T cell cross-reactivity and the Herd immunity threshold

By Nic Lewis

An interesting new paper by Marc Lipsitch and co-authors, “Cross-reactive memory T cells and herd immunity to SARS-CoV-2”, has recently been published.[1] It discusses immunological and epidemiological aspects and implications of pre-existing cross-reactive adaptive immune system memory arising from previous exposure to circulating common cold coronaviruses. They argue that key potential impacts of cross- reactive T cell memory are already incorporated into epidemiological models based on data of transmission dynamics, particularly with regard to their implications for herd immunity. I believe that they are mistaken on the herd immunity point, as I will show in this article.

The first point to make is that cross-reactive T cells were never thought to be the main cause of the herd immunity threshold (HIT)[2] being lower for COVID-19 than the oft-quoted {1 – 1/R0} level, which generally applies for vaccination. Heterogeneity in social connectivity (contact rates) is typically estimated to lower the HIT much more than heterogeneity in biological susceptibility to the causative SARS-CoV-2 virus.[3]

Possible effects of cross-reactive T cells on infection progression

Lipsitch and co-authors note that recent reports have shown that SARS- CoV-2 cross-reactive memory T cells, very largely CD4+ T-cells arising from previous exposure to circulating common cold coronaviruses, are detectable in ~28–50% of individuals not exposed to SARS- CoV-2. They say that only tissue-resident memory T cells (TRM cells) can mount a fast response, with recirculating TCM and TEM T cells taking several days to start fighting an infection. They point out that CD4+ T-cells generally limit disease severity, reduce the viral burden and/or limit the duration of the disease rather than preventing an initial infection.

While I do not intend to challenge any of the foregoing points here, it should be noted that they treat an ‘infection’ as including a case where so few cells have been infected that any (RT-)PCR test for the virus would be negative.

The paper states that CD4+ T cell-mediated memory responses to a virus may involve some or all of CD4+ TFH cell types (required for B cell help and thus almost all neutralizing antibody responses), TH1 and CTL cell types (with direct antiviral activities in infected tissues), and that the CD4+ T cells involved may be TRM cells, or slower to respond recirculating TCM/TEM cells.

The authors go on to propose four immunological scenarios for the impact of cross-reactive CD4+ memory T cells on COVID-19 severity and viral transmission. The four model scenarios they put forward are:

  1. Reduction of lung burden: CD4+ T cells reduce COVID-19 symptoms and lung viral load but have minimal impact on upper respiratory tract (URT) viral load.
  2. TFH cell-accelerated antibodies: CD4+ TFH cells trigger a faster and better antibody response, resulting in accelerated control of virus in the URT and lungs.
  3. TRM cells in the URT: CD4+ TRM cells at the site of infection enable rapid control of virus in the URT and lungs.
  4. Transient infection: TRM cell immunity ‘blitzes’ viral replication in the URT leading to the elimination of all infected cells within a day of the initial infection, at the portal of entry.

The first three scenarios, along with the case where no cross-reactive T cells exist, are represented in Fig.1 of the paper, reproduced below.

Which models do the data fit?

The authors argue that biological evidence implies model scenario 4 is very unlikely where only CD4+ T cells are involved. They point out that if pre-existing CD4+ TRM cell immunity was so extreme as to preclude significant viral replication, seroconversion (that is, a de novo antibody response to SARS- CoV-2) would not occur. Such individuals would not be detectable by virological (e.g., PCR) or serological diagnostic tests and would not shed virus; effectively, these individuals would be immune to infection and not reported as cases. The authors say that evidence for other human coronaviruses makes this implausible, and that when epidemiological evidence of very high attack rates in some ship-based outbreaks is added scenario 4 is highly unlikely.

However, in the most studied ship-based outbreak the proportion infected was under 20%.[4] Moreover, the results of a study that Lipsitch et al. do not cite[5] show that, in households where one person was confirmed as having COVID-19, a substantial proportion of other household members had negative PCR test results, implying that they were not infective, despite most of them having typical COVID-19 symptoms. Moreover, these individuals did not develop detectable SARS-CoV-2 specific antibodies, but did develop SARS-CoV-2 specific (as opposed to cross reactive) T cell responses, implying that they had been infected to some degree by SARS-CoV-2 .

Notwithstanding that the sample size was small in that study, it appears to cast some doubt on Lipsitch et al.’s assertion that scenario 4 is highly implausible. It also casts doubt on their subsequent assertion that almost all people infected by SARS-CoV-2 seroconvert (develop antibodies against it), although the test used might have been insufficiently sensitive to detect low antibody levels. In that connection, Lipsitch et al. say that a recent study[6] observed [only] about 3 cases of non-PCR confirmed potentially asymptomatic COVID-19 cases with T cell responses in the absence of seroconversion, but their interpretation of that study’s results has been challenged.[7]

A substantial proportion of PCR-test positive individuals – in some localised outbreaks, the vast majority of them – have asymptomatic infections. In the most studied ship-based outbreak4 almost half of infected individuals remained asymptomatic throughout.[8] If that is due to T-cell cross reactivity, acting in combination with innate immune responses, then only model scenarios 3 or 4 would fit, since model scenarios 1 and 2 imply significant symptoms.

In the remainder of this article I will not pursue the possibility of model scenario 4 being relevant. Rather, I will focus on showing that the implications for herd immunity of model scenario 3 (possibly involving also model scenario 2), as varied to take account of variation in viral dose and innate immune system strength, are very likely not already taken into account in simple epidemiological models based on transmission dynamics data. In this connection, it should be noted that the extent and quality of the available data, both biological and epidemiological, does not provide high quality evidence, so drawing firm conclusions either way is difficult.

The low level of asymptomatic transmission

Importantly, there is quite strong evidence that infected individuals transmit SARS-CoV-2 much more weakly if they are asymptomatic (and not just presymptomatic). Biological evidence neither proves nor disproves that a positive PCR test for SARS-CoV-2 implies significant infectivity (although a negative PCR test can be taken as implying a lack of significant infectivity).[9] However, epidemiological evidence strongly suggests that transmission by asymptomatic individuals is far lower than that by symptomatic or presymptomatic individuals.

A number of studies have investigated transmission from index cases who remained asymptomatic throughout their infections. A review study[10] estimated that the mean household secondary attack rate from asymptomatic cases was only 3.5% of that from symptomatic cases. As that study noted, household secondary attack rate provides a useful estimate of both the susceptibility of contacts and infectiousness of index cases. However, both in that study, and in another review study[11] that estimated a much higher ratio than 3.5%, the statistical analysis appears to be seriously flawed.[12] It is therefore necessary to consider the actual results of the relevant original studies that they reviewed. Two of those studies[13] [14] found no instances of asymptomatic transmission, although the number of contacts concerned was very small in one case. Two other studies each found one case of asymptomatic transmission, out of respectively 305 and 119 contacts,[15] [16] with corresponding relative risks of 6% and 19%. Averaging the risk ratios of all four studies, in a way that gives appropriate weight to the evidence each provides, gives an overall transmission risk ratio estimate of 8% for asymptomatic cases, relative to symptomatic and presymptomatic cases.[17]

That is, an asymptomatic infected person, as in Lipsitch et al. model scenario 3, appears to be only one-tenth or less as likely to transmit the virus as does a symptomatic or presymptomatic person. This conclusion does not have to depend on asymptomatic infectees having a much lower viral load in their URT, which may not be the case. They could for instance transmit less because of an absence of coughing (particularly that involving expectoration15), less deep breathing or a similar factor; because more of their PCR-measured viral load does not represent viable viruses; and/or because their viral load remains at an infective level for a shorter period.

The likely importance of viral dose (inoculum) and innate immune responses

Two factors that Lipsitch et al. do not include in their model scenarios, but which seem likely to be very relevant, are the magnitude of the viral dose and the strength of a person’s fast responding innate immune system. Both the symptoms, as to their likelihood and severity, and the infectivity of an individual exposed to SARS-CoV-2 are expected to depend on the viral dose that their exposure involves[18] [19] and on the strength of their innate immune system, as well as on any cross-reactive T cell and/or antibody adaptive immune system memory. I will concentrate here on differences arising from the interaction between viral dose and cross-reactive T cells, but in reality differences in innate immune system strength, and in general health and other factors, will likewise affect how somebody reacts to viral doses of varying strength and to what extent they become ill and/or infective.

Box 1: Might low viral dose explain Tokyo’s COVID-19 epidemic?Evidence from a study[20] of 1877 asymptomatic (at time of testing) company employees from 11 disparate locations in Tokyo is consistent with the importance of viral dose. The study showed seroprevalence increasing from 6% to 47% between late May and late August. If the sample is representative of the Tokyo metropolitan area, which the authors suggest it may be, that implies seroconversion of about 5.7 million individuals during the study period.
Since the corresponding number of deaths attributed to COVID-19 appears to have been little more than 30, that implies an infection fatality rate in Tokyo that might be as low as 0.0006% – around a thousand times lower than generally estimated. In Japan, the very high rate of mask wearing (and generally high personal hygiene standards) may have reduced viral doses sufficiently for the vast majority of infections to be asymptomatic, and for almost all symptomatic cases to be mild, irrespective of the presence of cross-reactive T cells.[21] [22]

It seems entirely possible that where the viral dose is sufficiently low, a person with cross reactive CD4+ T cells might either be infected so little that – whether or not a PCR test would be positive, at a sufficiently large cycle threshold (high sensitivity) – they not only remain asymptomatic but also have negligible infectivity. In effect, given a sufficiently low viral dose, Lipsitch et al.’s model scenario 3 might produce rather similar effects to what their model scenario 4 would do for a high viral dose. It appears, for most purposes, to be inappropriate to regard such a non-infective, healthy person as a COVID-19 case or even as being infected at all.[23] Such persons are accordingly treated here as not having been infected. However, it appears possible that a low viral load might, without resulting in symptoms or non-negligible infectivity, nevertheless induce effective immunity through the development of SARS-CoV-2 specific antibodies and/or T cells.

By contrast, Lipsitch et al. appear to regard someone as having been infected even if only a single cell in their body has been invaded by a virus. While this definition may be logical from a technical biological angle, it does not seem appropriate from an epidemiological viewpoint. For epidemiological purposes, what is relevant is whether and to what extent a person is or will become ill, infective and/or immune.

Where the viral dose is fairly high, even if a person has cross reactive CD4+ T cells, they would almost certainly test PCR positive, and be more likely to develop symptoms. Model scenarios 2 and 3 in the paper may both be relevant in these cases. While in such a case the person concerned would be infective, albeit much less so if asymptomatic, if they had cross reactive CD4+ T cells they would probably be considerably less infective (and be much more likely to be asymptomatic or to have mild symptoms).

Insofar as infected individuals are asymptomatic and of low (but non-negligible) infectivity, it may be that in cases where they do transmit infection the viral dose is usually sufficiently low for the person thereby infected also to be asymptomatic and of low infectivity, in which case such asymptomatic transmission will contribute to the gradual spread of immunity while not leading to disease.[24]

Modelling the effects of varying susceptibility and infectivity arising from cross-reactive T cells

I have built a greatly simplified toy model that illustrates the possible implications for epidemic progression and herd immunity of cross-reactive T cells that have the effects discussed in this article. The model stratifies the population into two equal parts, one possessing cross-reactive T cells and the other not. It distinguishes symptomatic and asymptomatic infections, the latter having only one-ninth as high a probability of causing infection as the former.

The detailed assumptions made in the model are set out in an Appendix. While these assumptions are purely illustrative, they are intended to be broadly consistent with existing evidence and the foregoing discussion in this article. The key assumptions regarding the effects of cross-reactive T cells are that their presence halves the risk of infection from a potentially infective contact, quarters the probability of any infection being symptomatic, and may result in immunity developing in a substantial proportion of those cases where infection does not occur.

The modelled epidemic is seeded by the symptomatic infection of one naïve individual (a person without cross-reactive T cells). The number of close contacts per generation is then adjusted to produce, after the epidemic has adjusted from the initial seeding pattern to its natural pattern, a reproduction number early in the epidemic – which will therefore closely approximate R0 – of 2.4.

The toy model’s projections show that, after initial exponential growth, new infections start to decline, indicating that herd immunity has been achieved. At that point, 41% of the population has been infected, with approximately 43% of infections being asymptomatic. At 41%, the HIT is slightly over two-thirds of the classical HIT level for a homogeneous population, being 58%.[25]

A further 20% of the population will have become immune without, for all practical purposes, having had an infection. If on the other hand no exposed but uninfected (i.e., asymptomatic and non-infective) individuals develop immunity, then the HIT is closer to the classical level, but still lies more than 10% below it. If the probability of being infected is reduced by 85% in the presence of cross-reactive T cell memory, the HIT could be one-third below the classical HIT even if no exposed but uninfected person develops immunity. It is not suggested that such a large differential is  likely. However, it does prove that cross-reactive T cell memory, in combination with varying viral dose (and innate immune system strength) can result in a substantially lower herd immunity threshold than that estimated from data earlier in the epidemic using homogeneous population compartmental SIR/SEIR models, as is routinely done.

A more realistic model would incorporate continuous probability distributions for all the key parameters. But the basic point illustrated by the very simple model would remain valid. Homogeneous population based compartmental models imply that epidemic growth will slow pro rata to the shrinking pool of uninfected people. But where there is variation within the population as to how susceptible people are to infection, so that more susceptible individuals are on average infected earlier, the epidemic growth is bound to reduce more rapidly than that. As a result, the herd immunity threshold will be lower than if the population were homogeneous, with the reduction of the HIT being greater if less biologically susceptible individuals also have, if infected, lower biological infectivity.

Conclusion

I have demonstrated that the claim by Lipsitch et al. that the potential impacts on the herd immunity threshold of cross- reactive T cell memory are already incorporated into epidemiological models based on data of transmission dynamics is mistaken, even assuming that they are correct in arguing that their model scenario 4 is highly implausible.

In this article I have only considered the possible effects of cross-reactive T cells. However, even when combined with other causes of interpersonal variation in biological susceptibility, including age, such heterogeneity is not thought to be the main reason why the herd immunity threshold will be lower than the classical level for a homogeneous population. In practice, interpersonal variation in contact rates (social connectivity) is usually thought to be a much more important reason. 3

Appendix – Assumptions made in the toy model of the effects of cross-reactive T cells

  1. The population is one million and is homogeneous except that only 50% of people have cross-reactive memory T-cells.
  2. The generation interval is fixed, infected individuals are only infectious in the generation interval after they become infected and are uninfectious and immune thereafter.
  3. Infections are by close contact only. The number of close contacts by an infected person is independent of their T cell status and whether or not their infection is asymptomatic (never symptomatic), and each person who becomes infected has only had one contact with an infectious person during the generation interval in which they become infected.
  4. A close contact between a symptomatic (including presymptomatic) infectee and a naïve individual (one without cross-reactive T cells) results in infection 90% of the time, with 80% of such infections being symptomatic, due to a high average viral dose being involved.
  5. A close contact between an asymptomatic infectee and a naïve individual results in infection 10% of the time, with 20% of such infections being symptomatic, the viral dose being lower.
  6. A close contact between a symptomatic infectee and a resistant individual (one with cross-reactive T cells) results in infection 45% of the time, with 20% of such infections being symptomatic.
  7. A close contact between an asymptomatic infectee and a resistant individual results in infection 5% of the time, with 5% of such infections being symptomatic.
  8. Where such a low viral dose is transmitted on a close contact that a resistant recipient not only has no symptoms but is completely non-infective, they are treated as not being infected but (except if stated otherwise) in 60% of such cases they nevertheless become immune.

Nicholas Lewis                          14 October 2020


[1]  Marc Lipsitch, Yonatan H. Grad, Alessandro Sette and Shane Crotty: Cross-reactive memory T cells and herd immunity to SARS-CoV-2. Nature Reviews Immunology 6 October 2020 https://doi.org/10.1038/s41577-020-00460-4

[2]  The herd immunity threshold is the proportion of the population that have become infected at the point where each new infection causes, on average, no more than one further infection. For an epidemic in a homogeneous population, it will be {1 – 1/R0}, where R0 is the basic (initial) reproduction number.

[3]  e.g., Tkachenko, A.V. et al.: Persistent heterogeneity not short-term overdispersion determines herd immunity to COVID-19. medRxiv 29 July 2020 https://doi.org/10.1101/2020.07.26.20162420

[4]  The Diamond Princess. 712 out of 3,711 on board tested PCR-positive, with at least 295 and probably closer to 334 cases (295 from Tokyo plus 40 returned on charter flights, one of whom died from COVID-19) remaining asymptomatic throughout their infection. https://www.mhlw.go.jp/stf/newpage_11441.html

[5]  Gallais, F., Velay, A., Wendling, M.J., Nazon, C., Partisani, M., Sibilia, J., Candon, S. and Fafi-Kremer, S., 2020. Intrafamilial exposure to SARS-CoV-2 induces cellular immune response without seroconversion. MedRxiv. https://www.medrxiv.org/content/medrxiv/early/2020/06/22/2020.06.21.20132449.full.pdf

[6]  Sekine, T. et al. Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19. Cell https://doi.org/10.1016/j.cell.2020.08.017 (2020).

[7]  https://twitter.com/WesPegden/status/1313649435642077184

[8]  That is consistent with the findings of Sakurai et al., Natural History of Asymptomatic SARS-CoV-2 Infection. New England Journal of Medicine. 2020 Jun 12 https://www.nejm.org/doi/full/10.1056/NEJMc2013020

[9]  https://www.cebm.net/covid-19/infectious-positive-pcr-test-result-covid-19/

[10] Madewell, Z.J., Yang, Y., Longini Jr, I.M., Halloran, M.E. and Dean, N.E., 2020. Household transmission of SARS-CoV-2: a systematic review and meta-analysis of secondary attack rate. medRxiv. [1 August version]

[11] Buitrago-Garcia D, et al. (2020) Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections: A living systematic review and metaanalysis. PLoS Med 17(9): e1003346. https://doi.org/10.1371/journal.pmed.1003346

[12] Madewell et al. included a study where the secondary attack case rather than the index case was asymptomatic. Buitrago-Garcia D, et al., who estimated a relative risk of 0.35 for asymptomatic transmission,  included in that estimate a study of presymptomatic transmission (their reference 111) and an estimate based on combined asymptomatic and presymptomatic transmission (from their reference 65), and they wrongly estimated very high asymptomatic transmission risk from studies that found zero cases of it.

[13] Cheng HY, Jian SW, Liu DP, Ng TC, Huang WT, Lin HH, et al. Contact Tracing Assessment of Covid-19 Transmission Dynamics in Taiwan and Risk at Different Exposure Periods before and after Symptom Onset. JAMA Intern Med. 2020. Epub 2020/05/02. https://doi.org/10.1001/jamainternmed.2020.

[14] Park SY, Kim YM, Yi S, Lee S, Na BJ, Kim CB, et al. Coronavirus Disease Outbreak in Call Center,

South Korea. Emerg Infect Dis. 2020. https://doi.org/10.3201/eid2608.201274

[15] Luo L, Liu D, Liao X-l, Wu X-b, Jing Q-l, Zheng J-z, et al. Modes of Contact and Risk of Transmission in Covid-19 among Close Contacts. bioRxiv. 2020 [March 26 version] https://www.medrxiv.org/content/10.1101/2020.03.24.20042606v1

[16] Zhang W, Cheng W, Luo L, Ma Y, Xu C, Qin P, et al. Secondary Transmission of Coronavirus Disease from Presymptomatic Persons, China. Emerg Infect Dis. 2020. https://doi.org/10.3201/eid2608.201142

[17] Averaging over the four studies, weighting by the number of contacts by asymptomatic index cases, gives a pooled relative risk estimate of 8.2%. A more sophisticated meta-analysis using the R software Fixed effects (Mantel-Haenszel) function in the rmeta package estimates a pooled study relative risk of 7.9%, with a 75% probability that it does not exceed 13% and a 90% probability that it does not exceed 20% (assuming that the confidence intervals are symmetrical).

[18] Steinmeyer, Shelby H., Claus O. Wilke, and Kim M. Pepin. “Methods of modelling viral disease dynamics across the within-and between-host scales: the impact of virus dose on host population immunity.” Philosophical Transactions of the Royal Society B: Biological Sciences 365.1548 (2010): 1931-1941.

[19] Goyal, Ashish, et al. “Wrong person, place and time: viral load and contact network structure predict SARS-CoV-2 transmission and super-spreading events.” medRxiv (2020) [7 August version].

[20] Hibino, Sawako, et al. “Dynamic Change of COVID-19 Seroprevalence among Asymptomatic Population in Tokyo during the Second Wave.” medRxiv (2020). [23 September version]

[21] Gandhi, Monica, Chris Beyrer, and Eric Goosby. “Masks do more than protect others during COVID-19: Reducing the inoculum of SARS-CoV-2 to protect the wearer.” Journal of general internal medicine (2020): 1-4.

[22] Gandhi, Monica, and George W. Rutherford. “Facial Masking for Covid-19—Potential for “Variolation” as We Await a Vaccine.” New England Journal of Medicine (2020).

[23] While such cases might give a positive result on a PCR test at some point, such a test result might represent  detection only of non-viable virus fragments, or a viable viral load that is too low to be infective.

[24] Unfortunately there are too few recorded cases of asymptomatic transmission to provide reliable evidence on this point, but what evidence does appear to exist is consistent with this argument. Zhang et al. identified one case of asymptomatic transmission, which resulted in an asymptomatic infection, while 73% of the eleven cases of symptomatic or presymptomatic transmission they identified resulted in a symptomatic infection. (Luo et al. unfortunately did not indicate the symptom status of the asymptomatic transmission case that they identified.)

[25] For an R0 of 2.4, the classical herd immunity threshold is {1 – 1/2.4} = 0.583

160 responses to “T cell cross-reactivity and the Herd immunity threshold

  1. Matthew R Marler

    thank you for the essay.

    In this connection, it should be noted that the extent and quality of the available data, both biological and epidemiological, does not provide high quality evidence, so drawing firm conclusions either way is difficult.

    It’s a classical ill-posed inverse problem. Many combinations of the rates/intensities of the microprocesses are compatible with particular parameter values in the epidemiological model. All of the processes contribute to the observed process, in different amounts in different people.

    Still worth study — no denying that — and this is a good essay.

  2. It’s been discussed that those who in the past have been exposed to an innumerable number of coronaviruses over a lifetime may in fact have a protective immunological responses to CoV19.

    • There may be individuals who have immunity to covid 19. If the percentage of the total population is low does it matter? (From a public policy perspective)

      Will any region ultimately be spared?

      • …no more than you can spare a region from the The consequences of common cold.

      • Depends on the definition of consequences.
        We know from the past that populations with no exposure to flu, can die from it in great numbers (North & Central American, Caribbean indigenous). Thus it seems very possible that partial immunity means merely having the sniffles and feeling bad as opposed to dying.
        Secondly, I haven’t seen this examined but there seems to be universally better outcomes in Asia vs. COVID-19 than in Europe or the Americas. This is not purely a government-based outcome because there are poor as well as shambolic governments there.
        India is probably the worst performing in Asia – and their COVID-19 mortality rates are 1/10th that of the Western democracies. This is no longer a minor difference.
        Whether this is environmental (pre-existing coronavirus exposure), societal (BCG vaccination) – something is very different.
        It isn’t age – Japan is really old and has done fine even as India is relatively young.
        It isn’t government response: some governments have imposed total lockdown. Others have no lockdown. And still others have switched between lockdown and no lockdown.

      • Wolf

        Notwithstanding Japan I do think age is a big factor. Many of the least affected countries have a very young population with a low obesity factor.

        As for Japan, social distancing and hand washing have been an integral part of their social customers for Years

        Tonyb

      • And, hydroxychloroquine cuts through all of that…

      • @Tonyb
        Age is a factor – but India is really young (27.6 years) and is the worst performing in Asia.
        Asia isn’t that young, overall though
        South Korea: 41.2
        Japan: 46.9
        Taiwan: 39.7
        China: 37.1
        Thailand: 37.2
        Vietnam: 30.1
        US: 37.9
        UK: 40
        France: 41.2
        Spain: 42.3
        Note that the US is younger than South Korea and Taiwan and isn’t much older than China.
        Secondly, even with low average age – the mortality rates for COVID-19 are very small: death rates per million are low 4 digits per million population even in the worst hit countries/cities/regions. Or in other words – even countries with low average ages have old people. I’ve looked closer at some of the actual demographic profiles – and the difference in the 60+ groups isn’t 10x between almost any of the 2 nations above.
        So again, it seems likely there is some other factor than lockdown and/or mask wearing.

  3. Nic, In several places you say Model 4. Figure 1 from the paper has a No cross reactive panel and 3 Models. When you say Model 4 do you mean Model 3? Or is there a 4th model as well?

    • Model scenario 4 is Transient infection – the one numbered 4 in my list. It is not included in Figure 1, as Lipsitch et al. considered it to be ‘highly implausible’. The headings of each panel in Fig. 1 state which model scenario is involved; none of them relates to model 4.

  4. Re: ” In that connection, Lipsitch et al. say that a recent study[6] observed [only] about 3 cases of non-PCR confirmed potentially asymptomatic COVID-19 cases with T cell responses in the absence of seroconversion, but their interpretation of that study’s results has been challenged.[7]”

    Challenged by Wes, who has no expertise nor competence in this topic, unlike the authors of the study he’s responding to; I know since I’ve dealt with Wes multiple times, and actually read the study he cited. Wes not even familiar with the literature. If he were, then he’d know the sensitivity for the assay used in that study is low, and thus one would expect it to yield a higher proportion of false seronegatives. That effect would be relatively larger, since the expected proportion of true seronegatives is low. This has been explained over and over and…

    Click to access 2020.08.05.20169128v1.full.pdf

    Click to access Evaluation_of_Diasorin_Liaison_anti_SARS_CoV_2.pdf

    Re: “If the sample is representative of the Tokyo metropolitan area, which the authors suggest it may be, that implies seroconversion of about 5.7 million individuals during the study period.
    Since the corresponding number of deaths attributed to COVID-19 appears to have been little more than 30, that implies an infection fatality rate in Tokyo that might be as low as 0.0006% – around a thousand times lower than generally estimated.”

    Give me a break. This was addressed weeks ago, covering how the sampling methodology for that paper in non-representative. It basically amounts to local workplace outbreaks from a non-randomized sample of volunteers, not representative of infections across the general population of Tokyo. This is at least the 4th time you’ve under-estimated the fatality rate of SARS-CoV-2, and at least the 2nd time you’ve done it using non-representative samples that over-estimate seroprevalence:

    Re: “While these assumptions are purely illustrative, they are intended to be broadly consistent with existing evidence and the foregoing discussion in this article. The key assumptions regarding the effects of cross-reactive T cells are that their presence halves the risk of infection from a potentially infective contact, quarters the probability of any infection being symptomatic, and may result in immunity developing in a substantial proportion of those cases where infection does not occur.”

    You’re again making the mistake of assuming cross-reactive T cells are significantly beneficial, since you think that helps you reach your politically-motivated conclusion that SARS-CoV-2 is less dangerous and thus you can avoid policies you dislike, like lockdowns. You’ve done this for months, besides being repeatedly corrected by those who know more on this topic than you.

    There’s every reason to think that immune cells may need to have not seen a virus before SARS-CoV-2 (i.e. be naïve) in order to be effective, such that it may be detrimental if they are cross-reactive and bind to another seasonal coronavirus before seeing SARS-CoV-2:

    “Antigen-specific adaptive immunity to SARS-CoV-2 in acute COVID-19 and associations with age and disease severity”
    Not yet peer-reviewed: “Pre-existing T cell memory as a risk factor for severe 1 COVID-19 in the elderly”

    There’s every reason to think that the TCR repertoire needs to shift to address SARS-CoV-2, where exposure to seasonal coronaviruses is insufficient for causing that shift, while exposure to SARS-CoV-2 eventually is:

    “Viral epitope profiling of COVID-19 patients reveals cross-reactivity and correlates of severity”
    Not yet peer-reviewed: “SARS-CoV-2 T-cell epitopes define heterologous and COVID-19-induced T-cell recognition”

    There’s every reason to think SARS-CoV-2 exploits the T cell response to cause illness, resulting in a hyper-inflammatory cytokine storm and T cell exhaustion that harms the patient, such that cross-reactive T cells would be useless and/or detrimental:

    “Robust T cell response towards spike, membrane, and nucleocapsid SARS-CoV-2 proteins is not associated with recovery in critical COVID-19 patients”
    “Pathogenic T-cells and inflammatory monocytes incite inflammatory storms in severe COVID-19 patients”
    “Systematic examination of T cell responses to SARS-CoV-2 versus influenza virus reveals distinct inflammatory profile”
    “Immunologic features in Coronavirus Disease 2019: Functional exhaustion of T cells and cytokine storm”

    And if cross-reactive humoral immunity (which is better designed to prevent infection and disease that is the T cell response, since the BCR and antibodies can recognize viral antigens without help, while the TCR needs MHC help) fails to prevent disease, then there’s every reason to think a cross-reactive T cell response would fail as well:

    Not yet peer-reviewed: “Pre-COVID-19 humoral immunity to common coronaviruses does not confer cross-protection against SARS-CoV-2”
    Not yet peer-reviewed: “Prior infection by seasonal coronaviruses does not prevent SARS-CoV-2 infection and associated Multisystem Inflammatory Syndrome in children”
    Not yet peer-reviewed: “Seroprevalence and correlates of SARS-CoV-2 neutralizing antibodies: Results from a population-based study in Bonn, Germany”

    So no, Lewis, the assumptions of your model are not “broadly consistent with existing evidence”. They are, at best, non-expert wishful thinking. This is not your field, and it shows. Your ideologically-motivated, epistemic trespassing is not helpful nor or informative to anyone with expertise in this topic, including the authors of the research you’re criticizing. Enough already.

    “Cross-reactive T cell memory may or may not affect COVID-19 disease severity in individuals.”
    https://www.nature.com/articles/s41577-020-00460-4

  5. The body has a number of different immune mechanisms.
    Of which Cross-reactive memory T cells activation is one.
    The concept that Cross-reactive memory T Cell activation on its own can be responsible for stopping a new viral infection on its own and without the need for development of B -cell antibodies is not new.
    Nic is not the first to go down what I think is a rabbit hole of logical reasoning.

    • Viral infections have a logical and consistent method of being dealt with by the body.
      The virus has a method of getting to its target cells.They often go through a number of different cell replications to reach the ultimate destinations.
      This is in the case of C19 and most other colds and viruses through both the respiratory tract and the blood circulation.
      Source viral load on surface to hand to mouth, nose or eye.
      Source viral load in air to mouth,nose, eye or airways.
      Source blood transfusion or bite, direct to blood stream.* rare.

      Step 1 – attachment to a cell in the eye, nasal passages, mouth or respiratory tract. Here the virus first enters a susceptible cell or cells depending on the load. Note not many T-cells available to block this step externally.
      Step 2 reproduction giving billions of virus particles released by either viral mediated cell lysis. [Did not need those T cells at all to kill a cell] or programmed continual extrusion of complete viral particles through the cell into the bloodstream. External release leads to infection of neighboring cells by local spread..
      Step 3 blood stream spread back to preferred sites in the nasal passages and airways. Because these are the sites from which it can spread to the next target. Incidental infection of non target cells liver spleen, anything really but not very interested as not useful.
      Step 4 blood stream spread to Immune system cells B and T system work in conjunction. The Immune cells have to be easily targeted because otherwise they cannot detect and overcome the viruses in the first place.
      This would pose a problem for an activated memory T cell that became infected.

      • The combined workings of the Immune system lead to the production of multiple antibodies to the virus shell components [including the spike]
        The Immune B cells multiply rapidly adding to the amount of antibody level.
        Cross-reactive memory T cells, very largely CD4+ T-cells, Follicular helper T (Tfh) cells are specialized providers of T cell help to B cells, and are essential for germinal center formation, affinity maturation, and the development of most high affinity antibodies and memory B cells.
        In other words they develop specifically with and in order to help produce more antibodies of the specific type needed.
        I see by the graphs of the study that this is in less than 48 hours.
        * A very salient point for previous infections.
        Any virus that gets to the stage of being blood borne and reaching target cells also always reaches the immune system cells and stimulates an antibody response.
        If the Immune system is normal, it includes working B cells that produce antibodies.
        Fact 1 in the normal person with a proven viral infection and response there will always be a detectable Antibody response within 2 days.

        Corollary, a normal person without an antibody response to a particular virus did not and cannot have had a viral infection with that virus.

      • Conclusions.
        “in households where one person was confirmed as having COVID-19, a substantial proportion of other household members had negative PCR test results, implying that they were not infective, despite most of them having typical COVID-19 symptoms.”
        Typical Covid-19 symptoms do not imply covid-19 in any way shape or form.
        Every mild covid infection is indistinguishable from a common cold.
        What is more likely? A group of people in a hose caught a viral cold and one then contacted symptonatic covid?
        or a bunch of people caught covid and only one got sick?
        Who coincidentally was always the only one with covid antibodies?
        Amazing.
        My cat has stripes, it must be either a juventus supporter, a zebra or a tiger.
        Same symptoms, typical really. Common sense would dictate that it is a cat [a cold[ with the other possibilities increasingly unlikely.

      • Final comment re rapid response. While it takes 48 hours to produce detectable new antibodies if there is cross reactivity with a previous corona virus there will be rapid induction of antibodies to that common antigen within hours , If it works, which it should it would lead to very little or no symptoms and quick resolution with no Covid specific antibody [recognised only as a cold antibody to a common compnent even though it worked.
        There would also be an activation of TRM cells to hasten susceptible cell death.
        and so called CD8 rsponse.
        T cell CD8 reactive populations would be virtually indistinguishable from a T cell CD8 activated for covid only cell response.
        No easy way of telling them a apart .
        If the cells are incapable of producing antibody to the virus then the T cells can have all the cross reactive memory they want and cannot affect a thing because if a B cell antibody response to covid or corona is not produceable then the T cells will also not be able to react to that virus.
        If the person has had a common cold at any stage in the preceding 3 months then of course there will be activated T cells with a meaningless Sars profile still persisting from that cold response but no way of reacting to covid or a covid related corona virus until they develop the specific antibodies to that virus
        How many covid cases have had a cold in the preceding 3 months?
        Why is this so hard to get through, other than the buckets of research cash available for dodgy ideas?

      • “Typical Covid-19 symptoms do not imply covid-19 in any way shape or form.”
        I didn’t say that they did.

        “Same symptoms, typical really. Common sense would dictate that it is a cat [a cold”
        So how come these individuals developed SARS-CoV-2 specific (as opposed to cross reactive) T cell responses, as I wrote in the next sentence?

        “Fact 1 in the normal person with a proven viral infection and response there will always be a detectable Antibody response within 2 days.”
        That is fantasy, not fact. Serological antibody tests typically have a low detection rate until more than a week after infection.

      • niclewis |
        “Fact 1 in the normal person with a proven viral infection and response there will always be a detectable Antibody response within 2 days.”

        That is fantasy, not fact. Serological antibody tests typically have a low detection rate until more than a week after infection.

        I could quibble. I hate losing an argument.
        You are referring to seroconversion which by definition is when antibody levels are detected in the bloodstream.
        In which and every case you are right.

        Virology science says that IgM is produced very early on in the disease and is not initially released actually going onto the membrane of the B cells. presumably detected by both EM and PCR techniques in the laboratory.

        An article
        “Chronological evolution of IgM, IgA, IgG and neutralisation antibodies after infection with SARS‐associated coronavirus”
        states
        “the present study showed clearly that IgG seroconversion can start as early as 4 days after the onset of illness.”

        Quibbles aside you are still right.

      • niclewis | October 15, 2020 at 5:09 am |
        “Typical Covid-19 symptoms do not imply covid-19 in any way shape or form.” I didn’t say that they did.

        Somebody did
        “Moreover, the results of a study that Lipsitch et al. do not cite[5] show that, in households where one person was confirmed as having COVID-19, a substantial proportion of other household members had negative PCR test results, implying that they were not infective, despite most of them having typical COVID-19 symptoms.”

        In fact, as you wrote in the next sentence
        “Moreover, these individuals …. did develop SARS-CoV-2 specific (as opposed to cross reactive) T cell responses, implying that they had been infected to some degree by SARS-CoV-2 .”

        I interpret, maybe wrongly, that here you do imply that people with covid-19 like symptoms do [implied] have an infection with Covid 19 when clearly there is no antibody proof of this, only guilt by association.

        “So how come these individuals developed SARS-CoV-2 specific (as opposed to cross reactive) T cell responses, as I wrote in the next sentence?

        SARS-CoV-2 specific T cell responses are not opposed to cross reactive responses, They are both similar reactive responses and unfortunately not at all that specific.
        You have a corona virus or other cold virus infection which causes a T cell
        reactive response.
        Multiple changes in multiple parameters definitely showing a recent infection.
        Cross reactive?
        There are thousands of different individual T cell activations to different protein sub segments.
        Sigh.
        Some of these will correspond to protein sub segments from covid 19,SARS, rubella, influenza virus, or, as my wife says, whatever.
        Inevitable.
        Activated T cell profiles are matched to the disease being tested for.
        “This is a Rubella specific response,this Covid 19, this SARS.
        What they should not say is not that an activated T cell response is specific for a viral disease, it is only associated with a viral disease in a particular laboratory.
        and we have no way of proving that this response must be a specific virus.

        I will put it this way, How many real people have been exposed to SARS and lived to tell the tale?
        Not many.
        How many real people are you now claiming to have preexisting exposure to a SARS like virus to develop this SARS like response when exposed to a common cold. Remember none of them have antibodies to Covid 19?
        So out of a handful of people with prior exposure to a lethal infection how do they keep turning up in all these studies?
        The obvious answer is that they do not.
        People are confusing normal activated or cross activated T cell profiles with SARS profiles because the profiles are not specific.

  6. Atomski’s missives are at best unreadable and at worst incomprehensible. He uses a scattergun approach of tweets, whole articles and a enclave of references that may or may not be relevant to an argument he is incapable of articulating. This is conflated with a purely adversarial stance and expressed with an arrogant assurance at odds with the complexity and uncertainty of the topic.

    • Robert I Ellison: Atomski’s missives are at best unreadable and at worst incomprehensible.

      Atomsk Sanakan’s post are usually worth reading in their entirety and usually refer to sources that deserve serious consideration.

      If you can’t understand them, well that’s on you.

      • Tweets, lists of irrelevant articles unhinged from coherent and succinct argument, dogmatically adversarial and with a fixed and rigid worldview. I’ve wasted enough time on the perennially oblivious.

      • Robert I Ellison: I’ve wasted enough time on the perennially oblivious.

        So write coherently about specific propositions. Avoid any perennially oblivious.

      • After decades of technical and creative writing – I think I can organise a coherent argument. Although I no longer have the patience to write for an audience. I write for fun in the way I want to on ideas that are only graspable if you are there or almost so anyway.

        Somewhere recently I have written that the creative and fun bit of science is to synthesise disparate empirical facts into a coherent worldview.

        I don’t get that sense of creative energy and excitement, wonder and awe, from either of you. More like pompous and self important pronouncements. Oh how Feynman warned us against you.

      • > dogmatically adversarial and with a fixed and rigid worldview.

        Unmatched in mastery of unintentional irony.

      • I did have a reply that used the logical fallacy of the loaded question ironically.

        Somehow ‘when did you stop flogging a dead horse’ crossed a line.

  7. Nik

    I pass no comment on the scientific correctness of the information in this link( scroll to foot to see the article)

    https://www.dailymail.co.uk/news/article-8839007/Almost-half-Britons-likely-catch-Covid-19-Type-O-blood.html

    It says that people with one blood type are much less susceptible to covid than other blood types

    Tonyb

    • I think the same from noted or suspected from studies of some of earliest cases in China.

    • Tonyb
      The findings reported look to me to agree with other results published a little while ago – unless they are referrring to a study that came out quite a while ago.

      • So, it seems your chances of being infected or of being seriously Ill from covid could be dependent on your blood group, your level of vitamin d, your level of obesity, your level of fitness, your health condition as well as your age.

        You can’t do anything about the first and last aspect, but it seems that to some extent we have our fortunes in our own hands, quite separately from taking such precautions as social distancing and hand washing etc.

        Incidentally nic, I have never had a clear idea as to the best condition for our homes as we approach autumn and winter. Should we have warm homes and a high humidity, cool homes and a low humidity?

        I think the well ventilated bit we can take as read

        Tonyb

      • Warm and high relative humidity is generally preferable, as far as I am aware.

      • Robert Starkey

        Nice

        Doesn’t the virus live longer on surfaces in higher humidity?

      • Robert Starkey

        Nic
        Sorry. Assuming it does live longer on surfaces in higher humidity, it’s complicated indoors in winter. Dryer humidity increases air transmission but…

      • If I was at high risk I would have a recirculating air filter unit with HEPA filtration and UVC sterilization. That or fresh air makeup is the best defense against aerosolized virus in a closed space IMO. There are some residential heat exchangers that provide air turnover without too much loss of heat also.

    • “This means that the immune systems of people with type A blood develop antibodies for B antigens, people with type B blood have antibodies for A antigens, and people with type O blood have antibodies for both. Blood type influences blood clotting, and a growing body of evidence suggests that COVID-19 pathology often involves overactive blood clotting. People with type O blood have lower levels of proteins that promote blood clotting.
      SARS-CoV-2 can replicate in cells that express blood type antigens, Jacques Le Pendu, a glycobiologist at the University of Nantes told Chemical and Engineering News. This means that when an infected person coughs or sneezes, there’s a possibility that they release viral particles coated with their blood type antigens.
      Explained more in depth, a person in the blood type O group will have antibodies against virus transmission from someone in the blood type A group, which can fight the virus. However, a person in the blood type A group won’t have those same antibodies.”

      Continuing the theme of baseline immunity existing 2 years ago and now. Lowering effective herd immunity. No immunity 2 years ago? Got it.

    • Relative vs. absolute risk is a relevant factor here.

      And it should have little to no impact on policies or behaviors.

  8. Here’s what I think you’re saying. Some people can have it and are very weak transmitters. That they have it is providing them with immunity. A weak transmitter lowers effective herd immunity. Look at a nursing home. An old person has it a lot and is a raging transmitter, who makes other raging transmitters and we get a death flash wave. (Then it’s blamed on Trump.) Where are the stories of a household being taken out and all are in the an ICU? Children are weak transmitters. Schools. Homes are what? One or two parents and children.

    I have been following this more than your average bear. Can you sum your main points up for marketing please? Nic, your audience is the world and you can do it.

    • The key point is that cross-reactive T cell memory is likely to be a source of variability between individuals in their biological susceptibility to being infected by SARS-CoV-2, alongside other factors such as innate immune system strength, genotype and age, providing one takes an operational definition of infection. By that, I mean defining infection as involving the development of symptoms and/or non-negligible infectivity, not as just involving at least one cell having been invaded by the virus.

      Lipsitch et al.’s illustration of their model scenario 3 suggests that, while no symptoms would occur, infectivity – although greatly reduced by cross-reactive T cells – would not be rendered negligible. However, this does not take into account the level of the viral dose, which will vary from one exposure to potential infection to another. There must come a point, at a lower viral dose level, when under this scenario the extent of viral replication reduces so much infectivity does become negligible, while it would not be negligible in the absence of cross-reactive T cells.

      The effect of cross-reactive T cells, in increasing variability between individuals in their biological susceptibility to being infected by SARS-CoV-2, and thus lowering the herd immunity threshold will not be taken into account in estimates thereof based on early epidemic growth and standard epidemiological models, contrary to the assertion by Lipsitch et al.

      Lipsitch et al. and I both focus on the possible protective effect of cross-reactive T cells. However, the implications for the herd immunity threshold (relative to that estimated from early epidemic growth) of their having the opposite effect, of making people more vulnerable to infection by SARS-CoV-2, would be similar. That is because such an effect would also increase variability in biological susceptibility, and it is the variability therein (along with variability in social connectivity/contact rates), not its average level, that determines the extent of overestimation of the herd immunity threshold when using early epidemic growth data.

  9. Pingback: T cell cross-reactivity and the Herd immunity threshold |

  10. Judith, please take Climate etc. back to what it once was. Nic Lewis’ thoughts and ideas are probably interesting to people who do not know a cat’s ass about virology, epidemiology and general sociology.

    Nic Lewis’ posts are at Tony Heller level dressed in a scientific suit. Neither Nic Lewis nor any of these Covid deniers have understood that the subject is not to count the dead on a fortnight basis.

    • Rune

      What is a “covid denier”? Are there people who don’t believe that any covid virus exist or just covid 19.

      You could disagree with Nic’s statistical analysis or the specific conclusions he has reached based on his statistics, but choose otherwise.

      • What is a “covid denier”? They come in many shapes, here is one:

        Stockholm will achieve herd immunity by end af May is another variant.

        What many seems not to understand is that if this epidemic is not kept in check, it is only a matter of time before the hospitals become overcrowded and the health care system is blown up. In Spain, people died on the floor in hospital corridors, in many cases younger people who probably should have survived.

      • Robert Starkey

        Rune

        So in your world, being wrong about at what rate HIT is achieved makes a person a covid denier?

        Imo you inappropriately use a hostile term as a part of a rant when the science of when HIT will be ultimately achieved in various countries is unknown.

    • Rune –

      I’m not sure what high quality days of yore you’re pining for. Here’s a link to four years ago, comments from jim2, AK , and ciscokid. All regular commenters at the time. Zero pushback from the rest of the regulars.

      https://judithcurry.com/2016/07/29/week-in-review-politics-edition-4/#comment-800836

      Seth Rich level conspiracy ideation has been a mainstay of Climate Etc. for a very long time.

      Anything that’s remotely political (and practically everything is) brings out this level of reasoning.

      • Perhaps you could apply for the job of moderator. Then you could filter stuff out so we poor souls are not at risk of being sullied by it. The generosity and sacrifice on your part by assuming this burden on behalf of the community would be nothing short of saintly.

        Rune was complaining about a blog post by a contributor, and you dig up random comments (not by him) from four years ago in affirmation. No matter how much they vexed you at the time, you really should have got over it by now.

      • > No matter how much they vexed you at the time, you really should have got over it by now.

        What is it that I need to get over? I enjoy reading the crazy conspiracy comments here. Always have. Enjoyed it then. Enjoy it now. They’re funny.

      • aporiac –

        I ejoyed them then, I moved on to enjoy the more recent series of wacky conspiracy theories oriole post here (some be the same crew). Rune mentioned a deterioration in quality so I used the Google for Seth Rich mentions here. Shockingly, I found as some. You’ve heard of the Google, havd you?

        So I enjoy them now, and offer them for your enjoyment as well. So take that gift and quit while you’re behind.

      • Well, you are half right. Those are quotes from an article in my case, not my original thoughts. The title of the blog is Climate, Etc. Not Climate, the-way-Rune-and-Joshua-like-it.

    • Rune Valaker: Neither Nic Lewis nor any of these Covid deniers have understood that the subject is not to count the dead on a fortnight basis.

      Do you have any criticisms of any specific propositions? Do you have any examples from here of “Covid deniers”?

  11. “The authors say that evidence for other human coronaviruses makes this implausible, and that when epidemiological evidence of very high attack rates in some ship-based outbreaks is added scenario 4 is highly unlikely.

    However, in the most studied ship-based outbreak the proportion infected was under 20%.[4] ”

    Diamond princess? again?
    to be favored because its the Most studied?

    Look Nic, there are other ship studies where the attack rates are above 20%
    even 100%.
    There are prison studies with attack rates well over 50%
    In recent work on Tokyo, a prevalence of 46%

    quit ignoring data

    Sumter Correctional Institution 62%
    Tomoka 60 %
    San Quentin 68%
    Eddie Warrior 72%

    and there are more, you never look for data to challenge your hypothesis

    Diamond princess fans never do.

    • 9/28 article:

      Six prisons have reported no cases, and the average inmate infection rate across all prisons is 4%. Snake River’s infection rate among its 2,700 inmates is 14%, second only to Eastern Oregon Correctional Institution in Pendleton, where 18% of inmates have been infected.

      https://www.eastoregonian.com/coronavirus/covid-19-infections-at-srci-nearly-double-in-one-month/article_c0a2252e-019c-11eb-87c5-03688f080ce0.html

      Do you have any links to back up your claims, Mosh?

      • https://www.cdc.gov/mmwr/volumes/69/wr/mm6926e2.htm

        Seventy-one additional cases of SARS-CoV-2 infection were detected in the five dormitories. Among 98 persons tested on day 1, 53 (54%) had positive SARS-CoV-2 test results (Table 2). Among the remaining 45 who had negative test results on day 1, 16 (36%) had positive test results on day 4. Two (7%) of 29 persons who had negative test results on days 1 and 4 had a positive test result on day 14. Of the 71 cases, three (4%) occurred in persons who were presymptomatic at the time of specimen collection, 29 (41%) were in persons who were asymptomatic, and two (3%) were in persons who had had unknown symptom histories. Among the 37 patients who reported COVID-19 symptoms before testing, 11 (30%) reported symptom onset ≤2 weeks before testing, and 19 (51%) experienced symptom onset >2 weeks before testing. Among 27 persons testing negative, 18 (67%) reported COVID-19–compatible symptoms in the previous 2 months, including eight (30%) reporting loss of smell and seven (26%) reporting loss of taste. Among the 98 persons who were tested, 55 (56%) reported at least one COVID-19 symptom during the 2 months before testing, including 37 (52%) who had positive test results and 18 (67%) who had negative test results. Headache (27, 38%) and loss of smell (25, 35%) were the most commonly reported symptoms. During the public health outbreak investigation period, none of the COVID-19 patients identified through serial testing developed severe illness requiring hospitalization.

        The attack rate by dormitory ranged from 57% in dormitory A to 82% in dormitory C. The number of days between the first identified COVID-19 case in each dormitory and day 1 testing ranged from 14–30 days. Dormitory A, which had the lowest attack rate, also had the shortest interval from day of first COVID-19 case to day 1 testing.

      • Seventy-one additional cases of SARS-CoV-2 infection were detected in the five dormitories. Among 98 persons tested on day 1, 53 (54%) had positive SARS-CoV-2 test results (Table 2). Among the remaining 45 who had negative test results on day 1, 16 (36%) had positive test results on day 4. Two (7%) of 29 persons who had negative test results on days 1 and 4 had a positive test result on day 14. Of the 71 cases, three (4%) occurred in persons who were presymptomatic at the time of specimen collection, 29 (41%) were in persons who were asymptomatic, and two (3%) were in persons who had had unknown symptom histories. Among the 37 patients who reported COVID-19 symptoms before testing, 11 (30%) reported symptom onset ≤2 weeks before testing, and 19 (51%) experienced symptom onset >2 weeks before testing. Among 27 persons testing negative, 18 (67%) reported COVID-19–compatible symptoms in the previous 2 months, including eight (30%) reporting loss of smell and seven (26%) reporting loss of taste. Among the 98 persons who were tested, 55 (56%) reported at least one COVID-19 symptom during the 2 months before testing, including 37 (52%) who had positive test results and 18 (67%) who had negative test results. Headache (27, 38%) and loss of smell (25, 35%) were the most commonly reported symptoms. During the public health outbreak investigation period, none of the COVID-19 patients identified through serial testing developed severe illness requiring hospitalization.

        The attack rate by dormitory ranged from 57% in dormitory A to 82% in dormitory C. The number of days between the first identified COVID-19 case in each dormitory and day 1 testing ranged from 14–30 days. Dormitory A, which had the lowest attack rate, also had the shortest interval from day of first COVID-19 case to day 1 testing.

      • “An Arkansas county so rural it has just three incorporated towns and not a single stretch of interstate suddenly emerged this week as one of the nation’s coronavirus hotspots. Ground zero in Lincoln County, about an hour’s drive south of Little Rock, is the Cummins Unit, a state prison farm known for producing cotton, rice and eggs.A farm employee was the first to test positive in early April. Now 14 staffers and more than 680 of the prison’s nearly 1,700 prisoners have the virus, according to test results reported this week.”

      • “When coronavirus cases began to spike at North Carolina’s Neuse Correctional Institution, 60 miles southeast of Raleigh, prison officials took the opposite approach, testing all 700 inmates and 250 staff.They found at least 65 percent of the prisoners have the virus, a number that may increase as all results come in. Notably, 98 percent of those infected were not showing symptoms, said John Bull, a corrections department spokesman.”

      • Steven Mosher

        San quentin

        https://www.cdcr.ca.gov/covid19/population-status-tracking/

        Did you think that I did not check?

        Look Nic never checked the diamond princess Strain.
        The less infectious D614 strain.
        I checked, I always check.
        Nic didn’t check all the ship cases… shall we start that route as well

        he didn’t check prisons.

        WHY?

        because he has to believe the diamond princess.

      • Steven Mosher

        https://www.iflscience.com/health-and-medicine/mysterious-covid19-outbreak-on-ship-after-35-days-at-sea-stumps-scientists/

        ‘Argentina is currently dealing with a mysterious Covid-19 outbreak onboard a ship that’s been out at sea for over 35 days. Considering all the sailors tested negative and self-quarantined before they set sail, no one is quite sure how the virus came aboard and infected dozens of crewmembers.

        At least 57 out of 61 people onboard the Etchizen Maru fishing trawler have tested positive for Covid-19, according to local health authorities in Argentina’s southernmost province of Tierra del Fuego in Patagonia. Two of the crew have tested negative, while the remaining two are still awaiting confirmation of their results. ”

        Somebody get those guys some cross reactive T cells.

        cause 61 tested negative before sailing
        and now 57 of 61 have tested positive.
        (index case was probably a 80 year old man they shared a plane with
        just prior to boarding the ship)

        Ignore this because Nic will

      • Steven Mosher

        Another reason why it is dumb to focus on the diamond princess

        https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326407/

      • Steven Mosher

        another ship 85%
        if you want to check for the genetic isolates be my guest
        I would bet its SG614
        Ascension numbers are USA/WA-UW-10027/2020 -USA/WA-UW-10138/2020 in the GISAID

        https://www.medrxiv.org/content/10.1101/2020.08.13.20173161v1

        85%

        Predeparture serological and viral RT-PCR testing along with repeat testing after return to shore was available for 120 of the 122 persons on board over a median follow-up of 32.5 days (range 18.8 to 50.5 days). A total of 104 individuals had an RT-PCR positive viral test with Ct <35 or seroconverted during the follow-up period, yielding an attack rate on board of 85.2% (104/122 individuals).

        Nic will ignore this data

      • Steven Mosher

        You see jim if there were this magic fairy dust cross reactivity
        you would not see countless types of situations, locations, and events
        with high attack rates.

        https://www.cdc.gov/mmwr/volumes/69/wr/mm6920e2.htm

        At the bottom Nic mistake is trying to use one R0.
        we’ve know for years this is an over simplification.

    • They also never look at the halotypes of the diamond princess virus

      https://www.medrxiv.org/content/10.1101/2020.03.23.20041970v1

      hint: ??? less infectious genetic isolate SD614 ( early Asian strain)
      10x less infectious

      https://www.biospace.com/article/mutated-covid-19-viral-strain-in-us-and-europe-much-more-contagious/

      In short

      By looking at the attack rate of the diamond princess you are
      BIASING your analysis because princess is the D614 strain of the
      Spike protein ( SD614)
      which is less infectious ( lower R0)

      You can see the japan data (genetic strains) here.

      https://nextstrain.org/ncov/asia?c=gt-S_614&dmax=2020-04-13&f_country=Japan&f_division=Japan&s=Japan/DP0184/2020

      only two samples of SG614, and the diamond princess was SD614
      as published

      Like I said before Diamond princess is junk, pretty much useless.

      psst deaths are up to 14 out of 712 ( as predicted)

    • Steven Mosher: Diamond princess? again?
      to be favored because its the Most studied?

      quit ignoring data

      I don’t think that Nic’s point is that attack rates are uniformly low but that they are sometimes (many times?) low, and (1) the variability has to be taken into account in modeling and (b) the mechanisms contributing to low attack rates are not fully understood.

      Attack rates are sometimes high as well. Something that might be called a “representative” attack rate, or mean attack rate, or median attack rate isn’t known, even for reasonably circumscribed areas like Stockholm or Los Angeles.

    • Steven,
      I do not get the gist of your argument, if there is one.
      Granted there are different strains of the virus with different infectivity rates.
      Part of the reason the Australian experience is so different to the Swedish.
      Good of you to note this.
      Granted there are countless examples of differing infective rates on ships, jails countries etc.
      Needs to be noted as well
      Granted Nic has upset the applecart of theories on ECS etc of a couple of your scientifically sloppy friends.
      Being nice to your friends.
      Where exactly is your beef with T cell cross-reactivity and the Herd immunity threshold?
      Nic has proposed a theory on herd immunity putting forward reasons for why one country, Sweden may have a much lower herd immunity threshold than expected. Not every country.
      You are putting up red herrings about different infective rates which Nic is fully aware of.
      Why don’t you discuss the premise of the infection threshold, the super spreader concept, and the figures he quotes to either support or refute his specific claims on herd immunity?
      Show your expertise rather than the niggled side.

  12. “The first point to make is that cross-reactive T cells were never thought to be the main cause of the herd immunity threshold (HIT)[2] being lower for COVID-19 than the oft-quoted {1 – 1/R0} level, which generally applies for vaccination.”
    Vaccination develops antibody cells [B cells,] it also activates the T4/8 systems. The point being that it is the antibodies that develop in response to a new infection that interact with the virus particles helping block attachment and identifying the virus as a FB which needs to be destroyed.
    The antibody presumably also provides a starting point for the chomping cells to start chomping, without destroying other proteins and components of the surrounding tissue and blood.
    T cells have no place in viral destruction. T4 cells identify and help destroy infected cells stopping belatedly further production and offering the B cell antibodies access to the viral particles to bind with them, inactivate them and hopefully make them indentifiable and capable of being destroyed.
    Activated T cells have no useful purpose or role without an antibody to attack the virus.

  13. Hello, Nic Lewis,
    I have been following your post for some while now. I have found them very interesting. I hope you keep up the great work.
    I have, nontheless a question. I am reading some doctors who say the initial viral content of an infection, doesnt have much impact on its repercusion. Patients may present severe simptoms from mild exposition to the virus, and viceversa. The say this is not specific for COVID-19 but pretty much established in the medical comunity.
    I am no expert in this, so I wonder, have you got any insight on this issue? You mention viral load as a meaningfull variable. ¿Do you have some reference to back it up?
    Thank you, very much

  14. Nic

    Have you seen this very interesting article by Mike Yeadon?

    https://lockdownsceptics.org/what-sage-got-wrong/

    It covers herd immunity and the composition of SAGE which appears to be comprised of people of little direct relevance to the subject they are being asked to advise on

    Tonyb

    • W/r/t the appeal to authority in regard to Ioannidis paper on fatality rate (and no mention of views other well qualified analysts). I have yet to see any response to what seems to me to be sound skepticism.

    • From the article.

      > (which, btw, has always happened)

      How many months have we seen these pronouncements being made? I remember David Young making such pronouncements here a couple of months ago.

      What’s funny to me about these ridiculously certain pronouncements in the face of such vast uncertainties is that it is largely being made by the sane crowd who hide behind uncertainties when the topic of climate change comes up.

      That it also happens from the crowd that ignores the uncertainties in projections in the Covid context, to do things like mischaracterize the IC projections, is only icing on the cake.

      If you know what I’m talking about, Tony.

      • Oops – wrong thing left in the cache. That should have started with…

        > If I am correct, the pandemic is weeks from being completely over and is already done and dusted everywhere south of the Midlands (with the possible exception of Wales

      • Joshua

        Unlike the climate uncertainties that rely on forecasts for events in a century we shall know by the end of November if in effect the virus has blown itself out In the south

        Tonyb

      • I see. Tony. So you’ve worked out all the uncertainties beyond that, eh?

        You know, lots of people thought they had dkne so here also. They told us months ago that the surge in infections was only because of more testing and more young people getting infected. But was over, they said. Before that, they were sure it would die outnjnce it for warm. Disappear by Easter, some said. Some famous ones like Michael Levitt who gets a lot of focus I’m the right wing, libertarian, crowd. Then the deaths went up also after the predicted lag. Most got a bit quite after that. At least for a bit (although it didn’t slow Levitt down one bit). But for others, clearly accountability is clearly no big deal.

        Disrespect Mr. Uncertain T. Monster if you wish, Tony. Me? I’ll wait ’til the fat lady sings.

    • Tonyb
      I’ve now seen that article. What it says about SAGE doesn’t surprise me at all, but I haven’t verified it.

    • I know I am really bad at math because these folks confidently assert that the IFR is 0.2%, and we’d reach a HIT at 20% (if not lower) – and my calculator tells me that would work out to reaching a HIT once we reached 132,000 deaths in the US (0.2% of 66,000,000 infections). And that it happened about 4 months ago.

      Now I know that the theory is that there’s “overshoot” and that deaths don’t just stop when a HIT is reached, but 4 more months of rapid spread and an additional 90k deaths or so (and counting) over four months would suggest to me there something wrong with their logic. And since they’re clearly much smarter than I, there just has to be something wrong with my math.

      For the UK it would mean they reached a HIT at about 27k, five months ago.

      Clearly I am really bad at math.

  15. This is interesting…

    > What we can conclude from this is that SAGE is wrong to rely on percentage seroconversion (antibodies) as a reliable guide to the proportion of the population who’ve been infected. This is a truly dreadful error, one that could not have been made but for the inadequate skillsets of the members of SAGE.

    So after appealing to Ioannidis’ authority, he puts Ioannidis into the group of people whose skills set is so lacking that they’d make such an obvious and “dreadful” error (not to mention Bhattacharya and the whole Santa Clara research team).

  16. I have stated this before but I will repeat it once again. What Nic and all the other covidsceptics do not understand is that there is a fine line between what the health service can handle and when there will be chaos and total collapse. Italy and Spain had these collapses in April / May when otherwise vigorous people died completely unnecessarily due to lack of capacity. In Sweden, they made a brutal choice, people over a certain age who became infected, were put straight on palliative care without even trying IC or respirators. Swedish health workers are exhausted after seven months of trying to achieve herd immunity, while the numbers per. October 16, several months after herd immunity should have been reached in Stockholm, now more than suggests a new round of massive pressure on the health care system.

    What was socially acceptable in 1920 during the Spanish flu, a few years after millions of teenagers had become meaningless victims during World War I, is not acceptable today. And that is among the valuations Nic and other Kovid skeptics do not include in their calculations, or should we say models.

    • It seems your point is that government should closely monitor “hospital utilization” vs “hospital capacity” and have plans to ensure capacity is not exceeded as a result of covid 19.

      In the US this has not been a problem. The problem with US hospitals currently is that many are loosing money due to under use.

    • Rune

      You don’t need to go back to the Spanish flu to observe high death numbers in Sweden . Here are ‘excess’ deaths.

      https://emanuelkarlsten.se/number-of-deaths-in-sweden-during-the-pandemic-compared-to-previous-years-mortality/

      In my lifetime in the Uk I have Lived through some four worse epidemics than today, especially if our expanding population is taken into account . Which is not to say of course that the current pandemic is not serious.

      Arguably flu is more serious as it happens every year and we should therfore be compelled to wear masks etc and take similar precautions to those for covid.

      I am hoping nic can give us an opinion on the link I provided above which seems to be an interesting study in herd immunity

      Tonyb

    • Rune. “vigorous people died completely unnecessarily due to lack of capacity.”
      Vigorous people do not die.
      “In Sweden, they made a brutal choice, people over a certain age who became infected, were put straight on palliative care without even trying IC or respirators. Swedish“

      Brutal, meaning you wish to disparage someone so choose an ugly word?
      Choice of medical treatment always involves making decisions on whom to treat and when to treat.
      In Norway, every day for the last 20 years, doctors and families made decisions to put people on palliative care not because they are brutal Norwegians but a decision had to be made whether it was kinder, more compassionate to stop or withhold treatment given that it would cause pointless pain and suffering to keep them alive.

      It is not a brutal choice, it is a Sophie’s choice, palliation is recognition that in a no win situation one option is much kinder and gentle, easing suffering than the brutal option you espouse.

    • “I have stated this before but I will repeat it once again. What Nic and all the other covidsceptics do not understand is that there is a fine line between what the health service can handle and when there will be chaos and total collapse.”

      Yup
      it does not fail over easy

    • “the numbers per. October 16, several months after herd immunity should have been reached in Stockholm, now more than suggests a new round of massive pressure on the health care system.”

      Where’s your evidence? I haven’t spotted any significant rise in Swedish intensive care admissions, which appears to be the main capacity limit of their health system (Sweden has a far lower number of ICU beds per head than the UK, which in turn has far fewer than some other European countries).

      “Swedish health workers are exhausted after seven months of trying to achieve herd immunity”

      Where’s your evidence? Hospital and ICU COVID occupancy appears to have been low since late spring. And total case numbers were quite low until recently.

      • Steven Mosher

        case numbers increased after you declared herd immunity.

      • Could just be “overshoot.” Looking less likely though. Or maybe the 4 x increase in infection rate will just end. Or maybe it’s just young people who are getting sick and tested (rember when yhey said that when Arizona and Florida and Texas spoked)?

        Or maybe Nic has some herd immunity magic fairy dust and a 4 X increase in cases rate won’t result in increases in hospitalizations. One can always hope so.

      • That said, just took a tour around Worldometers. Cases up dramatically in many countries, but for the most part deaths up only a little in almost all. Maybe something fundamental really has changed.

        And now, there’s this – which independent of the distribution of a vaccine and with the article that ragnaar recently linked really suggests good news and dramatic improvements in treatment going forward.

        https://scitechdaily.com/johns-hopkins-researchers-identify-immune-system-pathway-that-may-stop-covid-19-infection/

  17. The big “Solidarity” international COVID drug study has just reported results – the drugs don’t work. Four treatments were tested:
    remdesivir,
    hydroxychloroquine,
    lopinavir/ritonavir,
    interferon

    None of them improved hospital outcomes in terms of deaths, days on oxygen and recovery time.

    So to date it’s only dexamethasone that improves survival and severe covid19 disease outcome.

    https://www.cnbc.com/2020/10/16/who-remdesivir-has-little-or-no-effect-in-reducing-covid-19-deaths.html#close

  18. An interesting juxtaposition that ice pointed to many times:

    -snip-

    Many of those who have praised Sweden’s “freedom-loving” strategy on coronavirus were the same people aghast at its liberal immigration policy in 2015. Some in Sweden see little to link the two. But for others there are more subtle ties.

    Mr Tegnell told the Financial Times in August that the concerns around both crises may be overblown: “The migration crisis wasn’t really a crisis. We absorbed those people and, of course, we are not the best country in the world in integrating them and, of course, they are still a problem. But it’s not a major problem. The economy went on living. The housing situation did not change very much.”

    -snip-

    Add to that the euthanasia-like healthcare “rationing” and nationalized healthcare that Sweden employed with sick older people to limit spread in their hard-pressed healthcare institutions – that would have the American rightwingers who suddenly love them some Swedish public policy, pearl-clutching about soshlism and “death panels” if any of that was employed here.

    https://amp.ft.com/content/71c8a636-4d40-4d0e-947f-af8de9b6b82c

  19. snip-

    Many of those who have praised Sweden’s “freedom-loving” strategy on coronavirus were the same people aghast at its liberal immigration policy in 2015. Some in Sweden see little to link the two. But for others there are more subtle ties.

    Mr Tegnell told the Financial Times in August that the concerns around both crises may be overblown: “The migration crisis wasn’t really a crisis. We absorbed those people and, of course, we are not the best country in the world in integrating them and, of course, they are still a problem. But it’s not a major problem. The economy went on living. The housing situation did not change very much.”

    -snip-

    • Many of those who have praised Sweden’s “freedom-loving” strategy on coronavirus were the same people aghast at its liberal immigration policy in 2015. Some in Sweden see little to link the two. But for others there are more subtle ties.

      • “…Tegnell told the Financial Times in August that the concerns around both crises may be overblown: “The migration crisis wasn’t really a crisis. We absorbed those people and, of course, we are not the best country in the world in integrating them and, of course, they are still a problem. But it’s not a major problem. The economy went on living. The housing situation did not change very much.”

        -snip-

      • Add to that the euthanasia-like healthcare “rationing” and nationalized healthcare that Sweden employed with sick older people to limit spread in their hard-pressed healthcare institutions – that would have the American rightwingers who suddenly love them some Swedish public policy, pearl-clutching about soshlism and “death panels” if any of that was employed here.

        https://amp.ft.com/content/71c8a636-4d40-4d0e-947f-af8de9b6b82c

        There’s a good quite from tTegnell in that passage also that won’t get past the moderation filter for some odd reason.

      • I hit a paywall on that link, sigh.

  20. Nic:
    “Very sensibly, the Swedish public health authority has surveyed the prevalence of infections by the SARS-COV-2 virus in Stockholm County, the earliest in Sweden hit by COVID-19. They thereby estimated that 17% of the population would have been infected by 11 April, rising to 25% by 1 May 2020.[5] Yet recorded new cases had stopped increasing by 11 April (Figure 1), as had net hospital admissions,[6] and both measures have fallen significantly since. That pattern indicates that the HIT had been reached by 11April, at which point only 17% of the population appear to have been infected.

    How can it be true that the HIT has been reached in Stockholm County with only about 17% of the population having been infected, while an R0 of 2.0 is normally taken to imply a HIT of 50%?”

    Facts: HIT has NOT been reached in

    but

    • Stephen, according to the CEBM, the main reason we are seeing increased “cases” is because of the increased testing, and because the PCR detects the viral remnants – NOT the actual virus itself. These RNA remnants can remain on the body (in airways etc) for weeks even months. So it’s likely the “second wave” is at least partly spurious. People are coming into contact with the virus, and either destroying it themselves, or picking RNA particles from people who have.

      The second part of your post alludes to this, and does not – necessarily – contradict Nic’s assertion that HIT has been reached. The reason is pointed out in Nic’s OP, it depends on how you define “infection”. The PCR test is very sensitive, and is picking up a lot of asymptomatic people. This would be the case with a vaccine as well – vaccines increase resistance, to the point that people who are “infected” can be asymptomatic, but they can still be very mildly infectious.

      What appears to be happening is that the virus is more wide spread than previously thought, but people have been getting low viral loads and developing immunity, and/or they have sufficient natural resistance such that the illness is trivial, and this would qualify as Herd Immunity…at least as Nic puts it “operationally” immune.

      There is only so much the PCR test can tell you. The best indication of HIT is probably through hospitalisation.

      • agnostic –

        > Stephen, according to the CEBM, the main reason we are seeing increased “cases” is because of the increased testing, and because the PCR detects the viral remnants – NOT the actual virus itself.

        The positivity rate is increasing. The tests haven’t gotten more sensitive. Increased testing is likely partially explanatory, but also not fully explanatory as you confidently assert – with no respect for uncertainties.

        Also:

        > An increased concentration of the virus in wastewater, the KTH researchers write, shows a rise of the virus in the population of the greater Stockholm area (where a large proportion of the country’s population live) in a way that is entirely independent of testing.

        https://www.kth.se/aktuellt/nyheter/avloppsvatten-visar-stor-okning-av-covid-19-i-stockholm-1.1016275

        Tegnell says they haven’t reached “herd immunity” status.

        -snip-

        “I think the obvious conclusion is that the level of immunity in those cities is not at all as high as we have, as maybe some people have believed,” he said.

        “I think what we are seeing is very much a consequence of the very heterogeneous spread that this disease has, which means that even if you feel like there have been a lot of cases in some big cities, there are still huge pockets of people who have not been affected yet.”

        -snip-

        https://www.businessinsider.com/sweden-shifts-away-no-lockdown-strategy-amid-growing-case-numbers-2020-10

      • There may be any number of reasons why the rate of hospitalizations and deaths in Sweden have it tracked with the increased rate of infections, as if yet.

        At what point does, say, a huge increase in infections in Stockholm falsify Nic’s assertion a that they reached a “herd immunity threshold” there 5 months ago? In an increase of some 400% over the past few weeks doesn’t do it, what numbers would? Post-hoc rationalizations based on a lack of increase of serous infections doesn’t do it. The “herd immunity threshold” status was based on a theoretical assertion related to rate of infections.

      • Sorry. You did acknowledge some uncertainty. But you also confidently assert a “main reason” (by way of CEBM) that ignores uncertainties.

    • “At what point does, say, a huge increase in infections in Stockholm falsify Nic’s assertion a that they reached a “herd immunity threshold” there 5 months ago? ”

      The point would be when the detections are CONFIRMED as covid, not merely as detections. It’s important to remember that the PCR only detects REMNANTS of the virus NOT the actual virus itself. By concentrating on the detections, it may give an incorrect account of what is really going on.

      Either you need to culture the virus from subjects, or wait to see if there are increasing hospitalisations. There has been an increase (at least in the UK) where ever we have seen second wave, but only a fraction of what we saw in the first wave. So at least some herd immunity – which is never a perfect thing – has been achieved.

      The important thing is to make sure the response is proportionate. No one is proposing nothing be done, but it’s not just lives at stake, it’s livelihoods.

      I have to stress, I don’t see much acknowledgement in these discussions that the PCR test only detects the PRESENCE of viral material – and no acknowledgement that it says nothing about whether the subject was infectious, or ill.

  21. “How can it be true that the HIT has been reached in Stockholm County with only about 17% of the population having been infected, while an R0 of 2.0 is normally taken to imply a HIT of 50%?”

    “The effective reproduction number, Re, sometimes also called Rt, is the number of people in a population who can be infected by an individual at any specific time. It changes as the population becomes increasingly immunized, either by individual immunity following infection or by vaccination, and also as people die.
    Re is affected by the number of people with the infection and the number of susceptibles with whom infected people are in contact. People’s behaviour (e.g. social distancing) can also affect Re.
    Unfortunately, the symbol R0 is often used in publications when Re is meant. This can be confusing.
    Herd immunity
    R0 predicts the extent of immunization that a population requires if herd immunity is to be achieved, the spread of the infection limited, and the population protected against future infection. To prevent sustained spread of the infection the proportion of the population that has to be immunized or have had the infection (Pi) has to be greater than 1 − 1/R0.”

    This is proposing a truly naive population with homogeneous susceptibility and spread and ability to spread.

    “How can it be true that the HIT has been reached in Stockholm County with only about 17% of the population having been infected, while an R0 of 2.0 is normally taken to imply a HIT of 50%?”
    o
    I believe that Nic is stating his ideas on the basis, Mosher, that the population is not homogeneous, not naive, not equally spread and that the spread of the virus is not equal.
    You should know that.
    Hence why his R0 differs from the expected R0.
    And why the Re differs with each scenario.
    Stick to the script, son.

  22. -snip-

    I think the obvious conclusion is that the level of immunity in those cities is not at all as high as we have, as maybe some people have believed,” he said.

    “I think what we are seeing is very much a consequence of the very heterogeneous spread that this disease has, which means that even if you feel like there have been a lot of cases in some big cities, there are still huge pockets of people who have not been affected yet.”

    -snip-

    https://www.businessinsider.com/sweden-shifts-away-no-lockdown-strategy-amid-growing-case-numbers-2020-10

  23. Matthew R Marler

    Right now there is some sort of message developing in the spread of the disease in Brazil, Argentina, Chile, Peru, Colombia and Mexico. Not just the European nations like Spain. Maybe also in India where the disease is spreading at a below exponential but non-negligible rate.

    The US is now conducting about 1.1 million tests per day, with looser exclusion criteria than last winter and spring, and turning up large numbers of positives with very low and (presumably) safe titers. So case counts are increasing faster than death counts (maybe treatments are better as well); death counts are not growing exponentially, but if rate of growth is declining it does not seem to be declining rapidly.

    Next up: what will happen with the onset of cold weather?

    • Where are you getting info on the titers among those who tested positive? Have you seen data on cycle threshold values?

      > Next up: what will happen with the onset of cold weather?

      Indeed. More people in close quarters, at lower humidity and less fresh air circulating, for longer period of time. Can only hope that the apparent trend of divergence in the ratio of infections to hospitalizations and deaths continues.

      • What exactly is an apparent trend?
        Why is it always trending in the opposite way to what we wish or expect?
        Pauses can do the same thing.
        Apparently.
        Perhaps the word apparently can give us a barometer on our unconscious biases.
        I don’t expect the trend to catch on.
        It is food for thought though.
        Apparently

  24. Herd immunity is a ultimately a myth that has been used as a rationale for vaccines. This discussion is moot, thankfully. Herd immunity is off the table.

    First, while the object of study, cross-reactive T cells appear to no functional involvement in either infectivity or pathogenesis of SARS2

    Given the fact that the protective immunity conferred by a SARS2 infection is shorter (< 90d) than the pandemic episode there will always be waves. Witness what is going on in the EU currently. Add to that, sterilizing immunity is not possible, While protected the infected are infectious.

    The Covid-19 is an immunopathology. When Trump was given the cocktail of mono-clonal antibodies, at a time when he slipping into a severe state, he was sero-negative for Sars2 Ab's.

    This should also guide one's vaccine choice. I wouldn't think that one would want the viral genome introduced in any way. But then, no vaccine will perform better that our body's response to a natural infection. The vaccine is a non-starter.

    I am betting on blockers.

    Good luck to us all.

  25. (Ooops and no edit)

    one would NOT want the viral genome introduced

  26. Hospitalizations still in a downward trend:

    https://gis.cdc.gov/grasp/COVIDNet/COVID19_3.html

    • > Hospitalizations still in a downward trend:

      Hmmm.

      Actually, upward trend pretty much in perfect synch with trend of increase in positive tests:

      https://covidtracking.com/data/charts/us-currently-hospitalized.

      Deaths starting to track upward with the predicted six week lag in upward trend in positive testing. This is a repeat of when “conservatives” said that the spike this summer was only due to more younger people getting tested and more peope getting tested ginky to see deaths spike 6 weeks after the positive tests spiked.

  27. Ivermectin, wonder drug for the ages?

    From 2012 onwards, there have multiple reports that ivermectin has antiviral properties [4,5,7,8,9,10,11,12,13,14,15,16,17] towards a growing number of RNA viruses, including human immunodeficiency virus (HIV)-1, influenza, flaviruses such as dengue virus (DENV) and Zika virus (ZIKV) and, most notably, SARS-CoV-2 (COVID-19) [17].

    https://www.mdpi.com/2073-4409/9/9/2100/htm

    • Jim2: Ivermectin is almost certainly not potent enough at inhibiting the growth of SARS-CoV-2 to be useful in treating humans. The data below compare the concentrations needed to inhibit viral replication in a cell culture experiment with the concentrations usually found in the blood after dosing. In the case of Remdesivir, peak blood levels are almost 10X HIGHER than the cell culture IC50 (Concentration the Inhibits growth by 50%) – and Remdesivir is only marginally useful in treating COVID. Likewise Tamiflu and related drugs have IC50’s in at least an order of magnitude lower than than peak blood levels. For drugs that treat HIV, the difference is even larger.

      “Caly et al.10 report a 5,000-fold reduction in SARS-CoV-2 RNA levels, compared with those in controls, after infected Vero/hSLAM cells were incubated for 48 hours with 5 μM ivermectin. The ivermectin IC50 for the virus was calculated at approximately 2.5 μM. These concentrations are the equivalent of 4,370 and 2,190 ng/mL, respectively, notably 50- to 100-fold the peak concentration (Cmax) achieved in plasma after the single dose of 200 μg/kg (14 mg in a 70-kg adult) commonly used for the control of onchocerchiasis.12 Pharmacokinetic studies in healthy volunteers have suggested that single doses up to 120 mg of ivermectin can be safe and well tolerated.13 However, even with this dose, which is 10-fold greater than those approved by the US Food and Drug Administration, the Cmax values reported were ∼250 ng/mL,13 one order of magnitude lower than effective in vitro concentrations against SARS-CoV-2.

  28. So 7-day average in infections in Sweden is up to 809 from 170. Is there any theoretical point where Nic’s assertion of reaching a herd immunity threshold, months ago, is falsified?

    • There are so many unknowns. Those are actually detected infections, not all infections known and unknown.

      • So many unknowns, yes,and yet people declared thst Sweden reached a “herd immunity threshold” dice months ago.

        Respect the uncertainties.

    • Yep. Falsified. It’s toast.

      Actually infections are likely a lot more.

    • As for “detected” infections resulting from testing, wastewater testing indicates an increase in spread recently, also. That’s independent of testing.

      • And from that same study, ICU populations are still down. This rise could be school children going back to school?

        https://www.kth.se/aktuellt/nyheter/avloppsvatten-visar-stor-okning-av-covid-19-i-stockholm-1.1016275

      • > This rise could be school children going back to school?

        Seems to some degree likely. In comparison to Finland it looks like they’ve had more school-based outbreaks.

        But one of the reasons why Sweden shouldn’t be used as an example for other countries like the US is that its probably much easier for Sweden to isolate older people from infected school children (extensive social safety net that helps to provide caregiving alternatives for vulnerable caregivers, low % of multi-generational households, easier for people to work from home – meaning people who do get infected by children in their household are less likely to contribute to community spread), etc.

    • Herd immunity has not yet been reached in Sweden. their policy to minimize impact on their economy made sense

      • Sweden was rather uniquely situated to employ such a strategy. A public that conforms to directives (they reduced activity at similar levels to neighbors), very high % of single-individual households, high standard of living and good baseline health (and low % of comorbidities), high % of people who could work from home, extensive social safety net (funded by extremely high taxes), low % of multi-generational households (and thus low % of primary-caregiver grandparents, etc.

        And yet thwy had many, many more deaths and illness per capita than the most comparable countries. With as if yet, little of any relative economic gain raealized. That might change over time but they don’t appear to be significantly more open at this point than other Nordic countries.

        And meanwhile, depending on the trajectory of a vaccine distribution – they will never equalize pwr capita rates of death and illness even if they have reached “herd immunity.” earlier than other countries.

        But keep putting gi has in the sand and looking at the issue from one side only.

      • We may be looking at the Sweden response through a US societal lens. Euthanasia is legal in Sweden. They may have considered the deaths of the susceptible vs the overall health of the economy and the well-being of the balance of citizens.

      • At what rate do you think herd immunity be reached?

        If hospitals are not being overwhelmed in any particular area why shut down the economy?

      • > Euthanasia is legal in Sweden. They may have considered the deaths of the susceptible vs the overall health of the economy and the well-being of the balance of citizens.

        They only gave limited care (e.g., didn’t even give oxygen) to infected older people in elder care housing – didn’t transport to hospital (to prevent spread). No way that flies here with the conservative (“death panels!!!”) block who are so in love today with SOSHLIST Sweden and “rationing healthcare!!!’

      • Joshua

        I didn’t write that all of Sweden’s policies were perfect.

        You ignore what I asked.

        If the US hospital system in any particular area is not being overwhelmed, why have shutdowns

      • Rob Starkey: If the US hospital system in any particular area is not being overwhelmed, why have shutdowns [?]

      • First, there was significant economic impact in Sweden despite their policies.

        Second, nobody at the moment is advocating shutting down the entire economy nor is that policy being pursued anywhere. If anything in the US, we are following almost the same policy as Sweden. Some reasonable mask wearing requirements and crowd size control is not the same as shutting down the entire economy.

  29. In a small study in San Francisco, Abbott’s BinaxNOW identified infectious people nearly as accurately as a P.C.R. test.

  30. JAMA on excess deaths in 2020, March through August:

    https://jamanetwork.com/journals/jama/fullarticle/2771761?guestAccessKey=3e8d8f2f-d583-44a3-9d53-8b0f57e49df2&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jama&utm_content=etoc&utm_term=102020

    snippet: Of the 225 530 excess deaths, 150 541 (67%) were attributed to COVID-19. Joinpoint analyses revealed an increase in deaths attributed to causes other than COVID-19, with 2 reaching statistical significance. US mortality rates for heart disease increased between weeks ending March 21 and April 11 (APC, 5.1 [95% CI, 0.2-10.2]), driven by the spring surge in COVID-19 cases. Mortality rates for Alzheimer disease/dementia increased twice, between weeks ending March 21 and April 11 (APC, 7.3 [95% CI, 2.9-11.8]) and between weeks ending June 6 and July 25 (APC, 1.5 [95% CI, 0.8-2.3]), the latter coinciding with the summer surge in sunbelt states.

    • Covid-19 deaths no longer correlate with infection but treatment and quality of care. Modulated Dexamethasone administration is attributed to reducing mortality by 30% alone. Antivirals including HQZ, Ivermectin and others as well as Vit D supplementation are reducing severity. Like AIDS, soon enough, no one need die from a SARS2 infection except in the case of extreme comorbidity.

      Covid-19 is an immune pathology that involves the central nervous system with symptoms that may not present well after the initial infection has cleared.

      Our highest priority is stopping the spread of the virus. For too long the epidemiologists have controlled the narrative. It is time we heard from hematology, endocrinology, pathology, gastroenterology and the immunologists. (This is a statement on the compartmentalization of medical research.) If the pubic understood the long term risk of infection articles such as this WUWT would be recognized as irresponsible..

      • Hmm. I’m not sure why you think the article was irresponsible – my take away is that it would be in broad agreement with the rest of your comment. I found both your comment and the article interesting.

  31. 7-day average of infections in Sweden up over 600% during the last 6 weeks.

    Is there any point at which the conclusion, based on theoretical modeling (that failed to account for many uncertainties and confounding variables, btw), that Sweden reached “herd immunity” months ago is falsified? If so, what would be the metric that would falsify it?

    Inquiring minds want to know.

  32. Case rate up 700% in Sweden. Doubled in NYC, reaching a level not seen since the end of May.

    At what point does Nic become conspicuous by his absence?

    • Joe - the non epidemiologist

      Josh – case rate up in Sweden by 700%

      So what ?
      daily death rate still in 1 to 3 per day, except yesterday with 7. Basically exactly what you want to happen. A lot of increase in immunity with virtually zero death

      • > So what ?

        1) The immidate question at hand is Nic’s declaration thst Sweden reached “herd immunity” 5 months ago

        2) illness occurs w/o death.

        3) it’s not clear that after accounting for lags, deaths won’t increase.

        4) related to #3, if the focus is on “protecting the vulnerable,” more infected people makes thst more difficult.

        5) Sweden is uniquely situated to minimize deaths resulting from infections as compared to countries such as the US. As such, Sweden shooting up in their infection rate should serve as a cautionary example for Americans looking to Sweden and touting “herd iinity” as a model we should follow.

        6) (at least in the US) with increases in cases comes increases in hospitalizations which means more pressure on frontline Healthcare workers. You may think “so what” in response to that. I don’t.

        7) with increased infections comes more fear of infection – particularly for the most vulnerable populations. That puts stress on people in a variety of ways. For example, they might be less likely to seek needed medical care. It might make them more likely to isolate, with deliterious effects.

        8) easy for you to say “so what.” A grandparent who is a primary caregiver for their grandchild might not be as cavalier about increases in infections as you are.

      • Sweden’s infection rate really started taking off about 6 weeks ago.

        We are starting to see a rise in death rates here just about 6 weeks after the infection rate started rising again. I don’t know about the lag time in Sweden but that has been pretty consistently the time lag between increases in infections and increases in deaths here in the US.

        I guess since you said “So what” you must know that the lag time in Sweden is shorter than 6 weeks and thus there’s no reason for concern. Would you mind providing a link to your source on that?

  33. CDC finally updated the Covid 19 hospitalization weekly numbers for 10/17. Hospitalizations are way down. These laboratory confirmed numbers are subject to revision.

    https://gis.cdc.gov/grasp/COVIDNet/COVID19_3.html

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