how likely is a second wave

This is crucial to understanding where we are with respect to the epidemic in the UK and the potential for a second wave of infections. Recent seroprevalence studies, which measure the proportion of the population displaying antibodies to the novel virus, are widely assumed to show the proportion of the population which has been infected. It needs studying, but our experience and evidence for coronaviruses (Le Bert et al, 2020) suggests that if you have memory T-cells, durability can be very long lasting. Sweden Did in Fact Lock Down When it Came to Care Homes. There was much speculation about whether a second wave of disease would sweep the world during the COVID-19 pandemic. Is the Increase in Cases Just an Artefact of Increased Testing? We understand the term ‘herd immunity’ can raise hackles in some quarters of the media. In limited studies to date, many researchers have shown that some subjects remain PCR-positive long after the ability to culture virus from swabs has disappeared. Instead, it is likely there will be local, small and self-limiting mini-outbreaks as areas previously unexposed come into contact with the virus. Infection , Genetics and Evolution. Repeat COVID-19 molecular testing: correlation with recovery of infectious virus, molecular assay cycle thresholds, and analytical sensitivity. Nothing is too small. Brit Med J. It may be of relevance to note that, on August 24th, the US CDC changed its guidance on when PCR testing is appropriate. GOVERNMENT, HEALTH The problem of using any assay to conduct surveillance on a low prevalence virus with a PCR test has been widely discussed (Heneghan, 2020). https://arxiv.org/pdf/2008.02475.pdf. COVID-19 transmission and children: the child is not to blame. Daily deaths from and with COVID-19 have almost ceased, having fallen over 99% from peak. Am. It is now established that at least 30% of our population already had immunological recognition of this new virus, before it even arrived (Le Bert et al, 2020; Braun et al, 2020; Grifoni et al, 2020). In his words, â It is so transmissible, and it is so widespread throughout the world, that even if our infections get well controlled and go down dramatically during the summer, there is virtually no chance it will be eradicated ." Why is the British Public so supportive of the Lockdown? Importantly, we emphasise there are additional schools of epidemiological work which show that variation in likelihood of becoming infected itself can greatly reduce the so-called herd immunity threshold and that this can be reached at even lower proportions of the population having been infected (e.g. Naturally, it varies depending on the population under study as well as the methodology used and, accordingly, researchers have arrived at a wide range of estimates for IFR. Long, et al. Science. This means that even a true positive does not necessarily indicate the presence of viable virus. So there’s an expectation of some duration of immunity. The shape of the deaths vs. time curve implies a natural process and not one resulting mainly from human interventions, given the widely varying non-pharmaceutical interventions in those countries. Re: How likely is a second wave? Pediatrics, e2020004879 DOI: 10.1542/peds.2020-004879. Sekine et al. medRxIV https://doi.org/10.1101/2020.04.17.20061440, Ellinghaus et al. Braun, et al. Le Bert et al (2020) SARS-Cov-2 specific T cell immunity in cases of Covid19 and SARS and uninfected controls. The Spectator, July 20 2020. Why Havenât our Points Landed and What Lies Behind the Hysteria? The authors recognise that the exact number in this example is speculative, but conversations with immunologists indicate that this principle is widely accepted as reasonable for community infection where viral load varies widely and contrasts markedly with seroconversion after vaccination, where the goal is close to 100%. Importantly, only Mateus performed detailed epitope mapping and found that epitopes present in each of the known endemic coronaviruses share sequence homology or close similarity to those in the new virus. There is no biological principle that leads us to expect a second wave based on the accumulation of data over the past six months. Based upon guidance from NHS England, our primary and secondary care service across the country are currently following protocols to limit access to care due to the dangers of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) pandemic. How Many Excess Deaths Are Due to COVID-19? So we have just installed donation buttons on our websites and ask that you consider this when you visit them. Vaccines: How Effective and How Safe Are They? Six weeks into an apparent surge of cases, the number of deaths remain completely flat and normal, in all age bands (as of mid-August when this document was written). Instead, cellular memory enables very rapid re-generation of antibodies upon re-encounter with the antigen, if that is required to defend the host. A reasonable hypothesis is that the lower intensity of immunological challenges tends to rely less on the generation of antibodies and more on innate and cellular responses. medRxIV https://doi.org/10.1101/2020.06.21.20132449. Scientific Information on Masks Against COVID-19, Slight Adjustments to Boris’s Famous Burkha Article, MASKS â manners, manipulation and maths. We predict there would be few genuine positive results remaining. Replying to Christopher Snowdon â Again! In a study of 23 people who survived SARS in 2003, every single one had memory T-cells that recognised the SARS virus 17 years later (Le Bert et al, 2020). However, our concerns with the Imperial model are not limited solely to T-cell memory mediated reduction in initial susceptibility. J. Clin Microbiol, 28(8), 1-7. Understanding the age divide in COVID-19: why are children overwhelmingly spared? Positive tests should be confirmed by testing a second sample and all positive tests should be reported along with the Cycle Threshold (Ct) obtained during the test to aid assessment of a patient’s viral load. This resulted not only in considerable time and money wasted by surgeries, but also other medical issues being delayed. However, by the end of May the occupancy had dropped back to pre-COVID-19 levels, well below the national baseline capacity and has shown no statistical change since. Instead, it is likely there will be local, small and self-limiting mini-outbreaks as areas previously unexposed come into contact with the virus.â If this is done, almost all the false positives will be removed. Current evidence allows for a greatly improved understanding of positive infectious patients and using the evidence to improve measurements and understanding can lead to sensitive measurements of active cases to give a more accurate warning of escalating cases and potential issues and outbreaks. Famously, Sweden has adopted an almost laissez faire approach, with qualified advice given, but no generalised lockdowns. A modification to the strategy involving PCR testing which would easily resolve any uncertainty is this: every positive test result is followed up as quickly as possible, ideally within 24 hours of the positive result, and every one is retested. (2020). Leaked Analysis of the Impact of the Lockdown by a Senior Official at the German Ministry of the Interior. (2020. Has the Government Granted Itself Too Many Draconian New Powers? Once that super-susceptible group were removed from the pool of susceptible individuals by the virus, it began a slower march through everyone else, slowing all the time, as the remaining population’s susceptibility fell continually towards the herd immunity threshold. In limited studies to date, many researchers have shown that some subjects remain PCR-positive long after the ability to culture virus from swabs has disappeared. 7 September 2020 / Updated 8 September 2020. We contend that the many claims in the media for outbreaks, spikes and second waves are all artefacts of amplified rates of testing. Am. Are Schools and Universities Over-Reacting? Since June 26th, the number of weekly deaths has now fallen so it is not only below the weekly average but has regularly dropped below the lower control limit, showing that we are now at the lowest number of weekly deaths recorded in many years. However, we do not believe the model is correct, and our assertions and inferences are based upon recently published science, some in highly eminent journals and some by researchers in pre-review online servers which have this year become crucial in keeping pace with emerging science. While this model may have had some limited value when we were faced with a novel virus outbreak, the evidence that has emerged over recent months, along with detailed analysis of previous outbreaks, implies that the model that is still being followed is unreliable and not consistent with both previously measured systems and current evidence. Herd immunity thresholds for SARS-CoV-2 estimated from unfolding epidemics. So there’s an expectation of some duration of immunity. Aguas, 2020). What are We to Make of the 40.5% Hospital Acquired Covid Infection? New UCL Paper on Contact Tracing Gulls Credulous Journalist, Another Computer Simulation, Another Alarmist Prediction. For example, calls to the NHS111 service captures all reports of what is termed ‘influenza-like illness’. We now know that children, especially young children, appear harder to infect and/or they are less affected by the virus. Inspecting the daily COVID-19 deaths vs. time curve for the UK we see a Gompertz-type curve (Rypdal and Rypdal, 2020) which are typical of natural, biological phenomena, well documented in biomedical scientific papers over the last 40 years. The result of continuing to use this test alone on a massive widescale screening program is inevitably to generate a high proportion of false positives. Public Health England: A Predictable Failure. Losing Baby as a Result of COVID Vaccine Doubles in Just 7 Days – MHRA Data, Copyright © 2012 - 2021 | TLB Project™ LLC. First it Current evidence allows for a greatly improved understanding of positive infectious patients; and using the evidence to improve measurements and understanding can lead to sensitive measurements of active cases to give a more accurate warning of escalating cases and potential issues and outbreaks. Current mass testing using the PCR test is inappropriate in its current form. There is no biological principle that leads us to expect a second wave based on the accumulation of data over the past six months. In such patients the majority do seroconvert (eg Theel et al, 2020). These papers showed this pre-immunity is geographically widespread and prevalent within each population studied, but it was only the Mateus paper that gave us the understanding as to why and how. Spain and France It is important to appreciate that much of the early serological studies were conducted on hospitalised patients who, by definition, are the most ill cohort. The Centre for Evidence-Based Medicine has done much work in this area and their current estimate is 0.1-0.4% (Oke and Heneghan, 2020). Critical Care Figures Cast Doubt on âSecond Waveâ, Close Analysis of Regional Notifiable Disease Data Bolsters the Case for the Epidemic Phase of COVID-19 Being a Spring phenomenon. J. Physiol (Lung Cell Molec. This implies that for every death from COVID-19, there were a preceding 100/0.26 or ~400 infections. Nevertheless, there is some evidence about the possibility of more immediate, less dramatic, second waves in the form of the number of new cases in a nation rising noticeably after having had a major decline from an initial peak. For example, below we see in the MERS CoV outbreak of 2015 what appears to be a significant double wave. https://doi.org/10.1016/j.cell.2020.05.015ll. Le Bert et al (2020) SARS-Cov-2 specific T cell immunity in cases of Covid19 and SARS and uninfected controls. Note the lack of discontinuities in the curve, suggesting no effective interventions have interrupted its development. That is a fortunate finding indeed, and goes some way in explaining why children have been relatively spared. It had previously been suggested that pre-pandemic immune responses in circulating T-cells might have occurred following exposure to one or more of the endemic coronaviruses. Long et al (2020) find that almost half of previously infected individuals are no longer seropositive a few months later. They now recommend not testing people with no symptoms who are not contacts in a contact-tracing activity. https://www.cebm.net/covid-19/global-covid-19-case-fatality-rates/, ONS coronavirus survey (Aug 14 2020). The key point about ‘cold positives’ is that they are not ill, not symptomatic, not going to become symptomatic and, furthermore, are unable to infect others. How Likely Is A Second Wave Of SARS-CoV-2? Specifically, careful examination of the weekly all-causes mortality data in France is completely clear. The shape of the deaths vs. time curve implies a natural process and not one resulting mainly from human interventions, given the widely varying non-pharmaceutical interventions in those countries. A continuation of the virus would be expected to manifest itself as an increase in both Critical Care bed occupancy and national All-Causes Mortality statistics. We contend that the many claims in the media for outbreaks, spikes and second waves are all artefacts of amplified rates of testing. This is crucial to understanding where we are with respect to the epidemic in the UK and the potential for a second wave of infections. COVID-19 and the Infantilisation of Dissent, The Hyper-Rationality of Crowds: COVID-19 and the Cult of Anxiety, Covid and the Religious Impulse: An Essay in Seven Parts, A Pandemic of Fear â the Psychology of Emotional Contagion, Liars, Fakers, and the Seductive Texture Of Authoritarianism, Lockdowns and the Death of Liberal Education, The Burden of Proof in the Irish High Court Case Should Not Have Fallen on the Applicant, The Catch-22 of Challenging Covid-19 Laws, âJail Bharo!â â Channelling Our Inner Gandhi Against the Covidcrats, The Failed Strategy of Lockdown Sceptics: We Appealed to Reason, Not Emotion. How Culpable are the Chinese Authorities for the Global Pandemic? Obviously, and perhaps it has already happened, there is the potential for emerging influenza to complicate the picture. If you wish to use copyrighted material for purposes other than “fair use” you must request permission from the copyright owner. Gomez et al. But even here, it is important to recall what it is that the PCR test measures, and it is simply the presence of partial RNA sequences present in the intact virus. Long et al (2020) find that almost half of previously infected individuals are no longer seropositive a few months later. What it is very poor at, however, is what is being asked of it now, namely estimating the percentage of people who are currently infectious in the community. As important, these T-cell responses also develop even in recovering patients infected with the new virus but who were asymptomatic (Sekine et al, 2020). The Role of Antibody Testing for SARS-CoV-2: Is There One? How Should We Value the Lives of Those Most at Risk? Cell 181, 1489–1501. Naturally, it varies depending on the population under study as well as the methodology used and, accordingly, researchers have arrived at a wide range of estimates for IFR. Nature Med 26, 1200-04. Nature Med 26, 1200-04. The Role of Antibody Testing for SARS-CoV-2: Is There One? There are at least four well characterised family members (229E, NL63, OC43 and HKU1) which are endemic and cause some of the common colds we experience, especially in winter. While there has been a very specific focus on the cancer and cardiology services, similar negative impacts can be seen across most services with, for example, neurological, dermatological and renal patients all presenting with more severe disease due to delays in receiving both diagnosis and treatment. Mateus, by using parts of these endemic coronaviruses which also exist within COVID-19 confirmed this. Physiol) https://doi.org/10.1152/ajplung.00183.2020, Lourenco et al (2020). Vitamin D: Did a Prescribing Ban in Care Homes Contribute to Fatalities? Restrictions have been progressively eased across the country for over three months. Clinical and immunological assessments of asymptomatic SARS-CoV-2 infections. Lingappan et al (2020). Other, theoretical epidemiological studies show that, with the extent of prior immunity that we can now reasonably assume to be the case, only 15-25% of the population being infected is sufficient to bring the spread of the virus to a halt (Lourenco, 2020; Gomez et al, 2020). Enforcement of this policy is at the discretion of this websites administrators. Here's why and what we can do to stop it By Nicole Chavez, CNN Updated 2325 GMT (0725 HKT) May 2, â¦ September 28, 2020 National weekly mortality data is useful for looking at the effect of the COVID-19 pandemic. This is because the antibody system is but one of several tools our immunology has to defend us. As the rate of hospitalisations, ICU utilisation and the daily death rate from COVID-19 all decayed steadily, it appears that several but not all countries have greatly expanded their testing capacity in the broader population of people who are not showing any symptoms of infection. Has the Evidence of Asymptomatic Spread of COVID-19 been Significantly Overstated? Viral evidence historically tells us that you don’t generally get infected by the exact same virus twice, certainly not within a short period of time. It is not efficient nor required for immunity to maintain high levels of antibodies to everything to which you are immune. Alternatively, innate and cellular memory responses can be sufficient. Theel et al (2020). (2020). It’d be a poor immune system which lets that happen and we’d probably not have made it as a species into the 21st century if that’s how it worked. Ambitious Interpretation of Results of the Oxford Vaccine Groupâs Latest Paper. This implies that for every death from COVID-19, there were a preceding 100/0.26 or ~400 infections. COVID-19 transmission and children: the child is not to blame. MedRxIV https://doi.org/10.1101/2020.07.15.20154294, Mateus et al (2020) Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans. Humans vary hugely, not only in our responses to viruses, but also in the ease or difficulty the virus experiences as it tries to invade us. Nature. As the rate of hospitalisations, ICU utilisation and the daily death rate from COVID-19 all decayed steadily, it appears that several but not all countries have greatly expanded their testing capacity in the broader population of people who are not showing any symptoms of infection. Wu et al (2020) Association between ABO blood groups and COVID-19 infection, severity and demise: A systematic review and meta-analysis. We thank you for all your support and your considerations … (TLB). Covid-19 testing, low prevalence and the impact of false positives. 1 Response to How likely is a second wave? Covid-19 testing, low prevalence and the impact of false positives. MedRxIV https://doi.org/10.1101/2020.07.15.20154294, Mateus et al (2020) Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans. (Le Bert et al, 2020). Population susceptibility Cell 181, 1489–1501. Sekine et al. Clinical and immunological assessments of asymptomatic SARS-CoV-2 infections. Responses to COVID-19 have been shown in dozens of blood samples taken from donors before the new virus arrived. It turns out that the levels of ACE2 are highest in adults and much lower in children, becoming progressively lower the younger they are (Lingappan et al, 2020). Let us take a midpoint value, especially as for months the US CDC displayed a value for IFR of 0.26% on their website. J. Clin Microbiol, 28(8), 1-7. Note that recent so-called ’spikes’ were never accompanied or followed by people getting ill, going to hospital and dying in elevated numbers. However, we do not believe the model is correct and our assertions and inferences are based upon recently published science, some in highly eminent journals and some by researchers in pre-review online servers which have this year become crucial in keeping pace with emerging science. Daily deaths from and with COVID-19 have almost ceased, having fallen over 99% from peak. In that simple statement is the key to science. DOI: 10.1126/science.abd3871, Oke& Heneghan (2020). Coronavirus: World must prepare for second and third wave of Covid-19, WHO warns Europe remains âvery much in gripâ of pandemic despite signs of â¦ It is not efficient nor required for immunity to maintain high levels of antibodies to everything to which you are immune. We saw early on in the pandemic that the number of daily deaths rapidly soar and at that time did we not know where and when it would stop rising. For example, calls to the NHS111 service captures all reports of what is termed ‘influenza-like illness’. Further, it is reasonable to conclude that the pandemic event has ended in those countries, too. DOI: 10.1056/NEJMoa2020283. (ONS prevalence survey Aug 14th 2020). There are practical alternatives to mass testing. There are very good reasons to believe that the population of the UK and of many heavily infected countries have arrived at a position where the prevalence of the virus is low and probably falling further because the reproduction number (R) has been below 1 for several months. Numerous estimates have been made of the infection fatality ratio (IFR) for this new virus. The COVID-19 pandemic has undoubtedly allowed for some very positive and rapid changes within NHS pathways, protocols and services which should be maintained. Specifically, careful examination of the weekly all-causes mortality data in France is completely clear. Consequently, two different and independent analytical approaches provide estimates that are at least in the same range for total population having been infected (overlapping at approximately 20%), and this is crucial in the argument put forward here. Another useful measure of disease impact is the Adult Critical Care Bed Occupancy which showed a peak in bed demand between April 7th and 23rd with the number of patients occupying critical care beds significantly higher than our national baseline capacity. Restrictions have been progressively eased across the country for over three months. Do Medical Complications and Lingering Effects Make COVID-19 an Unusually Dangerous Diseases? While published data on deaths ‘with’ COVID-19 is dependent on testing regimes and therefore liable to inaccuracy due to missing information – for example undetected asymptomatic patients – the data does allow a sound approximation of the flow of the outbreak. Change in this parameter is likely to be a much more sensitive measure of the presence of increasing prevalence of SARS-CoV-2 infection than flawed PCR testing without modifications. If 7% is the mean for UK, then perhaps 14-21% of the population has actually been infected (which would imply, very approximately, 9-14 million people infected). Heneghan (2020). (2020). Spain and France So what is happening in terms of second wave concerns in France and Presence of SARS-CoV-2 reactive T cells in COVID-19 patients and healthy donors. In this case the first major peak was seen in Saudi Arabia with a second peak some months later in the Republic of Korea. (2020). “Is it flu or is it COVID-19?” is a question easily answered. A complete event of the pandemic Note that recent so-called ’spikes’ were never accompanied or followed by people getting ill, going to hospital and dying in elevated numbers. The proportion of the population that need to be resistant to an infection, in order to stop it spreading, depends on the proportion who were originally susceptible and the initial reproduction number, or R0. This means that even a true positive does not necessarily indicate the presence of viable virus. Instead, cellular memory enables very rapid re-generation of antibodies upon re-encounter with the antigen, if that is required to defend the host. Essentially a second wave is the result of you taking your foot of the pedal. This is a conservative value since current literature finds that between 20% and 50% of the population display this pre-pandemic T-cell responsiveness, meaning we could adopt an initially susceptible population value from 80% to 50%. We have now seen this in a number of nations, in a small number quite dramatically. So what is happening in terms of second wave concerns in France and Spain? medRxIV https://doi.org/10.1101/2020.07.23.20160762. Whilst work has begun to restore NHS services (the “restoration”), there remains a strong focus on preparing for a second wave as implied by the Imperial College epidemiological model designed by Professor Neil Ferguson and his team. Infection , Genetics and Evolution. If 7% is the mean for UK, then perhaps 14-21% of the population has actually been infected (which would imply, very approximately, 9-14 million people infected). There are approximately eight million children aged 0-10 in the UK and 12.7 million aged 0-15. This is the basis of all the second wave fears we hear about. In addition, other groups have shown that infectivity is significantly reduced in individuals with the O-blood group (Wu et al, 2020; Ellinghaus et al, 2020). This is because there are factors other than T-cell mechanisms which alter a person’s susceptibility to the virus. The key point about ‘cold positives’ is that they are not ill, not symptomatic, not going to become symptomatic and, furthermore, are unable to infect others. It is not rational and may even be dangerous to use these results to drive policy. https://doi.org/10.1101/2020.07.23.20160762, https://doi.org/10.1101/2020.04.17.20061440, https://doi.org/10.1101/2020.06.21.20132449, https://doi.org/10.1101/2020.04.27.20081893, https://doi.org/10.1016/j.cell.2020.05.015ll, https://doi.org/10.1152/ajplung.00183.2020, https://doi.org/10.1101/2020.07.15.20154294, https://www.cebm.net/covid-19/global-covid-19-case-fatality-rates/, https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/bulletins/coronaviruscovid19infectionsurveypilot/latest, https://ourworldindata.org/coronavirus-data-explorer?yScale=log&zoomToSelection=true&time=2020-03-02..latest&deathsMetric=true&interval=smoothed&aligned=true&perCapita=true&smoothing=7&country=TWN~GBR~SWE~FRA&pickerMetric=location&pickerSort=asc, https://doi.org/10.1101/2020.06.29.174888, https://doi.org/10.1101/2020.08.05.20168963, Norway health chief: lockdown was not needed to tame Covid, Coronavirus: Elderly Europeans Targeted, Denied Treatment, Bill Gates Could Supply Your Next Coronavirus Test Kit. Background Transmission models, such as the one used by the Imperial team, are highly sensitive to the input parameters they are based on, and we argue that a modification of the current model should be applied with, at most, 70% initial population susceptibility.