1 

  
 

 

 

 

 

 

 

 
Citation: L. Corbetta, L. M. Fabbri, D. 

Cavalieri, P. Bonanni, A. Mantovani, B. 

Thompson, F. Luo (2021) Stand on the 

Same Side Against Covid – 19: Scientific 

Evidence on Vaccine for Covid-19. 

Substantia 4(1) Suppl. 1: 1233. DOI: 

10.36253/Substantia-1233 
 

Received: Feb 04, 2021 
 

Revised: Mar 09, 2021 
 

Just Accepted Online: Mar 09, 2021 
 

Published: Mar 09, 2021 
 

Copyright: © 2021 L. Corbetta, L. M. 

Fabbri, D. Cavalieri, P. Bonanni, A. 

Mantovani, B. Thompson, F. Luo. This is 

an open access, peer-reviewed article 

published by Firenze University Press 

(www.substantia.net) and distributed 

under the terms of the Creative 

Commons Attribution License, which 

permits unrestricted use, distribution, 

and reproduction in any medium, 

provided the original author and source 

are credited. 
 

Data Availability Statement: All rel- 

evant data are within the paper and its 

Supporting Information files. 
 

Competing Interests: The Author(s) 

declare(s) no conflict of interest. 

Firenze University Press 

www.fupress.com/substantia 

 
 
 
 
 
 
 

Webinar 

Stand on the Same Side Against Covid – 19: 

Scientific Evidence on Vaccine for Covid-19 
 

 

 

This document is the direct transcription of a Webinar organized by Prof. L. 

Corbetta of the University of Florence on December 10th, 2020. 

 

 

 

Scientific coordination: 

Lorenzo Corbetta 

Associate Professor of Respiratory Diseases - University of Florence 

Scientific and Website Director of the European Association for Bronchology and 

Interventional Pulmonology (EABIP) 

 

Organizing Secretary: 

Consorzio Futuro in Ricerca 

Via Saragat 1 – Corpo B – 1° Piano | 44122 – Ferrara 

cfr@unife.it 

 

Translation Coordination and Editing: 

Giorgia Biagini, MD 

info@covid19expertpanel.network 

 

Webinar’s partecipants: 

Prof. Lorenzo Corbetta - University of Florence 

Prof. Leonardo M. Fabbri – University of Modena and Reggio Emilia 

Prof. Duccio Cavalieri - University of Florence 

Prof. Paolo Bonanni - University of Florence 

Prof. Alberto Mantovani - Humanitas University of Milan 

Prof. Bruce Thompson - Swinburne University of Technology 

Prof. Fengming Luo - West China Hospital, Sichuan University 

 

 

Corresponding author: lorenzo.corbetta@unifi.it 

 
 

 
 
 

 

 

 

Substantia. An International Journal of the History of Chemistry 4(1) Suppl. 1: 1233, 

2020 ISSN 2532-3997 (online) | DOI: 10.36253/Substantia-1233 

http://www.fupress.com/substantia


L. Corbetta et al. 
  

 2 

 
“STAND ON THE SAME SIDE” Videoconferences 

 

https://www.covid19expertpanel.network 

 

“Implementing a science-based lockdown exit strategy is 

essential to sustain containment of COVID-19. China’s 

experience will be watched closely, as other countries start 

considering—and, in some cases, implementing—their own 

exit strategies” 
 

The Lancet, Volume 395, Issue 10232, 18–24 
April 2020, Pages 1305-1314 

 

This phrase expresses the purpose of this program called 

“Stand on the Same Side against Covid-19” that takes 

advantage of the new and rapid digital technologies to put 

together several experts worldwide. It’s a global space were 

many countries hit by SARS-COV-2 can share only 

scientific information in order to face the pandemic. 

 

December, 10th 2020 

 

“STAND ON THE SAME SIDE AGAINST COVID – 

19: SCIENTIFIC EVIDENCE ON VACCINE FOR 

COVID-19” 

 

Lorenzo Corbetta:  Good afternoon, welcome to the first 

webinar on the educational project for medical 

practitioners called Stand on the same side against COVID-

19. The proposal of this programme is to take advantage of 

the new rapid digital technologies to put together several 

experts worldwide. It's a shared space where many 

countries hit by SARS-CoV-2 can share only scientific 

information in order to face the pandemic. Today, we will 

focus on scientific evidence on vaccines for COVID-19. I 

would like to express my deepest thanks and gratitude to 

the panel of experts who accepted the invitation to speak 

today. First of all, I would like to introduce my co-

chairman and mentor, Professor Fabbri. Please, Professor 

Fabbri.  

 

Leonardo M. Fabbri:  Thank you, thank you all. I think 

that this is a very interesting and informative initiative that 

goes on for several months and thanks to Lorenzo Corbetta 

for organising it. Without further ado, I'd like to ask him to 

introduce the first speaker.  

 

Lorenzo Corbetta:  Thank you. Please join me in 

welcoming our first speaker, Professor Paolo Bonanni, 

who is a Professor of Public Health at the University of 

Florence, and his topic will be the point on the vaccines.  

 

Paolo Bonanni:  Okay, thanks a lot Professor Fabbri and 

Professor Corbetta. It's a pleasure to be invited again to this 

very important webinar, and I will try to give you some 

highlights on the current status of COVID-19 vaccines. Of 

course, it's a big topic and it's difficult to give you all the data 

that is coming from the research in this moment, but I will 

try to make a summary. Of course, it might be different, but 

I will try my best. So, we are waiting to have a solution to 

this big, big issue of the pandemic at the world level, and we 

are all waiting of course for a COVID-19 vaccine or more 

COVID-19 vaccines. What should we ask of a COVID-19 

vaccine? First of all, safety and efficacy, effectiveness. We 

will see the effectiveness in the coming months when 

vaccines will be applied in a large scale mass vaccination 

programme. The second question is how many doses do we 

need? Up to now, we have vaccines that will be used mainly 

with two doses, but there might be some vaccines that could 

require only one dose. Available since? We know that in the 

UK for instance they started very recently, and in other 

countries, they also started with the different vaccines, but 

we should have vaccines available in all countries from the 

beginning of next year. Then, also, a big problem is the 

logistical needs and the cold chain requirements for the 

vaccines that are coming first. So, what do we know today? 

So, what are the known concepts about vaccines and 

immunity? Of course, there will be the presentation of 

Professor Mantovani after mine that will highlight these 

issues, but anyway. Coronaviruses SARS and MERS induce 

an antibody response, and we don’t know how long it lives. 

So, is it a short-lived or long-lived antibody response? 

Studies on mice suggest that T lymphocytes have an 

important role in protection. So, even if antibodies are no 

longer present, there might be a role for T lymphocytes. 

There is a possibility and there is a risk of antibody-

dependent disease enhancement, which is possible, but up to 

now all vaccines have been studied for this potential threat 

and none of them was shown to have this kind of problem, 

although we will have to monitor this situation in the future. 

 

     The other known is that infected subjects may remain 

positive for many weeks. Probably not knowing that we would 

experience such a dramatic pandemic in 2017, the Coalition 

for Epidemic Preparedness Innovation, also called CEPI, was 

created with the aim to prompt the development and stocking 

of vaccines against diseases that may cause dreadful 

epidemics. So, in a way, the big leaders in the world already 

forecasted that there might be such a dramatic situation like 

we are experiencing today. So, with an investment initially of 

$2 billion for this purpose. I would like to go back to this paper 

that I already presented in a previous presentation, but I think 

that this still remains a paper that gives us a good light on what 

are the expected issues to be solved while developing a 

vaccine. So, what are the main challenges for the development 

of a SARS-CoV-2 vaccine? First, define what is protective 

immunity. So, can we find a correlate of protection? Up to 

now, no, but we should strive to find one if possible. The 

duration of immunity, of course, is never known at the 

beginning of vaccine development, but we have to monitor 

and to study this duration. 

https://www.covid19expertpanel.network/


Stand on the Same Side Against Covid – 19: Scientific Evidence on Vaccine for Covid-19  

 3 

Then, we have variable endpoints for the concept of efficacy. 

Are we speaking of protection from infection? Or reduction 

of viral replication or reduction of number of diseases? These 

are different concepts. Of course, in the first phases we have 

verified the ability of vaccines to avoid the diseases but we 

should also study if they can avoid transmission of infection 

from vaccinees to the other population. Then the role of 

neutralising antibodies and T cells. The difficult 

understanding of the real incidence of infection, how many 

people are symptomatic or asymptomatic, and this makes 

things more complicated for us in public health. Then, the 

creation of independent labs with identical validated 

serological tests to confront different candidates and 

different clinical trials. Every vaccine producer is developing 

vaccines according to their own tests, their own protocols, 

but we should try to have a common denominator, a common 

lab that could also make comparisons among the different 

vaccines. 

 

     Then there is the big issue of also from the ethical point 

of view of human challenge trials. Are they useful and 

ethically acceptable or not? Then also we have to monitor, as 

I said before, the immune enhancement risk, but I don’t want 

to go into more depth on this. So, when we decided to start 

this enterprise and to study these new vaccines, I showed this 

slide already in July, but I have added some concepts. So, we 

must pay attention to vaccine safety, we cannot run the risk 

of approving a vaccine which has not undergone all possible 

scrutiny of safety, because we could endanger the perception 

of all vaccines for the population. But, today, I would add 

that as a matter of fact, the preclinical development and the 

regulatory evaluation phases of submitted dossiers were 

accelerated, but the clinical trials involved the same numbers 

of volunteers and study phases as for all other traditional 

vaccines. So, we sped it up, but not the phases that are crucial 

for evaluation of safety and efficacy. We sped up the 

preclinical development, we are speeding up the regulatory 

verification of the data, but not the data themselves. So, this 

should make us confident that what we have available today 

has undergone the same evaluations as for traditional 

vaccines. The target for our vaccines is the spike protein 

which binds to the ACE2 receptor as we all know. And as of 

the day before yesterday, so December 8th, the coronavirus 

vaccine tracker tells us that we have thirteen vaccines in large 

scale efficacy trials. We have overall 58 candidates in clinical 

trials, and 86 candidates in the preclinical phase of 

development. As we know, the DNA and RNA vaccines are 

the ones that are closer to approval and especially the RNA, 

messenger RNA vaccines which include vaccines that have 

an mRNA encoding for the spike protein encased in a lipid 

coat so that they can enter the cell. And the two candidates 

that are closer or have already started to be administered are 

the ones from Pfizer and BioNTech and the one from 

Moderna. So, regarding the Pfizer BioNTech, the proposed 

indication is for an active immunisation for the prevention of 

COVID-19 caused by SARS-CoV-2 in individuals of sixteen 

years and older, with two doses at least 21 days apart. 

The primary efficacy endpoints are the incidence of COVID-

19 in participants without serological or virological evidence 

of past SARS-CoV-2 disease. The first primary endpoint, but 

also a secondary endpoint, also in those who already had an 

infection, with evidence of past SARS-CoV-2 infection. 

Yesterday, there was an announcement from Pfizer that said 

that the second generation vaccine should be developed soon 

over summer. The aim is to make the cold chain requirements 

less stringent because you know that this vaccine has to be 

stored at minus 75 or minus 80 Celsius. These are the results 

that were published in July with the preliminary result in 

phase one, in 45 healthy adults, where they gave the two doses 

one month apart, and the conclusions of this preliminary 

report were that neutralising antibodies were detected in all 

participants, which is good news also in terms of possibility 

to prevent infection, and not only the disease. Also an 

acceptable safety profile. Regarding the Moderna vaccine, 

these are the studies of safety and immunogenicity of this 

vaccine in older adults, and the conclusions of this study 

published in the New England Journal of Medicine are that in 

this small study involving older adults, adverse events 

associated with this vaccine were mainly mild or moderate. 



L. Corbetta et al. 
  

 4 

The 100 microgram dose induced a higher binding and 

neutralising antibody titres than the 25 micrograms, so this 

supported the 100 micrograms continuation of studies. 

Regarding the phase three of these two vaccines based on 

mRNA technology, both of them are double blind 

randomised efficacy trials, with inclusion of 30,000 

participants for Moderna and 45,000 for Pfizer. The two 

doses are given four weeks apart for the Moderna vaccine 

instead of three weeks apart for the Pfizer vaccine. The 

participants are constantly monitored to evaluate if they 

developed COVID-19 symptoms and if they tested PCR 

positive. Also, the possible safety signals are carefully 

monitored. There is a predetermined number of cases that 

should occur before the study can go to an evaluation which 

is, for a 60% theoretical efficacy, this was 151 cases for the 

Moderna vaccine and 164 for the Pfizer vaccine. 

 

     So, these are the results that were made available very 

recently for the Pfizer vaccine, which shows that in all 

participants we have a 95% vaccine efficacy in preventing 

confirmed COVID-19 occurring at least seven days after the 

second dose of the vaccine. So, there was a striking 

difference in the occurrence of COVID-19 in the placebo 

compared to the study group which received the mRNA 

vaccine in this study. The safety was studied in 

approximately 38,000 participants over 16 years, and there 

was no major signal of safety concern. Of course, there was 

no signal of vaccine enhanced disease but we have to 

evaluate further this aspect when the vaccine will be 

distributed and administered to a large population of 

subjects. What is the news from the European Medicine 

Agency, the EMA? On December 1st they announced that 

they were starting rolling the review for one vaccine that is 

the COVID-19 adenoviral vaccine based from Janssen. There 

is not yet a deadline here, but for the two vaccines that are 

based on mRNA, you see here that they received the 

application for conditional marketing authorisation both for 

Moderna and for the BioNTech vaccine. They foresee to 

conclude their assessment by 12th January, at least, at the 

latest for the Moderna vaccine and by 29th December (EMA 

has recommended granting a conditional marketing 

authorisation for the vaccine Comirnaty, developed by 

BioNTech and Pfizer, to prevent coronavirus disease 2019 

(COVID-19) in people from 16 years of age 

https://www.ema.europa.eu/en/news/ema-recommends-

first-covid-19-vaccine-authorisation-eu) for the Pfizer 

BioNTech vaccine at the latest. So, this is the status in 
Europe, and especially in the UK. So, the vaccine appears to 

be safe, these are the evaluations of the UK Public Health. 

The vaccine appears to be safe and well tolerated, and there 

were no clinically concerning safety observations. So, the 

community advises that the vaccine should be used in the 

first phase of the programme according to a priority of 

groups. Of course, healthcare workers, elderly people, and 

people with chronic diseases that are discussed further in this 

slide. So, the Joint Committee on Vaccination and 

Immunisation, so the body that, in the UK, gives advice on 

the use of vaccines, they advised that at the start of the 

vaccination, there will be no definitive reply according to the 

ability of the vaccines to prevent transmission. 

     Regarding the two vaccines that will be the first probably 

to be used in the UK, they say that for organisational ease, 

since the Pfizer vaccine should be given at least 21 days apart 

and the AstraZeneca vaccine 28 days apart, they will probably 

go for the 28 days for both vaccines to make the organisational 

issues and the administration of a second dose easier from the 

logistical point of view. Of course, there is also the issue, if 

you have to complete a vaccine course and you started with 

the vaccine but the same vaccine is not available for the 

second dose, and they advise is, if possible, you should 

complete the vaccination with the same vaccine, but if not 

possible, all vaccines are producing S proteins, you should 

complete the vaccination with the available vaccine 

irrespective of this problem if there is nothing else to do. 

Regarding other vaccines, I mentioned the DNA vaccines, this 

is still the data from the preclinical studies on rhesus 

macaques for the DNA vaccine that was produced by the Beth 

Israel Deaconess Medical Center at the Harvard Medical 

School in Boston with the collaboration of Janssen. Here, they 

show that vaccinated animals had developed humoral and 

cellular immune response including neutralising antibodies 

with titres comparable to those found in convalescent humans 

and macaque serum. And that the viral load was decreased 

both in the lower but also in the upper respiratory tract. 

Regarding the adenoviral vaccines, we know that regarding 

the vaccine from AstraZeneca, the vaccine induces a robust 

humoral and cell-mediated immune response in mice, and in 

vaccinated macaques virus-specific neutralising antibodies 

are detected. After challenge, there was a significant reduction 

of viral load in the lower respiratory tract in vaccinated 

primates, while no difference was found in the viral load in 

the higher respiratory tract. We must say that the viral load 

that they gave for this challenge was a very high dose, so we 

don’t know if this resembles or not the natural infection as it 

occurs in nature. 

 

     However, the vaccine was very efficacious in preventing 

pulmonary damage with this high challenge dose, and no 

signal of immune-enhanced disease was revealed and 

detected. So, we know that also for this vaccine there is a big 

phase three trial over 30,000 participants. There was a stop in 

this vaccine, and this should be seen as a signal of attention to 

the possible association of side effects to the vaccine, and 

when the adverse events following the vaccine were ruled out 

as to causality, the phase three trial started again with no 

problem. AstraZeneca announced recently on November 23rd 
that they had a higher efficacy when they gave the first dose 

with a half dose compared to the two full doses, and this was 

reported recently, 2 days ago, in The Lancet with a study 

where they showed that for those who received the two full 

doses, the efficacy against clinically significant disease was 

62%, while in those which were younger, however, who 

received half a dose with the first dose and a full dose for the 

second dose, the efficacy was 90%. 

(https://www.thelancet.com/action/showPdf?pii=S0140-

6736%2820%2932661-1)  

So, now there should be some extra study to evaluate and to 

understand why there was such a difference. We have also the 

https://www.ema.europa.eu/en/news/ema-recommends-first-covid-19-vaccine-authorisation-eu
https://www.ema.europa.eu/en/news/ema-recommends-first-covid-19-vaccine-authorisation-eu
https://www.thelancet.com/action/showPdf?pii=S0140-6736%2820%2932661-1
https://www.thelancet.com/action/showPdf?pii=S0140-6736%2820%2932661-1


Stand on the Same Side Against Covid – 19: Scientific Evidence on Vaccine for Covid-19  

 5 

adenoviral vaccine by Johnson and Johnson, which is 

involving 60,000 participants in phase three trials. This is 

also the one which is under evaluation. The interesting thing 

for this vaccine is that also this was stopped, but the 

interesting thing is that this might require one dose only 

instead of two. This has to be evaluated, but this would make 

vaccination courses much easier if it is confirmed that only 

one dose is needed. Then we have the adenoviral vaccine 

from China, from CanSino, 40,000 participants, a very 

interesting vaccine too. Concerning the inactivated viral 

vaccine, we have two candidates, Sinovac phase three and 

Sinopharm phase three. This is the data from Sinovac, the 

preclinical data where they showed that they induced a high 

level of neutralising antibodies. Sorry, I couldn't translate 

this, it's in Italian. Anyway, the neutralising antibodies for 

this vaccine seem to be very high and very constant in all 

vaccines 

https://jamanetwork.com/journals/jama/fullarticle/2769612 

      

     Then we have the vaccine from Sinovac and the 

conclusion of this preliminary communication is that they 

authors report a good tolerability profile in the absence of 

serious vaccine-related side effects, and more than 97% of 

participants seroconverted in terms of neutralising 

antibodies. I will go quickly to the last part of my 

presentation. We also have a potential protein-based vaccine 

in subunits or virus-like particles, but we are lagging a little 

bit behind with these vaccines. We also have other 

approaches like the pathogen-specific artificial antigen-

presenting cells, that could be sensitised and stimulated with 

viral structural proteins. But also, pathogen-specific 

autologous antigen-presenting cells that could be taken by 

plasmapheresis, charged with the S proteins, and reloaded in 

the same subjects, an individualised approach to vaccination. 

The last slide, again, we speak of the issue of human 

challenge trials. So, in the UK, they say 'Dozens to be 

deliberately infected with coronavirus in the human 

challenge trials', is this feasible, is this useful, and is this 

ethically acceptable? The questions are open for discussion. 

The UK also highlighted the problem with the logistics, 

especially with the Pfizer vaccine which requires minus 75 

or minus 80 degrees, so this is a challenge for the logistics. 

We have to vaccinate many people at the same time, when 

you open the box containing the vaccine, that must be used 

within a few hours from opening it. I would like to finish with 

two or three slides, but the last two are very quick. These are 

my conclusions, in a way. What are the prominent problems 
and opportunities in the development and availability of 

COVID-19 vaccines? The development process of safe and 

effective vaccines against COVID-19 has been sped up. The 

urgency to contrast the pandemic never impacted on our first 

aim when we develop a vaccine. In Latin, it's primum non 

nocere, for those who do not know Latin, it means first, do 

no harm. We needed to be extremely stringent on safety and 

we are all, not the damage the credibility of SARS-CoV-2, 

but also all other traditional vaccines. 

 

     Strategies of use of COVID-19 vaccines will depend on 

the expected effect of each product. A vaccine against 

disease only will be targeted to healthcare workers, the elderly 

and subjects of any age with chronic diseases, but a vaccine 

able to prevent also the infection could also be used in those 

responsible for the spread of infection, maybe in 

schoolchildren, young adults and adolescents, and might be 

crucial in obtaining the community protection. I prefer 

community protection compared to herd immunity effect. Just 

to finish, also in the USA, they highlighted how in the first 

phase when few courses are available, we must prioritise 

adults aged 65+, adults with high-risk medical conditions and 

health care workers, and only after we can go to the other 

groups of the population. This is the final. So, when there are 

limited doses available, highly targeted administration is 

required to achieve coverage in priority populations. Then, 

when a larger number of doses are available, we should 

enlarge this to the other populations, non-healthcare critical 

workers, people in congregate settings and all other older 

adults. Finally, when many doses are available, all the other 

population that could impact on infection transmission at the 

population level. With this, this is my email for those who 

want to write to me for further discussion. I thank you very 

much for your attention.  

 

Leonardo M. Fabbri:  Thank you Professor Bonanni, I'm 

pleased to introduce now the second speaker, Professor 

Alberto Mantovani, who is Emeritus Professor of Pathology 

and Scientific Director at Humanitas Milano institution. The 

title of his presentation is Immunity and vaccines, scientific 

and sharing challenges. Thank you.  

 

Alberto Mantovani: So, good afternoon, and I would like to 

thank Leo and Lorenzo for the pleasure to be with you and 

Professor Paolo Bonanni for a fantastic talk. We have really 

touched only one selected aspect of vaccines. So, this is the 

virus and this is a picture of the virus prepared by three of my 

grandchildren, and when we were confronted with the virus, 

we were brought back to our culture in the Western world, 

Greek culture, and I know that we don’t know, that was my 

feeling.  

     Together, I am going to share with you some of the 

progress that we have made in the understanding of the 

interaction of the virus with the immune system. I'll also draw 

your attention to this website of the National Academy of 

Science of Italy, Accademia Dei Lincei, where Guido Forni 

and I have updated our understanding of vaccines. Naturally, 

we are going to release the December report. So, here is an 

attempt to summarise the natural history of COVID-19. 

https://jamanetwork.com/journals/jama/fullarticle/2769612


L. Corbetta et al. 
  

 6 

 

 

The virus, in terms of vaccine, we should not forget that there 

may be the possibility after introduction of the virus of the 

appearance of escaping variants. So, we should be prepared 

for that. And interaction with the host, and the end result of 

the interaction with the host is dictated by viral load. We had 

summertime of course, ageing, there is a general paradigm 

related to the tone, inflammatory tone in relation to ageing, 

inflammageing, lifestyle, obesity for instance, and genetics. 

I would like to comment on genetics because we have 

contributed to the field, we did I think one of probably the 

first genetic analyses of the Italian population, and then we 

were part of a European effort. I want to emphasise that in 

this European effort, we found that chromosome genes 

located on chromosome three, and these genes include 

chemokine receptors, and I’ve long been interested in 

chemokines and my laboratory was one of the groups that 

discovered chemokines. Chemokine receptors are there, 

inflammation. In the same in this Manhattan plot, you can 

also see blood group. 

 

     I'm aware of work in the UK that again points to this, to 

chromosome three and this region of chromosome three. So, 

downstream of the interaction and genetics of course, there is 

innate immunity, the directors of the immunological 

orchestra, T cells and B cells in production of antibodies and 

plasma therapy. I would like to emphasise that, again, what 

Paolo already said, we don’t have standards, we don’t have 

standards for measuring antibodies. We don’t have standards 

for measuring neutralising antibodies or standards to measure 

T cell activity as we I should emphasise that in three 

controlled trials, plasma, hyperimmune plasma therapy has 

failed. There may be good reasons, a long time in the natural 

history of the disease, and in addition, hyperimmune plasma 

contains many things and I will get back to that. Of course, 

downstream is uncontrolled cytokine release syndrome, 

macrophage activation, involvement of the microvascular bed 

in the lungs, and uncontrolled inflammation, including a new 

disease, multi-inflammatory syndrome see for children, as a 

late consequence of infection. So, this is an early study that 

we did, starting in April.  

(https://doi.org/10.1101/2020.05.24.20111245) 

 

     We are monitoring a population of 4,000 people in our 

community and this is the Bergamo region with high 

prevalence of seral positivity. Interestingly enough, and we 

were discussing this before the meeting and it's hard to dissect 

whether this is some hint, the lower disease burden in this 

region now may in part reflect previous exposure, as well as 

better behaviour, having been so dramatically affected by the 

first wave. Therapy: well, the only therapy proven to change 

mortality is glucocorticoids. Dexamethasone in the early 

study done by Hornby et al., published in The Lancet, NHS 

UK, and this has now been confirmed in larger studies and my 

research according in our own institution was part of this. So, 

this is pretty solid. Let me voice a concern I have. Based on 

what I hear, and what I hear in my hospital. 

 

     I keep hearing of patients admitted to the hospital and 

treated with glucocorticoids at the early stages of the disease. 

We should emphasise that the evidence in this study, in the 

Hornby study, shows benefit of glucocorticoids in a well-

defined window, when there is need of oxygen, let's simplify 

things a little bit. Outside of that window, if anything, there is 

a hint, and there was a recent opinion written by Tony Fauci 

published in JAMA, and again he was concerned about 

inappropriate usage of glucocorticoids by practitioners 
outside of the window of efficacy of these agents. The virus 

interaction-, let me go back to the first interaction of the virus, 

it interacts with innate immunity, the cellular arm of innate 

immunity, macrophages, myeloid cells and the humoral arm 

of innate immunity complement, and I will get back to that in 

a moment. Early on, some of us hypothesised that there should 

be, based on previous evidence on SARS, a mechanism 

whereby the virus blocks this pathway of resistance. These are 

two studies, done under the leadership of NIH with 

contributions from several hospitals in Northern Italy. Jean 

Laurent Casanova at NIH and Gigi Notarangelo again, at NIH. 

So, there are in-borne errors of the pathway leading to the 

https://doi.org/10.1101/2020.05.24.20111245


Stand on the Same Side Against Covid – 19: Scientific Evidence on Vaccine for Covid-19  

 7 

production of type one interferon, so hidden 

immunodeficiency accounts for severe diseases in a fraction 

of the patients. In addition, in other patients, there are auto-

antibodies directed against and blocking the same interferon-

dependent pathway of resistance to viruses. I should say that 

in part  it has also been shown that autoantibodies, for 

instance, similar to the antiphospholipid syndrome 

autoantibodies appear in patients, and are likely to play a role 

in thrombosis, which is a major problem in these patients. So, 

I would summarize that this may be one of the reasons why 

hyperimmune plasma therapy didn't work. So, the emerging 

picture is that COVID-19 actually displays that interception 

between autoimmunity as I mentioned, genetic 

predisposition, chromosome three, immunodeficiency up 

here, and uncontrolled inflammation, and I want to discuss 

some work that we have done on uncontrolled inflammation. 

 

     So, we have long been interested in pathways of innate 

immunity, including the humoral arm of innate immunity and 

many years ago we cloned a molecule, cloned a mouse gene 

and human CDNH genomic. It's a distant relative of C 

Reactive protein, and it has functions, there is genetic 

evidence that it is important for resistance against selected 

microbes in humans including fungi, and it behaves as a 

functional ancestor of antibodies. So, we have been 

dissecting innate immunity in the patients, in our hospital, 

and we have been collaborating with Alessandro Rambaldi 

at Giovanni XXIII Hospital in Bergamo. This is an analysis, 

and among the genes that popped up in this analysis, PTX3 

was prominent. 

(https://doi.org/10.1038/s41590-020-00832-x) 

 

Then, we looked at Bronchoalveolar lavage fluids, we looked 

at adaptations, we looked in silico at patients in Israel and the 

United States. The take home message is that in peripheral 

blood, as well as in lungs, myelomonocytic cells are a major 

source of this protein. And in autopsy examples, the 

molecule is there, it's there in the lungs, and it's there for 

instance in vascular cells surrounding a clot. So, we then 

measured with a high-cost sophisticated technology.  

 

     These are the results of our cohort, 96 patients and as you 

can see, it turns out-, and the endpoint here is a hard endpoint, 

death at 28 days, and it turns out to be an independent, and I 

will accelerate a bit, an independent risk factor for death. 

Apparently, better than anything else, and the same results 

were obtained in an independent cohort in Bergamo. I'm 
aware of a third study with identical results to those that are 

shown here. So, this is the take home message. We need 

biomarkers. We need to dissect the diversity of the disease, 

and tailor therapy to patients based on genetics, 

autoimmunity and degree of inflammation with biomarkers 

predicting outcome. This is our contribution stemming from 

our own work, PTX3. In terms of mechanism, we assume 

that this molecule-, we have evidence actually that it is 

involved in microbe recognition, regulation of compliment 

activation and regulation of inflammation, and this is again 

the Kaplan-Meier work. 

 

     I should mention that the main people here were Brunetta, 

Folci and Bottazzi in my lab. So, vaccines. I will not repeat 

what Paolo said, absolutely, so clearly. It has been depicted as 

a race and it is a race, but it's a peculiar race because it's not 

so important to get there first, but it's important to get well at 

the end of the race. This is where the race is actually a 

marathon, and we should not forget that the data that we have 

seen referred to two months after the second administration of 

the vaccine. Paolo has already gone through the various 

platforms that are used to generate vaccines and we have a 

review coming out with (mw 41.39) and I, and again I direct 

you to the website of the Accademia dei Lincei where you can 

find references and a summary. This is the adeno in the paper 

that again Paolo already beautifully commented on. So, this is 

a painting from a painter called Ligabue. This painting 

conveys a message, and the message I think is from polio. We 

may live in a polio-free world, a couple of months, three 

months ago, Africa was declared free of wild type polio and 

this amazing result was obtained thanks to two vaccines which 

have been used in a complementary way. In addition to living 

in a polio-free world, we need a third vaccine, I will not be led 

by the point. So, I feel that it is very important that we have 

an array of vaccines available, and I'm very worried about 

clinical trials now based on the conditional approval and 

emergency approval. I am worried and this may be a point of 

discussion. How are we going to have people enrolled in 

clinical trials with at least two vaccines, possibly three 

vaccines approved, conditional and emergency? Finally, there 

is an aspect of vaccines or at least of selected vaccines that we 

should not forget, and that's pathogen agnostic protection. We 

have known for a long time that usage of selected vaccines is 

associated again with protections against pathogens which are 

antigenically unrelated to the target of the vaccine itself. A 

major mechanism of pathogen agnostic protection is the 

general fitness of the first line of the immune system, of innate 

immunity, and this is an essay that Mihai Netea and I wrote 

recently and published in New England, because I did some 

of the early work and Mihai did all this, underlying molecular 

mechanisms. 

(https://doi.org/10.1056/NEJMcibr2011679) 

 

     So, selected vaccines increase the baseline tone. We call it 

trained innate immunity of myelomonocytic cells at the level 

of precursors, and mature cells. This is mediated by epigenetic 

remodelling and trained innate immunity involves microbial 

killing, production of cytokines, and triggering of adaptive 

immune responses. And I feel that we should ask the question 
whether the upcoming COVID-19 vaccines do elicit trained 

innate immunity. In addition, there are a number of 

prospective trials designed to try and take advantage of trained 

innate immunity, of immunological fitness if you pass me the 

word as a strategy to decrease the risk of COVID-19. Finally, 

general message, we wrote this paper before COVID-19, Rino 

Rappuoli, Angela Santoni and myself. Both Angela and 

myself-, I have been part, she is part of the global alliance for 

vaccines and immunisation, and which is making a 

tremendous effort to share vaccines with the poorest countries 

in the world, including COVID-19. I feel that this general 

tenet that vaccines are an achievement of civilisation, a human 

https://doi.org/10.1038/s41590-020-00832-x
https://doi.org/10.1056/NEJMcibr2011679


L. Corbetta et al. 
  

 8 

right, and I feel that we should not forget that one newborn, 

one kid out of five does not have access to fundamental 

vaccines on health, let alone COVID-19. And we know it 

now based on COVID-19 that vaccines represent a health 

insurance, a safety belt for humanity. Once more, Leo, 

Lorenzo, thank you for having me on board today.  

 

Leonardo M. Fabbri: Thank you Alberto. We will have a 

discussion at the end, we will have some minutes at the end 

to discuss all the presentations. Now, I introduce Professor 

Duccio Cavalieri, Professor of General Macrobiology of my 

university, the University of Florence, with a presentation on 

SARS-CoV-2 gene stability and its implications.  

 

Duccio Cavalieri:  It's totally expected that new variants of 

the virus have developed since its first appearance in Wuhan. 

All viruses mutate as they make new copies of themselves to 

spread and thrive. There are many thousands of different 

versions, or variants, of Covid circulating.  According to 

evolutionary theory most of these differences are likely 

neutral. A few can even be harmful to the virus's survival, 

thus leading to their disappearance. But some can make it 

more infectious or threatening. What I'll discuss today is the 

current knowledge on how the variation in the virus indeed 

plays a role in the dynamics of the infection. I will also try to 

show convincing evidence that understanding the genetic 

background of how the virus varies is a crucial point to 

develop effective strategies for its containment. The first 

slide below, shows how the first set of sequences from 

Wuhan were basically identical, and how they basically 

clustered differently from the first isolate of the virus. This is 

the first paper published in Nature. It's impressive that this 

paper basically was received on the 20th January and 

published, accepted on the 29th, and published on the 3rd 

February. What this paper describes is basically entering the 

“heart of darkness”. I would say, taking the name from 

Conrad’s book, describing the trip into the study of genetic 

variation of Sars-Cov2 is the discovery of the “heart of 

darkness” of the pandemic. In the following slide you can 

find the metagenomic analysis of the viral sequences from 

the lungs of one of the patients. The majority of the viral 

sequences were SARS-CoV-2. The description of how we 

are entering the unknown, the heart of darkness of the human 

viriome, is given by the discovery of the first evidence that 

Saccharomyces cerevisiae killer virus M1, an RNA virus 

previously described only in yeast, is found within the lungs 

of this patient. But besides this, again what was impressive is 

that the first sequences of bat CoV, of SARS-CoV-2 had 

really a very low level of divergence. These were basically 

claiming that we were looking at the early stages of the virus 

evolution. The other interesting part was that the nearest 

neighbour was bat SARS-CoV-2 RATG13, a virus came in 

from bats that had 88, 89% homology to the virus.  

 

     This is one of, again, the first papers in which two of 

Wuhan's patients' viruses were sequenced, and this paper that 

uses a specific technology for the purification of the RNA 

only, and the sequencing of the viral RNA, proposes that 

actually SARS-CoV-2 is derived from four recombination 

break points for recombination events in the groups of the beta 

coronaviruses, that is creating the emergence of this novelty 

that is finally infecting humans. 

 

     Now, the history of coronavirus research in terms of 

sequences has seen maybe for the first time the joining of 

forces from several groups and the fact that everybody 

working in the field has made the sequences available. This is 

GISAID website, from which I derived this information. The 

last update unfortunately is the 22nd June 2020. At that time, 

more than 4,000 genomes had been sequenced by the 

scientific community. GISAID had the largest SARS-CoV-2 

genome collection, but the problem is that it doesn't provide 

the general metadata information since August 2020. So, this 

is an effort that has seen an explosion at the beginning of the 

pandemic but now, for some reason that I don’t know, is not 

keeping up the pace.  

 

     We need to support as much as possible these initiatives. 

What's really important from these datasets is that it's 

becoming increasingly clear that the virus is novel and it's 

novel because its variation that is less than other 

coronaviruses of the same family, it can basically be used to 

track down, with a small subset of mutation, the origins of the 

virus. What we know is the vast majority of the sequences 

available come from males. There are a few more males than 

females with more than 40 years of age. Some patients have 

missing gender information but this is really a minority, and 

the other thing that we can notice is that the country that is 

contributing the most is the USA, then Belgium, China, 

unfortunately Italy has sequenced only approximately 93 

genomes on GISAID and maybe 120 genomes, but indeed it's 

not in the top ten nations for the number of genetic sequences 

uploaded to public databases. I really think that this trend must 

be overturned to ensure a precise and correct tracing of SARS-



Stand on the Same Side Against Covid – 19: Scientific Evidence on Vaccine for Covid-19  

 9 

CoV-2 infections because Italy, in particularly Lombardy, 

plays a major role in the understanding. It has basically 

probably an understanding of the generation of one of the 

most important mutations that led the success of the current 

form of the virus that is spreading through the world. This is 

data from my group, we have a paper submitted currently on 

a meta-analysis of the existing sequences. 

 

     The 93 Italian strains on GISAID clearly showed, came 

from two different clades, so there were two clades of these 

strains, and these two clades have moved both to Spain and 

to France. So, we have been the seed of the infection that 

arrived probably from Germany and then disseminated 

initially to Spain and to France. And then the Italian strain 

moved to the USA, actually this is a fantastic paper applying 

phylogenetic theory, phylogenetic network analysis to the 

SARS-CoV-2 genome. I have to advise that this paper was 

initially heavily criticised because the extension of the theory 

of the Darwinian evolution to viruses is actually criticised.  

 

     I mean, it's not clear if the algorithms that we use to 

calculate the evolutionary constraints in bacteria, yeast or 

humans can be applied to viruses, but according to this theory, 

it was quite impressive to notice that in one month, the virus 

moved from Wuhan to Shanghai, from Shanghai to Munich, 

from Munich to Milan, and then from Milan to Mexico. We 

could follow and track the movement of the virus by means of 

this technology. Then, again, it was even more impressive q 

paper where the authors are using this network analysis to 

follow the movement of the virus into the USA, and they show 

there have been two separate events of arrival of the virus in 

the USA. (https://doi.org/10.1126/science.abc8169) 

 

     The first event directly from Hubei to Seattle, was not 

successful. The second event, that traced the virus that 

actually arrived via Milan, indeed was extremely successful, 

because the majority of the infections on the East Coast are 

seeded by this entry.  

     Another important problem is the dating of the mutation. 

This is one of the papers that dates the emergence of the virus 

in Hubei in China, and it dates back basically to October, 

November, the first development of the virus in China, but 

some of the phylogenomic analyses are currently telling us 

that the virus in China was already present probably at day 

one, the day of the beginning, in two forms. 

 

     There was a type one and type two clade of the virus. This 

paper published in Nature (https://doi.org/10.1038/s41586-

020-2355-0) shows that basically these two clades might have 

potentially different clinical outcomes. Independently from 

the clinical outcomes, (that in my opinion the data presented 

here do not really support), what's really impressive is that in 

one form of the virus, type one, the number of mutations, in 

particular of synonymous substitutions is very low. It seems 

that selection is neutral for this variant. On the second form of 

the virus, there is a significant amount of non-synonymous 

substitution in the virus and the rate between synonymous and 

non-synonymous substitutions clearly indicates the evidence 

of selection. This is telling us that the second form of the virus 

is indeed under selection, and why is this interesting? Because 

https://doi.org/10.1126/science.abc8169
https://doi.org/10.1038/s41586-020-2355-0
https://doi.org/10.1038/s41586-020-2355-0


L. Corbetta et al. 
  

 10 

the number of sequences is small, thus strengthening the 

indication of natural selection in action. With the increasing 

of the number of sequences that are taken into account, 

(already from 7,666 viral genomes), there are 198 recurrent 

mutations that are emerging independently (homoplasy). 

80% of the mutations are inducing non-synonymous 

changes, so they have an effect, very likely they are derived 

from the second form of the Chinese virus. We have four 

sites that have the same mutation in more than fifteen patients 

and these are the four sites.  Now, starting from this paper, 

let's try to see how the analysis on the four sites progressed.  

The next slide describes another interesting publication that 

was published on molecular phylogenetics and evolution.  

The authors were suggesting that the origin of the SARS-

CoV-2 was not China, but was actually India, and maybe 

Bangladesh, but what's interesting besides looking at where 

the virus comes from, is that the authors do a proper 

evolutionary analysis trying to track down the origins of 

selection in the mutations that appear in more than ten 

sequences in the subset. 

 

     And they discovered two extremely interesting things. 

First, there are eight sites that show positive selection. One is 

a site that changes an amino acid in a very important gene, 

it's the RNA polymerase. And SARS-CoV-2 is supposed to 

be so stable because of the particular proofreading capability 

and fidelity of its RNA polymerase. It's more stable than 

influenza, it's more stable than HIV and several other viruses, 

probably for these characteristics. But if you knock off the 

proofreading ability of the RNA polymerase, then you might 

give rise to a more evolvable form of the strain. The second 

mutation is a mutation in the spike protein, it's the GS614 

mutation, that actually is the mutation that has been taking 

over in Italy. It is the most represented mutation in Italy. 

Now, this is a paper from the group of Davide Zella, it’s the 

University of Trieste, so it's a very good group of geneticists 

working in Italy. What they show, they actually claim that 

the emerging mutation in the polymerase could be one of the 

most problematic ones for the emerging of the virus, because 

it could favour an increased variation in those strains that 

carry this mutation. They also follow the spread of this 

mutation following the lockdown in several countries in the 

world, but what's most interesting is that from the beginning, 

from the early days of infection, ( as shown in the first paper 

published on the sequencing of the first two SARS-CoV-2 

strains in Italy), you find both the original Chinese form of 

the strain that has the D614 mutation, and what I would call 
the European variant, the GS614 mutation. Now, why is this 

relevant to the discussion today? Because from the 

beginning, a few papers suggested that the spike mutation, 

GS614 was associated with a higher transmissibility of the 

virus. 

 

     These are actually the dynamics of the two alleles. In 

yellow, you see the D614 allele, in blue, you see the GS614 

allele, this is March. 

(https://doi.org/10.1016/j.cell.2020.06.043) 

     This is then through March the progressing of the 

infection, and you see that the blue variant, the G614 variant 

is taking over the other variant. Now, the authors claim that 

this confers a higher transmissibility. There has been a lot of 

debate on this subject, and in my opinion, one of the most 

interesting contributions came from the group of Sara P. Otto. 

Sara P. Otto is a well-established evolutionary biologist. I had 

the honour of meeting her when I was in Harvard many years 

ago. Sara published in my opinion one of the most interesting 

papers on the evolution of SARS-CoV-2, it's on the evolution 

epidemiology of SARS-CoV-2. What Sara shows is that based 

on genomic sampling over time, the substitution rate you can 

estimate for SARS-CoV-2 is 0.00084% per site per year, this 

is two to sixfold lower than the rate of influenza and is 50 

times less than the original SARS virus.  So, this was the 

original sequence, the Chinese sequence. Sara also built a 

mathematical model predicting the development of the 

infection, and before the summer, Sara predicts that in the 

countries that went under lockdown there is going to be a 

second wave of infection probably in October, so the timing 

was correct because this is exactly what happened. Then, Sara 

predicts that the virus, will increase the transmission rate, with 

a reduction of the asymptomatic fraction, an increase in the 

duration of the incubation phase and slowly reduce the 

virulence. But what Sara also shows is that the search for an 

adaptive mutation in SARS-CoV-2 is indeed hampered by the 

fact that the sampling is not done properly, so the sampling is 

not statistically correct because the number of sequences that 

we have from different countries are different. As we see, Italy 

has a very small number of sequences, China and the US have 

a lot, so this imbalance in sampling could lead to a false 

statement on the selection that occurs on the different forms 

of the spike protein. This is clearly said by Sara in this paper. 

(https://doi.org/10.1016/j.cub.2020.06.031) 

     So, the non-neutral sampling process could indeed lead to 

the fact that you could find differences in sequences that are 

not really associated with the difference in aggressivity of the 

viral infection, but they are due to a bias in the statistical 

sampling. Yet, what Sara could become realistic with the 

increase in sequences, the field has progressed enormously in 

these months and maybe Otto’s models could lead to 

increased precision in the predictions. I think that rarely we 

have seen such an explosion of publications and research in a 

specific field like what we have seen in the past 12 months. A 

recent publication in Nature Genetics proposes a fantastic 

computational tool that models the interactions and the effect 

of the mutation in the virus, on, let's say, the receptor. This 

modeling tool indicates which mutation sites could be the 

most relevant, and predicts if a mutation in the Spike could 

https://doi.org/10.1016/j.cell.2020.06.043
https://doi.org/10.1016/j.cub.2020.06.031


Stand on the Same Side Against Covid – 19: Scientific Evidence on Vaccine for Covid-19  

 11 

reduce the affinity of neutralizing antibodies. 

And now comes in my opinion one of the papers that I 

consider to be the first strong evidence of the fact that the 

spike mutation, D614G alters SARS-CoV-2 fitness, because 

this mutation shows first on cell lines and then on lung tissue, 

that this mutation increases the replication of the virus in cell 

cultures, increases the level of spike protein within the 

infected cells, increases the infection ability in the upper 

human airways, so here in red you see the gene mutation in 

the spike and most importantly you see here in this graph the 

GS614 mutation and the D614 form of the original form of 

the virus, this mutation affects, in particular, reduces the 

susceptibility of SARS-CoV-2 to neutralizing antibodies.  

 

     In August and September 2020, a SARS-CoV-2 variant 

linked to infection transmitted from humans to farmed mink 

and/or subsequently transmitted to humans, was identified in 

North Jutland, Denmark and called “Cluster 5” variant due 

to a combination of mutations that may result in reduced 

virus, decreasing immune protection following natural 

infection or vaccination. Minks were suppressed and this 

variant does not appear to have spread widely. 

 

     Experts' concerns since december 2020 focus on a small 

number of additional new variants of coronavirus that are 

apparently dominating the scene in the first months of 2021, 

that could be much more contagious or elusive than earlier 

versions: 

• A UK variant that has become dominant in much of 
Britain and has spread to more than 50 other 

countries 

• A South Africa variant that has also been found in 
at least 20 other countries, including the UK 

• A variant from Brazil 
 

     All three have undergone changes to their spike protein - 

the part of the virus which attaches to human cells, in 

addition to other parts of the virus.  As a result, these variants 

seem to be better at infecting cells and spreading.  

 

     The UK variant, called SARS-CoV-2 VOC 202012/01 

(Variant of Concern, year 2020, month 12, variant 

01),contains 23 nucleotide substitutions and is not 

phylogenetically related to the SARS-CoV-2 virus 

circulating in the United Kingdom at the time the variant was 

detected. This variant is rapidly expanding in the rest of 

Europe, has a total of 17 coding mutations (in each one 

changing or missing an amino acid), in four different proteins 

of the virus. Eight mutations are in the spike protein, the one 

against which the vaccines of BioNtech, modern and Astra 

Zeneca were developed (18). Three of these have potential 

effects on the ability to infect and cause severe symptoms. 

The N501Y variant could increase affinity with the Ace 

receptor by facilitating the entry of the virus into our cells. 

Deletion 69-70 del was described in the context of the ability 

to evade the human immune response by altering the 

maturation of the spike, ie in that site cut by one of our 

enzymes, with a crucial role in promoting infection. Nothing 

can be said about any other effect at the moment, but it is 

definitely important to know that another prediction of the 

models is that the lethality of the virus should slowly decrease 

by increasing the fraction of paucisymptomatic carriers. 

Since October, the UK variant has become dominant across 

much of Britain and has spread to more than 50 other 

countries. Recent research from Public Health England 

indicates that the English variant may be between 30% and 

50% more contagious than previous ones. So we can certainly 

say that it is more diffusible than the others, this data also 

shows how sequencing the virus can allow us to understand 

which variants are taking over and associate them with a 

phenotype, even simply by measuring their statistical 

distribution. 

 

     The South Africa variant, the so called 501Y.V2 variant, 

emerged in October, and it has more potentially important 

changes in the spike protein than the UK variant. While 

SARS-CoV-2 VOC 202012/01 from the UK also has the 

N501Y mutation, phylogenetic analysis has shown that 

501Y.V2 from South Africa are different virus variants, since 

it carries two more that scientists think may interfere more 

with vaccine effectiveness. The N501Y mutations in the spike 

protein of coronavirus is 50 percent more transmissible than 

previous variants, genomic sequencing data highlighted that 

the 501.V2 variant rapidly displaced other lineages circulating 

in South Africa. 

      

     The Brazil variant emerged in July and has three key 

mutations in the spike protein that make it similar to the South 

Africa one. One of them E284k could make spike hard to be 

recognized by the antibodies induced by the current version 

of the vaccines.  

 

     The current vaccines were designed around the Wuhan 

variant, but the ability to generate a number of different 

antibodies against different epitopes strongly suggests they 

should still work against the above mentioned variants, 

although perhaps not quite as well. In the worst case scenario, 

the vaccines could be redesigned in a matter or weeks or 

months, to target the new version of the Spike. 

What I mean here, I am confident that the vaccines that we 

have developed will work on the short term, and that we will 

be able to modify them to capture the virus evolution. Thus 

it's really important that we follow up very carefully the 

evolution of the virus to make sure that we will develop future 

vaccines that will work on the future forms of the virus. I want 
to conclude with the fact that I do think that we have to really 

consider what's the best vaccination strategy because one of 

the ways to take into account the high variability of the spike 

is maybe to introduce other antigens besides spike in the 

generation of the vaccine. Regarding differences in mortality 

rate, there is currently no evidence to suggest that any of them 

cause more serious illness, and on the contrary evolutionary 

theory would predict that slowly the virus should decrease its 

lethality. 

 

Leonardo M. Fabbi: Thank you Professor Cavalieri. Even 

now we have no time for discussion, questions will be at the 



L. Corbetta et al. 
  

 12 

end to respect the schedule. It is now my pleasure to 

introduce the next speaker, Professor Bruce Thompson, he is 

Professor at Alfred Health, and now is Dean of Health 

Science of Swinburne University of Technology. The title of 

his presentation is Different Approaches, Different 

Outcomes. Professor Thompson.  

 

Bruce Thompson: Thank you so much for the invitation to 

speak tonight, and I'm speaking on the other side of the globe 

with the wonders of modern technology. Here it's about ten 

past midnight, so if I'm sounding a little tired then just bear 

with me. I've actually talked a little about this, it has got not 

a lot of straight science in it. This is really what's happened 

in Australia, and we've had a very different experience of 

COVID than other areas of the globe. I really just wanted to 

talk a little bit about the Australian response to this particular 

virus, and in particular start talking a little bit about some of 

the issues that we've had actually in the hospitals where we've 

actually had significant healthcare worker transmission of 

virus. Not necessarily from the patient to the workers, but the 

workers to each other. So, we'll talk a little bit about some of 

the things that we've done to actually start preventing this 

because it's started to become a very real issue. It's almost 

where COVID meets occupational health and safety. I'd just 

like to acknowledge a couple of people who've passed me 

some slides. In my current role as the President of the 

Thoracic Society of Australia and New Zealand, I had a lot 

to deal with our Federal Deputy Chief Medical Officer, Dr 

Nick Coatsworth, and also Professor Lou Irving from the 

Royal Melbourne Hospital. I'd also like to acknowledge 

Brigitte Borg from The Alfred Hospital who passed me a 

couple of slides about the laboratory experience. So, this is 

the Australian curve.   

 

     It looks quite different to other countries around the globe, 

it's very different to the US experience. As you can see, we 

had a first wave that peaked just before April, the end of 

March, and then we had some isolated cases, and then we had 

a significant peak starting at the beginning of July. 

Unfortunately, that peak was actually due to our state that I 

live in, Victoria, where actually we had pretty well the 

majority of the cases in the second wave. That's another story 

in itself on potentially how that actually occurred, but I'll start 

talking a little bit about what we did to basically lead to 

where we are at the moment. So, this is some data of where 

we are in Australia, here, right now, as I collected the data this 

morning. 

 

     If we actually look in this particular column here, overall 

Australia had the best part of 28,000 cases which is really 

nothing compared to what we're hearing around the globe and 

if you look at the US which is actually having in excess of 200 

cases a day, we really have a very, very different experience. 

Indeed, this column here is actually the number of new cases 

across the whole country, and we've only had six new cases.       

 

     We actually only have 48 active cases in this country at the 

moment. If we actually look at the days since last case, in 

Victoria, we're actually very proud to say we actually haven't 

had a new case for 40 days. So, that's quite significant 

compared to actually us leading the number of cases that we 

had in the second wave by a huge amount, we're now actually 

in a situation where we actually haven't had a new case for 40 

days. This is the number of days since the last death, and in 

some cases in other states you can just see it's actually the best 

part of the year, and in Victoria it's actually nine days. That 

last case that actually happened nine days ago was an 

historical case from about 30 or 40 days ago. So, as a society 

what did we do? 

 

     We locked down extremely hard and very, very quickly. 

Our international state borders were closed, and indeed if you 

actually did have to cross the state border for whatever reason 

you had to be in quarantine for two weeks. Our international 

borders are closed only for people who are-, you're only 

allowed into Australia if you're an Australian who wishes to 

return home for a very good reason. Once you've done that in 

Australia you have to quarantine for fourteen days, and that 

quarantine actually has security. So, you're actually locked 



Stand on the Same Side Against Covid – 19: Scientific Evidence on Vaccine for Covid-19  

 13 

into a hotel room for fourteen days and then you obviously 

have to be tested and proven to be negative. Masks were 

mandatory across the whole of the community, and even 

though we've been, in Victoria, 40 days without a case, 

masks are still mandatory in areas such as public transport, 

shopping centres and malls and what have you. So, in 

Victoria it's, sort of, about a third of the way of that second 

wave. We had, what we called, Stage Four Lockdown. 

You're not allowed to travel more than five kilometres from 

your own house. The only reason you're allowed outside of 

the house was due to go to the supermarket, a medical 

appointment, pharmacy and you are only allowed to exercise 

for one day, so they closed down the state. They closed down 

all retail, restaurants, no public gatherings, no sporting 

events. Our Chief Medical Officer of the state, basically, at 

the point, actually has control of the actual legal system, and 

that's what we did. So, I actually haven't gone to work, been 

on my campus at my university since March, I now work 

from home. 

 

     With the healthcare workers, what they did and what they 

are still doing and they are just now unravelling this, they 

basically divided up the whole of the hospitals in to three 

working groups. So, if someone became infected in that 

group, they would basically remove that whole team. And 

that would seem to have been highly effective. Then, finally, 

the government really did step in because, basically, you 

think of closing down the whole of the workforce, people still 

need to earn and income and the government provided a 

baseline income for all people who were unable to work due 

to to the lockdowns that we experienced. 

 

     So, if we look at healthcare infections, up until the time of 

eighteenth of September, that's the latest data that we had, 

9.1% of all the cases that we actually had were due to 

healthcare workers. So, it was a significant component of the 

total number of cases that we had were actually due to 

healthcare infections. 

 

     So, if we look at the period of the first wave, 530 

healthcare workers were infected and that's about 11%, so it's 

still roughly the same ratio and there was about 32 outbreaks 

of healthcare workers across the state. But if we look at the 

actual second wave, clearly there are a lot more healthcare 

workers who are infected, which makes sense because there 

was such a strong response that we had, and that was actually 

8.4% of all infections during this period was due to healthcare 

worker infections and there were 88 outbreaks. 

 

     So, one thing I just briefly want to talk a little bit about is 

PPE. And this became a real issue for my role in The Thoracic 

Society of Australia and New Zealand and also within the 

federal government. There was significant anxiety amongst 

the healthcare workers about adequate PPE. So, and I call 

myself actually having PPE PTSD, because I actually had a 

significant number of physicians write to me personally with 

letters of demand that we need to actually increase the amount 

of PPE available. And part of it was thought to be around the 

use of N95 masks because, basically, there was a strong view 

at that time that the transmission of this virus was purely by 

aerosol transmission as the predominant cause, and that is still 

yet in debate. And so, however, we only have a finite resource, 

it's expensive and also it needs to be fit tested and it's not 

necessarily straight forward. But senior physicians who were 

working on the front line had significant levels of anxiety and 

this, sort of, led to us having to actually change our policies 

across the nation, more in line with the precautionary 

principle. And this is a slide that I got from our Deputy Chief 

Medical Officer about this, because we were basically forced 

to go down this pathway. However, the precautionary 

principle, as we know, doesn't necessarily eliminate all risk, it 

basically potentially reduces and you actually have this trade 

off between over-regulation and then, basically, the actual 

under regulation and uncertainty of the risk.  

 

      Also, the precautionary, if it's applied, the more infections 

that we avoid, the more often that it turned out that we might 

have actually acted too excessively, and we actually went in 

too hard. And don't forget, we have a number of physicians 

who were given no choice but to work in to, what would seem 

to be, a high-risk environment. 

 



L. Corbetta et al. 
  

 14 

     And then on top of that, if you look at the precautionary 

principle, there's actually ignoring the costs of associated 

with doing this, and it's basically, 'Hang the expense, let's just 

do this.' 

 

     The other thing that we learned, and again being 

significantly involved in this, is the various levels of 

government. 

 

     Australia actually has three levels of government, and it 

has basically, Local Government for your community, State 

Level Government and then the Federal Government. And 

then we also have various jurisdictions in terms of the 

infection control expert group which is a government run 

organisation, various jurisdictional quality and safety federal 

and state committees as well. And they, actually, didn't agree 

with each other. Now, half the problem is we had such an 

affective response, with actually now having really almost 

eliminated the virus out of this country, and we're now still 

arguing about why we let this thing break out so much. I'm 

sure other people in this audience are thinking, you know, 

'You do not have a problem,' and we really don't compare to 

other areas around the globe. 

 

     So, the other thing is, hospitals are actually the 

responsibility of State Government. Federal Government 

cannot actually intervene and tell them what the actual state 

hospitals can do. And, again, that led to a timed confusion 

and also irregularities in terms of having a consistent 

response to the actual infection. So, this particular hospital, 

where I've had a little bit to do with as well, The Royal 

Melbourne Hospital in Victoria, had really pretty well every 

case of COVID for a while because, don't forget, Victoria in 

the second wave had the majority of these cases. And so there 

was significant learnings that we can get from this. It's a 

number of campuses, it's a 550 acute bed hospital in it's main 

campus. It's a pretty old hospital, it's actually not really 

designed under modern guidelines however, I am talking to 

many people from Europe at the moment who are probably 

thinking it's a relatively new hospital compared to some 

others. But it also has significant resident aged care facilitates 

as well and it has about 10,000 staff. And, as you can see, 

there's actually many open wards that had to open up for 

these patients and the ventilation is not necessarily all that 

great. 

 

     So, what was actually happening is we started getting a 
number of reports that healthcare workers were contracting 

the virus and, on top of that, the nation that we are, we have 

many who people who have family and colleagues who are 

overseas and we started to hear significant issues of 

healthcare infections and, indeed, fellow colleagues actually 

dying of this virus overseas, and that actually led to 

significant anxiety. And it was originally thought that the 

healthcare infection from COVID in the first wave, was 

potentially the inadequate or the unavailability of PPE, 

potentially large numbers of COVID positive patients that 

they were exposed to. We had worker fatigue of people 

working long hours and also there was limited testing, and 

our contact tracing just frankly wasn't good enough to start off 

with, paper based and it took an inordinate amount of time up 

to, sort of, seven to eight days before we got results. 

 

     So, in the first wave, we had ten positive patients in a single 

negative pressure room and that was, sort of, described as 

what we call a 'Hot Ward,' In March, they established a staff 

screening clinic and a separate community clinic as well, and 

this was ultimately to keep everybody away from each other. 

But it was also, what they were particularly interested in, is if 

they had to lay off staff if they actually became symptomatic 

or indeed contracted the virus. So, in the first four weeks in 

the first wave, they had over 1100 symptomatic staff, which 

eleven of those were positive and would seem to be, even 

though they thought it might have actually been contracting 

the virus from the patients they cared for, it was actually 

community acquisition rather than the workplace infection 

and they published this in one of our local journals. So, even 

though there was significant anxiety of people contracting the 

virus from patients they cared for, in reality, it was actually 

community acquisition as opposed to a workplace infection.  

 

     So, this particular figure here, we've got a number of lines 

drawn on this one. This is the Victorian prevalence and this is 

on the Y axis on this side, is basically 0.1% of the Victorians 

were contracting the virus. But if we look at the catchment 

area of Royal Melbourne Hospital, you can see actually the 

prevalence is higher in that particular catchment area and it's 

probably due to the socioeconomic group that this particular 

hospital lies in, and also the ethnic backgrounds from this 

particular group as well. However, if you look at the actual 

prevalence of virus amongst the healthcare workers at Royal 

Melbourne Hospital, you can see it's actually a magnitude 

higher than the actual prevalence of the community being 

about 1.2% of the actual staff contracting the virus compared 



Stand on the Same Side Against Covid – 19: Scientific Evidence on Vaccine for Covid-19  

 15 

to 0.1% of the community contracting the virus. So, this is 

obviously a very significant concern.  

 

     So, with the second wave, we're looking between the 1st 

of July and the 31st of August. 262 healthcare infections were 

actually-, this particular hospital we're talking about, the 

majority were actually the nursing staff which makes sense, 

they're the ones spending the most time with the actual 

patients, and there's also significant support staff in terms of 

Allied Health and other groups of people and only 8% of the 

medical staff actually acquired the virus. In the main though, 

it was actually a relatively mild illness for all the staff of 

varying ages. 89% of the healthcare workers that contracted 

the virus, it was a relatively mild illness, would even go as 

far as significant influenza, is was just a relatively mild 

experience. However, 11% and in fact fifteen patients were 

actually admitted, thirteen patients, this is Hospital in the 

Home, a programme that we run in this country in particular, 

but two of those were admitted to intensive care. One was 

actually intubated although, no one died. And here's a CT 

scan of a 30 year old healthcare worker who was in ICU for 

35 days, now four weeks post discharge and you can see 

there's significant ARDS associated with his. So, even 

though you could argue, sort of, for 90% of the people who 

contracted this virus it was a relatively mild illness, clearly for 

10% of healthcare workers it was definitely not the case and 

of significant concern. However, as we talked about before, 

this virus as we know, it contributes mostly to an elderly 

population, and what we had is significant numbers of people 

contracting the virus in aged care facilities, and these actually 

were admitted in to acute care hospitals and this became a 

significant problem. So, over a one week period in early 

August, an intake of COVID positive elderly patients from 

residential aged care, but they were sitting in open wards. Two 

weeks later though, there was a rapid increase of inpatient 

infections, up to 60 happened within a couple of weeks. And 

this also led to 101 healthcare worker infections. So this was 

becoming a significant problem, trying to manage these 

patients and actually endangering the staff and putting them 

in a relatively unsafe environment.  

 

     So one of the potential reasons we end up having a lot of 

patients sitting in very small area and very large viral load. 

We had open wards, which seemed to be a significant problem 

with confused patients, they were calling out and actually not 

aware of their environment with high and significant nursing 

care. Potentially poor ventilation in some areas, and then a 

breakdown in infection control. So, not so much the use of 

N95 masks or not having them, it was really a breakdown in 

infection control relative to removal of PPE in inappropriate 

ways, and also potentially people walking in to, sort of, tea 

rooms and other public areas still with PPE on, which is not 

necessarily a great thing. We had a large number of staff who 

potentially came in to contact with positive people with 

COVID and so, therefore, we had to actually isolate those 

large numbers of staff so, therefore, the staff sitting behind 

had significant staff fatigue and then also staff working across 

multiple sites which is potentially a problem. And then finally, 

community acquisition of virus from people who-, because 

healthcare workers tend to share accommodation with each 

other for the various reasons. 

 

     So, some of the things that were done. For starters, actually 

close the open wards and start transferring people to single 

rooms and actually start reducing the actual critical burden. 

Upgrading the levels of PPE to N95 and face shields which 

was above government guidelines. Putting spotters and senior 

staff who are basically ensuring people were not getting a 

breakdown of their PPE. Extra cleaning, (TC 01:30:00) rapid 

testing of staff, looking at prevalence testing of all staff and 



L. Corbetta et al. 
  

 16 

then service support of infected and furloughed staff, and at 

one point in time this particular had 680 staff who were 

actually laid off from work which was a potential issue.  

 

     But this figure I actually found quite interesting and again, 

as I said, I had significant concern and anxiety of staff about 

adequate PPE and if you look at it in terms of hierarchy of 

risk, PPE is probably the actual least effective and really what 

we need to try and do is eliminate and isolate a virus to try 

and reduce harm. 

 

      So, if we start looking at our laboratories, as we know 

this spirometry and other types of respiratory functions tests 

are aerosol generating procedures and there was significant 

concern about continuing testing. Now my background is as 

a respiratory scientist and laboratory-based and I could not 

believe, as one of my roles as the President of The Thoracic 

Society of Australia and New Zealand, that they closed down 

all respiratory function laboratories across the country on the 

25th of March. And that was, basically, close down all 

services unless it was totally, clinically essential that the tests 

were done. However, it was the appropriate thing to do 

because, again, we had significant concern of basically 

transmission of virus inappropriately. So, it's interesting with 

biofilters which we try and protect, actually, transmission of 

viruses and bacteria between each other via the actual 

spirometer or the lung function equipment, but this is more 

an environment issue that we don't want to have people 

contacting the virus from patients coughing and what have 

you.  

 

     So, and then there was a significant amount of work about 

ventilation of laboratories and the European Respiratory 

Society is about to come out with a document on that 

particular topic. I don't think I need to talk about the way we 

accessed our PPE and what have you, but clearly, there's been 

a significant amount of work in the policy space about this 

area. 

 

     So, what have we learned? We've learned a lot about 

managing this particular condition, especially in the hospitals 

and aged care facilities. Aerosol transmission is likely to be 

a significant issue in managing these people and we need to 

start thinking about this as an occupational health and safety 

issue, more than just straight contracting the virus off the 

patients. So, even though there are people sat thinking that 

this might be similar to an influenza, I think we'll all agree 
on this webinar, this is a very, very different infection and the 

way we have to manage it. 

 

     So, thank you so much again for the invitation to speak, 

and I look forward to any questions that might appear later. 

Thank you. 

 

Leonardo M. Fabbri:  Thank you. Thank you very much, 

Professor Thompson. We have the same problem in Europe 

with the elderly residents, it's a global problem. Thank you 

for the recommendation. We can move directly to Professor 

Fengming Luo, who is a Professor/Chief Physician/Doctoral 

Supervisor at West China Hospital, Sichuan University who 

had a very, very big experience in the city of Wuhan. He will 

speak about how to prevent future SARS. Please.  

 

Fengming Luo:  Okay, thank you, I want to talk about how 

to fight COVID-19 in China, and I want to talk about our 

experience and the situation in China now and the future in 

China. The West China Hospital on January 18th, we made a 

protocol for patients with a fever, all patients with travel 

history to Wuhan should be screened for COVID-19. We also 

prepared a special ward and more beds in case of more 

patients. We also prepared ICU for severe patients in our 

hospital. And on January 25th, all staff should be recalled 

from vacation and be ready for treating COVID-19 patients. 

We also prepared PPE and other things for a medical team to 

Wuhan and our hospital at the same time. We also established 

a headquarter for our hospital to fight COVID-19. So, the 

medical team from West China to Wuhan, we had three teams. 

In total we have more, almost 200 doctors and nurses and RTs 

to Wuhan. We worked in different hospitals and took care of 

severe patients and returned to Chengdu in March and April. 

Across the country, the highest level response to the epidemic 

situation in most provinces, that means all people should stay 

home and wear masks in public areas. In my experiences of 

organising an emergency medical team to help other places, 

we should have doctors and nurses from department of 

Pulmonary Critical Care Medicine, Department of Infection 

Diseases also from ICU. We should bring PPE, ventilators and 

medicines to the city so where we support. Now we made a 

working flow chart and protocols for treatment of the patients 

and also to protect ourselves. As to the PPE, we made the 

protocol to put on the PPE and then take off the PPE and if 

you perform a high-risk procedure, they should put on the 

positive ventilator. After these protection measures, all the 

doctors and nurses returned from Wuhan tested negative for 

COVID-19. In fact, I think that the aerosol transmission is in 

some situations, but if you protect yourself with suitable PPE, 

I think it will decrease the risk of infection. 

 

     To prevent the spread of disease in Wuhan, we locked 

down Wuhan on January 23rd. That means, 'Don't go to 

Wuhan and don't leave Wuhan,' and published the data of our 

patients, and also performed the early protection, early 

detection, and early diagnosis and early isolation. Wearing a 

mask is required in public places. Help from other cities. We 

sent 42,600 doctors and nurses to Wuhan and they brought 

PPE, ventilators, high flow and medicines and test reagents to 
Wuhan. We also sent three ECMO to Wuhan from West 

China Hospital. 42,600 doctors and nurses returned from 

Wuhan with negative tests of COVID-19. We also have 

Fangcang shelter hospitals, all the mild symptoms of all the 

people should isolate in the Fangcang shelter hospital, and the 

doctors and nurses take care of them and if the disease 

progressed and we sent them to the hospital immediately. 

(https://doi.org/10.1016/S0140-6736(20)30744-3) 

Also, wearing masks in a public area, advise the people to 

wash hands and you can see here, lockdown Wuhan, and after 

two weeks lockdown the number of diseases reaches a peak, 

and four weeks later under basic control.  

https://doi.org/10.1016/S0140-6736(20)30744-3


Stand on the Same Side Against Covid – 19: Scientific Evidence on Vaccine for Covid-19  

 17 

     And the strategy for the treatment of COVID-19, all 

patients with COVID-19 under the monitor of healthcare 

staff in healthcare facility in order to identify the rapid 

progress of COVID-19 in the early stage. We gave sufficient 

respiratory support at an early stage to reduce tissue and 

organ hypoxia. We gave regular oxygen therapy, high flow, 

non-invasive ventilation, and also mechanical ventilation and 

also ECMO for the patient. This is an indicator for ECMO.  

And sometimes we perform a bronchoscopy for the patient 

with ECMO and perform the lavage and you can see here 

after the lavage, the right lower lung becomes very clear and 

the saturation of oxygen improved. 

(https://doi.org/10.1159/000507898) 

 

     And we also used the prone or lateral position, high flow 

intervention, the Oxygen Saturation Index improved. And 

also ROX index improved and the Borg score improved at 

the same time. Sometimes we used the high dosage of 

steroids when the patient's symptoms progressed very fast 

and the CT scan worsened in two or three days, we maybe 

used the high dosage of steroids to deal with the 

inflammation. And discharge standard is that normal body 

temperature and symptoms improved and lesions on CT 

improved, and the nucleic acid is negative twice. And after 

discharge from the hospital, quarantine at the designated 

place for two weeks.  

 

     We reopened Wuhan on April 4th and after that there are 

several new cases in Helong Jiang Province, Jilin Province, 

also Wuhan, and Beijing, and Xinjiang, Dalian, and also 

Quingdao. Right now, we have several new cases in Chengdu 

so we took some measure to prevent the spread of the disease. 

And right now, sometimes there are new cases in several 

cities during winter. But almost normal life, the stores, 

restaurants, schools remain open and a mask is required in 

public transportation, a mask is required in a crowded room 

but sometimes it is not necessary to put on a mask. And we 

always advise people to wash their hands and test COVID-19 

if close contact with a patient. To the hospitals, all patients 

who enter a hospital should measure temperature and they 

should test for COVID-19 and the same as to the family 

members. We also have a quick response code which records 

your travel history.   

 

     And it's very strict measures to prevent the spread of 

COVID-19 in most hospitals. If there are new cases in a city, 

all the local people may be tested for COVID-19. For 

example, we test more than 10 million people within five days 

in Quingdao when there are new cases. Isolating people with 

positive results and all the costs of the patient were paid by 

the government. And if there were people from abroad over 

the pandemic, we will pick up the people from the aeroplane 

and send them to a specific hotel in a single room for each 

person, and we perform the first test and also isolation for 

fourteen days, and then perform the second test. After that, we 

have a self-quarantine for another seven days. Because we 

have some patients affected by the cargoes from abroad so we 

test the seafood and other cargoes for COVID-19 from abroad. 

All workers dealing with these things should be screened 

regularly. I think Chinese model is good for China because 

there are many people in the country and there almost six 

cities whose population are more than 10 million in China. If 

the situation in Wuhan had happened in two or more big cities, 

https://doi.org/10.1159/000507898


L. Corbetta et al. 
  

 18 

I think the healthcare system would maybe break down. So, 

we should take strict measures to prevent the spread of 

COVID-19 in China. 

 

    In the future, I think the vaccine is very important. We 

have five types of vaccine in China under development and 

two vaccines almost finished their stage three clinical trial. 

In fact, I took a shot, one month ago for COVID-19 vaccine 

and I think I will take another shot tomorrow. In our hospital, 

we have one recombined protein vaccine developed, finished 

stage one and under the stage two clinical trial and will begin 

stage three clinical trial soon. In fact, in China right now, we 

have a vaccine so people with high risk, for example 

pulmonologists, staff of Emergency Room, and the staff in 

custom and airport can take this vaccine. Also, in the next 

stage, people with risk to progress in to severe if they are 

infected with COVID-19. For example, older people, people 

with chronic diseases should maybe have the vaccine. 

 

     To prevent the transmission the measure for prevention 

depends on the situation of the pandemic. We maybe lock 

down a specific area when there are new cases. Preventing 

transmission from pandemic areas, we should test COVID-

19 for the people and also at the same time, the cargo, to 

prevent the transmission. 

 

     In summary, I think lockdown for preventing the spread 

of the disease in Wuhan is very important. Early diagnosis, 

early treatment and early isolation is very important to 

prevent the spread of the disease. Track people who have 

contact with patients with new technology, especially with 

the cell phone signal. I think the vaccine may be helpful to 

end this pandemic. I think only protect yourself and then our 

healthcare staff can help more people. Thanks for your 

attention.  

 

Leonardo M. Fabbri:  Thank you very much for this very 

informative and interesting presentation. Now, the general 

discussion is opened. We have twelve minutes but if we need 

it, we can stay some minutes longer. If I may ask the two 

initial speakers the first question, Paulo and Alberto. The 

fragile population is elderly and multimorbid, and certainly 

treated with multiple drugs. My question is, is there any 

evidence that any of the treatments that they may be on, may 

influence the effects of adverse events of the vaccine? I know 

it's a difficult question but from a theoretical, Alberto, and 

practical, Paolo, point of view, do you think that the trials 
should take these variables in to account?  

 

 

Alberto Mantovani: Paolo, shall I start with immunology, 

and then we move to the real stuff, you are the real stuff. I 

mean, there are data on the immune response of the vaccines, 

and there is a paper that came out, I would say, four weeks 

ago, five weeks ago, and they had been presented at a 

meeting from the Oxford group, on the response of elderly 

people. To be honest, I was surprised. I mean, Paolo knows 

better than I do, that with influenza we have geriatric 

vaccines to elicit some kind of immune response so more 

antigen inoculant and I was surprised to see the data suggests 

that even people like me or you have as good a response as 

Duccio, which doesn't make sense. Okay, anyway, so that's 

the background. 

 

But, anyway at face value, I would accept that it's a good 

response. I didn't see a major difference in response between 

males and females which is, again, something with other 

vaccines that does occur. And that's more or less it. 

Concerning drugs, I'm very concerned about inappropriate use 

of drugs. I mean, in the first wave, patients were given a lot 

antivirals. Absolutely useless. You get toxicity because of that 

I keep hearing people taking that drug and it's inappropriate. 

The data suggests that it may have, of course, cardiac toxicity, 

central nervous system toxicity, and no reason why. And now 

I'm worried about glucocorticoids, I mean glucocorticoids 

being given outside of the-, I mean, you and Lorenzo are the 

real experts. I mean, but in early COVID, if they get early 

COVID I don't want to get glucocorticoids early.  

 

Leonardo M. Fabbri: You're right. You're right.  

 

Alberto Mantovani:  I'm an immunologist, I assume I 

understand something, and early on I wouldn't-, and the 

evidence is not there for that. So, those are inappropriate uses, 

concerning the multi-treatment of elderly people, I am not 

aware of data I'm afraid.  

 

Leonardo M. Fabbri: Thank you. Paolo?  

 

Paolo Bonanni:  Yes, of course. Alberto has already replied 

to the question. I don't think we have the data now, at this 

point in time, to understand the difference in the antibody and 

the immediate response after a vaccine in people with chronic 

comorbidities. Of course, I agree that if you give any vaccine 

to someone who is under a heavy immunosuppressive 

treatment, the vaccine usually doesn't work as it works in 

normal people without any treatment. But this is too early to 

understand now. I think we have to vaccinate all risk groups 

and we will have a lot of material to understand this in the 

next months. We cannot know everything since the beginning. 

So, it's the same when people ask me, 'How long will the 

protection last?' and I have to say, 'I don't know,' we have to 

follow up the vaccines and see if the protection is there for 

one year, two years and three years. So we would like to know 

everything since the beginning but, in this case, even more we 

have to follow up to see what happens and we will have 
dozens of thousands of people on which we could evaluate 

this in different studies in the coming months and the coming 

years.  

 

Leonardo M. Fabbri:  You will have a lot of work in the next 

month. There are two questions from the audience. One is 

from a Doctor: is Corona, as I said, being used in China 

already? It's a question for Professor Fengming, yes.  

 

Fengming Luo:  We have a vaccine for emergency use, we 

have the vaccine for some doctors with high risk for infection, 

for example, the Department of Pulmonary and Critical Care 



Stand on the Same Side Against Covid – 19: Scientific Evidence on Vaccine for Covid-19  

 19 

staff and also Emergency Room staff, also staff who work in 

the airport. These kinds of people can be injected with the 

vaccine right now based on their waiting.  

 

 

Leonardo M. Fabbri:  When will you begin with the 

vaccination? To the doctors-,  

 

Fengming Luo:  Vaccinations, probably one or two months 

ago.  

 

Leonardo M. Fabbri:  Two months ago, okay. So, you have 

more experience than us. There is another question from Dr 

Mohamed Amin to Professor Bonanni. It is very difficult. 

Based on representation, which vaccine will have the best 

chance to succeed?  

 

Paolo Bonanni:  Probably I would say that a vaccine which 

is highly effective, a vaccine which also prevents infection in 

addition to disease but we want a vaccine which is able to 

prevent the vast majority of diseases and possibly, to add to 

that, an effect on infection and a vaccine which is practical. 

Because, the other problem is the logistics and the cold chain. 

That's the reason why, I think, that the Pfizer BioNTech 

vaccine is an excellent vaccine according to what we know 

today. The problem is, the difficulty is in the logistics, and 

it's not by chance that they already announced that they are 

preparing a second-generation vaccine for the coming 

months, because they realised that having to deal with minus 

80 for transportation and to have to distribute the vaccine 

very quickly a few hours after you open the box is something 

that is okay for the first phases of application, but it cannot 

be done on a vast scale for a mass vaccination programme.  

 

Leonardo M. Fabbri:  Any other questions from the panel? 

From the faculty?  

 

Alberto Mantovani:  Can I comment on the last point? And 

then a question to Paolo. Or to everybody, I mean, not to 

Paolo but to everybody. We should not forget that 

BioNTech-, we all talk about Pfizer, but it is actually the 

BioNTech vaccine and that was developed by Christoph 

Huber and, I mean, that strategy was designed for cancer and 

for selected tumours such as melanoma, so small numbers 

and very restricted. So, I think there is this original sin, it 

comes from cancer research and for a very specific tumour 

and experimental therapy. 
 

     My general comment, I'm very worried about how are we 

going to get results? I mean, the vaccine is in marathon, 

Paolo, correct me, and we are getting results after the first 

five kilometres so how are we going to get the long term 

results with many vaccines? And we heard about China, we 

have Russia the same and here were are going to have at least 

two, probably three vaccines available. I mean, in my 

hospital, how can I have-, it's an issue that we are discussing. 

How can I have physicians and nurses involved in a trial 

while we have available the emergency or the-, how are we 

going to solve that, you see?  

Paolo Bonanni:  No, it's a challenge and I think there is no 

solution evident for us for this challenge. And also, the mixing 

of vaccines that will be given in the next months. So, if you 

have three, four, five, six vaccines available and we will give 

all of them, we will have issues in understanding the real 

effect of each vaccine. We should follow all groups of people 

vaccinated with a certain product, but we are also mixing 

populations so also the herd immunity effect might change the 

real picture. Because, if a vaccine has a permanent effect, and 

another one which does not have that effect, but the people 

who got the second vaccine are living together with the ones 

who got the first vaccine, we are mixing up a lot of data and 

it's absolutely not easy. We should think of how to organise 

these kind of follow up studies, but I must admit it's very hard. 

 

     And another thing I wanted to stress, I didn't stress this in 

my presentation, we have to be able to make a very complete 

and timely surveillance on adverse events following 

vaccinations, because this might be an incredible tract to the 

credibility of vaccination. So, there must be task forces on the 

territory able to take the notifications of adverse events 

following vaccination, and be able to verify the causality 

between the vaccine administration and adverse events. 

Otherwise, I'm afraid we will be in trouble with millions of 

doses given at the same time and events occur statistically 

because they are there, but if we mix them and verify them 

after vaccination there might be people, and be sure that there 

will be people that will say, 'This is due to the vaccine and not 

by chance,' so, we must be very careful on this.  

 

Fengming Luo:  Maybe you can test the antibody before you 

take the vaccine? Or it will cost a lot.  

 

Paolo Bonanni:  Yes, that's possible also to verify the 

genetics of antibodies but we must plan very, very well done 

studies and it's not easy with all these vaccines that will be 

used at the same time.  

 

Leonardo M. Fabbri:  One question for Bruce Thompson, I 

mean, having such a low prevalence, what is the country's 

strategy for the vaccination?  

 

Bruce Thompson:  This is a really interesting question and in 

fact, plenty of people in the media and other areas are, sort of, 

saying, 'Well we're not in, necessarily, a type of rush,' because 

our borders are closed, they're going to remain being closed, 

especially when there's a main tourist from Europe, Asia, and 
the US. So, they're not going to open in a hurry. So, we've got 

time to wait, to actually start seeing which is going to be the 

most likely effective virus, and so, it was almost a comment, 

'Well let's see someone else take their lead first and see how 

it goes,'  

 

     Ultimately, what we're going to be doing is rolling out the 

Pfizer vaccine, looks like it's going to happen in late March 

and the cold chain issue that we'd talked about before is a real 

issue for us, we're obviously, a very warm country as well and 

a very sparse country so, actually, transport and what have you 

is very difficult and also to roll out virus in such a sparsely 



L. Corbetta et al. 
  

 20 

large nation is actually very difficult. So, we're lucky in that 

we basically don't have any cases really, and it's a matter of 

now just sitting back and looking at the most effective way 

of rolling out the virus. But, as I said, we'll be starting to use 

the Pfizer vaccine in March.  

 

Leonardo Maria Fabbri:  Thank you very much. There is a 

question from Bruno Horta from Brazil saying, 'Brazil is 

facing varying infection cases nowadays. How comfortable 

should we be with vaccines facing 4,000 genomes of this 

virus?' That's a good question for Alberto and Paolo, I 

believe, and also Duccio. 

 

Alberto Mantovani:  I mean, there is an issue of reinfection. 

I think that a conservative of summarising the evidence is 

that it is a relatively rare event. Very few documented cases 

there but of course, it's a relatively short follow-up. The 

second point concerns the stability of the virus, the spike 

protein which, as was illustrated by Paulo, is the target of the 

vaccines in the pipeline, it is relatively stable. Duccio 

discussed the 614 mutations, it doesn't affect recognition by 

the response elicited by vaccines, fortunately enough. Of 

course, we may have variants coming up and they may be 

selected, I mean, Duccio discussed about the evolution, they 

may be selected by deployment of the vaccines. I guess that 

is a possibility and we will see, we should be ready.  

 

Leonardo Maria Fabbri: Thank you. Paolo, do you want to 

comment?  

 

Paolo Bonanni:  No, I totally agree with Alberto so no 

further comment. I think that a vaccine should be able to 

prevent for the coming months and probably, and hopefully, 

years, the Coronavirus we know today, but we have to follow 

up and to verify that this is true also for the coming months 

and years.  

 

Leonardo Maria Fabbri:  Well, thank you all. I give the 

lead to Lorenzo to close the meeting. It was very interesting, 

thank you very much for devoting your time to this 

interesting event and instruptive event that will be posted on 

the website. Lorenzo.  

 

Lorenzo Corbetta: Thank you very much. We had 

thousands, maybe 5,000, 6,000 participants from China as 

usual, and hundreds, 500 of participants from the rest of the 

world. So, I thank you all for your very informative 
presentations and I hope to see you again and to have you in 

the next webinars because now it is a very, very hot topic the 

vaccine, and maybe in some months we will have many, 

many more information. Thank you all, and see you soon.