap out variants several times already in 2022, and there is little reason to doubt it won't happen again. 

Stay tuned. 

EID: Highly Divergent SARS-CoV-2 Alpha Variant in Chronically Infected Immunocompromised Person

 

#16,931

Thousands of SARS-CoV-2 variants have been detected around the world since the virus emerged in 2019, but only a couple of dozen or so have been classified as VOIs (Variants of Interest), and fewer still achieved VOC (Variant of Concern) status.

Some variants, after initially raising concerns - have passed quietly into obscurity (e.g. Denmark's `mink variant') - unable to successfully compete against more aggressive VOCs like Delta and Omicron .

Other, more successful VOCs -  like Alpha and Delta - reigned supreme for a time, only to be supplanted by newer, more `fit' Omicron variants.  

But gone doesn't necessarily mean extinct. 

Last February, in Preprint: Evolutionary Trajectories of SARS-CoV-2 Alpha and Delta Variants in White-Tailed Deer in Pennsylvania, we looked at a report finding that a highly divergent Alpha variant was still circulating in deer long after Alpha had been supplanted by Delta in the human population. 

The authors wrote:

The alpha lineage persisted in deer after its displacement by delta in humans, and deer-derived alpha variants diverged significantly from those in humans, consistent with a distinctive evolutionary trajectory in deer.

          (SNIP)

Our findings of alpha persistence in deer after replacement of alpha by delta in humans, and the divergence seen between our deer and human alpha genomes, are all consistent with long-term persistence and spread of the alpha variant in deer. 

Since we've seen SARS-CoV-2 successfully spillover into other species (see here, here, and here), there may very well be other examples out there we aren't aware of.  

Chinese researchers have continually warned that these types of spillover events are capable of  dramatically altering the evolutionary trajectory of future COVID variants (see China CDC Weekly Perspective: The “Wolf” Is Indeed Coming: Recombinant “Deltacron” SARS-CoV-2 Detected).

But there is also a human reservoir capable of harboring older variants, although it doesn't appear to happen very often.  Immunocompromised individuals have been known to carry the virus for weeks, and it has been widely suggested (see below) that these persistent infections may contribute to the creation of new variants. 

• A year ago the NEJM carried an article warning of the potential risk of new variants emerging from long-term infections among immunocompromised individuals (see SARS-CoV-2 Variants in Patients with Immunosuppression).

• While in December of 2020, the ECDC Threat Assessment Brief On UK SARS-CoV-2 Variant speculated that the large number of concurrent mutations in the B.1.1.7 variant may have arisen from a single chronically-infected, likely immunocompromised, individual.

All of which brings us to a fascinating report in the EID Journal from the Erasmus Medical Center in the Netherlands on an immunocompromised patient who appears to have carried the Alpha variant for 42 weeks, testing positive for it long after the virus had been supplanted by Delta.  

Follow the link to read the report in its entirety:

Research Letter
Highly Divergent SARS-CoV-2 Alpha Variant in Chronically Infected Immunocompromised Person
 
Bas B. Oude Munnink , Roel H.T. Nijhuis, Nathalie Worp, Marjan Boter, Babette Weller, Babs E. Verstrepen, Corine GeurtsvanKessel, Maarten L. Corsten, Anne Russcher, and Marion Koopmans 

Abstract

We detected a highly divergent SARS-CoV-2 Alpha variant in an immunocompromised person several months after the latest detection of the Alpha variant in the Netherlands. The patient was infected for 42 weeks despite several treatment regimens and disappearance of most clinical symptoms. We identified several potential immune escape mutations in the spike protein.


Persons with an immune deficiency can be infected with viral pathogens for a prolonged period. This occurrence has been reported for noroviruses (1) but also has been documented for SARS-CoV-2 (2). We report a patient with type 2 diabetes mellitus and chronic lymphocytic leukemia who had been infected for 42 weeks with SARS-CoV-2. The patient was hospitalized on April 23, 2021, and received optiflow treatment with dexamethasone, tocilizumab, and remdesivir. After May 11, 2021, the patient recovered and experienced no residual symptoms. Almost 9 months later, on February 3, 2022, the patient was readmitted to the hospital for leukemia-related anemia and tested positive for SARS-CoV-2 once again. A month later, the patient died of causes unrelated to SARS-CoV-2. 

 

Overall, the patient tested positive for SARS-CoV-2 in 6 nasal or pharyngeal swabs. We performed whole-genome sequencing on all specimens by using an amplicon-based sequencing approach, as previously described, with the updated ARTIC primers version 4.1 (ARTIC Network, https://artic.network/mcov-2019) (3). The sequencing was successful for 2 specimens from mid-2021 and 2 specimens from early 2022 (Table). Pangolin version 4.0.6 PLEARN-v1.8 classification using default settings demonstrated that all sequenced viruses belonged to the Alpha (B.1.1.7) variant of concern (VOC) (5), Nextclade version 1.14.1 strain 20I (6). The samples were run on flowcells containing 96 samples, including a positive and negative control (pangolin lineage B.1.77.50) to exclude potential contamination.

GISAID’s EpiCoV database (https://www.gisaid.orgExternal Link) showed that the latest isolate identified as Alpha in the Netherlands was collected on October 13, 2021, suggesting that the variant had not been circulating in the Netherlands since that time. Phylogenetic analysis by IQ-TREE (7) using all unique downsampled Alpha sequences available in GISAID (8) from the Netherlands showed that the viruses detected on January 31 and February 3, 2022, were identical but distinct from previously observed Alpha lineages in the Netherlands (Figure). A zoom-in of the phylogenetic tree showed that all sequences of the virus in the patient cluster together in a separate branch, suggesting that the patient was chronically infected with this specific variant of SARS-CoV-2 (Appendix Figure 1).

Over time, we identified 24 nucleotide mutations when we compared sequences from the earliest and latest timepoints. Of these mutations, 19 mutations were nonsynonymous, resulting in 13 amino acid mutations in open reading frame 1ab and 6 amino acid mutations in the spike protein (Table; Appendix Figure 2). Of the 6 mutations in the spike protein, 3 are located in the receptor-binding domain (G339D, N439K, and V483F), 2 are located in the N-terminal domain (W64R and G142V), and 1 is located in the transmembrane domain (P1263L). The mutation G339D can also be found in all Omicron VOCs. 

G142V has coevolved independently in >1 immunocompromised person with a long-term Alpha variant infection (S.A.J. Wilkinson et al., unpub. data,(https://doi.org/10.1101/2022.03.02.22271697), and a mutation in the same position (G142D) has also been described in the Delta (B.1.617.2) and in all Omicron variants.

Our data imply that, despite receiving treatment with dexamethasone, tocilizumab, and remdesivir and being discharged without residual symptoms, the patient had not cleared the infection. Unfortunately, ex vivo rescuing of the viruses from the swabs to assess potential immune escape from circulating neutralizing antibodies was not successful, but some of the mutations we observed in this immunocompromised person with long-term SARS-CoV-2 infection could be linked to immune escape.

Previous studies suggest that the G339D mutation affects neutralization in a subset of neutralizing antibodies (9) and that the N439K mutation causes immune escape and enhances binding affinity for human angiotensin-converting enzyme 2 (10,11). In addition, the V483F mutation has been shown previously to cause immune escape (12).

The constellation of this particular set of mutations has not been found elsewhere yet despite active ongoing genomic surveillance, which indicates the virus did not spread in the population (Appendix Table). Nonetheless, the detection of an Alpha variant infection in an immunocompromised person in a time when Omicron was the primary circulating variant indicates that reinfection is unlikely, which is also supported by phylogenetic analysis.

This occurrence illustrates that this VOC did not completely disappear although it was last detected on October 13, 2021, in the Netherlands. In addition, several mutations were found that are also present in other VOCs, suggesting that VOCs might have emerged in long-term infected immunocompromised persons as suggested previously (13).

Our findings illustrate that in previously unidentified reservoirs, such as immunocompromised persons, virus variants might still be present even when these variants are regarded as extinct and are no longer circulating among the population. In addition, we show that several mutations associated with immune escape that maintain virulence and fitness can accumulate in such an immunocompromised person. Continuous genomic surveillance in long-term infected persons is essential to elucidate their potential role in the emergence of future VOCs.

Dr. Oude Munnink is a researcher at the Erasmus Medical Center. His research interests include genomic surveillance of genomic pathogens and viral zoonoses.

 

While this particular Alpha variant does not appear to have spread in the population, this is a reminder of the wide range of opportunities and tools SARS-CoV-2 has to reinvent itself.  

Most of these field experiments are doomed to fail, of course. 

But it just takes one overachiever to reinvigorate the pandemic. 

NEJM: A Novel Henipavirus With Human Spillover In China

Credit WHO

 #16,930

Henipaviruses - of which Nipah and Hendra are the most infamous - belong to the Paramyxoviridae family of viruses, and have sparked a number of deadly spillovers into humans - and epidemics - across South East and Central Asia - and to a lesser extent Australia - over the past 25 years.

Normally carried by Fruit bats, these viruses can carry a high mortality rate in humans, and human-to-human transmission of Nipah has been demonstrated.  

The deadlier of the two - Nipah - was only first discovered 25 years ago after an outbreak in Malaysia, which spread 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 - particularly in Bangladesh and India - often with a case fatality rate of between 70% and 90%.  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.

Last year, researchers announced the discovery of a A Novel Variant Of the Hendra Virus in Australia, and it is a fair assumption there are other as yet undiscovered variants in the wild.  And while bats are  presumed to be the primary reservoir host for Henipaviruses, they may not be the only ones. 

All of which brings us to a correspondence from researchers from Beijing Institute of Microbiological Epidemiology and a team from the National University of Singapore - published late last week in the New England Journal of Medicine - that describes the discovery of a novel zoonotic henipavirus in China's eastern Shandong and Henan provinces.

A Zoonotic Henipavirus in Febrile Patients in China

Although this report is normally part of the subscriber only content on the NEJM, it is accessible with a free account registration. You'll want to follow the link to read it in its entirety. 

Briefly, however, researchers described a phylogenetically distinct henipavirus - dubbed Langya henipavirus (LayV) - which they isolated from the throats of 35 fever patients who reported recent animal exposure.  

Genetic testing of 25 animals found low levels of the virus in dogs (5%) and goats (2%), but much higher levels (27%) in shrews, which they suspect may be the reservoir host for this virus. 

While the virus was found in 35 patients - all exhibiting a range of symptoms (fever, cough, fatigue, anorexia, leukopenia, and for some - liver or renal damage)  - they haven't fully established a causal relationship between the viral infection and the disease, although it is strongly suspected. 

It is far too soon to even speculate how much of a threat - if any -  this virus may pose in the future. But it is sobering when you consider how many of these zoonotic threats there are out there.  

Some of the `lesser' novel viruses we've seen emerge over the past decade include:

Nosocomial Outbreak of SFTS Among Healthcare Workers in a Single Hospital in Daegu, Korea

Alaska Reports 3rd & 4th Case of A Novel Zoonotic Orthopoxvirus (Alaskapox) Near Fairbanks

EID Journal: Bourbon Virus in Wild and Domestic Animals, Missouri, USA, 2012–2013

EID Journal: Novel Poxvirus in Proliferative Lesions of Wild Rodents in East-Central Texas, USA

mBio: Contemporary EV-D68 Strains Have Acquired The Ability To Infect Human Neuronal Cells

MMWR: A Little Bit Of Seoul (Virus)

EID Journal: Influenza A(H6N1) In Dogs, Taiwan

New Phlebovirus Discovered In Missouri

While we tend to concentrate on the `big ticket' threats, like Avian flu, Nipah, Ebola, and MERS-CoV, there are scores of unknown, or lesser known threats that could - like COVID did in 2019 - suddenly come out of left field as our next pandemic contender. 

Fifty years ago, it seemed as if we had entered the golden age of medicine, and were on the verge of conquering infectious diseases. 

Eradication of smallpox and polio though vaccination seemed not only possible, but imminent.  Childhood diseases like mumps, measles, and whooping cough were now preventable, and modern antibiotics could cure almost any bacterial infection. 

• While smallpox was eradicated, polio lingers on, and childhood diseases like measles and whooping cough are making a comeback. 
• Starting with Ebola in 1976, and followed by HIV in the early 1980s, we've seen a procession of emerging zoonotic disease threats which now includes avian flu, Nipah, and COVID. 
• And our antibiotic armamentarium erodes a bit more with each passing year, due to overuse and a lack of new drugs in the pipeline. 

Instead of a `golden age', we've entered an age of emerging and reemerging pandemic threats (see PNAS Research: Intensity and Frequency of Extreme Novel Epidemics), one where an obscure virus from a far off land can spark a global crisis with little or no warning. 

The Langya henipavirus (LayV) currently ranks pretty far down our threat list, and may never amount to anything more than a local concern and a scientific curiosity.  

But Nature's laboratory is open 24/7, and it always has an abundance of experiments underway.