More than two years into the pandemic, SARS-CoV-2, the virus that causes COVID-19, continues to challenge us. Its ability to rapidly mutate has seen the evolution of increasingly infectious variants that are getting better at hiding from our immune response.
Vaccines are a huge achievement of modern-day science and have played a crucial role in reducing the very worst impacts of COVID. But are the vaccines we currently have able to deal with the newest COVID variants?
The current COVID vaccines are all based on the genetic building blocks, or the DNA sequence, of the original ancestral strain of SARS-CoV-2. The majority of these vaccines target the spike protein – the part of the virus that attaches to our cells to gain entry.
The vaccines work by enabling our immune cells to mount a targeted response to the spike protein, including generating antibodies known as neutralising antibodies. These stop viruses getting into our cells, and help other immune cells find and destroy any viral intruders.
But SARS-CoV-2 is a slippery customer and has been mutating with notable changes to the spike protein. That means those vaccine-induced neutralising antibodies are less effective than they once were.
Is it time for a new generation of COVID vaccines?
The idea to vaccinate against variants rather than the ancestral strain is gaining traction. This is not a new concept in vaccine development. Our annual flu shots, for example, target circulating variants.
One approach is to create what’s called a “bivalent” vaccine that targets the spike protein from omicron (BA.1) as well as the ancestral strain. Moderna is currently testing this option in combined phase 2 and 3 human trials. Data yet to be peer-reviewed suggests this results in around a two-fold increase in neutralising antibodies against BA.1, compared with the original COVID vaccines.
Other Moderna trials are looking at different bivalent combinations, including vaccines that target the ancestral and beta strains, which look promising.
Pfizer has also released trial data on its booster candidate specifically tailored against BA.1. The company says this reformulation induced an immune response to BA.1 superior to that produced by its original COVID vaccine.
So should we be investing in these new vaccine candidates? The US Food and Drug Administration seems to think so, having recently approved the use of these omicron-specific shots later this year.
However, investing in and rolling out new vaccines is not cheap, and there are important questions we need to address. As we know, SARS-CoV-2 is ever mutating and changing. It was less than a year ago that the delta strain dominated around the world, and before that we had alpha and beta. So are omicron variants the right ones to be targeting? Will they still be dominant a year from now? We simply don’t know.
Even with omicron strains there is variation. The BA.1 variant that these new vaccine candidates target has recently been outcompeted by BA.4 and BA.5. The BA.4 and BA.5 variants are even more resistant to neutralising antibodies, typically three- or four-fold, than BA.1. So the question is, if omicron pervades, would these omicron BA.1 vaccines work better against BA.4 and BA.5 than the original vaccines? Data still to be peer reviewed suggests the bivalent vaccines may be a little better than the original vaccines.
However, omicron may be a poor vaccine candidate as recent data shows that omicron infection doesn’t produce robust immunity and is characterised by low levels of neutralising antibodies, which need to be higher and more persistent to prevent rapid reinfection. This could go a long way to explaining why so many of us are catching COVID multiple times. If we see the same thing with our vaccine-induced immunity to omicron, omicron-specific vaccines may not be a worthwhile investment.
None of this means we should stop looking for long-term protective vaccines. But perhaps there’s scope to focus on different strategies. Two exciting avenues are emerging.
The first is vaccines that target other parts of the viral structure that are more stable, or vaccines that target multiple parts of the virus. This might not result in a vaccine that can fully prevent infection, but may be more durable than the current vaccines.
Another avenue involves capitalising on the ability of neutralising antibodies in the nose and throat to target SARS-CoV-2 at its point of entry. These antibodies create a barrier that stops the virus getting into the body, so a vaccine that generates neutralising antibodies in the nose and throat could stop the virus in its tracks. Studies trialling nasal vaccines look promising, although these are still at early stages.
Where does this leave us now? An ideal vaccine candidate would elicit long-lived neutralising antibodies and give us life-long immunity. Instead, we’ve learnt that for COVID, our immune system needs boosters to top up those neutralising antibodies and bolster the numbers of memory cells that support immunity.
The last UK-wide booster campaign was in December 2021. Studies had shown that COVID vaccination followed by infection lead to months of immunity, but this was before omicron, which we now know doesn’t produce robust immunity. Against omicron, many of us will have minimal neutralising antibodies left.
With the high likelihood of another variant in the autumn, alongside fears of a bad flu season, it would seem prudent to embark on an autumn booster campaign with much wider coverage than the spring campaign. This means not just targeting over 65s and others at higher risk as is currently planned, but extending eligibility to younger age groups.
Crucially we must reach those who are not fully vaccinated, so any campaign should include targeted community education. This should also happen alongside other mitigation strategies like mask-wearing to keep us safe and allow us to live with COVID.
Sheena Cruickshank does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.vaccine testing genetic antibodies dna pandemic covid-19 mitigation uk
Coronavirus dashboard for October 5: an autumn lull as COVID-19 evolves towards seasonal endemicity
– by New Deal democratBack in August I highlighted some epidemiological work by Trevor Bedford about what endemic COVID is likely to look like, based…
- by New Deal democrat
Back in August I highlighted some epidemiological work by Trevor Bedford about what endemic COVID is likely to look like, based on the rate of mutations and the period of time that previous infection makes a recovered person resistant to re-infection. Here’s his graph:
Gonorrhea became more drug resistant while attention was on COVID-19 – a molecular biologist explains the sexually transmitted superbug
The US currently has only one antibiotic available to treat gonorrhea – and it’s becoming less effective.
COVID-19 has rightfully dominated infectious disease news since 2020. However, that doesn’t mean other infectious diseases took a break. In fact, U.S. rates of infection by gonorrhea have risen during the pandemic.
Unlike COVID-19, which is a new virus, gonorrhea is an ancient disease. The first known reports of gonorrhea date from China in 2600 BC, and the disease has plagued humans ever since. Gonorrhea has long been one of the most commonly reported bacterial infections in the U.S.. It is caused by the bacterium Neisseria gonorrhoeae, which can infect mucous membranes in the genitals, rectum, throat and eyes.
Gonorrhea is typically transmitted by sexual contact. It is sometimes referred to as “the clap.”
Prior to the pandemic, there were around 1.6 million new gonorrhea infections each year. Over 50% of those cases involved strains of gonorrhea that had become unresponsive to treatment with at least one antibiotic.
In 2020, gonorrhea infections initially went down 30%, most likely due to pandemic lockdowns and social distancing. However, by the end of 2020 – the last year for which data from the Centers for Disease Control and Prevention is available – reported infections were up 10% from 2019.
It is unclear why infections went up even though some social distancing measures were still in place. But the CDC notes that reduced access to health care may have led to longer infections and more opportunity to spread the disease, and sexual activity may have increased when initial shelter-in-place orders were lifted.
As a molecular biologist, I have been studying bacteria and working to develop new antibiotics to treat drug-resistant infections for 20 years. Over that time, I’ve seen the problem of antibiotic resistance take on new urgency.
Gonorrhea, in particular, is a major public health concern, but there are concrete steps that people can take to prevent it from getting worse, and new antibiotics and vaccines may improve care in the future.
How to recognize gonorrhea
Around half of gonorrhea infections are asymptomatic and can only be detected through screening. Infected people without symptoms can unknowingly spread gonorrhea to others.
Typical early signs of symptomatic gonorrhea include a painful or burning sensation when peeing, vaginal or penal discharge, or anal itching, bleeding or discharge. Left untreated, gonorrhea can cause blindness and infertility. Antibiotic treatment can cure most cases of gonorrhea as long as the infection is susceptible to at least one antibiotic.
There is currently only one recommended treatment for gonorrhea in the U.S. – an antibiotic called ceftriaxone – because the bacteria have become resistant to other antibiotics that were formerly effective against it. Seven different families of antibiotics have been used to treat gonorrhea in the past, but many strains are now resistant to one or more of these drugs.
Why gonorrhea is on the rise
A few factors have contributed to the increase in infections during the COVID-19 pandemic.
Early in the pandemic, most U.S. labs capable of testing for gonorrhea switched to testing for COVID-19. These labs have also been contending with the same shortages of staff and supplies that affect medical facilities across the country.
Many people have avoided clinics and hospitals during the pandemic, which has decreased opportunities to identify and treat gonorrhea infections before they spread. In fact, because of decreased screening over the past two and a half years, health care experts don’t know exactly how much antibiotic-resistant gonorrhea has spread.
Also, early in the pandemic, many doctors prescribed antibiotics to COVID-19 patients even though antibiotics do not work on viruses like SARS-CoV-2, the virus that causes COVID-19. Improper use of antibiotics can contribute to greater drug resistance, so it is reasonable to suspect that this has happened with gonorrhea.
Overuse of antibiotics
Even prior to the pandemic, resistance to antibiotic treatment for bacterial infections was a growing problem. In the U.S., antibiotic-resistant gonorrhea infections increased by over 70% from 2017-2019.
Neisseria gonorrhoeae is a specialist at picking up new genes from other pathogens and from “commensal,” or helpful, bacteria. These helpful bacteria can also become antibiotic-resistant, providing more opportunities for the gonorrhea bacterium to acquire resistant genes.
Strains resistant to ceftriaxone have been observed in other countries, including Japan, Thailand, Australia and the U.K., raising the possibility that some gonorrhea infections may soon be completely untreatable.
Steps toward prevention
Currently, changes in behavior are among the best ways to limit overall gonorrhea infections – particularly safer sexual behavior and condom use.
However, additional efforts are needed to delay or prevent an era of untreatable gonorrhea.
Scientists can create new antibiotics that are effective against resistant strains; however, decreased investment in this research and development over the past 30 years has slowed the introduction of new antibiotics to a trickle. No new drugs to treat gonorrhea have been introduced since 2019, although two are in the final stage of clinical trials.
Vaccination against gonorrhea isn’t possible presently, but it could be in the future. Vaccines effective against the meningitis bacterium, a close relative of gonorrhea, can sometimes also provide protection against gonorrhea. This suggests that a gonorrhea vaccine should be achievable.
The World Health Organization has begun an initiative to reduce gonorrhea worldwide by 90% before 2030. This initiative aims to promote safe sexual practices, increase access to high-quality health care for sexually transmitted diseases and expand testing so that asymptomatic infections can be treated before they spread. The initiative is also advocating for increased research into vaccines and new antibiotics to treat gonorrhea.
Setbacks in fighting drug-resistant gonorrhea during the COVID-19 pandemic make these actions even more urgent.
Kenneth Keiler receives funding from NIH.cdc disease control pandemic covid-19 vaccine treatment testing clinical trials spread social distancing japan bc china world health organization
Measuring the Ampleness of Reserves
Over the past fifteen years, reserves in the banking system have grown from tens of billions of dollars to several trillion dollars. This extraordinary…
Over the past fifteen years, reserves in the banking system have grown from tens of billions of dollars to several trillion dollars. This extraordinary rise poses a natural question: Are the rates paid in the market for reserves still sensitive to changes in the quantity of reserves when aggregate reserve holdings are so large? In today’s post, we answer this question by estimating the slope of the reserve demand curve from 2010 to 2022, when reserves ranged from $1 trillion to $4 trillion.
What Are Reserves? And Why Do They Matter?
Banks hold accounts at the Federal Reserve where they keep cash balances called “reserves.” Reserves meet banks’ various needs, including making payments to other financial institutions and meeting regulatory requirements. Over the past fifteen years, reserves have grown enormously, from tens of billions of dollars in 2007 to $3 trillion today. The chart below shows the evolution of reserves in the U.S. banking system as a share of banks’ total assets from January 2010 through September 2022. The supply of reserves depends importantly on the actions of the Federal Reserve, which can increase or decrease the quantity of reserves by changing its securities holdings, as it did in response to the global financial crisis and the COVID-19 crisis.
Reserves Have Ranged from 8 to 19 Percent of Bank Assets from 2010 to 2022
Why does the quantity of reserves matter? Because the “price” at which banks trade their reserve balances, which in turn depends importantly on the total amount of reserves in the system, is the federal funds rate, which is the interest rate targeted by the Federal Open Market Committee (FOMC) in the implementation of monetary policy. In 2022, the FOMC stated that “over time, the Committee intends to maintain securities holdings in amounts needed to implement monetary policy efficiently and effectively in its ample reserves regime.” In this ample reserves regime, the Federal Reserve controls short-term interest rates mainly through the setting of administered rates, rather than by adjusting the supply of reserves each day as it did prior to 2008 (as discussed in this post). In today’s post, we describe a method to measure the sensitivity of interest rates to changes in the quantity of reserves that can serve as a useful indicator of whether the level of reserves is ample.
The Demand for Reserves Informs Us about Rate Sensitivity to Reserve Shocks
To assess whether the level of reserves is ample, one needs to first understand the demand for reserves. Banks borrow and lend in the market for reserves, typically overnight. The reserve demand curve describes the price at which these institutions are willing to trade their balances as a function of aggregate reserves. Its slope measures the price sensitivity to changes in the level of reserves. Importantly, banks earn interest on their reserve balances (IORB), set by the Federal Reserve. Because the IORB rate directly affects the willingness of banks to lend reserves, it is useful to describe the reserve demand curve in terms of the spread between the federal funds rate and the IORB rate. In addition, we control for the overall growth of the U.S. banking sector by specifying reserve demand in terms of the level of reserves relative to commercial banks’ assets.
There is a clear nonlinear downward-sloping relationship between prices and quantities of reserves, consistent with economic theory. The chart below plots the spread between the federal funds rate and the IORB against total reserves as a share of commercial banks’ total assets. When reserves are very low, the demand curve has a steep negative slope, reflecting the willingness of borrowers to pay high rates because reserves are scarce. At the other extreme, when reserves are very high, the curve becomes flat because banks are awash with reserves and the supply is abundant. Between these two regions, an intermediate regime–that we refer to as “ample”–emerges, where the demand curve exhibits a modest downward slope. The color coding of the chart reflects the shifts in the reserve demand curve over time. In particular, the curve appears to have moved to the right and upward around 2015 and then moved upward after March 2020, at the onset of the COVID pandemic.
Reserve Demand Has Shifted over Time
This chart highlights two of the main challenges in estimating the slope of the reserve demand curve. First, the curve is highly nonlinear, which means that a standard linear estimation approach is not appropriate. Second, various long-lasting changes in the regulation and supervision of banks, in their internal risk-management frameworks, and in the structure of the reserve market itself have resulted in shifts in the reserve demand curve. A third challenge is that the quantity of reserves may be endogenous to banks’ demand for them. Therefore, to properly measure the reserve demand curve, one must disentangle shocks to supply from those to demand. As we explain in detail in a recent paper, our estimation strategy addresses all three of these challenges.
Estimating the Slope of the Reserve Demand Curve
Our approach provides time-varying estimates of the price sensitivity of the demand for reserves that can be used to distinguish between periods in which reserves are relatively scarce, ample, or abundant. The chart below presents our daily estimates of the slope of the demand curve, as measured by the rate sensitivity to changes in reserves. Although we do not have a precise criterion for when reserves are scarce versus ample, during two episodes in our sample, the estimated rate sensitivity is well away from zero. The first episode occurs early in our sample, in 2010, and the second emerges almost ten years later, in mid-2019. In two other periods—during 2013-2017 and from mid-2020 through early September 2022—the estimated slope is very close to zero, indicating an abundance of reserves. The remaining periods are characterized by a modest negative slope of the reserve demand curve, consistent with ample (but short of abundant) reserves. The overall pattern of these estimates is robust to changes in the model specification, such as including spillovers from the repo and Treasury markets or measuring reserves as a share of gross domestic product or bank deposits (instead of as a share of banks’ assets).
Rate Sensitivity Changed over Time, Following the Path of Reserves
Interest Rate Spreads Alone Are Not Reliable Indicators of Reserve Scarcity
As we discuss in our paper, the time variation in the estimated price sensitivity in the demand for reserves is based on observations of small movements along the demand curve due to exogenous supply shocks. The location of the curve itself, however, also changes over time. That is, there is not a constant relationship between the level of reserves and the slope of the reserve demand curve.
In our paper, we find evidence of both horizontal and vertical shifts in the reserve demand curve, with vertical upward shifts being particularly important since 2015. This finding implies that the level of the federal funds-IORB spread may not be a reliable summary statistic for the sensitivity of interest rates to reserve shocks, and that estimates of the price sensitivity in the demand for reserves provide additional useful information.
In summary, we have developed a method to estimate the time-varying interest rate sensitivity of the demand for reserves that accounts for the nonlinear nature of reserve demand and allows for structural shifts over time. A key advantage of our methodology is that it provides a flexible and readily implementable approach that can be used to monitor the market for reserves in real time, allowing one to assess the “ampleness” of the reserve supply as market conditions evolve.
Gara Afonso is the head of Banking Studies in the Federal Reserve Bank of New York’s Research and Statistics Group.
Gabriele La Spada is a financial research economist in Money and Payments Studies in the Federal Reserve Bank of New York’s Research and Statistics Group.
John C. Williams is the president and chief executive officer of the Federal Reserve Bank of New York.
How to cite this post:
Gara Afonso, Gabriele La Spada, and John C. Williams, “Measuring the Ampleness of Reserves,” Federal Reserve Bank of New York Liberty Street Economics, October 5, 2022, https://libertystreeteconomics.newyorkfed.org/2022/10/measuring-the-ampleness-of-reserves/.
The views expressed in this post are those of the author(s) and do not necessarily reflect the position of the Federal Reserve Bank of New York or the Federal Reserve System. Any errors or omissions are the responsibility of the author(s).
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