October 30, 2020
December 17, 2020



This is the sixth of a series of Covid-19 newsletters from FDIME (Foundation for the Development of Internal Medicine in Europe). The aim of the newsletters is to present qualified answers to the public, specifically on issues in which internists have a saying.
In this newsletter (FAQ) you may read the latest and important news on the vaccines.
FDIME is a non-profit organizations, which aims to improve medical care for patients in Europe and has several activities promoting medical research and medical education of young European specialists in internal medicine. FDIME supports young internists to attend the European School of Internal Medicine, participate in the European Exchange program and also provide grants for research in Internal Medicine.

You are also invited to pose additional questions, which we can try to answer in one of our next newsletters.

Some new information about vaccine and antibody response in Covid-19 infected patients.

1Pfizer and Biontech and others just announced a protective vaccine tested. Is it safe and soon available for everybody?

More than 38’000 people received the vaccine twice (day 1 and day 21) and seem to have protection. Generally, study persons are more likely to be healthy and young. But vaccines have to be safe and effective independent of the age of the person and also in high risk, e.g. persons with lung disease or diabetes, etc. It is not known yet, how many doses of vaccine are needed and for how long immunity and protection lasts. In large clinical trials also side effects have to be looked at. Independent review is needed too. All this information is needed before a vaccine is approved by national registries. The Biontech Covid-19 vaccine is available most likely early to mid 2021 and gives protection for at least 90 %. At the same time Moderna announced their mRNA-1273 vaccine of more than 94% efficacy. The commercial production of the vaccine will start in Switzerland next year by Lonza. Another frontrunner vaccine was developed by the university of Oxford and pharmaceutical company Astra, which induced an immune response in young and old adults when exposed to non-replicating weak viral vector containing the target antigen of SARS-CoV-2. Due to a low infection rate during summer, the study is delayed. Now (231120) it has been communicated that this vaccine will be available soon and gives protection for 60 – 90 %. CanSino, a Chinese company uses the same vaccine type. Sputnik V is also an adeno-viral vector based vaccine registered by the Russian Health Ministry.

2Will there be only one kind of vaccine against SARS CoV-2 but various companies distributing it?
No, about 50 scientific groups are studying various methods to produce a vaccine. The target is the site against which the vaccinated person produces antibodies to neutralize the virus and get rid of it. The vaccine can be the inactivated or weakened SARS-CoV-2 virus, a fragment of the virus such as a protein. The newer methods use genetic engineered material of the virus (RNA) to generate a protein that itself promotes an immune response. Another virus such as adeno virus gets the genetic material of SARS-CoV-2 inserted. The Astra and BionTech vaccine is based on mRNA. The latter vaccine has to be stored in -70°C. To keep the cold chain will be a challenge in the world wide distribution.
3Are there any other vaccine, such as against seasonal flu, which also provide some protection against Covid-19?
Currently there is no evidence for this. However, seasonal flu can weaken an individual and, in the case of a simultaneous or short-lived Covid-19 infection, can possibly lead to a more severe course. Seasonal flue can have a severe course and require hospitalization. The flu vaccination may protect against this and thus, hospitals can be relieved of patients with seasonal flue.
4Currently we do throat swab in Covid-19 suspected persons. If genetic corona virus material (RNA) is detected in the throat swab, is this equivalent to living viruses in the throat?
No. The swab sample is analyzed in the lab by RT-PCR (Reverse transcription- polymerase chain reaction) method. A French group has shown that the result does not correlate with viral growth in a culture. It has been shown that the higher the number of sample amplification cycles used for PCR, the fewer intact viruses could be cultivated! This means that a positive PCR result of SARS-CoV-2 RNA in the throat swab and negative viral culture is either very early in the course of the disease and the patient gets sick soon or the disease already lasts and the patient is probably no longer infectious. That means that after 10 days RT-PCR swab may be positive but virus culture negative. It is an important finding for both, the evaluation of infectivity and the duration of quarantine. Recently, a quick test was developed to analyze the nasopharyngeal swab for antigen of the virus. Although the results are less accurate (sensitivity 80%), the test is approved, because it is much faster (20 minutes) than the PCR method (24 to 48 hours) and currently the quantity of PCR test material is not enough to test all the desired persons. In various countries, for example in Switzerland, the test can also be performed outside of certified laboratories, e.g. in pharmacies.
5When are antibodies against SARS-Cov-2 detectable in the blood?
The majority of test assays we use, are detecting only one single corona virus antigen binding site (most spike protein). A group from Milan has shown the complexity of the immune response in Covid-19 infection. Their patients developed various antibodies (IgG, IgA, IgM) against multiple SARS-CoV-2 sites. The IgG antibodies against the receptor binding domain was predictive of survival independent of other factors (age, sex)! The concentration did rise and up to three months after recovery. Spike IgA antibodies was associated with a faster clearance of SARS-CoV-2 form the upper respiratory tract. The antibodies were detectable in almost all patients within 4 weeks after the onset of infection. The titer level of antibodies correlated directly with the severity of the disease. Currently it is not known if the antibodies against SARS-CoV-2 derived from the infection protects from second SARS-CoV-2 infection. In the literature recurrences after a proven Covid-19 infection are published. Uncertainty also exists about the protection after vaccination. Maybe different vaccines have different effects.
6Are the antibodies specific against SARS-CoV-2 viruses?
According to a newer study, there is some cross-reaction between SARS-CoV-1 and -2 antibodies. However, only SARS-CoV-2 antibodies have a neutralizing effect on the Covid-19 virus and are therefore protective.
7Can serum from convalescent (recovering) patients be given to infected patients to prevent the disease or reduce the severity of the disease?
Yes, this is possible, as for example also in case of an injury with a hepatitis B contaminated needle, serum with anti-hepatitis B can be administered (passive immunization) and hepatitis prevented. In Covid-19 infection, serum was obtained from one patient with a severe course. The antibody he produced against SARS-CoV-2 was isolated. The company Eli Lilly produced synthetically an identical antibody called LY-CoV555. Now, they are testing this antibody in Covid-19 patients in phase 2 study programs.

Science is like a puzzle. Many pieces are needed to see the whole picture. Interpretation of only one piece can be risky. Still, scientists are excited about every piece, pharmaceutical companies are ambitious to be first with new products, politicians are obliged to provide good health care, etc. New puzzle parts reveal new insights and are taken into account and might change the whole interpretation. That is science. But with every puzzle part we get closer to the aim: better health for humans.

Author: Verena Briner

The Foundation for the Development of Internal Medicine (FDIME),

Daniel Sereni, Ramon Pujol, Jan Willem Elte.

With the help of Imad Hatem, Nica Cappellini, Lorenzo Dagna, Chris Davidson, Runolfur Palsson, Stefan Lindgren, Vereny Briner, Werner Bauer (in random order).