1 

  
 

 

 

 

 

 

 

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

Cavalieri, P. Bonanni, M. Munavvar, A. 

Cruz, A. Rendon, L. De Paoli (2020) 

Stand on the Same Side Against Covid-
19 – The Future Strategies Against an 

Unknown Enemy. Substantia 4(1) Suppl. 

1: 1059. DOI: 10.13128/Substantia-1059 
 

Received: Aug 13, 2020 
 

Revised: Sep 04, 2020 
 

Just Accepted Online: Sep 07, 2020 
 

Published: Sep 07, 2020 
 

Copyright: © 2020 L. Corbetta, L. M. 

Fabbri, D. Cavalieri, P. Bonanni, M. 

Munavvar, A. Cruz, A. Rendon, L. De 

Paoli. 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 – 

The Future Strategies Against an Unknown 

Enemy 
 

 
 

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

Corbetta of the University of Florence on July 7th, 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, Italy 

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

Prof. Duccio Cavalieri - University of Florence, Italy 

Prof. Paolo Bonanni - University of Florence, Italy 

Prof. Mohammed Munavvar - Lancashire Teaching Hospitals, UK 

Prof. Alvaro Cruz - Federal University of Bahia, Brazil 

Prof. Adrian Rendon - Universidad Autónoma de Nuevo León, Mexico 

Prof. Laura De Paoli - World Health Organization 

 

 

Corresponding author: lorenzo.corbetta@unifi.it 

 
 

 
 

 

 
 

 

Substantia. An International Journal of the History of Chemistry 4(1) Suppl. 1: 1059, 

2020 ISSN 2532-3997 (online) | DOI: 10.13128/Substantia-1059 

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. 

 

July, 7th 2020, 

CHINA-EUROPE VIDEOCONFERENCE 

 

“STAND ON THE SAME SIDE AGAINST COVID-19 

– THE FUTURE STRATEGIES AGAINST AN 

UNKNOWN ENEMY” 

 

Lorenzo Corbetta: Good morning, good afternoon or good 

evening, depending on where you are. My name is Lorenzo 

Corbetta. I am a professor of Respiratory Diseases in the 

University of Florence and director of the educational 

programme in Interventional Pulmonology. This is the fourth 

webinar on the educational project called Stand on the Same 

Side Against COVID-19, and now with the title 'The Future 

Strategies Against an Unknown Enemy.' Our aim today is to 

update you on the evolution of the pandemia and on 
evolution of the virus that we have called 'unknown enemy,' 

but maybe during the webinar we'll find out something more 

about it thanks to the presentation of Professor Duccio 

Cavalieri, Professor of Microbiology in the University of 

Florence. Then we will talk about the development of a 

vaccine for COVID-19 with Professor Bonanni, Director of 

Specialisation in Hygiene and Preventive Medicine of the 

University of Florence, and about clinical recommendations 

and clinical trials in progress with Professor Mohammed 

Munavvar, who is the current President of the British 

Thoracic Society and President of the European Association 
of Bronchology and Interventional Pulmonology. 

     Furthermore, we have important guests from countries 

that are now still in full outbreak, the Professor Rendon, 

President of the Mexican Pulmonology Society, who is 

already attending the latest webinar with us, and another old 

friend from Brazil, Professor Cruz, Professor of Allergology 

and Pneumology at the Federal University of Bahia. Last but 

not least, we have the pleasure to have with us Dr Laura De 

Paoli, who represents a very influential body, the WHO, 

World Health Organisation, and she have been working for 

several international organizations to provide medical 

assistance worldwide, recently in Africa. Now it's my pleasure 

to introduce my mentor, Professor Leonardo Fabbri, who is a 

Professor of Respiratory and Internal Medicine in the 

University of Modena & Reggio Emilia, who will chair with 

me the webinar. Please, Professor Fabbri.  

 

Leonardo Fabbri: Thank you Lorenzo, and thank you for 

organizing these very interesting seminars. I'd like to thank 

the speakers for supporting this initiative. Without further 
ado, I give it back to you to introduce the first one.  

 

Lorenzo Corbetta: Okay. I introduce Professor Duccio 

Cavalieri, Professor of General Microbiology of the 

Department of Biology of the University of Florence, with the 

title, 'Evolution of a viral spillover.' Please, Professor 

Cavalieri.  

 

Duccio Cavalieri: Thank you. So, I had the task here to try to 

make sense of where this virus came from and what are its 

dynamics. I've been trained in Harvard for six years in 

evolutionary biology and that's why my interest spreads 
through several kingdoms of microbes, from bacteria to yeasts 

and viruses. I have been studying specifically a yeast virus. 

It's called killer virus. It has some similarities with SARS-

CoV-2, but kills yeasts not humans. So, in genomics the 

evolution of the genome it's a process that is basically 

constant, and since the times of Darwin we know that change 

is brought up by mutations that occur hypothetically randomly 

along the genome. The same maybe holds true for COVID-

19. COVID-19 is not a complete novelty. We have had here 

in this life two previous emergencies, MERS-CoV with a 3.4 

case fatality rate, 2,494 cases, 858 deaths, SARS, 8,000 cases, 
774 deaths, and now COVID-19, 11.6 million cases, 537,000 

dead, where the numbers below are Italy. 242 cases, 34,869 

deaths. This data is as of yesterday.  

     A relevant point is that coronaviruses have passed through 

human evolution several times in the past. Probably we have 

met at least 40 different coronaviruses, and four of which have 

been associated to common cold. One actually at the end of 

the 19th Century which started in Russia was probably a 

coronavirus. Two of them came from mice, two of them came 

from bats. Bats are a perfect incubator for coronaviruses 

because they rarely develop the disease. They harbour the 
virus and they harbour large communities of viruses. 

https://www.covid19expertpanel.network/


Stand on the Same Side Against Covid-19 – The Future Strategies Against an Unknown Enemy 

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 3 

     Today there are at least 61 different bat coronaviruses that 

can infect man and have been described in detail. Jumping 

species is a crucial mechanism for coronavirus evolution and 

survival. The virus is alive only in the host, and so bats 

provide the reservoir and evolution place. Interestingly, 

mutation rate in SARS-CoV is apparently low with respect 

to flu and HIV, but recombination between different 

coronavirus infecting the same host is indeed frequent. Some 

bat species can carry up to twelve different coronaviruses 

simultaneously. 
     This work has been made by a researcher from Wuhan, 

Zhengli, the 'Bat Woman,' and the work from the Ralph Baric 

Laboratory in University of North Carolina Chapel Hill. 

Interestingly, since the time of SARS, this review came out 

in 2007 and it's a summary of the conclusion of the SARS 

episode. The last author, Kwok Yung Yuen, said: 'The 

presence of a large reservoir of SARS-CoV-like viruses in 

horseshoe bats together with the culture of eating exotic 

mammals in southern China is a time bomb.' His words come 

from this review. 'The possibility of re-emergence of SARS 

and other novel viruses from animals or labs, and therefore 

the need for preparedness, should not be ignored.' I think we 
probably have not read this review carefully enough, because 

recently, as we all know, this is exactly what happened. This 

is the first paper that describes in detail the composition of 

the RNA viruses in the lungs, this is BAL, in the lungs of a 

patient, one of the first patients in Wuhan. As you see, the 

vast majority of the patient that was suffering from this 

disease, COVID-19, was actually SARS-CoV-2. From the 

first regional work published by the group of Zheng-Li Shi, 

we see that the author already suggests as the origin of this 

bat and puts at the basic of this, at 97% identity with the 

SARS-CoV-2, the coronavirus that we've come to know so 
well, RaTG13. Remember this name because this probably is 

the missing link, is the virus screen in the bat that differs from 

the one that infects the humans, but could be the backbone. 

It's the nearest neighbor to what we are seeing here. The 

differences between the bat virus and the human virus are 

substantial. So, indeed the potential origin and the nearest 

neighbor are bat viruses, but the differences are substantial. 

This is the paper from the Andersen group that suggests the 

natural origin of this virus and shows that this virus has 

unique traits, as we all know. The spike region is unique with 

respect to the other SARS and MERS. 
     The sequence of the spike with the binding sites to ACE2 

is so diverse that in the early days for the whole month of 

January, February, the scientific community was doubting 

that actual ACE2 was the target for the binding. But then we 

know now that this is a degenerated site that is more efficient 

of the one from SARS for binding to ACE2. The second trait 

that we should all remember is relevant for the infectivity of 

the strain is the presence of a furin-like cleavage site that is 

absent in coronaviruses of the same clade. These two traits, 

in particular the second trait, have never been described in 

another coronavirus before, are unique to this virus that is 

attacking the humans, and probably this second trait that has 

been seen before in viruses like HIV-, the second trait, this 

furin splicing site, is, kind of, interesting because it's probably 

within the ability of this virus to escape the immune system. 

Now there are more than, today, 7,000 genomes of this virus 

sequenced, okay? The data I report here and which I'll talk 

during my presentation do a summary of what is known 

around 4,256 of those for which we have an almost complete 

assembly. We have a sequence of at least 85% of the sequence 

of the virus. Amongst these, we have 350 Italian genomes that 

are currently being published by the group of researchers from 
the Sacco Hospital in Milan and their collaborators. 

Immediately from the beginning, probably we have been 

exposed to two different strains of SARS-CoV-2. I know the 

definition of 'strain' within virus infection is quite peculiar 

because there is not a real boundary. As I have seen, 97% is 

the boundary between the nearest neighbour from the bat and 

what happens in humans, but these are the sequences extracted 

from the first 5,000 genomes. We see that there are two clades, 

one clade in which is predominant the Shanghai signature, and 

one clade in which is predominant the Wuhan signature. 

     What does it mean? This means that even if the virus 

mutates slowly, evolution occurs, and this is not something 
surprising. In fact, this paper that is accepted in Nature should 

come out in the next days. This preview of an accelerated 

article preview shows exactly this fact. You can discriminate, 

based on specific mutations, the two different clades. It's 

interesting this because there are several mutations, 80% of 

which are non-synonymous mutations. What it means that the 

virus mutates, mutations are not evenly distributed along the 

sequence. There are some regions that are enriched in non-

synonymous mutations, so in mutations that lead to an amino 

acid change. The fact that they lead to an amino acid change 

means that the protein is changed. The big challenge is 
showing that there is a change in functions, and this we don't 

know, but you have to know at the moment that 198 recurrent 

mutations describe homoplastic sites. Four sites are mutated 

in more than fifteen patients of those that have been 

sequenced, and one site is mutated in over 40 patients. Why is 

this interesting? How can we use this information? We can 

use this information to track the flow of the virus. This is a 

paper published on PNAS. All of these papers have been 

heavily criticized. That's the way science goes. The 

applicability of network theory of evolution to the evolution 

of virus sequences is not trivial because you do not have the 
models of evolutionary theory that we have for yeast or for 

bacteria, but the applications of the nearest proxies suggest 

that we can track the virus that started from Wuhan, arrived in 

Shanghai, moved to Munich, arrived from Munich to Milan, 

and from Milan to Mexico City in 30 days for a precise set of 

mutations. This approach allows, let's say, to estimate the 

success rate of the entry of coronavirus into a country.  

     This is the American example. This is a paper published 

by the group of Lemey, and they analysed the sequences and 

asked how many times the virus arrived in Washington State. 

They found a first aborted entry that was not successful 

around January 15, and the second successful entry on 



L. Corbetta et al. 
  

 4 

February 15. The interesting thing of the model they built is 

that they could see that the first arrivals were not successful. 

The two arrivals that brought the virus into the US were one 
from Hubei to Seattle on February 13, and the second that 

brought the virus that probably expanded in Milan to New 

York City on February 20th. So, this allows us to follow the 

routes, and what we know now is that these two viruses were 

slightly different. These are not enormous differences, but 

were slightly different, and what we know now is that the 

exact two same differences that had been discovered in China 

were present in Milan, were present in Lodi and in Bergamo. 

This is the paper of the first published publication from an 

Italian group. It's the group of Stefanelli Paola, you recognise 

the name, Maria Rita Gismondo, Giovanni Rezza. They 
described the presence of two specific strains. Now here's the 

caveat of this story. Some of these papers, some of the 

research groups, are making claims that are currently hard to 

support. This paper here from Montefiori and Korber, it's a 

very interesting one but suggests that the spike mutation that 

we have seen being present in at least 25 of the genomes 

sequenced leads to a less transform to discriminate two forms 

of the virus, one that can be transmitted more efficiently and 

one that can be transmitted less efficiently. Now, the big 

issue with these assumptions is the sampling error. The paper 

I'm reporting you here just came out on Current Biology from 

the group of Sarah Otto, an excellent evolutionary biologist.  
(https://www.cell.com/current-biology/fulltext/S0960-

9822(20)30847-2) What Sarah shows is that based on the 

genomic sampling over time, the substitution rate can be 

estimated. We can estimate one mutation per week during the 

movement of the virus in the world. We can see that the 

substitution rate is much less the one from influenza, and we 

can make assumptions on which will be the dynamics of the 

mutation using evolutionary theory. 

     According to the models that Sarah Otto has developed, 

the mutation should increase transmission, reduce 

symptomatic fraction, increase the duration of the incubation 
phase, reduce virulence, and the models predicted that the 

lockdown period, the whole experience, will probably lead to 

the emergence of a second wave of the virus in mutated form 

in the fall, September, October. This model is supported 

mathematically in quite an interesting and convincing way, 

and this model draws a few fine lines about the searching for 

that mutation of SARS-CoV-2 and basically puts an 

important caveat. Currently, the lack of a neutral sampling 

strategy, so the fact that we have sequenced not really at 

random, but we have sequenced in areas where we were 

having hotspots of the virus is leading to a potential sampling 

error that makes it very hard to say whether one variant is 
associated to an increased rate of transmission or to an 

increased pathogenesis. But very likely the virus is 

dynamically changing. 

     This paper here shows very interestingly that we have not 

identified a single recurrent mutation convincingly associated 

with increased viral transmission, and we have to keep in mind 

that mutations could even make the virus worse. So, my 

suggestion to the audience is that when we look at the virus and 

its evolution, we should keep in mind what Dobzhansky said. 

'Nothing in biology makes sense unless observed using evolution 

as a lens.' So, selection acts on the whole genome, on the genes of 

the virus, of the host, and of the other microbes that are carried by 

the host, but why there is no evidence currently of the outcome of 
SARS-CoV-2 adaptation? The analysis in the study of the rate of 

change of this virus is important to adjust and potentially drive the 

strategies for its containment and to make conclusions supported 

by evidence. Thank you. 

 

Lorenzo Corbetta: Thank you very much, Duccio, for your very 

nice presentation. We will have many questions for you at the end 

of the other presentations, and for the audience, they could post 

the questions in the chat and we will respond later. Now I 

introduce Professor Paolo Bonanni with a presentation on 

perspectives for the development of a vaccine for COVID-19.  
 

Paolo Bonanni: So, thank you Lorenzo for the invitation to join 

you in this very interesting webinar. My task is to give a 

perspective for the development of a vaccine for COVID-19, and 

you know that a lot is moving around this topic. I would suggest 

our colleagues to read this paper if they did not already read it. The 

authors are colleagues from the US, including Anthony Fauci, and 

in this paper we have some interesting perspective regarding the 

challenges for the development of a vaccine against COVID-19. 

     First one is define what is protected immunity. So, we would 

need to have a correlate of protection which we don't still have. 

Another point is how long the immunity could last, so the duration 
of immunity. The second point is we have variable endpoints for 

the evaluation of a vaccine. Are we speaking of protection from 

infection or of reduction of viral replication or reduction of the 

severity of the disease? These are different endpoints that should 

be considered separately. Then the role of neutralising antibodies 

and T cells. We have difficulties in understanding the real 

incidents of infection because we don't know exactly what the 

percentage of asymptomatic subjects is, compared to the 

symptomatic ones. We have a challenge in the potential creation 

of independent labs with identical validated serological tests to 

confront different candidates and different clinical trials. We 

https://www.cell.com/current-biology/fulltext/S0960-9822(20)30847-2
https://www.cell.com/current-biology/fulltext/S0960-9822(20)30847-2


Stand on the Same Side Against Covid-19 – The Future Strategies Against an Unknown Enemy 

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 5 

should be able to compare the very many vaccines that are in 

development today to see what the comparative ability of each 

candidate is.  
     Then an ethical point, the human challenge trials, are they 

useful first of all, and are they ethically acceptable? The last point 

is the immune enhancement risk. We must remember that 

vaccines against respiratory virus may induce an excessive 

immune response that in case of infection, instead of preventing 

the disease, could worsen its course, attacking the patient tissue. 

So, a candidate vaccine must undergo severe safety evaluations. 

This is a mechanism of antibody mediated immune enhancement 

with an increase of growing inflammatory cycle times, but also 

the mechanisms of antibody-dependent enhancement where no 

neutralising antibodies could increase the potential for the virus 

to enter the target cells. For sure our target is the S protein, the 
spike protein of the coronavirus, where there are these three 

identical binding domains, all of which must bind to the host cell. 

Here we can see that when the virus needs to enter the cell there 

is this opening up of the spike with the receptor binding domain 

which can bind to the ACE2 receptor. If you look at the different 

vaccine trackers in the web you can find sometimes different 

numbers on the same day because it's very difficult to keep up 

with the many research groups that are working on this topic. 

Here you can see, this is from WHO, 129 pre-clinical studies, 

fifteen in phase one, nine in phase two, two in phase three, but 

none approved today. If you look at another tracked which is 
from the London School of Hygiene and Tropical Medicine 

you'll find different numbers. This is also very recent from 

yesterday, but what is amazing is the number of projects that are 

in the pre-clinical phase, but some of them then are progressing 

to the phase one, two or three before they get approved and 

licensed. 

     So, what are the possible approaches to a vaccine against 

COVID-19? One of the most advanced approaches is based 

on DNA and RNA-based vaccines.  

(https://www.nejm.org/doi/full/10.1056/NEJMp2005630) 

Why an RNA vaccine? An RNA vaccine is probably very 

much scalable in a big way. How do they work? The mRNA, 

which is the coding for the spike protein, is encased into a live 
lipid code, then it's introduced into the cell, it goes into the 

cytoplasm and produces the spike proteins that are then 

released for the contact with the immune system. But there are 

also the DNA vaccines, which are introduced by an 

electroporation system and they must enter the nucleus and 

integrate into the nucleus and then produce mRNA to produce 

the spike proteins. So, what is the advantage of mRNA 

vaccines? The use of mRNA vaccines has several beneficial 

features over subunit, killed and live attenuated virus, as well 

as over DNA-based vaccines because safety is important and 

mRNA is a non-infectious, non-integrating platform. There is 
no potential risk for infection or insertional mutagenesis. Then 

the efficacy, because various modifications make mRNA 

more stable and highly translatable. There is an efficient in 

vivo delivery that can be achieved by formulating mRNA into 

carrier molecules, allowing rapid uptake and expression into 

the cytoplasm. The production also, I already mentioned this. 

MRNA vaccines have the potential for rapid, inexpensive and 

scalable manufacturing, mainly owing to the high yields of in 

vitro transcription reactions. We have two sub-types of 

mRNA vaccines. The first one is the simple mRNA, you 

introduce the mRNA which produces the spike proteins, but 

we have also some self-amplifying mRNAs. In this case not 
only the mRNA which is encoding for the spike proteins is 

introduced, but also some non-structural proteins that allow 

the self-amplification of mRNA, and so a higher production 

of spike proteins. There is already a vaccine with this 

characteristic developed by a college in London. 

 

     Then the most advanced RNA-based vaccines are these 

two. Of course I cannot mention all of them, but the most 

advanced are the ones from Moderna. This vaccine uses 

messenger mRNA to produce viral proteins. The American 

company is eyeing phase three trials in July and hopes to have 
vaccine doses ready for early 2021. Then there is another 

vaccine of some biotechs together with Pfizer, which have 

also been announced on July 1st that all the volunteers for 

phase 1/2 trial produced antibodies against SARS-CoV-2 with 

some moderate side effects. So, this warrants further studies 

that are going on at this time. So, this is the plan of the phase 

one study for Moderna, and here you see it's foreseen to end 

in September 2021. 

     The other one from Pfizer, they had several studies with 

many participants. You can see here 7,600 participants in this 

https://www.nejm.org/doi/full/10.1056/NEJMp2005630


L. Corbetta et al. 
  

 6 

phase 1/2 randomised observer blind dose-finding study. 

Then again this is a dose escalation study, so it foresees to 

verify what is the right dosage of this vaccine. Let's turn to 

the DNA vaccines. DNA vaccines are also important because 

DNA is easy to manipulate, it can allow rapid design and 

construction of potential vaccines. Another advantage of 
DNA vaccines is that they are extremely stable, and so they 

could reduce the need for a cold chain and increase the 

production shelf life, which is important, for instance, for 

developing countries where the cold chain could not be 

assured in some instances. 

     There are some pre-clinical data of some of these 

vaccines. They are studied in rhesus macaques, 35 of them. 

They induced an important humoral and cellular immune 

response, including neutralising antibody titers comparable 

to those found in convalescent human and macaques infected 

with SARS-CoV-2. Following vaccination, the animals were 
challenged and it was possible to demonstrate that the level 

of viral presence had a very important reduction in median 

viral loads in bronchoalveolar lavage and nasal mucosa. 

There are other DNA vaccines, one is from Inovio. There is 

also an oral vaccine based on the DNA technology where 

there are billions of colony-forming units of Bifidobacterium 

longum, which has been engineered to deliver plasmics 

containing synthetic DNA, encoding spike proteins from 

SARS-CoV-2.  

 

     Another type of vaccine that is under development now is 

the one based on viral DNA vector. This is a variation of the 
design of the expression plasmid, which are used to construct 

a DNA expression system that can amplify the level of RNA 

and protein expression as occurs in a live virus infection. The 

most popular ones are those based on adenoviruses, but 

anyway, there are around 25 groups that say that they are 

working on viral vector vaccines. The virus is like measles or 

adenoviruses that can be genetically engineered so that they 

can produce coronavirus proteins in the body. Then we can 

have replicating viral vectors such as with measles or also the 

vesicular dermatitis virus that was used recently to produce 

the first Ebola vaccine which was licensed, but also non-
replicating viral vectors such as adenoviruses. In this case, 

booster shots can be needed to induce long-lasting immunity. 

So, the adenoviral vector is particularly useful if you want to 

get a CD8+ cytotoxic T lymphocyte response, because in this 

way the antigens that are carried by the adenoviral vectors can 

be presented to T cells via MHC class 1 molecules and this 

causes a robust CTL response. 

     So, in this way they can also, the intracellular virus could 

be killed. We have two important adenoviral-based vaccines 

presently underway, the Ad5 coronavirus produced by 

CanSino, a Chinese company, but also the vaccine based on 

the chimp adenovirus 5 developed by the University of 
Oxford. Here you can see that the pre-clinical studies of the 

vaccine developed by the University of Oxford showed to be 

able, under challenge, to reduce the possibility to have 

pneumonia in the macaques that were immunised compared 

to those who were control group. The other important data is 

that the nasal fluid, the ability of the vaccine to reduce the 

viral load is not as much important as is the bronchoalveolar 

fluid. So, there might be some doubts that this vaccine is able 

to avoid the disease but not the transmission of infection. So, 

we have here again phase 1/2 studies with different numbers, 

but also the vaccine from CanSino, from the Chinese company 
is very well studied. We have this phase two clinical trial to 



Stand on the Same Side Against Covid-19 – The Future Strategies Against an Unknown Enemy 

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 7 

evaluate the safety and immunogenity of the recombinant 

novel coronavirus vaccine, and also this trial which is a dose 

escalating phase one clinical trial.  
     We have the first result of this study where they showed 

that giving a low dose, a medium dose or a high dose, they 

had 75 to 83% participants declaring they had the side 

effects, but they were not bad side effects, so there was no 

serious adverse event noted within 28 days post-vaccination. 

They also studied the ELISA antibodies and neutralising 

antibodies which increased significantly at day fourteen and 

peaked at 28 days post-vaccination. So, they are going on and 

should be one of the first groups to get a vaccine close to the 

license route. 

     So, they also have another study here. Then we turn to the 
other approach, which is the one of inactivated vaccines, and 

a vaccine which is advanced is the one from Sinovac, a 

private Chinese company. In June, the company announced 

its phase 1/2 trial on 743 volunteers, and they found no severe 

adverse events and produced an immune response. So, they 

are launching a phase three trial in Brazil in this month, in 

July. Then there is also the Wuhan Institute of Biological 

Products, the other vaccine. In June they are moving to a 

phase three trial, so they are in advanced phase. Again, we 

have data from the Sinovac vaccine on pre-clinical data 

showing that it's a good response and the possibility to work 

with this vaccine licensed are rather high at this moment. One 
of the last things I wanted to report is that some groups are 

also studying the possibility to use the MMR vaccine, the 

measles, mumps and rubella vaccine, for its potential to give 

cross-reactivity and cross-protection also for the COVID-19. 

We have the first subunit vaccine available today in clinical 

trials. This is very recent news that a first subunit vaccine 

underwent the first phase one study. Here it's a vaccine which 

has two different adjuvants. They are AS03 adjuvant, which 

was used also for the H1N1 pandemic vaccine in 2009, and 

also the CTG, the repeat of the cytosine and guanosine 

sequences that are a good adjuvant also for this kind vaccine. 
Then we also have the pathogen-specific artificial antigen-

presenting cells, where genetically modified artificial 

antigen-presenting cells can express conserved domains of 

the viral structural proteins delivered by lentivirus vector, 

which are supposed to evoke the naïve T cells in the human 

body and lead to differentiation and proliferation. We also 

have autologous antigen-presenting cells that are charged 

with the antigen and re-infused in the nurses and doctors that 

will undergo this first study in China. Final considerations. I 

have rushed to show you what is going on on the vaccine 

studies, but we have to remember that usually a vaccine takes 

fifteen years to be developed, and so this is the timeline we 

would get a vaccine if we had a normal development. We 

would have a vaccine in May 2036. We are rushing, so one 
caveat is that we cannot run the risk of approving a vaccine 

which has not undergone all possible scrutiny of safety 

because we could endanger not only the COVID vaccine but 

also all vaccines that we are using today with exceptional 

results.  

     With this I thank you for your attention and this is my 

address for any questions you want to address. Thank you 

very much.  

 

Lorenzo Corbetta:  Thank you very much Paolo. We will 

have many questions for you, and now we carry on with 
Professor Muhammed Munavvar, Consultant Chest Physician 

of the Hospitals of Preston (UK). His presentation will be an 

update on the current experience and plans for the future from 

the Thoracic Society's perspective. Thank you Mohammed.  

 

Mohammed Munavvar: Thank you very much. It is indeed 

a pleasure and privilege to be here, to be able to speak and 

update you. I had given a similar presentation in the first event 

of your excellent series of webinars. What I am going to do 

basically is cover this topic with a very brief introduction, then 

an update about thoracic society-related statements and 

guidelines, a brief overview of clinical trials in the UK, some 
of which you will already read about, and then conclude this 

presentation. First of all, I don't have any conflict of interest. 

I work for Lancashire Teaching Hospitals, British Thoracic 

Society and EABIP, as you have already mentioned. The 

global incidence, just checked about an hour ago, as 

mentioned already with the first speaker, it has crossed 

unfortunately more than 11 million cases and more than half 

a million people have died. So, this unprecedented global 

pandemic has left a trail of devastation, despair and deep 

distress to a whole lot of people around the world, and it does 

not respect royalty or indeed position, as we have seen in the 
last few months. The UK data, again checked yesterday, was 

nearly 300,000 cases and unfortunately more than 44,000 

people have passed away. The only good news is that although 

there was a peak in April, latter part of April and early May, 

we are starting to see a decline in the numbers and also in the 

number of deaths. So, what have we done as British Thoracic 

Society during this period? We have produced a great deal of 

guidance in relation to COVID and I'm going to take you 

through some of this guidance in the next few minutes of my 

presentation. We have set up a separate section in the British 

Thoracic Society. I don't know whether any of you had had 

the opportunity to visit, but it's something that we can share 
free downloads of a variety of information on COVID for the 

respiratory community. 

     Now we have started to move to this section, where we are 

trying to focus on how to resume services, and I'll touch upon 

this as well in the next few minutes. A whole lot more than 25 

different statements have been produced at a record pace in 

the last three to four months, where they would have normally 

taken three to four years to put together all this guidance. A 

team of people have worked round the clock to produce 

guidance on various aspects of pulmonology, but also other 



L. Corbetta et al. 
  

 8 

conditions such as venous thromboembolism, oxygen 

therapy, etc. So, essentially every aspect of respiratory 

medicine, how should the pulmonologist or how should we 
non-pulmonologists manage is what we are focused on. As I 

said, now we have not surprisingly found that a whole lot, 

thousands and thousands of patients who do not have 

COVID, who have non-COVID-related respiratory problems 

have suffered a great deal as a consequence of the pandemic 

because their care has been severely affected because 

appointments have been delayed, elective care has been 

affected, even semi-emergency care has sometimes been 

affected. So, we put together some documents on how to plan 

the resumption of these services, particularly lung function 

tests, how to do it safely step-by-step, because there have 
been very few lung function tests carried out during this 

period. Sleep physiology and sleep medicine, a crucial part 

because of its wide-ranging implications for the patient and 

the wider public. Procedures related-, how to resume 

procedures which I'll come to in a minute. Specific guidance 

has also been produced with regard to pulmonary 

rehabilitation and long-term ventilation services. And this is 

part three and then we're going to stretch to all the other 

respiratory services. We have also focused on guidance for 

healthcare professionals because I presume it's happening in 

your countries as well, where patients who are over 70 but 

also patients with respiratory illnesses and a variety of other 
illnesses, have been shielding during the lockdown period. 

     The other big tsunami that is going to hit us, or has already 

started to move towards us, is the large workload of post-

COVID pneumonia patients. How do we systematically 

ensure that these patients are cared for in the weeks and 

months after they recover, fortunately, from COVID 

pneumonia. This has been divided into two sections, those 

who have had severe pneumonia and needed admission to an 

intensive care unit, or high-dependency unit and those who 

have had mild to moderate pneumonia. Patients in the severe 

category are given details of a helpline, this varies around the 
country and they are given a call or face-to-face consultation 

about four to six weeks following discharge from hospital. 

These patients then-, we have to do a systematic workup, 

look at-, consider new diagnoses of PE, liaise with localised 

CU team, post-COVID holistic assessment to pick up any 

new problems that developed as a consequence of COVID 

pneumonia. And twelve weeks after discharge, they have a 

thorough assessment, including full lung function test, where 

necessary a CT scan, other lung function tests, functional 

assessment such as a six minute walk test, consider an 

echocardiogram and where appropriate even repeat the 

CTPA required. And then we pick up a percentage, we think 
we'll pick up cases of interstitial lung disease, they'll go to 

the specialist interstitial lung disease and some may end up 

requiring attention from the pulmonary vascular disease 

specialist. In the milder category, we could relax a little bit 

more and have a more-, a less proactive approach but where 

necessary, on demand we can provide service but also twelve 

weeks post-discharge we will carry out an assessment 

initially to see how they are and then if necessary proceed to 

a more detailed systematic assessment as has happened in 

this category. All these documents are available in the British 

Thoracic Society website and are free to download and as you 

can see here from March to April to May, more than 100,000 

people have-, 100,000 times it has been downloaded, each of 
these documents, to cover all these aspects. 

     Change in practice is also required, I'm just giving you an 

example from being an interventional pulmonologist like 

Lorenzo, giving an example of what is happening in the 

bronchoscopy suite but this applies to every procedure in the 

hospital, every visit to the hospital. So, the moment we receive 

a referral, we do an assessment remotely and then ask the 

patient to isolate. Ideally for fourteen days but of course in the 

lung cancer field or cancer field, that is not possible, every 

minute is crucial so, we ask them to isolate but continue with 

the diagnostic part. We are undergoing a PET-CT scan, a CT 
scan, have a COVID swab 24-48 hours in advance. What is 

becoming more widespread, is the availability of IGG 

antibody tests and then at that point we check and sometimes 

we need a repeat CT scan if they have not had a PET-CT scan. 

On the day, they will have a questionnaire done, potentially in 

the future they can have a point of care lateral flow assay, to 

check for antibody test, or even point of care swab to make it 

safe for those patients to undergo whatever procedure they 

need to. We cannot keep postponing procedures, so far we've 

postponed some of the elective procedures. And at the same 

time, we want to ensure that our staff are safe. How do we do 

that? We want to make sure by this pathway, that it's a green 
area, not a red area but a green area by admission and 

recovery. We want to ensure that everybody's wearing full 

PPE. Maybe we have to adapt the area, the environment as 

well with regard to negative pressure rooms or the whole 

room. The suite needs to be changed, the layout needs to be 

changed to have a separate dining area, separate exit or 

doffing area etc. Majority of procedures we try to do under 

general anaesthesia, as has been demonstrated by myself here 

with an EG tube. That is the closed circuit but sometimes and 

this applies also in the intensive care unit, where you have a 

sheet along with an EG tube and a T-piece but sometimes you 
have to carry out this procedure under local anaesthesia and 

sedation and a number of different devices have been put 

together imaginatively. 

     And one such is the slotted surgical mask or face mask, 

make a little incision and through that you introduce the 

bronchoscope while oxygenating the patient through the nasal 

cavity. A number of other boxes are available for this purpose 

as well. Moving on to the next major section that I want to 

spend a few minutes on, it is about research and therapeutic 

trials and when the pandemic hit us, the UK got involved in a 

number of studies. If you look worldwide and if you type into 

the US ClinicalTrials.gov, there are more than 2,000 studies 
underway currently in the COVID world and there have in fact 

been more than 27,000 publications. What happened in the 

UK very early on, it was decided that the government will 

pump in a great deal of money through the National Institute 

of Health Research into a variety of trials, everything from 

vaccines to epidemiology, to policy development and research 

and so on. And a previous speaker very nicely covered the 

vaccines and some of the couple of vaccines which are being 

developed here. A number of clinical trials were initiated, 

multi-centre clinical trials, so that we get proper randomised 



Stand on the Same Side Against Covid-19 – The Future Strategies Against an Unknown Enemy 

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 9 

trials, with meaningful conclusions and one in particular I 

will touch upon in a minute. The trials are plasma 

transfusions, trials of vaccines and a variety of other areas as 
well. The Recovery trial is the biggest trial that was 

conducted in the UK, the randomised control trial and this 

was engineered from Oxford, a team, on a national basis. 

Almost every hospital in the UK was involved in this trial. 

Initially the trial design looked like this. You had five arms, 

two is to one, is to one, is to one, is to one, no additional 

treatment or HIV-, anti-HIV drug lopinavir/ritonavir, 

dexamethasone low dose, hydroxychloroquine, or 

azithromycin. Later on what was added was convalescent 

plasma or no additional treatment, another randomisation. In 

the second week, if the patients continued to deteriorate 
despite the initial intervention, then they were randomised to 

tocilizumab or no additional treatment when the cytokine 

storm was considered to be important. 

     So, what happened? That trial was started in-, end of 

March early April and first week of June, on the 5th of June, 

the data from more than 1,500 patients, 1,542 patients, in 

comparison with usual care in double that number. 

Hydroxychloroquine, it was found that there was no 

significant difference in the primary end point of 28-day 

mortality, between the hydroxychloroquine arm and the 

usual care. There was also no evidence of beneficial effects 

on hospital day duration or other outcomes. This indicated 
that there was no meaningful mortality benefit with 

hydroxychloroquine and therefore hydroxychloroquine arm 

was removed from the randomisation. And on the 16th June 

2020, there was groundbreaking results from this trial and as 

you would have all seen, a total of more than 2,000 patients 

were randomised to receive dexamethasone 6mg, once daily 

for ten days and were compared with double that number of 

patients who were in usual care. And what it showed is that 

dexamethasone reduced deaths by one third in ventilated 

patients. For the first time, there was a medication that has 

proven beyond doubt to bring about mortality benefit in 
ventilated patients one third and in patients requiring oxygen, 

outside of the critical care unit, one fifth mortality benefit. 

Based on these results therefore, it was concluded that one 

death could be prevented by treatment of around eight 

ventilated patients with dexamethasone and around one death 

could be prevented in 25 patients requiring oxygen alone. 

Next came the results on the 29th June, remember 

dexamethasone was the 16th June. On the 29th June it was 

shown that lopinavir/ritonavir, the anti-HIV drugs, did not 

bring about any clinical benefit. Again, more than 5,400 

patients and comparing it, more than 3,000 patients and it 

showed there was no mortality benefit and there was no 
evidence of beneficial effects on the risk of progression to 

mechanical ventilation or length of stay. So, anti-HIV drugs 

also have been removed from the recovery trial recently. That 

is a quick overview of what has been happening and I'd like 

to conclude by making the following points. 

     Future, as far as COVID is concerned, one of the biggest 

things that has happened, is training and teaching has been 

severely affected by COVID because students, trainees, 

fellows, are not allowed into the COVID ward. We need to 

think outside the box and think of ways and means to provide 

the training, continue to provide the training and we are trying 

to evaluate a few different techniques, such as the use of 360 

degree camera, the HoloLens and augmented reality and so 
on. The pandemic curve has indeed flattened and started a 

downward trend in many countries around the world. 

However, we can expect further low incidents with waves. It 

could also become endemic, therefore we need to remain 

vigilant, there is no room for complacency. Primary and 

secondary care services need to restructure and work 

collaboratively. I've spoken about post-COVID follow up and 

need to resume services. We cannot continue to ignore all 

those other patients who have non-COVID related conditions. 

We have seen a tremendous expansion of digital healthcare, 

telehealth, minimising face-to-face consults and this is here to 
stay and we've just got to expand on it and do it properly. 

Every patient who comes through for interaction in the 

hospital, will need to be isolated, tested, screened, prior to any 

interaction, any procedure in the hospital. We need to find 

novel methods, innovative approaches to ensure that this is 

speedy, accurate and effective. We're also looking at therapy 

remotely, example virtual pulmonary rehabilitation. We've 

already looked about and talked about the importance of 

research into therapy, vaccines and prophylaxis and this needs 

to be a collaborative, collective and consistent approach 

across the world. As I said in my first talk, nobody should 

think that they can be safe without making everybody else 
safe. Thank you very much indeed for your attention.  

 

Leonardo Fabbri:  Thank you very much Dr Mohammed 

Munavvar. And it's now my pleasure to introduce the next 

speaker, Professor Alvaro Cruz from the University of 

Salvador, Bahia. Alvaro is a professor of medicine, has 

contributed tremendously to the science and education in the 

field of asthma and allergic disease. Today he will address the 

topic of controlling the COVID-19 outbreak in Brazil. Is it 

possible? Alvaro, privileged to have you with us.  

 
Alvaro Cruz: Thank you very much to you. I'm honoured to 

be part of this most relevant discussion with such 

distinguished chairs and speakers. I'm especially pleased by 

the title of the programme, 'standing on the same side'. This is 

exactly why I chose this title. 'Controlling COVID-19 

outbreak in Brazil. Is it possible'? We are facing this combat 

regretfully completely divided. This is a dark side of Brazil 

that many of you know unfortunately. We have a minority 

living in good conditions and a lot in underprivileged 

neighbourhoods. This is the major split of inequalities in 

Brazil. The leaders should have been taking care of for a long 

time and trying to reduce this. Now we have another problem. 
This is my conflict of interest disclosure. My major links are 

with ProAr Foundation, Federal University of Bahia, the 

National Research Council in Europe that is developed to 

supervise me in Brazil. I divided this talk, brief talk, in four 

topics, the dimension of the Brazilian COVID-19 tragedy, the 

dangers of national division in fighting COVID-19, the strong 

response from the public health system and respiratory health 

as a global priority. You see the division of the Brazilian 

tragedy, the national trend in cumulative deaths to COVID-

19. Over 60,000 deaths, 602 the last day, mortality of 4%. 



L. Corbetta et al. 
  

 10 

Over 1,600,000 cases. And here you see the distribution of 

cases from the big cities at the seashore, towards the 

countryside in every state. And you see some white areas not 

affected by cases, it's because the population is scarcely 

distributed.  

     Now, some information from the City of Sao Paulo, the 

first one that was affected. The first case was somebody 

coming from Italy, as you know Sao Paolo has strong links 

with Italy. And what you see in this upper panel here, is an 
estimate of adherence to social distancing by anonymised 

geolocation monitoring Sao Paolo. You can see the numbers 

but they are all around 50%. So, it's social distancing that was 

in place that was happening in Sao Paolo, was never beyond 

60%, it got up to 59% in the beginning and now it's around 

47%.  

     I guess this is not enough, it's part of the reason that things 

are not well in Brazil. Some information which is important 

for coronary physicians, comorbidities amongst subjects 

dying with COVID in Sao Paolo. This is an estimate by May 

23rd, over 6,000 cases, 10% of them had lung disease, some 
sort of lung disease, and 3.4% had asthma. Asthma was not 

a lung disease but this problem of reporting comorbidity, 

especially the respiratory comorbidity, is a problem all over 

the world. An underscore of the fact that many chronic lung 

disease such as asthma and COPD are under-diagnosed, 

under-recognised. Now, some good news. Despite all of the 

problems we have and I will show you some of the 

background of the problems but now some good news. The 

numbers of deaths per day in Brazil in your upper left, 

apparently it's reaching a plateau and perhaps a trend to 

decline. The same you'll see here in the number of deaths per 
day in the state of Sao Paolo, a plateau and in the city of 

Salvador in the left lower graph where I live, there also seems 

to be a trend, or plateau or even decline. And the same 

happens in the city of Sao Paolo. There is certainly a plateau 

and perhaps a trend to decline. This is an interesting paper 

published recently from the US, that studied the association 

between mobility patterns and COVID-19 transmission in 

the USA, using a mathematical modelling study, in which 

they calculate the daily mobility information derived from 

aggregated and anonymised mobile phone data, as it was 

done in Sao Paolo. And what they have shown, is that the 

mobility patterns dropped by 35 to 63%, relative to the 
normal conditions, very similar to Sao Paolo as I mentioned. 

Mobility patterns are strongly correlated with decreased 

COVID-19 case growth rates for the most affected counties 

in the USA. They observe now, that individuals apparently 

anticipated public health directives where social distancing 

was adopted despite a mixed political message. Again a 

similarity with our situation in Brazil. 
      Now, I wish to share with you some facts. I will try to 

abstain from making judgements. The dangers of national 

division in fighting COVID-19. We'll see here some of the 

President's-, Jair Bolsonaro's recent statements and action. He 

has said in a national TV broadcast, that COVID-19 is just a 

bit of flu, that the priority should be for economic activity, this 

has been always behind his statements and he attempted to 

fight states and municipalities when they tried to promote 

social distancing. There was no real lockdown in Brazil in any 

major area and he said there was no need for social distancing 

because this would be bad for the economy. Then due to this, 
the first Minister of Health was fired, who was doing a very 

good job at the time. Then, he often took part in 

demonstrations with no mask, as you see in the picture. He 

ordered massive production of hydroxychloroquine in Brazil 

and due to this reason, the second of Minister of Health 

resigned because he didn't agree with using this bribery with 

no scientific basis. And the Ministry of Health has been led 

by a general so far. Another quote from President Bolsonaro, 

when he was asked about increasing numbers of deaths, he 

said, 'And so what, I make no miracles,' and he has attributed 

the responsibility to the governors and mayors. Then he said, 

'Those from the right take chloroquine. The lefties take 
Tubaina which is a popular soft drink,' making a joke about 

the political divides on medical matters, that has been 

unbelievable. But a strong response has been set up in Brazil. 

We have universal public health coverage from the 

constitution of 1988, it's far from ideal but it's there. It's one 

of the largest countries in the world in terms of population and 

you see as universal public health, by law everybody is 

covered. There was an emergency cash transfer to the 

undeserved and informal workers from the federal 

government, which was a law passed in agreement with the 

congress. There was support to employers and workers to 
avoid massive unemployment. 

     There were various aids from municipalities and states, 

direct involvement of many governors and mayors with the 

policy to combat COVID. There were shelters for subjects 

with COVID-19 and the war hospitals and ICU beds with 

ventilators built. Some other examples of a good response 

throughout Brazil, Sao Paolo University Hospital complex 

offered 1,000 beds exclusively to COVID-19, including 300 

ICU beds. There was a network developed in my university in 

collaboration with the FIOCRUZ, Foundation through the 

Ministry of Health, and a centre for big data called CIDACS, 

to analyse date and publish trends, daily updated from more 
than 5000 municipalities in all states of the country. We set 

up a tele-coronavirus hotline, in Bahia my state to help guide 

people on whether they should go to the health service. The 

state of Bahia and the city of Salvador are building COVID 

war hospitals and shelters. There was the SOS Favela in Rio 

trying to watch what happens in other certain populations. 

These are only a few of many good initiatives. Another thing 

that is worth mentioning, is the rapid generation of knowledge 

and I bring two examples here. A report from minimally 

invasive autopsies of COVID showing and confirming that it's 



Stand on the Same Side Against Covid-19 – The Future Strategies Against an Unknown Enemy 

. 

 

 

 11 

a systemic disease with major events in the lungs and 

involvement of various organs and tissues. The pulmonary 

changes are the result of severe epithelial injury, with 
microthrombotic vascular phenomena. You see here, in 

patients with diffused alveolar damage in fatal COVID-19, 

fibrinous microthrombotic in small sized pulmonary 

arterioles observed in eight out of ten patients. My 

colleagues, I wish to bring you to this broader scenario of 

respiratory disease. As you see here, COPD is responsible for 

5.72% of the deaths globally. Lower respiratory infection, 

5%. Lung cancer, tuberculosis, asthma, interstitial lung 

disease, the major respiratory disease were responsible, the 

cause of 16.92% of all deaths in 2017. It's going to be much 

more this year. The dimension of the Brazilian COVID-19 
tragedy is 63,000 deaths already. 

     There is national division which leads to major weak 

flanks in many fronts, regretfully. A strong response from the 

public health system has prevailed however in states and 

municipalities and respiratory disease are the leading cause 

of deaths globally. Some thoughts to share with you. Health 

specific hospital beds and ventilators are not enough to solve 

the problem. Social distancing has to be taken seriously from 

the beginning of the fight. Collaboration is key to planning 

strategically and preparedness. Capacity for research, 

surveillance and manufacturing essential products is crucial. 

WHO is vital for global health security co-ordination and 
response. Respiratory infections are a major threat to 

mankind. Cannons and bombs are useless to fight it but 

science, solidarity and sharing knowledge, work. Political 

leaders must engage with health authorities, not fight them 

and health is the most precious asset one has. Health 

problems respect no border and everyone must be cared for 

to protect all. And top priority has to be given to protect 

respiratory health, hopefully in a cleaner and greener role. 

Thank you very much.  

 

Leonardo Fabbri:  Thank you very much Professor Cruz for 
your nice presentation. We now move to the next 

presentation by Professor Adrian Rendon from Nuevo Leon. 

Professor Rendon is also President of the Mexican 

Pulmonary Society and today he will address the issue of the 

coexistence of two pandemics, TB and COVID-19. Professor 

Rendon.  

 

Luis Adrian Rendon:  Thank you. Okay. I live in a country, 

that is endemic for tuberculosis and now it's suffering the 

severe attack of COVID. So, I may speak a little bit about the 

coexistence of these two pandemics. I'm a member of the 

Green Light Committee from the World Health 
Organization, actually for PAHO, the branch for the 

Americas. Here, in these two maps, you can see the global 

distribution of COVID. Here, the darker the worse and the 

TB distribution. I put these two maps together because it 

seems that COVID territories respect tuberculosis territories 

but we will see later that this is not true, actually the opposite. 

The WHO report, averages about 10 million new cases of 

tuberculosis, incident cases and for COVID just in seven 

months we have overpassed that number with 11.5 million. 

About deaths, tuberculosis is in the top ten cause of death, 

tuberculosis is the number one infection, leading counts of 
deaths from an infection, with 1.5 million cases a year. But in 

just seven months, COVID is reaching more than half a 

million and if it was a race, maybe COVID is going to win 

this race if things are going on as we are seeing. Early this 

year before TB Day, the WHO launched this information note, 

before TB Day because there was some concern and they were 

pointing out two main questions. Number one, are people with 

TB likely to be at increased risk of COVID infection, illness 

and death. The main concern at that time was that the TB 

patients would suffer in their treatment because of the 

pandemic. We didn't know too much about the coexistence of 
the two infections, actually we don't know yet about that. And 

the second question was, 'Can we maintain and support the 

essential services for TB as prevention, diagnosis and 

treatment.' For prevention, it was clear that we have to limit 

the transmission of TB to COVID patients and COVID 

patients to TB because they may have similar clinical 

presentation, they can share some symptoms and they are 

often in the same places. If we were doing well with the 

respiratory protection measures, we shouldn't be worried, but 

we know that all around the world we were suffering from TB 

outbreaks among healthcare workers.      

     So, bilateral transmission is a real risk. For diagnosis, we 
have the proposal that all the TB patients and COVID patients 

at the moment with suspect cases, should have available the 

two tests, the one for TB and the one for COVID. But on the 

field, those two problems work independently and there is a 

real concern about biosafety. Nobody wants to test for TB if 

they are not sure the patient is not a COVID case. For 

treatment and care, most of the TB programmes have very 

specialised staff, including the physicians, immunologists, 

nurses and whatever was needed and they were supposed to 

be a group that could help in the COVID pandemic, sharing 

their expertise. But what happened in real life, is that expertise 
was transferred to COVID programmes, leaving alone the TB 

programmes. What about the coexistence of TB and COVID. 



L. Corbetta et al. 
  

 12 

What do we know now, we don't know too much. Now, I'm 

using this map to point out the endemic regions for 

tuberculosis. The red dots are COVID and you can see that 
COVID is anywhere.  

     It seems that there are more COVID on the industrialized 

countries but we can see the numbers, we can see that this is 

different because of the magnification in the map. Actually 

you can see here, we just listened to the case of Brazil, I can 

tell you about the case in Mexico. Mexico, Brazil and Peru, 

are the three countries in Latin America with more TB cases 

and they are also the three countries with more COVID cases. 

So, they don't respect each other, they are together. I'm going 

to present this case briefly. The coexistence of cases with TB 

and COVID, there are not too many. These cases, are cases 
in my institution. It was a young physician, a female who 

presented with a classical, clinical picture of pleural 

tuberculosis that was confirmed by culture. The patient was 

put on regular treatment, standard treatment. She returned to 

work and when she was in the hospital they performed 

screening for COVID on all the healthcare workers and she 

resulted positive. She was on six months of TB therapy, she 

has no symptoms and the chest X-ray taken at that time didn't 

show any findings suggestive of COVID. Currently the 

patient is doing well, she's continuing the TB treatment and 

she didn't receive any COVID treatment.  

This is the first cohort report, of the coexistence of the two 
diseases, tuberculosis and COVID. They collected patients 

from Russia, from Europe and from Brazil and they put 

together 49 cases. The median age was 48 years old, most of 

them were male, half of them were migrants, BCG has been 

applied in 63% of those cases. A minority was HIV positive 

and most of the cases were pulmonary tuberculosis. For the 

COVID presentation, 90% of the patients were symptomatic 

and 48% had COVID pneumonia. Regarding the time for the 

diagnostic, TB was diagnosed first in half of the patients, 

COVID first in almost 30% of the patients and the diagnosis 

was simultaneous in the same week in 88%.  
     The second paper is a kind of continuation of the previous 

one. They put together the 49 patients they already had, plus 

twenty more from Italy. They had a total number of 69 

patients and they look at mortality in this group and mortality 

was 11%. The risk factors they found, were the same we 

already know for COVID, the elderly population with 

comorbidities. They found less mortality in migrants and we 

can guess that one of the considered reasons was the younger 

population. This is a new paper that we are participating in, 

it was just submitted. This is a global study that includes all 

the continents in the world and we are looking at the impact 

of COVID on TB services. We are comparing the study of 

statistics, the TB statistics from February to May 2019, to the 
same period 2020. I wasn't allowed to present the results but I 

wanted to give you some numbers from my institution. What 

is the possible impact of COVID on TB services? This is a 

short list, a summary list of those. Shortage of supplies 

because of lack of mobilization and for the patients that are 

not going to the clinics, so we are suffering from inadequate 

follow-up with the patients. There is also a lack of services for 

TB, the small periphery clinics have been closed. 

There is a lack of TB experts because they are working with 

COVID, so that counts as poor quality of TB care. Also, the 

money is moving to COVID, the TB programmes were not 

prepared for it. We may guess what is the role on the severity 
of the two diseases when they are together. If one has got TB 

and they've got COVID, it's going to be a more severe case 

and the opposite is also true? In the case I just presented to 

you, it didn't happen, it was a priority here for a permanent TB 

infection and the COVID was an asymptomatic case. And 

what about the drug interactions. We don't know how to treat 

COVID yet but we're using many drugs, often labelled, and 

the MDR patients, XDR patients, using a lot drugs that can 

have very dangerous interactions with those drugs that we 

shouldn't' be using as we are. All of these issues lead to less 

TB diagnosis, delay in TB diagnosis, so we are expecting to 
have more TB cases there in the community but we're not 

aware of them. All of this is happening in my country, in 

Mexico. I've seen that and I can tell you that we are suffering 

from all of this and maybe in some countries like Brazil, they 

have the same situation. Here I'm going to show you some 

numbers that I have from Mexico and from my state, Nuevo 

Leon, which is very close to the border with the United States. 

This is last year, this is the current year, the period January to 

May. On this year, TB suspects, we have more than 60,000 

and in the same period we have about half.  

     We've decreased the number of TB suspects that we're 

studying and the same happened in my state. What about the 
TB cases diagnosed in my state. This is last year, this is 

current year. Over January and February, we were having an 

increasing number of TB cases, we were doing well but then 

the lockdown started in March and you can see that after that 

the number of diagnoses decreased a lot. And the worst 

scenario happened in my hospital. Our TB clinic was closed 

with the lockdown because of safety reasons, you had more 

than two months, actually three now, because we haven't 

diagnosed any TB cases.  



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Those cases are there but we haven't diagnosed them. 

The WHO was expecting to reach the milestone for 2025 

through the strategy, End TB elimination. This is the curve 

that they expect, this is what really was happening until 2019, 

this is for incidents and this is for deaths. When the pandemic 

hit this program, we can say that the expected is very difficult 

to reach for incidents and for deaths and maybe we should 

expect a resurgence of TB. We must be prepared to have 

many more TB cases, many more viral-resistant cases and 

also many more TB deaths and we need a damage control 

plan to deal with that. COVID is supposed to stay, it's very 
probably going to stay. TB wasn't really there. TB is going to 

stay and actually is going to be a stronger pandemic. Thank 

you very much for your attention.  

 

Lorenzo Corbetta:  Thank you very much, it is very 

interesting this correlation between TB and COVID and 

maybe Professor Laura De Paoli will talk about it in her 

presentation. I introduce Laura De Paoli who is the Platform 

Co-ordinator of WHO Europe and she will talk about the 

resurgences after COVID-19 in Europe. Please Laura.  

 
Laura De Paoli: Thank you very much indeed and good 

morning and good afternoon to everybody. Thank you for 

inviting me here Lorenzo, we've known each other for a long 

time. Okay, so this is a Situation Report of resurgences in 

EURO Countries. So, my name is Laura De Paoli, I'm the 

coordinator of the COVID-19 platform at WHO EURO at the 

moment in Copenhagen, at the moment I'm working from 

home. So, just a few words on the WHO structure. So, we all 

know that the headquarters are in Geneva, where there is the 

making of policy, protocols and there are experts on a 

number of businesses. And, then we have the regions. The 

regions are coordinating entities and also support of 
countries. Also, they do have experts there as well. So, there 

are six regions, AFRO, which is mainly the African 

continent, but countries can actually choose where they 

belong. So, we have Sudan, for instance, which is an African 

country, also Northern African countries, but Sudan is not 

really a Northern African country, which are actually they 

are affiliated to EMRO, which is Eastern Mediterranean 

Region. So, there are social, cultural, political and religious 

regions for belonging to a region rather than another one. So, 

for instance, Sudan belongs to EMRO because EMRO is a 

collection of Islamic countries and Sudan is mainly an 
Islamic country. EURO, which is the region I am working 

for, for instance, contains countries which don't belong to the 

European continent, but they are Central Asian countries, 

we'll see after. Then, there is PAHO, I think, and my 

colleagues from America, South America can tell me if I'm 

wrong, so it's Pan-American Health Organisation which is 

affiliated to WHO and I believe PAHO comprehends the 

whole of American countries. And, then we have SEARO, 

which is South-East Asian Region and WIRRO which is 

Western Pacific. 

    So, a very quick overview of the countries which belong to 

WHO EURO, which is 50 different countries and as you can 
see, I actually highlighted them in red, one is Azerbaijan, 

Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, 

Uzbekistan, which are not really considered normally, 

geographically, European countries. 

     Now, a very quick overview of the Sit Rep of which I'll 

give you a bit of a wrap up. We have over 200,000 deaths now 

in the EURO region. Since a few weeks, the number of new 

cases is no longer decreasing but has reached a plateau and is 

fluctuating at a relatively stable rate. And, we see small 

increases week by week, or small decreases. At this rate, we 

are seeing over half a million new cases per month, a very 
significant number of cases and this is happening at a crucial 

moment where countries are about one or two months from 

having lifted their lockdown measures. The picture is very 

mixed. In Western Europe, we still see countries where there 

is a stable decrease of cases, but in the Balkan region, Eastern 

Europe, the Caucasus and Central Asia, we see very 

significant increasing trends and in some cases, community 

transmission, which is the blanket transmission, which was 

not seen in early months. In Central Asia, numbers have been 

kept low in the early months and then with the lifting of 



L. Corbetta et al. 
  

 14 

containment measures, we see the health system of those 

countries struggling, with hospitals overwhelmed by the 

increasing number of patients. We see localized outbreaks 
which are explosive and have the potential to see new 

community transmission. What we also see, in some 

countries, is very prompt action and reintroduction of 

localized widespread measures to control those outbreaks. 

And, these outbreaks in school settings as we see in 

countries, such as Asia. You know, the countries we see 

localized outbreaks, in specific sectors of society, for 

instance, food processing factories. Lately, we saw an 

outbreak in a slaughterhouse in Westphalia, West Germany, 

where the cold surfaces promoted the stability of the virus 

and the outbreak. 
     Other important factors are who is working in those 

factories, are they migrant groups, do they live in 

overcrowded settings, which is a facilitating situation for 

spreading the virus? Other outbreaks have happened in coal 

mines as in Poland, where there are specific environmental 

factors, there's lack of ventilation that facilitates the 

transmission of the virus in confined settings. These 

localized outbreaks must be kept under control, otherwise 

they can easily spread out to community transmission. WHO, 

obviously, recommendation includes the three Ts, testing, 

tracing, and obviously, treating. And, localized isolation, it's 

important to know that isolation is not only for individuals 
who test positive or are suspect, but also of the very place 

where the outbreak has taken place. For instance, the 

factories and the mines. Over the summer months, we will be 

able to take action while the situation is under control, in a 

number of European countries. The situation will become far 

more encompassing in Autumn as the influenza virus will 

start circulating in the region and the complexity of 

managing two respiratory viruses at the same time, with 

similar symptoms, will be a major public health issue, that 

will require a multi-sector approach with agencies at 

community level. There is a specific importance in this 
situation of recommending influenza vaccination at a 

political level. About the influenza vaccine, we will see a 

shortage of vaccines, unfortunately, due to the very situation 

we find ourselves in with the pandemic. There is not a 

specific WHO recommendation for pneumococcus 

vaccination or BCG vaccination, which has been suggested 

in many instances by different sources over these past few 

months. About BCG vaccination, we have seen observational 

studies in mice and humans suggesting a protection against 

COVID-19. 

     But we need hard evidence in the form of a randomized 

control trial which has been now carried out over the last few 
months and now we are waiting for results which should be 

coming by the end of October, at the latest, the end of the 

year. Now, I would like to show you the, how do you get out 

here. Share, and then share again. I would like to show you 

very quickly because I know, that's it. Can you see the 

situation report? Can you see the coronavirus disease? So, 

this is the Sit Rep that WHO Geneva publishes every night 

after 9:00PM, more or less. And it's a daily report, they close 

gates around 10.30 in the morning, so this is the one of 

yesterday, the Sit Rep of yesterday until 10.30. So, here we 

have a map that shows where the most cases have happened 

yesterday. So, happened in the last seven days, so this is 

United States, Brazil, unfortunately, India and then we have 
Russia and also Saudi Arabia, Iran and Iraq, also and then 

Egypt and South Africa, in Africa, you can see that Africa is 

actually not terribly touched by the virus. Here, we have a 

graph that shows the new cases per day and here we have the 

Western Pacific, where China, Japan, South Korea are, we can 

see they are the very first to spike up and then there are still 

cases but they're under control, now lately there have been, 

maybe a few more cases. Now, there is South East Asia, now 

this is India probably carrying out the line towards the up, but 

again, we don't see the spike that we saw here in Europe, this 

is Europe and we see in America, it's quite a linear arithmetic 
line. Then, we see Europe here in orange, so we see the 

exponential curve here and then the plateau and then now, a 

bit of descent. And, now we have reached a second plateau, 

with as I said, some countries in Western Europe have a 

downwards curve at the moment, but in the Eastern European 

countries, Balkans and Central Asia, we have cases going up, 

we'll see it in a second. Then, we have Eastern Mediterranean 

which is receding but again, it's not exponential. 

     We see America which is definitely exponential right now. 

And, Africa, again, I worked in Africa until a couple of 

months ago and we could see that the cases just didn't have at 

all that spiky tend that we saw in Europe. So, is it the heat, is 
it the BCG vaccination, or most African countries have a 

policy whereby children from zero to six months of age are 

vaccinated with a BCG vaccine to avoid military TB in 

infants. So, now we go down through the countries. Again, we 

have South Africa, which is very high for an African country. 

We have many cases, 8,773 new cases yesterday, so it's a very 

high number. And, then we have Nigeria with 190, now South 

Africa is about 50 million people, inhabitants, Nigeria, I think 

190 plus million people and you can see that the number of 

cases are not very high. Some people say, do they find them 

all, are they able to identify them to diagnose them, now, 
being COVID, I'm sure you will agree with me, particularly 

in Africa, where I worked for many, many years, it's actually 

a city disease. It expands particularly in capitals or where 

there is a lot of incoming people, particularly from Europe, or 

from other countries where the incidence and the prevalence 

is higher. So, and then we have the Americas, with the United 

States as well all know, 57,000, the new cases of yesterday, 

Brazil, 37,900, so Brazil is also still going up and then Chile, 

Mexico and Columbia are quite high, considering, well 

Mexico is a very populated country, but the other countries 

are not as populated. Then, Easter Mediterranean, Iran, still 

very high, Iran was one of the first countries to be hit in the 
Eastern Mediterranean region. Then, we have Pakistan, one of 

the countries that should belong to South East Asia, but is with 

Eastern Mediterranean for the reasons that I spoke about 

before and Saudi Arabia, they have seen a very high number 

of new cases. Egypt as well and Iraq as well, we saw it before. 

     And, then we come to Europe, so the Russian Federation 

is by far the one with highest number of new cases and also 

the highest number, in Europe, of total cases, but keeping the 

number of the total number of deaths, not very high compared, 

for instance, to the UK, where we have a much lower number 



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 15 

of total cases, but a much higher number of total deaths. 

Now, these are official numbers, so we can believe them or 

not, but these are the official numbers that we do have. And, 
then we have Spain, we have Italy, which is on the coming 

down, fortunately. The UK has reached a plateau and it's now 

on the descending curve. It took it a while and it's due to the 

political choices really, the policies that weren't put in the 

place, the policies of lockdown, use of mask etcetera, were 

put in place much earlier in continental Europe and 

particularly Western Europe and they weren't put in place, or 

they were put in place very loosely in the UK. Turkey is still 

very high. Germany, after seeing a resurgence a few weeks 

ago due to what I was talking about, this resurgence in 

positive cases, over 600 positive cases in Westphalia in this 
factory, meat processing factory, where they went up to 700 

and 800, now it's on the coming down again. Then, I just 

wanted to show you in Eastern Europe, with Israel as well, 

with quite a high number of new cases, considering the 

number of inhabitants and that's due to the resurgence we 

were talking about. And, then, I just wanted to show you 

what we were talking about. Eastern Europe, for the number, 

when we compare the total numbers, for instance, of Ukraine, 

which is 49,000, with the number yesterday of new cases, 

1,366, there is a disproportion. We can see it's a very high 

number of new cases, so that's why we see Europe being on 

a plateau again, which is not really going down, because in 
Eastern Europe, as we said, Balkan and Central Asian 

countries, we see the curve going up still and it's the same for 

Kazakhstan, again a disproportion between the total cases 

and yesterday’s new cases, which is very high.  

     So, the recommendations, immediate action in testing and 

contact tracing and isolation when we find ourselves facing 

localized outbreaks and time is of upmost importance. 

Strengthening of influenza vaccination policy, influenza 

vaccination noting particularly for at risk groups and BCG 

vaccination or second dose is not yet recommended, awaiting 

results of randomized control trials. Thank you.  
 

Lorenzo Corbetta:  Thank you very much Laura. We have 

concluded the presentation so we can open the discussion, if 

somebody of the faculty has some questions, please.  

 

Mohammed Munavvar: Well, Lorenzo, if I may start. This 

is a question to the last speaker, Laura De Paoli, if you don't 

mind. Very interesting data that you presented, with regard 

to the African scenario, or generally even otherwise, one of 

the things that is missing in the data is the denominator, 

which is the number of tests which were carried out in each 

place. Because, what would be very useful, is a percentage 
of positive tests and secondly, also to get to know, another 

surrogate marker, is the number of excess deaths in that 

particular area compared to, say, last year. I just wondered 

whether you want to comment on those two points.  

 

Laura De Paoli: No, unfortunately we should have that, we 

don't have that in the Sit Rep of COVID, we should have 

more studies about there, to be honest with you, I have 

actually come across anything. The problem is, when we do 

our meeting, we have people presenting, but of course, being 

in Europe now, I'm only seeing people presenting about 

Europe. And, basically, what they're presenting, the platform 

is formed by WHO, UN agencies, they're all UN agencies 
operating in Europe and they are cross movement. So, we 

have people presenting on their work, what they do in the 

country, but we don't tend to have very scientific 

presentations, unfortunately and this is something I'm actually 

trying to work on, trying to invite people from academia to 

present more scientific work. It's basically, a forum formed by 

managers and so, we don't have enough scientific leverage on 

that and I wish we had more. I am not able to answer the 

question, unfortunately.  

 

Duccio Cavalieri: I have another question on a similar trend. 
If you look at the crude epidemiological models, that have 

been proposed for SARS-COV-2, Africa is not the only 

exception, there are several countries where the models do not 

behave as they should, I mean, as they hypothesized to and I 

have been collaborating with Mohammed there, and the group 

from University for years on innate immunity activation. So, 

I was wondering whether anyone has overlayed the data on 

vaccination in general and the rate of SARS-COV-2 cases, 

because I find the BCG hypothesis fascinating, but not 

sufficient to explain the differences also between the different 

African countries. And, the other question, several data just 

published by Harvard and other universities that show the 
crucial role of UV and transmission of the virus on micro-

particles that could be limited thanks to UV radiation, why it 

could be enhanced in conditions where there's a lot of fog and 

I'm thinking about several areas where the numbers were very 

high. So, let's say, I know you don't have an answer, but it's 

more for a discussion point, I have looked into the 

mathematics of the epidemiological models and they basically 

ignore, like, with the theory of the black box, to put numbers 

that control for the environmental factors and for the 

variability of the virus. So, in basically all the models, the 

virus is like a black box, you know, it's given as constant and 
in my opinion, delving into those variables could be maybe 

possible by looking into details on the data that we derive 

from Africa or other countries where things are unclear. But, 

as I said, it's true that we would need more samples, more 

stops, more analysis of the action presence of the virus 

throughout the world. But, it was an excellent presentation.  

 

Laura De Paoli:  You're welcome, thank you. Yes, it is for 

sure, it's a multifactorial situations, so we have the heat, also, 

well correct me if I'm wrong, I'm not actually a specialist, but 

we know that at 70 degrees, the virus is denatured, so maybe, 

now, I was in Central African Republic and there was, not a 
constant temperature, but for a good part of the day, we were 

over 40 degrees centigrade, so that must have a degree of 

importance. For instance, in South Africa, we have cold 

winters, I lived in South Africa for a long time and I know that 

in Cape Town it gets as cold as in Europe over the winter. So, 

for sure, climate plays a role, I agree with you, mostly likely 

as you said, the micro-particles with the fog, pollution, in 

Africa we don't have that. And also with vaccination, because 

also at some stage, also the polio vaccination, anti-polio 

vaccination was put on the table of discussion as a possible 



L. Corbetta et al. 
  

 16 

protection factor, because they switch the innate immunity 

on, basically, there is a modulation of T cells. So, it is 

probably multi-factorial, the thing is that just as well, in 
Africa, we don't have as many cases as we had in Europe, for 

instance, because in Africa, like in Central Africa, we didn't 

have any ICU beds, we had only a few ventilators, they 

belonged to some NGOs that worked in surgical units, so 

they needed the ventilators for the operations. We have very 

few oxygen concentrators, so fortunately, there is this 

situation of non increased exponential line in the number of 

cases, otherwise all of Africa will be wiped out, or a number 

of African people will be wiped out. We all know that the 

trend of an epidemic is towards a benign, it goes towards a 

benign outcome, the bell curve show that, but still we could 
have an extremely high mortality, if we had the conditions, 

whatever they are, that we had in Europe and the States, for 

instance. 

     We should find out about BCG very soon, because by the 

end of the year we should have the results of the BRACE 

study and I'm really hoping that there is something good 

coming out of that. And, there is no harm in vaccinating 

people, I don't know why WHO didn't put, okay, we have a 

policy of non-recommendation of BCG vaccination against 

COVID-19, but as it has been shown, the BCG vaccination 

operates such a good protection against a number of bacteria 

and viruses, or in general, also, inflammatory diseases of the 
respiratory system that why not have it, you know, like 

everybody. I had it, so I felt quite secure, a bit safer. I actually 

feel quite safe because I had it.  

 

Lorenzo Corbetta:  Professor Fabbri, have you any 

questions?  

 

Leonardo Fabbri:  Not really. I was intrigued by the 

presentation on tuberculosis and COVID-19 and obviously, 

it's a very relevant epidemiological and clinical issue, but it's 

also a stimulating immunologic open question, because one 
of the predictive factors of worse outcome in COVID is 

lymphopenia, whereas in tuberculosis, you have specific 

expansion of lymphocytes, particularly lymphocytes and I 

wondered whether in some cases, there might be actually a 

sort of protective effect of tuberculosis with respect to 

COVID, but it's just an immunologic question. I wondered 

whether Professor Rendon may make comment to that.  

 

Luis Adrian Rendon:  We may argue and we may verse 

against and in favor of theories, because talking about BCG, 

BCG is supplied to all newborns in Latin American, in many 

countries in Asia and in Africa and with all that, everything 
starts in China, BCG is supplied there, in India, BCG is 

supplied, they've had many cases. In Latin America, BCG is 

supplied and we are so far in a whirlwind pandemic, so if we 

have any kind of potential, we would expect less cases. Let's 

say that BCG doesn't protect against infection, but protects 

against severe forms of COVID, we are having a daily 

pandemic in Latin America, so you may guess against BCG, 

just because of the numbers. But, for instance, in my case, 

the case I present, there was a young physician, with BCG 

who has a primary TB infection and then got COVID with 

no symptoms. Was that because of the BCG primary 

infection, I mean the BCG vaccination or because of the TB 

primary infection that protected her from severe forms, we 
don't know, we are just arguing about that. But, anyway, if we 

think that BCG is good, well BCG is already played in most 

of these countries, so the people are already protected, they 

need that protection, we may argue about getting a second 

shot from BCG, nobody knows about that and I wondered if 

these studies that are being performed right now are going to 

give us that answer. Because, it's going to be very difficult to 

control many ambient factors for that. And, my main worry 

about Latin tuberculosis, that is highly prevalent in countries 

like mine, is when people got COVID a severe form and get 

dexamethasone or another kind of immunosuppressive 
therapy, they are in danger to have a reactivation of Latin TB. 

We should worry about that and we should be aware of that, 

it's going to be a great problem.  

 

Lorenzo Corbetta:  Thank you. I have one question from 

China, we have 2,000 people connected with us from China 

now and the question is about the vaccine for Professor 

Bonanni. They say, we all care when the vaccine will launch, 

could the speaker estimate the launch month? They are 

waiting for the vaccine. We are all waiting for the vaccine.  

 

Paola Bonanni:  This is an extremely difficult question, 
because we are all waiting for the vaccine to be available but 

we really do not know when it will be and which vaccine, 

because you have seen from my presentation that there are 

several candidates, some people who are developing the 

vaccine are also claiming that we might have a vaccine 

available in the next few months, maybe, some say that it 

might be the end of the year. But, I'm not sure on which data 

this is relying, because you have seen that most of the phase 

one, two and we need phase three studies of course, before 

launching a vaccine, there are at present one, two and a couple 

of studies in phase three. The others are in phase two, all 
companies and biotechs are rushing to get the vaccine, but 

actually, I would like to stress once more what I reported in 

my final slide. We must be very careful, because if we fail on 

safety on this vaccine, it might be an enormous danger for the 

credibility of all vaccines, because we have to consider that 

we have the problem of immune enhancement and that 

problem does not seem to be very heavy up to now for the 

studies we have seen up to date, but it's still a problem to solve 

and to exclude. And, the other thing is that we are squeezing 

research, pre-clinical research, clinical research, which 

usually lasts for seven, ten, twelve years into one year and we 

must be aware that we shouldn't be so anxious of having a 
vaccine if we are not sure that the vaccine is totally safe. I'm 

telling this, I am a vaccine lover, I define myself, because I'm 

working almost exclusively on vaccines and I love vaccines, 

they have improved the health of mankind in a way that is not 

comparable to any other measure or therapeutical 

preventative, but I am also conscious that we must preserve 

the reputation of vaccines. So, we need to be really very sure 

that if the vaccine is put on the market it is for sure, first of 

all, safe and of course it should be also effective. But, I don't 

want to give false messages, saying, oh we will have it in 



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December, or January, I don't know actually but I hope that 

when we start, we have a good vaccine.  

 
Lorenzo Corbetta:  We will have another video conference 

in September for updating. I have, maybe the last question, 

for Duccio Cavalieri The question is, are there countries who 

exhibited only one strain of the virus and does this explain 

the different incidence found in Africa?  

 

Duccio Cavalieri: No one knows. I mean, I don't have an 

answer for this question and it is true that the variance of the 

virus is something expected, there's nothing unexpected on 

the fact that the virus evolves. In virology, the definition of 

mutation has an interesting meaning, because there is genetic 
mutation and then there is a mutation sensed as usually a 

change in the virus phenotype, okay. There are indeed 

changes in the virus phenotypes, so far the two viruses 

described in China have a different phenotype. It's hard to 

say whether one is better and one is worse, apparently both 

viruses have been travelling and they have been all 

apparently, the most of them have been travelling via 

Munich, or Germany. So, Germany has been one of the hubs, 

because it's a commercial hub. So, the other reason why in 

Africa, potentially, there has been less of an explosion, it 

could be that the travelling of the virus has been less efficient, 

because maybe transport means have been less efficient and 
so, I think that mapping the evolution of these viruses is 

important for one reason. The theory behind the assessment 

of evolution of viral infection is quite complex and not 

necessarily seen from only one perspective. The naïve point 

of view says that the virus should attenuate, okay, which is 

what we usually expect, but the point is that viruses that can 

jump very rapidly from one host to another, so viruses that 

have a high rate of diffusion can escape this general theory, 

because they can basically get to the second host, when 

basically, irrespective of the fact that the first host is dead or 

alive. For sure, one of the tendencies will be to expand the 
phase where the individual has the virus, can transmit the 

virus, but the disease does not manifest, so the symptoms are 

not there and this is what the model that I showed is telling 

us, okay. I think, in general, that the summer would be a 

bottle neck and this is because this is the lesson we've learned 

from the Spanish flu, if you read through the history of 

viruses, summers have always been a bottle neck. 

    And, I think, the reason why they are a bottle neck is 

exactly related to the main factor, the transmission, how easy 

and how fast, what is the transmission rate. That number, 3.5 

is not the same throughout the entire year, sometimes it's 

probably five, sometimes it's 3.5 and it could be two. And, 
from that number depends the attenuation, because when that 

number goes down, in theory, the virus should decrease it's 

pathogenicity, it should become less aggressive, because it 

has to survive within the same host for longer. But, this is all 

to see, we have to see what will really happen. But, I don't 

know how many viruses go through Africa and this points 

out the fact that we should expand enormously the potential 

of sequencing the virus, rather than simply detecting the 

presence by means of real time PCR. Currently, I work in a 

laboratory that has the last level of sequencing facilities, we 

are hoping to sequence the strains from Tuscany. Sequencing 

has almost the same cost of doing the real time PCR test. We 

could boil down to maybe twice as much, but the amount of 
information that you get is significantly higher, so I hope that 

what is happening to us will lead to a technological leap that 

will allow us to change completely the way we look at viruses 

and we understand their movements.  

 

Lorenzo Corbetta:  Thank you, very clear. We have to 

conclude if the chairman wants to say something, Leonardo?  

 

Leonardo Fabbri: Thank you Lorenzo, thank you once again 

for organizing this initiative, I think we had a fantastic 

overview, very informative and very clear presentations. I'd 
like to thank all the speakers for putting so much work on 

these and I wish all of them to keep going with enthusiasm, 

but at the same time to protect themselves in their local 

situation. Thank you very much, once again for the privilege 

to co-chair with you this session, Lorenzo, thank you.  

 

Lorenzo Corbetta:  Thank you all, thank you for your 

presentations and see you all soon in another video conference 

with some updates on your studies. Thank you very much and 

thank you to all the attendees. Thank you, bye.