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A scientist’s opinion : Interview with Prof Massimo Galli about covid-19 treatment

Interview Prof Massimo Galli, Coronavirus Covid-19 treatment illustration banner

Massimo Galli is Professor of Infectious Diseases, Director of the Department of Biomedical and Clinical Sciences Luigi Sacco, University of Milan, and Director of Infectious Diseases III Division, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, Milan, Italy. He is one of Italy’s leading COVID-19 experts. He has published hundreds of scientific articles in international peer-reviewed journals.

Compared to the beginning of the pandemic, there is currently a greater knowledge of how to treat COVID-19 patients. Has this factor – and in particular a more rational use of non-invasive ventilation – reduced the impact of the pandemic?

Massimo Galli: During the last few months a great number of patients have been treated, and this has allowed us to know how to better manage the disease. This contrasts strikingly with the early stages of the pandemic, when it was difficult to understand what we were facing. For example, the ability to manage blood-clotting complications during the disease was an important step forward. We now also have a greater ability to manage Remdesivir, the only antiviral drug currently available.

The use of non-invasive ventilation was almost obligatory in the acute phase of the pandemic, where entire medical wards were transformed into COVID wards, and certainly it was very useful.

Is solid primary care key in containing a pandemic?

Massimo Galli: I believe that there is an absolute need to radically review the primary care activities, which can play a fundamental role in preventive strategies in general. In the case of a pandemic, it must be feasible to rapidly implement surveillance strategies.

The experience we had was devastating, and certainly a more efficient primary care could have played a greater role in reducing the impact of the pandemic.

Long-term consequences of the disease – pulmonary fibrosis, coagulation problems, post-traumatic stress disorder: what can you tell us about this?

Massimo Galli: We are organising longitudinal studies to find out more. A number of patients discharged from hospital give accounts of chronic respiratory insufficiency: the loss of smell and taste, which affects many patients with COVID-19. In many cases people recover, in some cases it persists for a long time.

There are also subjects who in the post-COVID phase complain of generalised asthenia associated with components of emotional stress, where organic and psychological conditions are linked. The psychological distress created by the disease is significant and should be monitored and studied carefully.

The results of the Recovery study show that in patients affected by COVID-19, subjects who benefit from corticosteroids are those in the advanced stages of the disease or those who have a disproportionate inflammatory response to the onset of the disease. What is your experience with corticosteroids?

Massimo Galli: The study published in the New England Journal of Medicine by British colleagues shows that dexamethasone, at not particularly high dosages, has the ability to significantly reduce mortality. The results of this study are interesting and will affect my clinical behaviour in the future. Let me say that my experience with dexamethasone is limited by the fact that it was not recommended or even contraindicated in the guidelines until recently.

Maybe it is easy to say now, but in the past months I was wondering why corticosteroids could not be used in clinical practice during COVID, when different drugs were used, even in randomised studies, without a solid rationale behind their use. I wonder if higher dosages can be helpful. But the need to clarify the most valuable dosage is one of the open questions with which the study ends, a sign that new research is needed.

Can you tell me what you think about the other major therapies?

Massimo Galli: Remdesivir is a direct-acting antiviral drug with an action that can be termed ‘aetiological’. I have the impression that the drug could work much better if administered earlier. Being an antiviral, in theory the sooner it is administered, the sooner it is able to inhibit the virus, reducing the damage it causes. However, there are practical implications – the drug must be administered parenterally – and this necessitates a certain organisation in its use.

Hydroxychloroquine has been a bad example of scientific/political instrumentalisation, both for the inappropriate comments by some well-known politicians, and also because illustrious scientists have been exposed as supporting treatments before having real data available, and unfortunately also for the fact that the data have been manipulated, doing a disservice to science and medicine.

Regarding hyperimmune plasma, the data are still anecdotal. The production capacity of neutralising antibodies changes a lot from person to person, as does the maintenance of the antibody titer. Judgment must be suspended pending the availability of more robust data. Instead, I have more hopes – but here too times and means are to be verified – for the development of monoclonal antibodies. Once produced on an industrial scale, hopefully with the ability to bite different targets, they could have a significant impact on the course of the disease.

Many COVID-19 patients have a diagnosis of secondary infection, for which they receive antibiotic treatments. Some suggest that using a lot of antibiotics in a short space of time could exert selective pressure on micro-organisms, bringing a further increase in anti-microbial resistance (AMR) levels.

Massimo Galli: The AMR problem is an enormous problem, not only in the intensive care and infectious disease wards, but in all hospital wards. The contribution of COVID to the general situation regarding AMR is – in my opinion – marginal. I believe instead that in Europe we will have to use the pandemic to implement innovative approaches against AMR.

It is possible that the assault of the coronavirus in Europe next winter will be even harder than the one we just went through, because we are going to have a flu epidemic and the coronavirus pandemic at the same time. What is your opinion?

Massimo Galli: The coronavirus is different from the flu, and it doesn’t have to reappear with the rhythm which the flu displays with each pandemic. Coronavirus also spreads somewhat differently to influenza. For example, the so-called superdiffusers play an important role for coronavirus, while for influenza we are all equally diffusers.

Certainly, if the two epidemics were to overlap they would put a strain on the health systems again. To stay out of trouble, greater effort and investment will have to be made at community level towards an effective surveillance activity, associated with other simple precautions.

Given that flu and COVID have an overlapping symptomatology, and that the flu has a mortality rate of 7 000 to 8 000 deaths per year in Italy, to reduce diagnostic doubts a widespread vaccination for influenza is crucial, not only for the elderly but also for younger people and children, who are the great reservoir of the flu.

Finally, I trust in the development of new diagnostic tests for COVID. I refer to a test that replaces the classic swab and that is immediately readable, for example a test which identifies the antigen at a salivary level. Serological tests, which look for antibodies, do not identify recent infections. It takes about ten days for the development of antibodies after the onset of symptoms. The problem is then complicated by the fact that around 30 % of those who are infected and develop antibodies are completely asymptomatic.

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