What we should take into account for the next global pandemic, according to virologist Pablo Goldschmidt (Chapter II)

For the Argentine professor and researcher at the Faculty of Medicine of the Pierre et Marie Curie University in Paris, it is highly probable that other pandemics will occur. Goldschmidt pointed out to Infobae why other already proven therapies for respiratory pathogens were not delved into. It is the second installment of a series of notes for reflection and retrospective analysis on the emergence of the SARS-CoV-2 coronavirus that caused a new disease, COVID -19. 

This conversation with Argentine virologist Pablo Goldschmidt occurred before the horror and carnage that was unleashed in the Middle East on Saturday, October 7 after the Hamas terrorist attack in Israeli territory. Goldschmidt experienced horror from the center of Europe, and it is an issue that hit him a lot. However, science continues its leafy course and deserves - perhaps more than ever - these reflections on what happened to global health in the pandemic and especially, on what to do with what is to come.

It is worth looking back at the CoVID-19 pandemic caused by the new SARS-CoV-2 coronavirus through the prism of Monday's newspaper, since this will help to dismantle some scientific-theoretical constructions that were believed to be absolute truths and can help problematize ideas for the pandemics that will come. This is what excites virologist Goldschmidt the most.

The first thing Goldschmidt makes is a list of clarifications - very pertinent - referring to the nomenclature of how journalists and those who spread science name the viruses and diseases of the pandemic. It must be said that given the volume of information that was generated in the pandemic, there are things that resulted in making the language of a global pandemic accessible and understandable for the majority and the Spanishization of terms from the original English. The Royal Spanish Academy has already ruled on several terms. Goldschmidt's little list:

-The viral disease (it is female), by international convention in Latin languages ​​is CoViD.

-The spelling would be CoViD (Coronavirus Viral Disease)

-The infectious agent is SARS CoV 2, acronym for Severe Acute Respiratory Syndrome Coronavirus 2.

From Monaco, where he resides, he begins this work and a series of subsequent dialogues with Infobae. Goldschmidt does not use the term vaccines to refer to the injections (1). Goldschmidt added that they reduced mortality in those over 65 years of age. He chooses to call them Prophylactic Pharmaceutical Preparations (PFP), understood as preventive medications. After the initial shock, when one listens to the rationale that emerges from his thinking: it became clear that vaccines against CoVID do not prevent infection or reinfection by the SARS-CoV-2 virus; nor do they prevent being a carrier and transmitter of the virus.

One of the great contributions of the CoVID vaccines is to prevent the severity that the SARS-CoV-2 virus has shown on some vulnerable organisms, and to prevent the disease from escalating and potentially causing death.

Three and a half years after the declaration of the pandemic, many of Dr. Goldschmidt's scientific definitions go against the so-called scientific consensus, because — as I already pointed out in the previous note — he affirms that in the initial phase of the pandemic previous experience available on how to treat respiratory viruses was not used, and this generated therapeutic approaches that led to more serious cases due to not resorting to appropriate strategies at the initial time of infection in people. They did NOT rise to the occasion, nor did they apply what was already known throughout the continent. 

This meant that, for several months, many of those infected and in vulnerable situations did not receive treatment in the initial stages of the disease. Added to this was a large number of patients with other disorders and pathologies who did not access adequate care, due to fear, a shortage of staff and resources, and the collapse of hospital services globally. Or, surely, all of this together.

—Dr. Goldschmidt, what would be the “other health strategies” that, according to you, should be taken into account in the event of future crises due to respiratory viruses?

—Goldschmidt: It is worth repeating that therapeutic strategies to deal with early and moderate forms of respiratory virus infections already existed in 2019, and their application depended on trained personnel. At that time, with hospital infrastructures neglected or non-existent, any position other than confinement raised suspicion, accusing that any point of view outside the tax was synonymous with adhering to this or that political interest. The irresponsibility of not accepting contributions from experience outside of a single idea showed its limits, and turned out to be responsible for having degraded the mental, physical and work health of the population.

Faced with future respiratory viruses, the effects of non-pharmacological interventions (social intervention strategies) would be potentially useful as long as they are established as integrated measures, early, and when virus incidence rates are low; which will depend on effective and flexible health systems, capable of reacting in time when cases of a new disease appear.

I insist that the initial key to public prophylaxis lies in protecting populations that are at risk from the complications of viral infections, limiting inflammatory complications.

Discuss and think

Under this premise, Infobae spoke with the renowned Argentine virologist Pablo Goldschmidt about the reasons why, if there was already extensive experience prior to the emergence of CoVID-19 about how to treat respiratory viruses, the imprint, nature and disruptive inertia posed by the pandemic meant that this prior knowledge was not applied to the medical treatment of SARS-CoV-2, neither by international authorities, nor by large health organizations in developed countries and emerging. 

Professor Goldschmidt left Argentina and moved to France more than 40 years ago and settled in Paris. Over the years, his career gained international relevance. With initial training as a Pharmacist and Biochemist from the National University of Buenos Aires (UBA) and a psychologist with clinical specialization from the same university, Goldschmidt expanded his studies in France. At the renowned Pasteur Institute he trained in Virology and later obtained a doctorate in Molecular Pharmacology from the Pitié Salpetrière Faculty of Medicine, part of the Pierre et Marie Curie University in Paris.

The role of vaccines

Thanks to the joint effort of the scientific system and the global pharma industry, in each of the countries, vaccines against CoVID-19 were developed in record time (2): between the end of 2020 and the beginning of 2021, they began to be available in almost all countries, under prioritized population strategies. The doses were first applied to the groups most vulnerable to the respiratory virus, such as those over 65 years of age and patients with comorbidities and the immunocompromised.

According to Professor Goldschmidt, there is no clear evidence that the reduction in mortality is entirely due to inoculations since the correct treatments also began to be applied in 2021.

—What is your scientific analysis regarding the efficacy and safety of - according to you - Prophylactic Pharmaceutical Preparations (PFP) against CoVID-19?

—Goldschmidt: a meta-analysis is available with data from 22 trials, and data from 3,404,696 adults over 60 years of age were also evaluated. It was confirmed that the three types of what I call Prophylactic Pharmaceutical Preparations (PFP), understood as medications against CoVID-19, were effective in preventing severe acute respiratory syndrome caused by SARS-CoV-2, reducing the number of deaths and subgroup analyzes showed efficacy in adults aged 65 years and older with at least one comorbidity, including obesity.

To date, it is not possible to establish definitive conclusions, probably due to the changes that occurred in the formulations over time, to which are added the typical circulating viral variants of mRNA viruses, the levels of immunity within a community. depending on previous infections, changes in public health measures (use of masks, educational level of the population, living conditions, hygiene, use of public spaces and transport, social distancing, travel, etc.)

The efficacy of PFP (N of R: vaccines) against severe forms of CoVID-19 decreased significantly six months after complete immunization, and the efficacy against moderate infections and diseases decreased by 30% in 6 months (from 4 to 6 months) after receiving the 2nd dose. Due to the ability to reduce levels of viral replication, vaccinated people who become infected will theoretically be transmitters of SARS-CoV-2 with lower viral loads (it is assumed without reliable evidence that transmission would be lower).

On this point, although not all the results of the clinical studies are available, it can be confirmed that they do not prevent symptomatic infection and do not eradicate the infectious agent. Taking the latter into consideration, vulnerable people who have received PFP are recommended to protect themselves when exposed in contexts of high viral transmission.

Myocarditis or pericarditis

— There is abundant scientific evidence on the efficacy and safety of vaccines against CoVID from innovative platforms produced with messenger RNA (3). You have gathered the latest statements from regulatory agencies on meta-analyses, which review whether there were or will be adverse effects from these vaccines. What consideration do you have for these ideas?

— Goldschmidt: The formulations, I repeat that they are not vaccines, but products based on mRNA, contain lipids that serve as a vehicle and protection for nucleic acids (ARM synthetic messengers that encode the synthesis of proteins of the viral spike). This carrier system is stabilized by conjugating it with polyethylene glycol, which forms a layer around the lipid nanoparticles that ensures the stability of the PFP.

The mRNA-based formulations of Pfizer/BioNtech (Comirnaty) and Moderna (Spikevax) received an emergency use authorization, confirming that there was no previous experience to explain the mechanism of the associated allergic reactions that they could cause in the population. The most common are early (generally within 24 hours after the injection) and transient (lasting between 24 and 72 hours) and most without serious criteria.

In clinical trials, these adverse effects were estimated at 4.5 cases of myocarditis or pericarditis per 100,000 injected, with a transient effect, which in the majority evolved favorably in a few weeks. Furthermore, between 3 and 48 days post-injection, rare cases of facial paralysis (Bell's palsy) were reported among 22,000 participants in a trial. In most cases, the paralysis disappeared within a week spontaneously or with appropriate treatment.

On August 28 of this year, the National Agency for the Safety of Medicines and Health Products (ANSM) of France and the French Network of Regional Pharmacovigilance Centers indicated that no new unknown forms of adverse effects have been reported in recent months. In France, nearly 157 million (156,788,000) injections against CoVID-19 have been administered since the beginning, of which more than 123 million are from Pfizer/BioNTech and more than 24 million from Moderna (data from June 2023).

Of all these injections, 193,934 reports of adverse effects were transmitted. The analysis indicates that no unknown pathology was identified in people who received a booster dose, either with the monovalent or bivalent PFP (N of R: vaccines), as well as after the administration of a heterologous booster.

The adverse effects demonstrated were high blood pressure, myocarditis/pericarditis, and heavy menstrual bleeding. Finally, the National Agency for the Safety of Medicines and Health Products (ANSM) continues to evaluate the appearance of arthritis, autoimmune hepatitis, deafness and events that are unexpected in severity, frequency and/or nature, since the information is not sufficiently substantiated to conclude on the role of PFP (N of R: vaccines).

In pregnant women, the reported spontaneous abortions do not allow us to conclude that these events are related to PFPs, especially because they were associated in several cases with other risk factors, also knowing that it is a relative event. common mind in the general population.

Public health strategies

— The images of collapsed intensive therapies in European and Asian cities and also here in Latin America shocked the global population in the first phase of the pandemic. Could the extreme tension in the health system that led to care have been avoided? deficient for vulnerable groups? Do you consider that the therapeutic approach during the first months of the pandemic was correct?

—Goldschmidt: Again... Respiratory infections cause inflammatory phenomena that progress from asymptomatic to critical forms. People with mild initial forms may present with fever, cough, sore throat, malaise, headache, muscle pain, loss of taste and smell, sometimes nausea and diarrhea, without difficulty breathing or abnormal chest images. During clinical evaluation (and/or by imaging), if the disease progresses towards the moderate form, evidence of airway inflammation is accentuated, with oxygen saturation greater than or equal to 94% in ambient air. Oxygen saturation of less than 94% in room air with a high respiratory rate indicates severe disease, which, if it progresses rapidly to respiratory failure, can lead to septic shock with multiple organ dysfunction.

SARS-CoV-2 causes severe inflammatory reactions in 5% of those affected. However, it was rare that in the initial presentations, the beneficial effects of active pharmacological agents that modulate the evolution of inflammatory phenomena were taken into account. Under these circumstances, neither ivermectin, nor hyperimmune sera, nor hydroxychloroquine demonstrated any clinical efficacy against CoVID.

The optimized management of each clinical presentation with anti-inflammatory therapeutics of validated efficacy significantly decreased the severity of the consequences caused by this viral infection.

The RECOVERY (Randomised Evaluation of CoViD-19 thERapY) project was launched to evaluate treatments for CoVID-19 in 175 hospitals of the National Health Service in the United Kingdom and confirmed the benefit of corticosteroids in the treatment of respiratory viral infections (with lung lesions) since they reduced mortality in a third of patients with severe forms (with a respirator) and by a fifth in patients who only received oxygen, without statistically significant benefits for patients with less severe forms who did not required respiratory assistance. In France, the Higher Council of Public Health (Haut Conseil a la Santé Publique) also recommends the RECOVERY protocol with details of the doses according to the type of corticosteroid to be used. And several studies proved years ago that corticosteroids reduced deaths in adults with severe pneumonia.

It was curious that, compared to the months that followed the identification of SARS-CoV-2, treatment with paracetamol and strict home isolation were recommended for those infected. The recommendations issued did not take into account either the consequences induced in virus-infected tissues—that is, the uncontrolled production and secretion of proinflammatory factors—nor the formation of often lethal thrombi due to viral attacks on the endothelium.

On the other hand, before 2020 it was known that viral pneumonia carries the risk of bacterial superinfections that should be treated with appropriate antibiotics, always keeping in mind the administration of corticosteroids. The most common adverse effects of corticosteroid treatments, if they are prolonged and at high doses, are the appearance of bruising, increased blood pressure, water and salt retention that can lead to heart failure, mood and/or sleep disorders. sleep, hypertension, weight gain, swelling and redness of the face, etc.

According to recent recommendations from a panel of experts from the US Centers for Disease Prevention (CDC), the main objective of the therapeutic management of non-hospitalized patients (which was already known) focuses on preventing progression to serious illness, hospitalization and death. Other goals may include accelerating recovery from symptoms, viral clearance, and prevention of long-term sequelae.

As indicated, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), steroids and antibiotics administered promptly, and monitoring risks of adverse effects, were and continue to be necessary therapeutics for respiratory virus infections in their initial, moderate and severe forms, to which the effects of paracetamol are insufficient.

—In addition to PFPs (N of R: vaccines), development and scientific research have provided a series of therapeutic tools against CoVID-19 during this time. What products - according to you - have demonstrated efficacy against SARS-CoV-2 and CoVID-19?

— Goldschmidt: New therapeutic alternatives are available, some directly antiviral that have shown clinical efficacy. It is possible to list the main ones: Paxlovid (Pfizer), which is administered orally and combines two molecules (nirmatrelvir and ritonavir); It interrupts the replication of SARS-CoV-2 by binding to protease, an enzyme necessary for the function and reproduction of the virus. In May 2023, the US Food and Drug Administration (FDA) approved Paxlovid for the treatment of mild to moderate CoVID-19 in adults at high risk of progression to severe form.

One of the active ingredients present in this medication, the ritonavir molecule, is a Cytochrome P 450 inhibitor, which implies that it can interact with other medications. Cytochrome P 450 converts substances circulating in the blood into removable molecules.

Therefore, all medications that interact with Cytochrome P 450 present a double problem: first with medications that are eliminated thanks to Cytochrome P 450, because by competing for functional sites, their concentrations can increase, with risks of serious or serious reactions. potentially fatal.

Molnupiravir (made by the biopharmaceutical company MSD and known in the United States and Canada as Merck & Co.) is an oral medication initially intended to treat influenza and hepatitis C that interferes with the replication of viral RNA. The results of Molnupiravir plus usual procedures for the management of respiratory virus infections were superior to usual care, with a significant reduction in the estimated mean time to clinical recovery. Molnupiravir was not authorized for prevention before or after exposure to SARS-CoV-2, nor for the initiation of treatment in patients hospitalized for CoVID-19 since no effects have been demonstrated when treatment was started after hospitalization for CoVID-19. severe forms. When this molecule was evaluated in two rodent mutagenicity assays, one study showed doubtful results and in the other study, there was no evidence of mutagenicity. Therefore it is not recommended for pregnant women. For patients who may urgently require this molecule, strict fertility control is recommended during treatment and afterwards.

On the other hand, it is not authorized for use in patients under 18 years of age because it could affect bone and cartilage growth. Its use is limited to situations where other treatments for CoVID-19 are inaccessible or not clinically appropriate.

Remdesivir is an adenosine analog drug that inhibits the replication of SARS-CoV-2. It was approved by the FDA for the treatment of CoVID-19 in adults and children older than 28 days and weighing more than 3 kg who are hospitalized with CoVID-19 and for those with mild to moderate CoVID-19 who are not hospitalized but at high risk of progressing to serious illness. In patients with mild to moderate form not treated with PFP (N: vaccines) and at high risk, treatment for 3 days with intravenous remdesivir resulted in a relative reduction in the risk of hospitalization and death.

Baricitinib (Olumiant) was approved on June 13, 2022 by the FDA as an alternative for the treatment of CoVID-19 in hospitalized adults, if initiated within 48 hours of invasive or non-invasive mechanical ventilation, or membrane oxygenation extracorporeal, with a recommended dose of 4 mg once daily for 14 days intravenously or until hospital discharge. Baricitinib is an inhibitor of the Janus kinase (JAK) enzyme that decreases the activity of the immune system.

Vilobelimab. The FDA issued an emergency use authorization (EUA) in April 2023 for Vilobelimab, an anti-complement fraction C5a monoclonal antibody. In Europe, the Health Authority also authorized the use of vilobelimab (Gohibic) for hospitalized adults within 48 hours of starting mechanical ventilation or extracorporeal membrane oxygenation (800 mg IV up to six times during treatment).

Tocilizumab (Actemra) is a monoclonal antibody that binds to both soluble and cell membrane-bound IL-6 receptors, preventing the binding of interleukin-6 (IL-6). It was approved by the FDA for the treatment of CoVID-19 in hospitalized adults if treatment is initiated within 48 hours of hospitalization. It is used alone or in combination with other medications to relieve symptoms in patients requiring supplemental oxygen, invasive or non-invasive mechanical ventilation, or extracorporeal membrane oxygenation. Tocilizumab is administered by 60-minute intravenous infusion, ideally in combination with a steroid equivalent to 6 mg dexamethasone. It should not be used on an outpatient basis and is not recommended for use in patients with CoVID-19 breathing room air (those who do not require supplemental oxygen).

All clinical trials and recent reports agree that the therapeutic management of non-hospitalized patients with mild to moderate CoVID-19 who do not require supplemental oxygen should be initiated early. For non-hospitalized patients with mild to moderate presentation and at high risk of clinical progression, the nirmatrelvir/ritonavir (Paxlovid) combination has proven to be effective and if no other agent is available, remdesivir or molnupiravir may be indicated.

— The SARS-CoV-2 virus is transmitted through aerosols in particles secreted into the air, hence its high transmissibility capacity. So, both for the coronavirus that causes CoVID-19 and any other virus, with a similar way of spreading, that should define specific strategies?

—Goldschmidt: Several strategies are known to combat the danger of spreading an infection, especially if it is transmitted by respiratory secretions in the air. The first consists of isolating the detected cases and their contacts, thanks to exhaustive screening, to limit and eliminate the infectious agent in a given territory. This “track, identify, isolate” strategy was adopted early on in South Korea and Singapore. Other countries tried to put it into practice without success, due to confusion of rules and general fear.

The second consists of isolating vulnerable people, as well as their caregivers, in humane conditions and with all the necessary material and emotional support. Sweden has partially implemented this strategy with limited initial success because the lack of rigorous isolation of vulnerable people led to deaths among the elderly in institutions that remained open, calling into question the quality of this poorly applied measure. This second strategy requires logistics to materially and emotionally support confined people, and seems the safest and most respectful in the long term. It would have been appropriate in the face of the risk of widespread spread of respiratory viruses.

*(N. of the R.) The bibliographic citations that support the statements and scientific assertions of Dr. Pablo Goldschmidt in this note are available through my email dablanco@infobae.com and were provided by him himself. Por Daniela Blanco. 

1: Professor Goldschmidt considers that they are not vaccines but prophylactic pharmaceutical preparations because they do not fulfill the function of a vaccine. "If they were vaccines, people wouldn't get infected as much." "... it's like when you say I'm going to Africa and I'm afraid of getting malaria. I take a malaria pills. With CoViD you're afraid and you take this pharmaceutical preparation, you get an injection to not to go to intensive care, but it is not a vaccine. It means that people who talk about vax and anti-vax are also misnaming. Those who are talking about immunity are also misnaming. Those who are saying that the pharmaceutical industry is behind it... No, the pharmaceutical industry profits from ignorance. When people are ignorant and make things done, well... There are people who say how I make money with the brutality of the experts", Pablo Goldschmidt said in an interview with journalist Samuel Gelblung.

2: The journalist believes that achieving the vaccines in "record time" has been a good thing. But science needs time to know, therefor... Time will tell... (Translator's note).

3: This is stated by the interviewer, a journalist, not a scientist. (Translator's note).

LINK TO THE ORIGINAL ARTICLE (Spanish