February 16, 2021
AstraZeneca’s COVID-19 vaccine: EMA finds possible link to very rare cases of unusual blood clots with low blood platelets
April 8, 2021

Coronavirus Update FAQ 10


This is the tenth 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.
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.

  1. What are the new strains? What about their contagiousness?
    Do vaccines give enough protection against them?

    Ewelina Biskup (China) and Daniel Sereni France)

There are several potential reasons for being concerned by the Covid 19 variants. First, the variant may be more contagious, meaning that it will spread more rapidly in a population. Second, the variant may be more aggressive: it may produce a more severe disease in infected persons. Third, the variant may have a reduced susceptibility to available treatments or vaccines.

In the case of Covid 19 it has been observed that the UK variant which appeared at the end of last year in the UK was more contagious than the “original strain”. Actually, this variant is rapidly spreading all over the world. Fortunately, the UK variant does not seem to produce a more severe disease in infected people or to be resistant to available vaccines.

Many other variants have recently been identified, among them one coming from South African and several in the USA. At this moment our knowledge on the risks caused by these new variant remains limited. Several national organizations are monitoring the development of dozens of variants and the information is shared internationally.

The question of a possible resistance to vaccines is crucial. Vaccines are made to produce an immune response targeted to a specific spot at the surface of the virus (the Spike protein). In theory a mutation could induce changes in this protein and render the virus resistant to vaccines. In this case previously vaccinated people could be reinfected by a new Covid 19 variant.

Laboratories are already working on the adaptation of the vaccines that will keep them efficient. In this matter we can look at the example of the Influenza (flu) vaccines. Each year flu vaccines are made and marketed after being adapted to the predominant influenza variants circulating in the world. In fact, these flu vaccines target several strains of influenza viruses to cover all possibilities. One can imagine that, if necessary, the same process could be applied to Covid 19 vaccines.

The hope is that when a large majority of the population have acquired immunity, the Covid 19 infections will become rare so that vaccination and revaccination will only be proposed to persons particularly at risk of developing severe complications.

  1. Why will the mutation rate continue to increase?

    Ewa Biskup (China) and Daniel Sereni France)

As the virus mutates, it changes its genetic information. The result are new variants, not a new virus. Nevertheless, or exactly because of that, this has an impact on immunity, for example after an illness. But the question is: will the mutation rate increase? Most probably yes, and it is nothing new or unexpected!

The virus cannot control whether the mutation is beneficent or harmful for the virus itself – but those mutations that interfere with the virus or hinder the virus cause it to die out. This means, just as in the Darwin’s evolution theory: the fittest survive! In terms of the virus, this means that whenever a fitter viral line is present, natural selection will remove the inferior viral line because the fitter viral line will multiply more successfully. It has more offspring, and so can affect more people.

Usually, such a fitter mutation is more virulent and that is why it becomes more widespread as it circulates in the population. It makes sense: the virus fights for survival. It means, it will try to produce virus types that have the highest transferability – meaning, people can transmit the virus easily one to another (more infected people). The more people get infected, the more of the virus can be produced. Therefore, we expect that the new strains will spread more quickly in the population (more new cases) but will not necessarily cause a higher death rate.

  1. New clinical features of Covid 19

    Jan Willem Elte (The Netherlands)

In FAQ 2 we already discussed which organs are most frequently affected. Since then new clinical features have been described and they will be dealt with in this FAQ 10. Acute arthritis/polyarthritis: viral infections are a well-known cause of acute arthralgia and arthritis and Covid 19 is no exception. Arthralgia is rather common in Covid 19 (about 15 – 25%) and arthritis has been reported. Usually patients have a history of recurrent arthritis in different joints. Viraemia seems to be a likely cause. Treatment with glucocorticoids and baricitinib have been applied, however, only in very few patients.

Skin manifestations: Covid 19 associated cutaneous manifestations have been increasingly reported in recent months. According to an Italian review article clinical patterns of Covid 19-associated cutaneous manifestations can be distinguished: 1. Urticarial rash: 2. confluent erythematous/maculopapular/morbilliform rash; 3. papulovesicular exanthem; 4. livedo; 5. purpuric “vasculitis” lesions. Treatment with low-dose corticosteroids and nonsedating antihistamines has been suggested. The rashes and exanthem are often self-healing.

Heart infection (of myocard and pericard): Covid 19 can affect most parts of the cardiovascular system. These include the myocardium (heart muscle) and the pericardium (pericardial sac). Myocarditis and pericarditis are rarely reported manifestations. Several explanations other than viral myocarditis may be of importance, such as hypoxia, pulmonary thromboembolism cytokine storm or stress cardiomyopathy rather than viral myocarditis. Pericarditis can be caused by a direct cytotoxic effect and/or an immune-mediated mechanism. Treatments include corticosteroids, colchicine and anakinra.

Subacute thyroiditis (infection of the thyroid): subacute thyroiditis can be caused by any virus, so also by the corona virus. A few patients with subacute thyroiditis have been described, usually some weeks after the occurrence of Covid 19. Cytokine storm can trigger and perpetuate the inflammation of the thyroid gland. The symptoms (painful, enlarged and hard thyroid gland or features of thyrotoxicosis) and laboratory data ( increased inflammatory parameters and abnormal thyroid function tests) are similar to the known picture of subacute thyroiditis. Thyoiditis may also occur after asymptomatic Covid 19.

Diaphragm dysfunction: it appears that dysfunction of the diaphragm, the principle respiratory muscle, is often noted in Covid 19 patients. Muscle fibrosis and possibly myopathy may result from a direct effect of the virus. Virus infiltration has been described. The myopathy may lead to diaphragm weakness, which might contribute to failure of weaning from ventilator treatment, persistent shortness of breath and fatigue in patients with Covid 19 who survive their stay on the Intensive Care Unit (ICU).

  1. A different winter

    Stefan Lindgren (Sweden)

The past winter differs from what we are used to in relation to community outbreaks of viral infections. We have been heavily affected by the Cocid 19 infection but much less so with other respiratory and gastrointestinal virus infections. This has been obvious both in children and with regard to health care visits and hospitalisation of adults. What is the reason for this dramatic change, noted in most parts of the world?

It is clear that the break of the chain of transmission of such viruses must be related to preventive measures put in action to reduce the spread of Covid 19, and of course to a high coverage in the population with vaccine against the seasonal flu. But since many actions have been initiated simultaneously it is difficult to identify specific measures that are more effective than others.

In contrast to scientific studies, where usually one variable is used in different ways while the others remain constant. So we can conclude that the combined effect of different actions is positive, but we cannot evaluate the effect of individual precautions.

It is likely that staying at home and keeping children at home when ill, handwash and keeping distance offer effective protection from the spread of many viruses, not only Covid 19. The use of face masks probably also protects from spread of infections entering the body through the airways. Thus, even after the end of the pandemic there are strong reasons to preserve good habits of staying home when ill, washing hands often and carefully and keeping distance whenever possible.

  1. Give information about side effects of the vaccines. There are variable side effects, sometimes after the first and sometimes after the second vaccination. Immune reactions are different, most side effects in young people.

    Verena Briner (Switzerland)

The two types of vaccine against SarsCoV-2 (the virus causing Covid-19) which are used are by the new method (mRNA PfizerBioNTech and Moderna), and an inactivated virus (AstraZeneca) are used most frequently. The Johnson & Johnson vaccine uses a double stranded DNA instead of single stranded RNA.

An immediate reaction at the injection site such as pain and pruritus occurred in >80% of people vaccinated with the first dose of mRNA vaccine. Delayed reaction is less frequent, less than 1% (induration, erythema, tenderness and resolved within 4 to 5 days).

After the second injection (0.2%), however, these were regularly accompanied by symptoms such as chills, fatigue, myalgias, fever. General adverse reactions were more common in people 18 to 55y of age but still less than 5%. The onset was within 1 to 2 days and last 1 day: fatigue, headache, muscle pain, chills. Severe reactions were equally frequent in the placebo (0.5%) and vaccinated (0.6%) group and encompassed medical events occurring in a general population.

Antibody production after the two mRNA vaccines is several times higher than after Covid-19 infection! Thus, the desirable effect outweighs the undesirable effects by far.

  1. Why do patients of the same age have such different severity of the disease? More especially: why do symptoms not only differ in severity in each age group, but also within the same age group? Are there indications that certain genes, medication or nutrition are of importance?

    Julià Blanco, Bonaventura Clotet and Ramon Pujol (Spain)

Although it is not well understood what drives the infection to cause a more severe disease, it seems that some sort of abnormal innate (genetic) immunity response could account for this.

In summary, our immune system responds to the virus activating the innate defense against infection. This innate response blocks the response to the infection, which may lead to severe COVID-19 independent of age.

Specific cells in the the smallest air sacs in the lung produce pro-inflammatory cytokines (molecules important in the immune response) which will cause acute diffuse pulmonary damage in SARS-CoV-2 patients.

Significant achievements for a better control of Acute Respiratory Distress Sydrome (ARDS) caused by SARS-CoV-2 have been reported recently.
Baricitinib plus remdesevir was superior and safer than remdesevir alone in reducing recovery time and accelerating clinical improvement especially among patients requiring high-flow O2 or non-invasive mechanical ventilation.

The RECOVERY study was the world’s first to show that dexamethasone - a cheap and available steroid - reduces the risk of dying from COVID-19. The latest results from the study also suggests that for COVID-19 patients who have significant inflammation and require oxygen, a combination of a corticosteroid - such as dexamethasone - alongside tocilizumab reduces mortality by about one third for patients requiring simple oxygen, and nearly one-half for those requiring invasive mechanical ventilation.

The use of convalescent plasma as well as hyperimmune immunoglobulins and monoclonal antibodies constitutes an important part of the armamentarium to block progression of the disease that are currently being assessed in different trials. Regarding the use of convalescent plasma, it has been recommended to be administered as early as possible (preferably within 3 days after diagnosis). When patients suffer severe pneumonia this strategy is not effective, probably because at that moment what predominates is the inflammatory component of the disease.

To date, there is limited evidence that high-dose supplements of micronutrients or vitamins will either prevent severe disease or speed up recovery, although results of clinical trials are eagerly awaited. In contrast, there is strong evidence that prevention of obesity, and its consequent type-2 diabetes, will reduce the risk of serious COVID-19 outcomes.

  1. What advice do you give to a patient, who is immunocompromised, e.g. before starting chemotherapy or with hematological malignancies? What is the best vaccine advice?

    Lorenzo Dagna (Italy)

Immunocompromised patients are at risk for severe form of COVID-19, and this seems to be particularly true for patients whose immune system is weakened by chemotherapies used to treat cancers and hematological malignancies. However, people treated with immunosuppressive drugs for autoimmune conditions might also be at increased risk for developing severe COVID-19.

In this context, all immunocompromised patients should receive a COVID-19 vaccine. Ideally, the caregivers, household members and close contacts of these patients should also be vaccinated in order to further reduce the risk of transmission of SARS-CoV2 to those high-risk patients.

There are not clear indications about which specific vaccine should be used in these patients. In this sense, local guidelines should be followed. Ideally, the vaccine should be received before starting a chemotherapy or an immunosuppressive treatment.

If this is not possible, patients should discuss with their caring physician about the best timing for vaccination and if a dose of the immunosuppressive treatment should be withheld or delayed in order to maximize the effects of the vaccination.

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).