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It took a few months to understand that to kill the sufferers not Sars-CoV-2, but the hyper inflammation triggered by the immune response. Today, two and a half years after the start of the pandemic, the deaths from Covid in the world are about 6 and a half million, of which 175 thousand in Italy. The daily deaths in our country have reached one thousand. At first there was no cure, no certainty about how the virus worked. Some sick people suddenly worsened, ended up in intensive care, often died. The question cleared up over time, thanks to the work of doctors and researchers from all over the planet. The coronavirus replicates quickly in the incubation phase, then the first symptoms appear. Over the next few days, an abnormal immune response develops in some patients, resulting in hyper inflammation. A very violent attack that starts from our own body and can damage organs, lead to the formation of thrombus, cause respiratory failure, interstitial pneumonia, acute kidney or myocardial damage (the myocardium is the muscle tissue of the heart), superinfections, and even death.

How they work

Inflammation itself a defense mechanism which is activated to respond to a pathogen attack or repair damaged body parts. But if excessive and out of control it becomes extremely dangerous. When it became clear that inflammatory levels play a key role in the progression of Covid it became clear that it is not enough to act on the symptoms (fever, aches), but it is crucial to hit the root of the problem. In the protocol of the Ministry of Health on home care (for patients who do not require hospitalization) the possibility of using i Fans (non-steroidal anti-inflammatory drugs), unless there is a clear contraindication to use. There are many NSAIDs, but they all have the same mechanism of action: they inhibit an enzyme called cyclooxygenase (Cox), of which there are two forms (Cox-1 and Cox-2, the latter linked specifically to inflammation). Exist Non-selective fanswhich to varying degrees block Cox-1 and 2 (acetylsalicylic acid, naproxen, ibuprofen, diclofenac, nimesulide, ketoprofen, indomethacin, ketorolac, piroxicam, meloxicam, dexketoprofen) and NSAIDs active almost exclusively on Cox-2 (celecoxib, etoricoxib, firocoxib, mavacoxib, robenacoxib).

Studies

The idea of ​​using non-steroidal anti-inflammatory drugs from the beginning of the symptoms linked to a double objective: to reduce the risk of aggravation of the disease and to avoid a good number of hospitalizations, given that the pressure on hospitals in 2020 and 2021 was very high – he explains. Giuseppe Remuzzi, director of the Mario Negri Institute of Pharmacological Research and renowned professor of Nephrology at the University of Milan, among the first in Italy to start studies on the early use of Fans in the treatment of Covid -. We asked ourselves: why i bats (one of the Sars-CoV-2 tank animals) don’t get seriously ill and don’t show extensive lung lesions? Probably the secret lies in the ability to regulate the immune response based on interferon, which in bats rapid and does not reach high levels. In humans, however, the response may be too strong and prolonged: Fans avoid this from happening. In our first two studies, conducted between 2020 and 2021 together with Professor Fredy Suter and published in eBioMedicine e Frontiers in Medicine, we have shown that in the group of Covid patients treated early with non-steroidal anti-inflammatory drugs there is a 90% reduction in hospitalizations compared to those who received only symptomatic therapies. Also, according to a 2020 study, NSAIDs simultaneously inhibit most inflammatory mediators. A mechanism similar to that of drugs recommended for the treatment of severe patients: I think of some monoclonal antibodies as tocilizumab o anakinrawhich are directed against specific pro-inflammatory cytokines (e.g. interleukins 1 and 6).

The therapy

Therefore, NSAIDs can be used in mild to moderate Covid cases (when hospitalization is not needed), at the onset of symptoms. In some cases they are bought without a prescription, but however, consult your doctor to choose the most suitable molecule for your case and the appropriate dosages. Brief therapy, 3-5 days: in this way the risks of side effects are minimized. As a precaution, and in the presence of particular disorders, it is advisable to combine the anti-inflammatory a gastroprotective drug (such as proton pump inhibitors), especially if taking it for several days. The motto “hit hard, hit fast” – underlines Matteo Bassetti, director of the Infectious Diseases Clinic at the San Martino Hospital in Genoa -. Since we discovered that Covid is a fundamentally inflammatory disease, the clinical picture has changed, but also the therapeutic modality. Paracetamol, recommended in the first months of the pandemic, useful for fever and not the main symptom of Covid. The sick died of a “paradoxical” inflammatory reaction: they were treated with high doses of cortisone, even at home, but we know that this drug has an immunosuppressive effect. Now the cortisone used only in the hospital, while at home correct to resort to the Fans: acetylsalicylic acid, ibuprofen, ketoprofen, or even others based on the characteristics and habits of the patient. Conversely, a big mistake to take antibiotics if there is no real (and proven) bacterial superinfection: in the past two years there has been an excess of prescriptions for azithromycin and we will pay the consequences, in terms of antibiotic resistance, for the next ten years.

The other weapons

The increasing knowledge on Sars-CoV-2 infection has led to a good management of the disease – continues Bassetti -: today patients are treated effectively even at home and we doctors see few cases of respiratory compromise, which is the first sign of a possible aggravation. In addition to the Fans we also have other weapons for mild and moderate forms: antiviralswhich we should use more (especially in people at risk of severe disease), e monoclonal antibodies directed specifically against Sars-CoV-2. Some have lost effectiveness with the new variants, but sotrovimab e il mix tixagevimab-cilgavimab they also work against Omicron 4 and 5. Both antivirals and monoclonal antibodies are expensive drugs, unlike NSAIDs, they must be prescribed by the doctor and taken under strict supervision. On the other hand, if used correctly, they allow to avoid many hospitalizations and therefore represent a saving possibility for public health, given that each hospitalization costs many thousands of euros. However, the main defense to defend ourselves from Covid remains vaccination.