These findings are shared for research purposes and indications for decision makers to help them broaden perspectives and expand understanding until they materialize in a reviewed paper.


Clusters

2.3 Contagion factors

Dissemination Factor (K)

https://cmmid.github.io/topics/covid19/overdispersion-from-outbreaksize.html  shows that overdispersion k is < 0.2 possibly 0.1 and R0 > 1.4  that indicates that 80 % of infections are caused by 10 % superspreaders.

https://wellcomeopenresearch.org/articles/5-67/v1

That means 80 % of secondary transmissions originate from 10 % of superspreaders.

Lloyd-Smith, J., Schreiber, S., Kopp, P. et al.  Explain how this was already the case for sarscov-1. They also remind that for a k value around 0.1 containment maybe obtained at ((1-1/R0)/2). This means that herd immunity is could be obtained depending on R0 value of an outbreak anywhere between 14 % and 39 % of sensitive population in most countries that have been prone to an outbreak. (Analysis of outbreaks explored later on this paper shows us how some countries, regions are somehow very insensitive to respiratory disease outbreaks)

 https://doi.org/10.1038/nature04153

A shenzen study confirms such overdispersion by observing that 8.9 % of cases caused 80 % of infections

 

 

https://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(20)30287-5.pdf

Successfully controlling superspreading may bring such epidemics to extinction as with SARSCOV-1.

 

Social susceptibility

M GABRIELA and M GOMES show how populations are not homogenous in susceptibility, in the sense that « superspreaders » the 10 % are often highly connected individuals and beyond biological aspects they need to be connected to « super spread ». If they are connected they are also more exposed and thus more likely to be infected early and more likely to spread early causing a much higher spread rate in the first phase of the epidemic where they become infected, spread, become immune.

An example would be a bus driver  who sells tickets, maybe more exposed, once infected he may contaminate a few dozen people. After he recovers he  no longer infects anyone. Once most bus drivers have become immune the epidemic slows down.

 This « natural selection » of superspreaders would mean that herd immunity could be as low as 5 % to 35 % depending on R rate which is dependent upon factors that lead to propagation and severity.

https://www.medrxiv.org/content/10.1101/2020.04.27.20081893v3.full.pdf+html

 Based on his paper  N Lewis tests susceptibility notion for Stockholm and reaches a herd immunity estimate between 7 % and 24 % depending mostly on correlation between susceptiblity and infectivity of individuals based on an R0 of 2.4.

https://judithcurry.com/2020/05/10/why-herd-immunity-to-covid-19-is-reached-much-earlier-than-thought/

Carefull analysis across countries, and taking into account that it was shown the virus was present in France since early December 2019 and indications it may have been present possibly weeks or months before, it does seem that R value and severity of this virus may vary significantly.

It may actually have a very low natural Rn that has maintained it active for a long time without being visible. This R value may vary slightly between seasons. The rare severe cases may have been confused with flu, pneumonia or other infections. Its mildness may have maintained it invisible until a set of conditions united for repeated consecutive super-spreading leading to this epidemic and consecutive world panic. 

Although there was a case in France early December, the epidemic was invisible in terms of over-mortality until March 16th and Hospitalizations until March 1st to peak in terms of death week 14 between March 30th and  April 5th as per Insee Data and EuroMomo. This is a combination of a very slow epidemic with an R that could be as low as 1.4 that picks up suddenly with and R that may have tripled when the right conditions of clustering accumulated.

Changes in R and severity maybe associated to changes in populations density, activation of HVAC, multiplications of reunions in closed spaces (ski vacation, occasional holiday gatherings, changes in commuting), presence or absence of competing/multiplying of other pathogens, UVs, vitamin D levels, relative humidity, mucosa, seasonal diet and other factors that have not been identified. Such factors may impact the virus itself or the host in terms of propagation, receptivity, course, symptoms or severity thus in turn impacting contagion and R value.

Clinical observations hint that infections have become milder in Europe. Since there is no indication of any mutation, this maybe because of natural selection mechanisms such as a minor evolution in the virus or that most vulnerable were infected more easily. This is often observed in epidemics towards the end. It may also be because spring or summer make the hosts transmit less viral load or resist better.

 

Association between susceptible and superspreaders would have been very strong if most transmission happenned because of social contacts. This would have taken the bus driver, cashier or the teacher, the waiter, the trainer, the physician, the nurse…. out of the equation very early on.

Much of the  superspreading seems to be related to places discotheques, hospitals, schools, dorms, slaughterhouses, malls, transport, supermarkets…..Workers of such places are more susceptible and more likely to superspread as they spend more time and have more contacts with others in such places. Yet, it could be anyone who spends enough time in such a place. HVAC may make dissemination more complex as it may become random within the place. This reduces impact of  such an association.

Such association remains significant because much of contagion seems to require prolonged exposure and/or significant viral load. A cashier in air conditionned supermarket would  be more exposed and would catch it earlier to pass it on earlier as it would stay longer in the supermarket.  Once most non resistant cashiers of supermarkets have become immune, they no longer contribute to superspreading. Superspreading becomes rarer in supermarkets. A customer may occasionnaly be at  the origin of a cluster but as he spends less time his impact, in most cases would be relatively low compared to the cashier infecting customers all through several days, then infecting other cashiers whom in turn would infect other customers.

A very similar situation would happen with a bus driver, transport salesperson, restaurant waiter, slaughterhouse employee, dorm inhabitant, Mall employee……

 

Sensitivity and resistance

Another significant factor in contagion is Population resistance, that is the presence of a population whom, under normal circumstances would not get infected because of past immunity or other reasons as observed in the past.

Evidence points to that children are less likely to contract the virus and less likely to transmit it. 

 

In addition, in the French aircraft carrier Charles De Gaulle case study, out of a population of 1760 sharing common dorms, common corridors, common cantines for a month, 1043 (59%) were infected, but the other 41% tested negative in spite of having been exposed to the significant viral load repeatedly. This is mostly a male rather young population. It is possible this resistance maybe lower in older population and probably higher in women and children.

 

It is also possible that a higher fraction of the adult population that may be resistant to virus under normal exposure.

 

Part of that protection may be due to genetics, cross-immunity, past immunity or other factors.

 

https://www.theguardian.com/world/2020/jun/07/immunological-dark-matter-does-it-exist-coronavirus-population-immunity

 

https://www.cell.com/cell/fulltext/S0092-8674(20)30610-3

A Griffoni

« we detected SARS-CoV-2-reactive CD4+ T cells in 40%–60% of unexposed individuals, suggesting cross-reactive T cell recognition between circulating “common cold” coronaviruses and SARS-CoV-2. » 

«  Importantly, pre-existing SARS-CoV-2-cross-reactive T cell responses were observed in healthy donors, indicating some potential for pre-existing immunity in the human population. »

 

https://www.medrxiv.org/content/10.1101/2020.04.17.20061440v1.full.pdf

J Braun

« We demonstrate the presence of S-reactive CD4+ 52 T cells in 83% of COVID-19 patients, 53 as well as in 34% of SARS-CoV-2 seronegative healthy donors (HD), albeit at lower frequencies »

https://www.biorxiv.org/content/10.1101/2020.05.14.095414v1

K NG

« we demonstrate the presence of pre-existing immunity in uninfected and unexposed humans to the new coronavirus »

 

 

https://onlinelibrary.wiley.com/doi/full/10.1002/jmv.26098

L Pinky H Drobovolny

« finding that SARS‐CoV‐2 replication is easily suppressed by many common respiratory viruses. According to our model, this suppression is because SARS‐CoV‐2 has a lower growth rate (1.8/d) than the other viruses examined in this study. The suppression of SARS‐CoV‐2 by other pathogens could have implications for the timing and severity of a second wave. »

https://www.biorxiv.org/content/10.1101/2020.06.29.174888v1

T Sekine, A Potti

Importantly, SARS-CoV-2-specific T cells were detectable in antibody-seronegative family members and individuals with a history of asymptomatic or mild COVID-19. Our collective dataset shows that SARS-CoV-2 elicits robust memory T cell responses akin to those observed in the context of successful vaccines, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19 also in seronegative individuals.

Serological antibodies test show inconsistent results both with known cases and comparatively with death counts making them unreliable to indicate protected population. Bergamo and Madrid Serological tests would indicate respectively 0.4 % and 0.92 % lethality whereas Bergamo’s population is older than that of Madrid.

Yet they still give some indication that 14 % to 57 % of hard hit regions have developped antibodies.

 

 

 

Based on above findings, it seems reasonable to assume that a tranche of populations ranging between 44 % and 70 % is resistant to the virus or protected from it and is unlikely to be contaminated and under normal or even severe exposure to the virus because of genetics, epigenetics, cross immunity, cellular immunity, T cells….

 

We are assuming based on existing history of cases, existing literature and usual reaction to other Corona Viruses  that those who recover become immune and either fully protected or retain some memory protection making new infections milder, shorter thus less contagious.

 

Clusters

Flu-like epidemics tend to propagate in clusters and this has been shown to be true for COVID as well in recent papers :

 

https://www.medrxiv.org/content/10.1101/2020.04.04.20053058v1.full.pdf  investigated 318 outbreaks involving 3 or more cases, all were indoors mostly home and transport.

https://www.medrxiv.org/content/10.1101/2020.02.28.20029272v2.full.pdf shows that closed environments promote contagion and superspreading 18.7 times more than open environments.

 

Epidemic clusters have been identified involving closed places with people gathering with little air circulation such as transport, worship places, slaughter houses, companies, hospitals, care facilities, police stations etc. On a more general level, major cities (London, New York, Paris, Madrid, Milan etc) with factories, air conditioned offices, dense public transport, regular social and religious crowded events offer higher superspreading opportunities than medium cities or rural areas where  the epidemic un-noticed when no superspreading happened

 

R A. HOBDAY provides an interesting view as to fresh air and sunshine hospitals mitigating contagion and even helping recovery

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504358/

« Records from an "open-air" hospital in Boston, Massachusetts, suggest that some patients and staff were spared the worst of the outbreak. A combination of fresh air, sunlight, scrupulous standards of hygiene, and reusable face masks appears to have substantially reduced deaths among some patients and infections among medical staff. » 

Y Li systematic review teaches us about effect of ventilation on airborne transmission

https://pubmed.ncbi.nlm.nih.gov/17257148/

« There is strong and sufficient evidence to demonstrate the association between ventilation, air movements in buildings and the transmission/spread of infectious diseases such as measles, tuberculosis, chickenpox, influenza, smallpox and SARS. »

Recent manifestations across the world in countries with tens of thousands of people gathering with close contacts in a very restricted open air space with few masks did not lead to cluster formation in spite of massive testing further confirming contamination happens indoor. Melbourne manifestation is particularly interesting as Melbourne is entering winter and Australia is tracing regularly and has to this date managed to keep virus under control.

 

Most identified clusters happenned in :

 

Health Care facilities or Hospitals

Slaughter houses

Schools

Hotels

Social facilities

Discotheques

Subway/Metro

Buses

Companies

Worship places

Family reunions

Gyms

Call centers