​When patients are admitted with COVID pneumonia, one of the treatment options is antivirus medicine - also known as monoclonal antibodies. New analyses of data from patients who were treated using monoclonal antibodies now show that there were differences in the effect, depending on whether the patients had developed antibodies themselves before they were admitted.

- Antibody treatment can have a beneficial effect if the patient has no measurable antibodies on admission. However, our results show that the same treatment can have an adverse effect, if the patient does have antibodies. This applied in particular for patients with a high level of antibodies in their blood, said Professor Jens Lundgren from Rigshospitalet. He is the head of the international research network, ACTIV-3, which has just published its results, in the scientific journal Annals of Internal Medicine.   ​

The 314 patients in the study were treated in 2020, half with a monoclonal antibody and half with a placebo. The study was stopped early, when the initial results showed that there was no difference between patient outcomes from the placebo or the treatment. However, in the new analyses, the researchers have looked more closely at the blood samples and virus measurements from nose tests and discovered that some of the patients who were treated with antiviral medicine had good effect from the medicine, while others did less well after receiving the medicine than if they had received a placebo. 

Of the patients with no antibodies in their blood, the group who received monoclonal antibodies treatment did better than those who received a placebo. They were discharged earlier, and there were fewer deaths. However, the opposite applied for the patients who already had antibodies in their blood when they were admitted.

- It depends on whether or not your own immune system has started to neutralise the infection, and this can be measured by examining whether the body is generating antibodies, said Jens Lundgren.

The monoclonal antibody examined in the study is no longer used to treat COVID-19 patients. The virus has mutated and become resistant to the antibody. Nevertheless, the new analyses are important knowledge for new patients and in future research. 

- That antibody treatment probably works for some but not for others, and perhaps may even have an adverse effect on them, is information that can get all physicians to stop and listen. Of course always we’re looking for something that can help patients, but if it actually turns out that it is downright harmful, it becomes a concern that considerably increases interest this type of study, said Jens Lundgren.

There is nothing new in the principle of treating patients with antibodies. During the Spanish flu pandemic in 1918, patients were treated with a serum extracted from people who had recovered from the infection. The monoclonal antibodies used to treat COVID-19 patients in hospital are produced in the laboratory with a view to helping the body to combat the acute infection.

- The principle has been used for various infectious diseases, but this is the first time that it has actually been documented to have a different impact, depending on whether or not the person receiving the treatment has already started to develop immunity, said Jens Lundgren.

Even though the results have been published today, the new knowledge is already being applied at Danish hospitals. After the analyses were completed in summer 2021 and published as a preprint, they have been included in the Danish guidelines on the use of monoclonal antibodies. Nevertheless, the new knowledge can still make a difference for future admissions. 

- The information has already been transferred into practice in Denmark. However, this does not mean that other countries have followed suit. The only other country that has changed its treatment guidelines in earnest on the basis of these results is the United Kingdom, where researchers conducted a parallel study with ours that arrived at more or less the same conclusion, said Jens Lundgren.

When a patient is admitted with COVID pneumonia, rapid action is required to determine whether or not the patient should be treated with monoclonal antibodies. Therefore, it is important to take a blood sample, which quickly can provide answers to whether a patient has antibodies in their blood. This is one of the issues the researchers are working on. 

- One of the challenges is how to get the analysis function close to the patient. You can't wait for a blood sample to be sent to the laboratory with a result five days later. This decision needs to be taken in a matter of hours. So we’ve been given access to a technology that can do a point-of-care blood test, analyse it by the bed, and come up with a result in just 15 minutes. In early next year, we’ll look around the world to see whether the results from this test are correct and reliable and can be used in the future, said Jens Lundgren.

The patients included in the study were infected with the original coronavirus. Today, the Omicron mutation will soon be the most prevalent. What this means for the option of treatment with monoclonal antibodies is a whole new question. 

- Omicron is a game-changer. We only found out last week that all these substances are challenged by Omicron. The changes in the surface of Omicron mean that antibodies don’t connect as well. This is the problem. A completely separate and very important problem has turned up, said Jens Lundgren.