ACIP: Framework for Booster Doses of COVID-19 Vaccines

#16,155

Although the big news to come out of yesterday's CDC ACIP (Advisory Committee for Immunization Practices) meeting was their endorsement of the Pfizer-BioNTech’s licensed COVID vaccine for people 16 and older (see CDC statement below), they also spent much of the day going over the latest data on Vaccine Effectiveness (VE) and safety, and the growing call for booster shots. 

CDC Media Statement: CDC Statement Following ACIP Pfizer-BioNTech Vote

Media Statement

For Immediate Release: Monday, August 30, 2021

Contact: Media Relations

(404) 639-3286

Today, CDC Director Rochelle P. Walensky, M.D., M.P.H., endorsed the CDC Advisory Committee on Immunization Practices’ (ACIP) recommendation for use of the Pfizer-BioNTech’s licensed vaccine for people 16 and older.

This recommendation follows FDA’s decision to fully approve Pfizer’s COVID-19 vaccine.

The ACIP recommendation comes 9 months after the committee’s interim recommendation and after an exhaustive review of the scientific evidence demonstrating safety and effectiveness, and supporting continued use of the vaccine.

“We now have a fully approved COVID-19 vaccine and ACIP has added its recommendation. If you have been waiting for this approval before getting the vaccine, now is the time to get vaccinated and join the more than 173 million Americans who are already fully vaccinated,” said CDC Director Dr. Rochelle Walensky.

As we've been noting for months, the high-flying VE rates reported very early (both in clinical trials and the opening months of 2021) - suggesting a > 90% protection by mRNA vaccines against SARS-CoV-2 infection - have begun to decline (see MMWR: Two Early Release COVID VE (Vaccine Effectiveness) Studies). 

Protection against severe illness, hospitalization, and death remain reassuringly high, however. 

For now, it isn't clear whether this drop is simply due to the time elapsed since the the initial shot, the introduction of a much more transmissible Delta variant, or both. Either way, since mid-July the debate has escalated over the need for, and the best timing of, booster shots (see Joint Statement from HHS Public Health and Medical Experts on COVID-19 Booster Shots).

While partially a political decision, it is one that must be guided by both logistical concerns and the best medical evidence available at the time.  

ACIP is currently deliberating the scientific evidence for their need, the likelihood of benefit from a booster shot, and the practicalities of promoting a booster when a large portion of the United States - and the world - has yet to receive their first shot. 

We've a series of slides (Framework for COVID-19 booster doses pdf [53 pages]) from yesterday's ACIP meeting that outline the questions on the table, the evidence to date, and what more we need to know before embarking down this road. 

I highly recommend downloading and reviewing the entire 53-slide set. But a few highlights include:

This presentation presents a series of slides (#11- #27) illustrating the significant decline in vaccine  protection against infection, along with a far more modest reduction in protection against hospitalization, particularly in those over the age of 75. 

It should be noted that if last year (see A COVID Vaccine Reality Check), had we been promised a vaccine that would be 80% protective against hospitalization in the most vulnerable ( age > 75) population, we'd have considered it a `win'. 

There are concerns, however, that the VE against severe illness, hospitalization, and death may continue to erode over time.  Hence the growing calls for offering booster shots. 

Although plans have been announced to begin offering booster shots as soon as September 20th, it is unlikely that we'll have much robust data by then on the (short-term) effectiveness of booster shots against the Delta Variant (or other VOCs), or how long any enhanced protection might last. 

Yesterday's presentation by ACIP offers no decision on booster shots, but suggests they may be leaning towards a more limited roll-out of booster shots to begin with, and they continue to stress the need to get unvaccinated individuals their initial doses.   

Slide #46 (below) illustrates a possible recommendation by the Committee, which would target the highest risk individuals (LTCF residents, HCW, Adults > 65/75 years of age) for booster shots initially. 

The report concludes with:

You'll find the entire day's list of slide presentations available at the following link:

ACIP Presentation Slides: August 30, 2021 Meeting


Note: These files are not yet 508

Slides will be added as they become available.
August 30, 2021

Welcome & Introductions

Introduction
Dr. G Lee
Dr. A Cohn 

Coronavirus Disease 2019 (COVID-19) Vaccines

Introduction pdf icon[9 pages]
Dr. M Daley

BNT-162b2 COVID-19 vaccine BLA safety and efficacy data pdf icon[39 pages]
Dr. J Perez

Safety update for COVID-19 vaccines: VAERS pdf icon[20 pages]
Dr. J Su

Safety update for COVID-19 vaccines: VSD pdf icon[29 pages]
Dr. N Klein 

VaST assessement pdf icon[21 pages]
Dr. G Lee 

Benefit-risk discussion for use of Pfizer-BioNTech COVID-19 vaccine in individuals ≥16 years of age pdf icon[30 pages]
Dr. H Rosenblum 

GRADE: Pfizer/BioNTech COVID-19 vaccine pdf icon[58 pages]
Dr. J Gargano

Evidence to Recommendations Framework: Pfizer-BioNTech COVID-19 vaccine pdf icon[77 pages]
Dr. K Dooling

Framework for COVID-19 booster doses pdf icon[53 pages]
Dr. S Oliver

Page last reviewed: August 30, 2021

Saudi MOH Reports Another MERS-CoV Case In Riyadh

 Saudi MOH 2021 MERS Case List

#16,154

For the 3rd time in 5 weeks, the Saudi MOH is reporting a new MERS Case in the nation's capital, Riyadh.  This is only the 12th case reported by the Saudi's in 2021, which is far below what we've seen reported since 2013. 

Today's case is a 69-y.o. male with reported camel contact. 

MERS-CoV was first identified in Saudi Arabia in 2012, and was subsequently discovered to be endemic in camels. Camel-to-human transmission continues to reseed the virus into the human population, where it can then be transmitted from human-to-human. 

Unlike COVID, MERS doesn't transmit well in the community, with most large outbreaks occurring in hospital settings. It has, however, a much higher fatality rate (est. 35%). 

Admittedly, the Saudi's surveillance and reporting on MERS has always been a bit spotty (see 2016's EID Journal: Estimation of Severe MERS Cases in the Middle East, 2012–2016), with many experts believing that we were only learning of a fraction of the symptomatic cases. 

We've also seen a reluctance by the Saudis to report cases in the past, sometimes going months without publicly acknowledging cases (see The Saudi MOH Breaks Their Silence On MERS-CoV), making the current reduction in MERS cases being reported a little less reassuring. 

Prior to SARS-CoV-2 successfully jumping to humans, MERS-CoV was considered the coronavirus with the greatest pandemic potential. It still carries that same potential, and therefore deserves our attention. 

Preprint: The Continuous Evolution of SARS-CoV-2 in South Africa (Lineage C.1.2)

 Global Detection of C.1.2 Sequences

#16,153

Although thousands of COVID variants have been detected around the world, only a dozen or so have been classified as VOIs (Variants of Interest), and fewer still are considered VOCs (Variants of Concern).   

Some VOIs, after initially raising concerns - have already gone extinct - unable to successfully compete against more aggressive variants like Delta.  What may look worrisome today, could become a brief footnote in the COVID pandemic's history a few months from now. 

The COVID viral landscape is highly dynamic, continually changing, and its future is very, very hard to predict. Last April when Alpha was on the ascendent world-wide, it was very hard to see it being supplanted within months by an upstart Delta variant coming out of India.   

But that's exactly what happened.  

With 99% of the COVID cases in the United States estimated to be from Delta, it is difficult to envision that variant being displaced anytime soon by something else, yet that possibility exists.  So researcher are on the lookout for potential contenders; variants that may have the ability to compete head-to-head with Delta. 

Last month's rising star was thought to be Lambda (see PrePrint: Infectivity and Immune Escape of the New SARS-CoV-2 Variant of Interest Lambda), with pockets of  Beta, Gamma, and Epsilon all still in the running.  

Unless and until Delta relinquishes its stranglehold, however, identifying a likely successor is nearly impossible.  

There are too many variables and interactions we don't fully understand, and always the possibility that a `new' and more `biologically fit' variant will emerge and join the fray.  

To that end we have a preprint which identifies a `highly mutated' COVID variant in South Africa (C.1.2) , that carries a large number of `red flag' mutations which have been shown to increase biological fitness in VOCs and VOIs. 

This preprint has gotten a lot of notice over the weekend, both on social media and in news media reports, including:

New variant, C.1.2, may be more infectious, evade vaccine protection: Study

New ‘most mutated COVID-19 variant’ found in South Africa

New COVID variant detected in South Africa, most mutated variant so far

Alarming headlines aside, the actual number of C.1.2 variants discovered to date is small (n < 100), and its geographic spread is limited.  That said, C.1.2 is most closely related to the Lambda variant - which has gained its own notoriety - and it seems to be evolving at a much faster clip than other variants. 

Both of which make this a variant worth exploring.  But whether that means C.1.2 will become the next `big challenge' in COVID, is far from clear.

C.1.2 lineage - which is a highly mutated form of C.1 first reported last January - was first detected in the Mpumalanga and Gauteng provinces of South Africa in May. It has since been detected across much of South Africa, as well as sporadic cases in England, China, and parts of Europe and Oceania. 

https://cov-lineages.org/lineage_list.html

Whether or not C.1.2 is the heir to Delta's throne, or another flash in the pan, is unknown. But it does serve as warning that not all variants evolve at the same rate, and that there are potential `wildcards' in play in this pandemic. 

While our immediate problem is dealing with Delta, it doesn't hurt to look ahead, as long as we don't focus too heavily on any one particular outcome. 

A link, and the abstract, from the preprint follow.  Those who don't mind slugging through some fairly technical text will want to read the preprint in its entirety.  I'll have a brief postscript when you return. 

The continuous evolution of SARS-CoV-2 in South Africa: a new lineage with rapid accumulation of mutations of concern and global detection

Cathrine Scheepers, Josie Everatt, Daniel G. Amoako, Anele Mnguni, Arshad Ismail, Boitshoko Mahlangu, Constantinos Kurt Wibmer, Eduan Wilkinson, Houriiyah Tegally, James Emmanuel San, Jennifer Giandhari, Noxolo Ntuli, Sureshnee Pillay, Thabo Mohale, Yeshnee Naidoo, Zamantungwa T. Khumalo, Zinhle Makatini, NGS-SA, Alex Sigal, Carolyn Williamson, Florette Treurnicht, Koleka Mlisana, Marietjie Venter, Nei-yuan Hsiao, Nicole Wolter, Nokukhanya Msomi, Richard Lessells, Tongai Maponga, Wolfgang Preiser, Penny L. Moore, Anne von Gottberg, Tulio de Oliveira, Jinal N. Bhiman

doi: https://doi.org/10.1101/2021.08.20.21262342

Abstract

SARS-CoV-2 variants of interest have been associated with increased transmissibility, neutralization resistance and disease severity. Ongoing SARS-CoV-2 genomic surveillance world-wide has improved our ability to rapidly identify such variants. Here we report the identification of a potential variant of interest assigned to the PANGO lineage C.1.2. This lineage was first identified in May 2021 and evolved from C.1, one of the lineages that dominated the first wave of SARS-CoV-2 infections in South Africa and was last detected in January 2021. C.1.2 has since been detected across the majority of the provinces in South Africa and in seven other countries spanning Africa, Europe, Asia and Oceania.

 

The emergence of C.1.2 was associated with an increased substitution rate, as was previously observed with the emergence of the Alpha, Beta and Gamma variants of concern (VOCs). C.1.2 contains multiple substitutions (R190S, D215G, E484K, N501Y, H655Y and T859N) and deletions (Y144del, L242-A243del) within the spike protein, which have been observed in other VOCs and are associated with increased transmissibility and reduced neutralization sensitivity. Of greater concern is the accumulation of additional mutations (C136F, Y449H and N679K) which are also likely to impact neutralization sensitivity or furin cleavage and therefore replicative fitness. While the phenotypic characteristics and epidemiology of C.1.2 are being defined, it is important to highlight this lineage given its concerning constellations of mutations.

(SNIP)

Discussion/Conclusion

We have identified a new SARS-CoV-2 variant assigned to the PANGO lineage C.1.2. This variant has been detected throughout the third wave of infections in South Africa from May 2021 onwards and has been detected in seven other countries within Europe, Asia, Africa and Oceania. The identification of novel SARS-CoV-2 variants is commonly associated with new waves of infection. Like several other VOCs, C.1.2 has accumulated a number of substitutions beyond what would be expected from the background SARS-CoV-2 evolutionary rate. This suggests the likelihood that these mutations arose during a period of accelerated evolution in a single individual with prolonged viral infection through virus-host co-evolution19–21. Deletions within the NTD (like Y144del, seen in C.1.2 and other VOCs) have been evident in cases of prolonged infection, further supporting this hypothesis22–24.

C.1.2 contains many mutations that have been identified in all four VOCs (Alpha, Beta, Delta and Gamma) and three VOIs (Kappa, Eta and Lambda) as well as additional mutations within the NTD (C136F), RBD (Y449H), and adjacent to the furin cleavage site (N679K). Many of the shared mutations have been associated with improved ACE2 binding (N501Y)25–29 or furin cleavage (H655Y and P681H/R)30–32, and reduced neutralization activity (particularly Y144del, 242-244del, and E484K)17,33–39, providing sufficient cause for concern of continued transmission of this variant. Future work aims to determine the functional impact of these mutations, which likely include neutralizing antibody escape, and to investigate whether their combination confers a replicative fitness advantage over the Delta variant.

The C.1.2 lineage is continuing to grow. At the time of submission (20 August 2021) there were 80 C.1.2 sequences in GISAID with it now having been detected in Botswana and in the Northern Cape of South Africa.

         (Continue . . . )

The authors suggest hat the rapid accumulation of mutations in C.1.2 may have occurred in a single, immunocompromised, individual who could have carried the virus for a prolonged period of time. This is not the first time we've seen this notion.

Last December, 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 arised from a single chronically-infected, likely immunocompromised, individual.

About the same time, COG-UK released a report on multiple escape mutants generated in a chronically ill, immunocompromised patient, after receiving convalescent plasma therapy. 

COG-UK: A Cautionary Tale On COVID Escape Mutants Generated In Patient Receiving Plasma Therapy

Three weeks 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), a concern we've seen raised previously. 

Below you'll find a link to  the press release from the Fred Hutchinson Cancer Research Center on their NEJM article mentioned above.

Persistent COVID-19 infections in immunocompromised people may give rise to variants of concern

Earlier this month, in COCA Call Tomorrow (Aug 12th): Therapeutic Options to Prevent Severe COVID-19 in Immunocompromised People, we looked at the importance preventing infection in immunocompromised individuals whenever possible.

You can find more information on the use of monoclonal antibodies in the NIH's August 4th update of their Anti-SARS-CoV-2 Monoclonal Antibodies page. 

Regardless of how C.1.2 jumped ahead in the mutation race, this is a reminder that COVID is perfectly capable of surprising us, and that this pandemic may still have some unexpected twists and turns ahead. 

NHC: Ida Now A 150 MPH Storm

 

#16,152

For the past 48 hours Hurricane Ida has had the `look' of a storm likely to blow up into a monster over the extremely warm waters of the Gulf of Mexico.  Overnight, it has grown from a 115 MPH storm, to a 150 MPH storm, as its central pressure drops rapidly.   This from the 6am CDT NHC update:

While still a CAT 4, this storm still has some time to intensify.  And the difference in impact between a high CAT 4 and a low CAT 5 is negligible.  It's exact path, and when it begins to turn more northerly, will determine who sees the worst of this storm. 

Key Messages this morning from the NHC: 

Ida has the potential to be a historic hurricane, and New Orleans - while not directly in the path - is not out of the woods.  Even a slight wobble to the east could greatly increase the threat to that city so heavily damaged 16 years ago today by Hurricane Katrina. 

Power outages across much of coastal and central Louisiana are likely to be extensive, and prolonged.  Some places may be without power for weeks. For some advice on preparing for prolonged power outages see Hurricane Prep: Some Simple Off-The-Shelf Solar Solutions For Power Outages.

All of this comes as COVID cases continue to surge, hospitals are already under pressure, and emergency services are stretched thin. This storm, and the disruptions it brings, could have serious impact on COVID cases. 

Those who have not already evacuated will find their window of opportunity rapidly closing in the next few hours, and will have to ride out the storm where they are.  This has the potential of being a life-altering event for thousands of people. 

And of course, this is still August, which the heart of hurricane season still ahead.  Over the next 60+ days, we are likely to see additional threats.   

While it is too late to prepare if you are in the path of Ida, it isn't too late to prepare if you live elsewhere in hurricane country.  And if you start now, you'll have more than the 48 hours that the residents of Louisiana had this week. 

WWL-TV New Orleans is broadcasting live coverage of the storm.  You can watch at:

https://www.wwltv.com/watch?vid=55f478f0-ee91-4ae0-93bc-cf71382c125d

NHC: Key Messages As Hurricane Ida Threatens Northern Gulf Coast

 

#16,151

With landfall expected in less than 36 hours, and the National Hurricane Center's forecast of Ida becoming a Major (possibly Cat 4) hurricane, residents of south-central Louisiana have only a few daylight hours left to prepare for the storm, and/or evacuate. 

Key messages this morning from the NHC on this storm follow:

While the impact of Ida may be tempered somewhat by it making landfall in a relatively unpopulated region of Louisiana, its effects may still be severe hundreds of miles inland.  Power outages may be numerous, and restoration times may take days, or even weeks, in some locations. 

Although we think about the first 24 hours of a hurricane's impact as being the most dramatic and newsworthy, the real impact often comes in the days, weeks, and months that follow, long after the evening news coverage has abated.

After the storm has passed, flood waters are often slow to recede, and they can leave behind a multitude of dangers. Downed electrical lines, dangerous debris, weakened and compromised structures, and even displaced wildlife (think : alligators, snakes, rats, etc.) can pose ongoing threats following the storm.

Not only do flood waters easily hide dangerous objects - like broken bottles, razor sharp metal sheeting, live electrical wires, and rusty nails – they can also harbor nasty viruses and bacteria (see
Flood Dangers Run Deep).

Thousands of homes and businesses may find themselves without electrical power, Internet or even cell phone service for days, possibly even weeks, after the storm has passed. In 2012, Hurricane Sandy left some parts of the Northeast without power for a week or longer, while Hurricane Maria left most of Puerto Rico dark for six months.

As we've discussed many times, the dangers from a hurricane often increase in the days and weeks after the storm has passed, due to injuries or illness that occur during the `recovery' period. Some of the many dangers include:

• Carbon Monoxide Poisoning (see CDC HAN 00415: Hurricane Florence — Clinical Guidance For Carbon Monoxide (CO) Poisoning)
• Food poisoning (see A Consumer's Guide to Food Safety: Severe Storms and Hurricanes)
• Chain saw accidents (see Preventing Chain Saw Injuries During Tree Removal After a Disaster)
• Toxic mold and mildew (see CDC Mold After a Disaster).
• And even psychological impacts (including PTSD) (see Sandy 1 Year Later: Coping With The Aftermath).

While the psychological impact of a major disaster cannot be fully prevented, individual, family, and business preparedness can go a long ways towards reducing the impact of any disaster. The CDC also has some advice on Coping with a Disaster or Traumatic Event.

A small reminder that in the wake of a disaster not all wounds bleed, not all fractures show on an X-ray, and that the best treatment doesn't always come from inside your first aid kit.

Note:  You should try and download and save much of the information from these websites onto your computer or smart phone before the storm - or even print some of it out - so you’ll have it even if there are disruptions in your power or Internet access.

The Lancet: Hospital Admission & Emergency Care Attendance Risk for SARS-CoV-2 Delta Variant Compared with Alpha

  CDC Nowcast - The Dominance of Delta

#16,150

Three months ago `UK' B1.1.1.7 (Alpha) variant seemed in complete control in the United States and appeared poised for eventual world domination. But at the same time, the the Delta variant - first detected in India - was making serious inroads in the UK, and we were beginning to see evidence that Delta might produce more severe illness. 

UK PHE Update, Technical Briefing & Revised Risk Assessment On COVID Variant B.1.617.2 (Delta) - June 3rd, 2021

Although several studies have suggested an increased risk of hospitalization with Delta over Alpha - and infection with the `wild type' COVID of 2020 - case fatality rates have continued to fall, suggesting that Delta cases were being better managed than previous cases. 

This makes some sense, as we have more than a year of experience dealing with hospitalized cases - and between increasing vaccine uptake, monoclonal antibody treatments, and the growing rejection of unproven therapies (see WHO Solidarity Therapeutics Trial) - survival rates have improved. 

Of course, many survivors must still deal with `Long COVID' or other sequelae (see CMAJ: Even Mild COVID-19 May Have Long-term Brain Impacts) - and the long-term health impacts of COVID infection are largely unknown.  But fatal outcomes - at least in regions able to provide modern medical care - have declined. 

With the `mixed signals' of increased hospitalizations - but lower deaths - researchers are trying to quantify the actual risks of infection with the Delta variant vs. older COVID strains.  Yesterday The Lancet published the following open access study, which suggests - as we've seen previously -  that Delta patients are more than twice as likely to be hospitalized as Alpha patients. 

This is a lengthy, detailed, and impressive analysis of more than 40,000 COVID Cases occurring the UK between March 29, 2021 and May 17, 2021, all sequencing-confirmed with either Alpha or Delta infections.

You'll want to follow the link to read the study in full, as I've only reproduced some excerpts from the Abstract and Discussion.  After the break I'll have a link to some expert commentary on the Science Media Centre website. 

Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study

Katherine A Twohig, MPH *, Tommy Nyberg, PhD *, Asad Zaidi, MSc, Simon Thelwall, PhD,
Mary A Sinnathamby, MPH Shirin Aliabadi, PhD,et al.s
Published:August 27, 2021 DOI:https://doi.org/10.1016/S1473-3099(21)00475-8

Summary

Background

The SARS-CoV-2 delta (B.1.617.2) variant was first detected in England in March, 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. It is suspected that the delta variant is associated with more severe disease than the previously dominant alpha (B.1.1.7) variant. We aimed to characterise the severity of the delta variant compared with the alpha variant by determining the relative risk of hospital attendance outcomes.

(SNIP)

Findings

Individual-level data on 43 338 COVID-19-positive patients (8682 with the delta variant, 34 656 with the alpha variant; median age 31 years [IQR 17–43]) were included in our analysis. 196 (2·3%) patients with the delta variant versus 764 (2·2%) patients with the alpha variant were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2·26 [95% CI 1·32–3·89]). 498 (5·7%) patients with the delta variant versus 1448 (4·2%) patients with the alpha variant were admitted to hospital or attended emergency care within 14 days (adjusted HR 1·45 [1·08–1·95]). 

 

Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients with the delta variant versus the alpha variant (adjusted HR for hospital admission 1·94 [95% CI 0·47–8·05] and for hospital admission or emergency care attendance 1·58 [0·69–3·61]) were similar to the HRs for unvaccinated patients (2·32 [1·29–4·16] and 1·43 [1·04–1·97]; p=0·82 for both) but the precision for the vaccinated subgroup was low.

Interpretation

This large national study found a higher hospital admission or emergency care attendance risk for patients with COVID-19 infected with the delta variant compared with the alpha variant. Results suggest that outbreaks of the delta variant in unvaccinated populations might lead to a greater burden on health-care services than the alpha variant.

Funding

Medical Research Council; UK Research and Innovation; Department of Health and Social Care; and National Institute for Health Research.

(SNIP)

Discussion

New SARS-CoV-2 infections in England are increasingly caused by the delta variant. Although the proportion of cases caused by the delta variant was 20% overall during the study period, this increased to 74% of new sequenced cases in the week starting May 31, 2021.

9

To our knowledge, this study provides the largest whole-genome-sequencing dataset for SARS-CoV-2 in a high-income country to date, enabling the assessment of hospitalisation risk for the delta variant compared with the alpha variant using linked administrative data. 

The results suggest that patients with the delta variant had more than two times the risk of hospital admission compared with patients with the alpha variant. Emergency care attendance combined with hospital admission was also higher for patients with the delta variant, showing increased use of emergency care services as well as inpatient hospitalisation. 

Similar results were observed for the subgroup of unvaccinated patients when comparing risks of both hospital care outcomes between the two variants. In the subgroup of patients who had received at least one vaccine dose (≥21 days since their first dose), the precision was too low to determine whether the risks of the outcomes were higher or similar for patients with the delta variant compared with patients with the alpha variant. It has previously been reported that vaccination leads to a similar relative reduction in the risk of hospitalisation for patients with the delta variant or the alpha variant.

12

This is consistent with the findings in the present study: overall, the number of hospital attendances were low in the vaccinated subgroup resulting in low-precision relative risk estimates.

          (Continue . . . )

 
You'll find several expert reactions available on the SMC website, including:

AUGUST 27, 2021
Expert reaction to study looking at risk of hospitalisation from the delta variant compared with alpha


A study published in The Lancet Infectious Diseases looks at hospital admission and emergency care attendance risk for SARS-CoV-2 variants of concern, delta (B.1.617.2) and alpha (B.1.1.7).


Dr Zania Stamataki, Viral Immunologist, University of Birmingham, said:

“The delta variant was responsible for the uptick in covid cases this summer in the UK, and many of us have heard of even vaccinated people that became infected. This study measures hospitalisations as a surrogate marker of severe disease, and the findings are clear: the delta variant increases hospitalisations compared to the alpha variant previously prevalent in the UK. The majority of cases (74%) were unvaccinated, and 24% were partially vaccinated, with nearly 2% double-vaccinated hospitalised with covid. Taken together with previous studies showing that delta is 50% more infectious than alpha, evidence mounts that we are dealing with a very dangerous variant. Both vaccine doses are needed for maximum protection.”


Dr David Strain, Senior Clinical Lecturer, University of Exeter, said:

“These data confirm what we are seeing in clinical practice, namely that, in addition to the Delta variant being more infectious than the original or the Alpha variants, it is also causing more severe illness, in populations that previously would have had only mild infections. It highlights the need for a comprehensive vaccine program in younger adults and it clearly demonstrates the pre-conception that they do not get severe covid is no longer true.

“This is not a surprise, as the two things that make the Delta variant more infectious will also have a role in the disease severity. Firstly the Delta variant produces up to a 1000 times more copies when it is replicating. This is not just pertinent when it comes to transmission between individuals, but also when it comes to spreading the virus throughout the body of the person who is infected. Secondly, the modification to the spike protein – the key, as it were, to the cellular lock – makes it easier for the virus to enter the cell thus making the move from viral carrier to infected person much quicker. This combination of more viral copies and better cellular penetration makes it more likely that the cells, tissues and organs will become overwhelmed before the immune system, particularly that of an unvaccinated individual, has had chance to mount a defence.”

(Continue . . . )

 
Although it is hard to see past the 99% dominance of Delta in the United States right now, the inevitable question is what happens next?  Once Delta has run its course, and community immunity (via infection or, preferably,  vaccination) lessens its impact, will it become endemic like the flu? Or will another antigenically different, and potentially more dangerous, variant take its place?

At this point, no one really knows.  

But the history of COVID has been one of escalating viral threats, with the D614G mutation upping the ante over the original Wuhan strain in early 2020 - only to be followed by Alpha, and then Delta - both of which have significantly increased the transmissibility and severity of the virus. 

We are unfortunately, still in uncharted territory. Stay tuned.  

Study: Impact of NSAIDs & Acetaminophen On COVID Infection

 

#16,149

In March of 2020, in The French MOH Warning Over Anti-inflammatory Drugs For COVID-19, we looked at a warning from France's Health Minister on the risk of complications from taking NSAIDs and other anti-inflammatory drugs for COVID-19.

Six weeks later, the WHO released a preliminary Scientific Brief on NSAIDs and COVID-19, and while the data was limited, they could find no evidence of severe adverse events as a result of the use of NSAIDs in COVID-19 patients.

That said, NSAIDs and other anti-inflammatory drugs (including synthetic corticosteroids), are linked to a wide range of side effects. For NSAIDs, there is a heightened risk of cardiovascular events and bleeding, and in the case of corticosteroids, lowered immunity to infections (see FDA Strengthens Warnings Of Cardiovascular Risks With NSAIDs). 

Also, in general, fever is our body's natural way of combating a viral infection. By taking antipyretics of any type, we not only produce a host environment conducive to better viral replication, it can allow someone who is still contagious to feel good enough go to work, or school, and further spread the virus.

After the initial concerns were largely dismissed, the use of NSAIDs (or preferably) Acetaminophen (aka paracetamol)  to control fever and body aches following COVID vaccination, or to reduce some of the symptoms of infection, has been generally green-lighted by public health entities (but ask your doctor first, of course). 

Today we have a retrospective study - published by researchers at the MRC Toxicology Unit at Cambridge University - that finds a statistically significant, but modest (6.6%) reduction in COVID infection risk among those taking paracetamol (acetaminophen). 

While a significant link to lowered COVID infection was not demonstrated with Ibuprofen, no increase in infection risk was found, either. 

This is all fairly preliminary - and there are always risks when taking any medicine - but for those who  regularly take acetaminophen (or Ibuprofen) for arthritis, or other body aches, this study might provide some reassurance during this COVID pandemic. 

You'll want to follow the link to read the study in full, as I've only reproduced the Abstract and Conclusion below.

Paracetamol Is Associated with a Lower Risk of COVID-19 Infection and Decreased ACE2 Protein Expression: A Retrospective Analysis

Nuno Santos Leal †,Yizhou Yu †, Yuwen Chen,Giorgio Fedele and Luís Miguel Martins *
MRC Toxicology Unit, Gleeson Building, Tennis Court Road, University of Cambridge, Cambridge CB2 1QR, UK 

Abstract

Ibuprofen is a common over-the-counter drug taken for pain relief. However, recent studies have raised concerns about its potential toxic effect with coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has been proposed that ibuprofen may increase levels of angiotensin-converting enzyme 2 (ACE2), the human receptor for SARS-CoV-2 infection.

 

Therefore, paracetamol is suggested as an alternative to ibuprofen for treating COVID-19 symptoms. Nevertheless, the relationship between intake of paracetamol or ibuprofen and either susceptibility to infection by SARS-CoV-2 or modulation of cellular ACE2 levels remains unclear.

In this study, we combined data from human medical records and cells in culture to explore the role of the intake of these drugs in COVID-19. Although ibuprofen did not influence COVID-19 infectivity or ACE2 levels, paracetamol intake was associated with a lower occurrence of COVID-19 in our cohort. We also found that paracetamol led to decreased ACE2 protein levels in cultured cells.

 

Our work identifies a putative protective effect of paracetamol against SARS-CoV-2 infection. Future work should explore the molecular mechanisms underlying the relationship between paracetamol and COVID-19.

(SNIP)

5. Conclusions

In this study, we showed that paracetamol is associated with a lower risk of COVID-19 infectivity and a decrease in ACE2 protein levels, while we found no association between ibuprofen and COVID-19 infection.

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UK COVID Daily COVID Cases & Deaths Continue To Climb

 

#16,148

Six weeks ago there were government projections suggesting that daily cases - which were rapidly  approaching 50K a day - could double once the UK lifted their COVID restrictions on July 19th. 

To just about everyone's surprise, the opposite happened, with the peak of 54 thousand cases occurring on July 17th, followed by a slow decline to 21K over the next 2 weeks (see UK chart above).

While some were declaring the UK's summer wave broken by early August, since then we've seen a slow, but steady, increase in cases.  Yesterday made the 9th consecutive day with over 30 thousand cases, and the highest one-day total since July 22nd (n=38,281). 

Although well below the worst case scenarios proffered in early July, today the UK is seeing roughly the volume of cases they were seeing in mid-January of this year.  And to put it into another context, yesterday's cases were more than 35-fold higher than they were a year ago on that date (n=1048).  

COVID deaths in the UK  - which tend to lag 3 to 4 weeks behind confirmed cases - have risen markedly over the past 30 days (see chart below).  Due to constant backfilling of data as it comes in, trends are tough to quantify, but the UK is reporting a 9-fold increase between June 1st and August 1st. 

As I've said before, I consider predictions a mug's game, and so I leave that for the experts to get wrong.

That we are seeing such high (and rising) numbers in the UK, the EU, and the United States in August is concerning, of course. The juggernaut that is Delta continues to surge, and there are legitimate concerns of what might come after.

To that we can add the potential burden of influenza's return this winter, along with a panoply of other respiratory viruses.  As weary as we all all of this pandemic, we may have a very challenging winter ahead, and some healthcare delivery systems may find themselves overwhelmed. 

It's been more than 600 days since we first learned of 27 cases of atypical pneumonia in Wuhan, China - and while we've made remarkable progress with vaccines and research into this virus - I still don't know if we are closer to the beginning of this pandemic, or to the end. 

NHC 11am: T.D. 9 Forms in Western Caribbean - Expected to Threaten Gulf Coast As A Hurricane

 

#16,147

Yesterday, in The Tropics Heat Up As We Approach September, I mentioned that there was a disturbed area in the Caribbean with the potential to threaten the northern Gulf of Mexico late this weekend or early next week, and that those living there ought to use this weekend to finish up their hurricane preps.

Not surprisingly at 11am, the National Hurricane Center upgraded the disturbance to a tropical depression, and forecast it to strengthen into a hurricane on Saturday after it crosses the western tip of Cuba. 

While the exact path, and future intensity, of what should be named Ida is subject to change, right now the NHC anticipates it may be threatening the northern Gulf coast by Sunday or Monday, potentially as a major hurricane. We'll know a lot more about where it is likely to go over the next 36 hours.

Key messages from the NHC are:

Although intensity forecasts are particularly difficult, particular this far in advance, right now the NHC is looking at a near Cat 3 storm by Sunday night. 

Residents from the upper Texas Gulf coast to the Panhandle of Florida should closely monitor this storm, and make preparations should the storm head in their direction. As always, you should follow @NHC_Atlantic on twitter, and visit the NHC for the latest updates, and of course take direction from your local Emergency Management Office.

Since we are still in a pandemic, you will need to take that into account if you need to evacuate to a shelter. This advice from Ready.gov.

If you must go to a community or group shelter remember to follow the latest recommendations from the Centers for Disease Control and Prevention (CDC) for protecting yourself and family from COVID-19. Be sure to review your previous evacuation plan and consider alternative options to maintain physical distancing to prevent the spread of COVID-19 and update your plan accordingly.

If you must evacuate, if possible, bring with you items that can help protect you and others in the shelter from COVID-19, such as hand sanitizer, cleaning materials, and two clean, well-fitted masks that have two or more layers for each person.

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For more preparedness advice, my (updated for 2021) hurricane preparedness blogs include: 

National Hurricane Preparedness Week: Day 1 - Determine Your Risk

Hurricane Preparedness Week: Day 2 - Develop An Evacuation Plan

Hurricane Preparedness Week: Day 3 - Assemble Disaster Supplies

Hurricane Preparedness Week: Day 4 - Get An Insurance Check-up

Hurricane Preparedness Week: Day 5 - Strengthen Your Home

Hurricane Preparedness Week: Day 6 - Help Your Neighbors

Hurricane Preparedness Week: Day 7 - Complete A Written Plan

 

ECDC: Influenza Virus Characterisation - July 2021

 

#16,146

Although there is currently very little influenza being reported around the world, for the second year in a row we are faced with the possibility of seeing a `twindemic' of both COVID and Flu this fall or winter.  Last year, between social distancing and face masks - and likely some degree of `viral interference'  from COVID - influenza remained a no-show. 

Hopefully we'll get lucky again this year. 

But we've already seen some signs of increased RSV transmission in the United States (see CDC HAN: Increased RSV Reports Across The Southern United States) and around the globe (see here and here), and some reports of influenza outbreaks (see Influenza cases rising amid Covid-19 pandemic - The Kathmandu Post). 

Six weeks ago, in UK Academy Of Medical Sciences: Looking Ahead To COVID-19 Over Winter 2021/22 & Beyond, we looked at a lengthy (133 page PDF) report on what this fall and winter - and beyond - might look like with both COVID-19 and other respiratory illnesses concurrently spreading in the community. 

The report outlined three key challenges the UK will face this winter and beyond: 

● A resurgence of respiratory infectious diseases, including COVID-19, influenza and respiratory syncytial virus (RSV). Our modelling suggests that there will be a third peak of COVID-19 infections over the summer of 2021, although the timing and magnitude of the peak are uncertain. Mortality may be less severe than last winter but a rise in infections will put pressure on the health service and lead to higher levels of long COVID. The possibility of a further new variant is also of concern. Outbreaks of RSV in the autumn and influenza in the winter could be around twice the magnitude of a ‘normal’ year, and might overlap (at least partially) with a peak in COVID-19 infections.

● Wider health and wellbeing impacts of the pandemic, including long COVID, mental and physical deconditioning, and the impact of delays in diagnosis and disease management during the pandemic. During the winter months, noncommunicable diseases (NCDs) such as asthma, chronic obstructive pulmonary disease (COPD), ischaemic heart disease, myocardial infarction and stroke are likely to be exacerbated.

● Continued disruption to health and social care service delivery, including managing the backlog of treatment and diagnosis, incorporating IPC measures, and the financial precariousness of social care. By the winter, staff across the sectors will have been responding to a prolonged pandemic for over 18 months, with many directly affected by COVID-19, thereby compounding issues of staff capacity and vacancies.

Added to these, ongoing uncertainties remain over the: duration of post-vaccination immunity in different groups (and safety in children); likelihood of and impact of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, including the possibility of vaccine-resistant variants. This is in addition to the development and availability of treatments and prophylaxis for COVID-19; and prevalence, duration, severity and ability to treat, long COVID

Complicating matters, with so little influenza being reported world-wide - and many public health departments overwhelmed by COVID - we've seen a 99% drop in  influenza samples submitted to reference laboratories for analysis.  

Influenza is still out there, of course, and continues to evolve.  But since March of 2020 we've had extremely limited real-world data, making this fall's flu shot - whose components were selected last February - perhaps an even longer-shot of matching this year's flu (assuming it arrives) than usual. 

Complicating matters even further, with almost no influenza exposure for 18 months, community immunity to influenza - which is expected to decline over time - is likely lower than we've seen in years (see COVID-19, The Next Flu Season, And The Temporary Immunity Hypothesis).

I'll still get the flu shot this fall, because even a little protection beats no protection at all. And once again, maybe we'll get lucky, and whatever flu does appear is covered by this year's vaccine. 

Besides, there is some evidence (see PLoS One: Potential Benefits of the Influenza Vaccine Against SARS-CoV-2 (Retrospective Cohort Analysis) that the flu shot may help ramp up our immune system against other viruses as well. 

The ECDC has continued to produce monthly Influenza Characterization reports, based on limited viral submissions, over the summer.  How probative they will be for this year's influenza season is unknown, but we have to go with the data we have - not the data we wished we had. 

Influenza virus characterisation - Summary Europe, July 2021
Systematic review
23 Aug 2021
Publication series: Influenza Virus Characterisation
 
This is the ninth report for the 2020-2021 influenza season. As of week 28 /2021, only 943 influenza detections across the WHO European Region had been reported to the European Surveillance System (TESSy); 51% type A viruses, with A(H3N2) and A(H1N1)pdm09 being approximately equally represented, and 49% type B viruses with only 16 having been ascribed to a lineage, 13 B/Victoria and three B/Yamagata. 

This represents a 99.4% drop in detections compared with the same period in 2020, probably due to measures introduced to combat the COVID 19 pandemic.

Executive summary

Since the June 2021 characterisation report report, one shipment from an EU/EEA country (France) containing six virus isolates was received at the London WHO Collaborating Centre, the Francis Crick Worldwide Influenza Centre (WIC): virus characterisation of these six viruses is ongoing. This report therefore focuses on genetic characterisation of the HA genes of seasonal influenza viruses submitted and/or released in GISAID during July 2021, together with sequences recently determined at the WIC. The data continue to show extremely low levels of influenza detections globally.

The 60 A(H1N1)pdm09 HA sequences derived from viruses detected in 2021 as deposited/released in GISAID during July, all originated in Togo and were subgroup 6B.1A5A+187V/A , represented by the vaccine virus for the northern hemisphere 2020 2021 season, A/Guangdong Maonan/SWL1536/2019 . Most of these sequences (35) encoded additional HA1 amino acid substitutions of I166T and A186T.

All 57 HA sequences that became available in July for A(H3N2) viruses , detected in fell in subgroup 3C.2a1b+T131K A. The viruses in this subgroup split into two antigenically distinguishable clusters originally defined by viruses from Cambodia ( n = 1 3 : with HA1 amino acid substitutions of G186S, F193S, Y195F and S198P, many also having K171N ) and Bangladesh n = 4 4 : with HA1 amino acid substitutions of Y159N, T160I (loss of a glycosylation site), L164Q, G186D, D190N, F193S and Y195F) with Bangladesh-like viruses showing the greatest geographic spread. The seven viruses from EU/EEA countries were Bangladesh like. An A/Cambodia/e0826360/2020 like virus (subgroup 3C.2a1b+T131K A) has been recommended for use in the 2021 2022 northern hemisphere influenza season.

The 45 B/Victoria lineage HA sequences derived from viruses collected in 2021 that became available in July were subclade 1A(  3)B Of these, 10 from Kenya were equally split between groups defined by HA1 G133R substitution or HA1 K75E, E128K, T155A, G230N and I267V substitution. All other sequences were from N150K group viruses with HA1 amino acid substitutions of N150K, G184E, N197D (loss of a glycosylation site) and R279K. N150K group sequences split into two subgroups one of which, defined by HA1 substitutions V220M and P241Q, was confined to viruses detected in China (n = 2) while the second (n = 33 sequences), defined by HA1 substitutions A127T, P144L, and K203R (with two having additional substitutions of T182A, D197E and T221A), showed significant geographic spread. The four viruses detected in EU/EEA countries all fell in the latter subgroup but lacked the additional amino acid substitutions, as was the case for a set of 19 viruses collected in Singapore in June. 

Antigenically, viruses in subgroups of the N150K group differ and show some loss of reactivity with post-infection ferret antisera raised against the B /Washington/02/2019 vaccine virus (recommended for inclusion in influenza vaccines for the 2020-2021 and 2021-2022 northern hemisphere seasons and 2021 southern hemisphere season). This was clearly the case for the three N150K group viruses from Sweden characterised by HI in the June report.

No B/Yamagata-lineage HA sequences from clinical specimens collected in 2021, and none with collection dates after March 2020, were available. All of the 77 sequences from viruses detected in 2020, inclusive of 12 from EU/EEA countries, belong to genetic clade 3 and carry three HA1 amino acid substitutions (L172Q, D229N and M251V) compared with B/Phuket/3073/2013-like viruses which have been recommended for use in quadrivalent influenza vaccines for the 2020-2021 and 2021-2022 northern hemisphere seasons and 2021 southern hemisphere season. The antigenic effects of these amino acid substitutions have been minimal, as assessed in earlier reports.

Influenza virus characterisation Summary Europe, Juy 2021 - EN - [PDF-1.95 MB] 

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Whether we see a little flu this year, or a lot, any flu on top of COVID will make things tougher this winter.  Both for healthcare delivery, and for anxious, mildly symptomatic patients who will need to be tested to rule out COVID. 

As I mentioned a couple of weeks ago in Through A Scanner Darkly, EMS traffic in central Florida in the middle of August is already heavier than you'd expect during the height of a bad flu season.

I'm continually hearing of long waits for beds in hospitals, ERs and ICUs either at capacity or on divert, and the terms `COVID Positive' and `Isolation Alert' fill the airwaves. Some EMS and public safety response times are suffering, as there are times when no units are immediately available to respond.

This is not only a bad time to have COVID, it is a bad time to have a heart attack, a stroke, or a car accident, as emergency services are stretched thin. And barring some kind of miracle, things will probably get worse this fall and winter. 

Hopefully, with all the challenges we have facing us already, we won't add a novel or particularly virulent seasonal flu virus to the list.