SARS-CoV-2/COVID-19, COVID-19 Vaccines and Mitochondrial Disease
Updated November 24, 2020
There have been questions posed to UMDF regarding recommendations about people with mitochondrial disease receiving one of the COVID-19 vaccines in development. As of this date, two candidate vaccines are being submitted for Food and Drug Administration (FDA) “Emergency Use Authorization” (EUA). The Scientific and Medical Advisory Board (SMAB) of the UMDF discussed the issue in detail, and these comments reflect the board’s discussion. The UMDF and SMAB of the UMDF strongly recommend following the policies set forth by the Centers for Disease Control and Prevention (CDC), which can be found at www.cdc.gov.
SARS-CoV-2 is the virus that causes a disease referred to as COVID-19. Some people who contract the virus remain asymptomatic but, at the same time, continue to spread the virus to others. Others experience a flu-like illness characterized by fever, cough, sore throat, runny or stuffy nose, body aches, loss of appetite, fatigue, and headache. Vomiting and diarrhea are reported in some cases. One of the common symptoms is loss of taste and smell, which may take months to resolve. These symptoms range from mild (treatable at home) to severe (requiring hospitalization and even intensive care). Some people may die as a result of their infection. Although the knowledge gained during the first wave of illness in the spring of 2020 has allowed for better therapies in the fall of 2020, the risks of serious long-term complications and death still remain. There have been patients with mitochondrial disease who have contracted COVID-19, and the course of the illness is similar in scope to what is seen in the general population. It is our opinion that COVID-19 poses a significant threat to those with mitochondrial disease, as would be the case with many viral infections, such as chicken pox, influenza and other common respiratory viruses.
The standard approach to viral illnesses in people with mitochondrial disease varies from treatment team to treatment team and discussions along these lines are documented in an article authored by members of the Mitochondrial Medicine Society (MMS), and is available at https://pubmed.ncbi.nlm.nih.gov/25503498/. This paper details some general recommendations that may be helpful to patients and physicians; however, there are no evidence-based guidelines that are specific for any given patient. If you think anyone in your family has symptoms of COVID-19, we advise that you seek out the recommendation of your health care team. As part of general medical practice, both fever and dehydration should be treated with standard medical management. Common measures such as bedrest, ibuprofen or acetaminophen and fluids are also recommended. Antiviral medications may be given for more severe cases. It is important to note that these medications have not been tested in the mitochondrial disease population but are believed to be safe. The use of high-dose glucocorticosteroids is often used in those with impending serious lung involvement or inflammatory disease, and the benefits and risks of these drugs need to be weighed accordingly. As with other viral infections, aspirin should be avoided.
Although technically not considered alive, viruses infest or exploit nearly all living things. A virus is essentially a small amount of genetic material (DNA (deoxyribonucleic acid) or RNA (ribonucleic acid)), which is surrounded by a protein shell called a capsid. When a virus infects a cell, its sole purpose is to make more copies of the virus. This is accomplished by hijacking the machinery inside cells to make more viral RNA (or DNA) and viral proteins. Inside each cell, hundreds of viruses are produced – causing the cell to eventually burst and die. The released viruses can then attack the surrounding cells leading to exponential growth in the number of viruses.
Immunization for COVID-19 will soon be available. As stated above, two companies (Moderna and Pfizer) have already filed for “Emergency Use Authorization” with the FDA. These two lead products that are near to market are mRNA (messenger RNA) vaccines, a technology that has been developed over the last decade. While most viral vaccines contain inactivated whole virus, or pieces of one or more viral proteins, the COVID-19 mRNA vaccines contain the genetic code or blueprint for a SARS-CoV-2 surface protein known as the spike protein. Studies have shown that a durable immune response can be elicited by the SARS-CoV-2 spike protein. The viral mRNA is packaged in a lipid carrier. It is important to note that this vaccine is NOT the SARSCoV-2 virus, nor can a functional virus causing infection be assembled in cells from this vaccine. During vaccination, the mRNA-lipid particle enters muscle cells, where the cellular translation factory turns the mRNA into a fragment of the spike protein. This protein fragment is then presented to the immune system by the muscle cell, which recognizes it as foreign, and elicits an immune response and the formation of protective antibodies. This is what protects us from or attenuates infection with SARS-CoV-2. Unlike DNA, which is very stable, mRNA degrades quickly unless kept at supercooled temperatures. Because of this, mRNA vaccines need to be stored and shipped in special freezers. While mRNA vaccines have never been used in humans before, recent human trials evaluating COVID-19 mRNA vaccines have been very encouraging: >95% effective in preventing infection and a high safety profile. However, children have not been included in the trials conducted to date, and it is unclear at this time when any of the vaccines will be available to children. This has prompted the American Academy of Pediatrics (AAP) to issue a statement encouraging the inclusion of children in clinical trials evaluating COVID-19 vaccines. Although these mRNA vaccines are leading in the development timeline, over 50 different vaccines are in development, many of which using traditional methods of vaccine production (i.e., pieces of viral proteins). As such, it is likely that in the future there will be multiple types of COVID-19 vaccinations.
This leads us quickly into questions and discussions regarding the safety and effectiveness of the current COVID-19 vaccines in people with mitochondrial disease or suspected mitochondrial disease:
1. Is the vaccine safe for people with mitochondrial disease?
The evidence from the current trials suggest the vaccine is safe and well tolerated in almost everyone. Side effects for the Pfizer vaccine include fever, fatigue, chills, redness, and swelling. The Moderna vaccine is reported to cause chills, fevers, headache, shortness of breath, and pain in the arm. These side effects normally resolve within 24 hours of the injection. The vaccine has not been evaluated for effectiveness and safety in individuals with mitochondrial disease. Because persons with mitochondrial disease tolerate the side effects from other vaccines, we do not anticipate these vaccines will be any different. However, we cannot know the answer with absolute certainty. Based on the current information, we would recommend that individuals with mitochondrial disease give strong consideration to being vaccinated for COVID-19 when available. Delaying vaccination and employing “split dosages” should be discussed with your treating physician. However, at this time, there is no data regarding the utility of “split dosages” with any of the COVID-19 vaccinations under development. As such, we do not suggest this approach.
2. Is the vaccine effective in people with mitochondrial disease?
There are some people with mitochondrial disease who do not respond to some vaccinations, and this could be the case with the COVID-19 vaccine. Because we do not have SARS-CoV-2 antibody testing that is in adequate supply with high sensitivity and specificity, it will take some time to answer this question with certainty in any one patient.
3. Is it reasonable to give one or several doses of acetaminophen or ibuprofen before and after the vaccine to help reduce the risk of the known side effects?
This therapy has been recommended by some mitochondrial physicians but has not been adequately studied to make any blanket recommendations. We suggest you review this question with your physician before the vaccine is given.
In summary, we emphasize the importance of following CDC recommendations regarding reducing risk of exposure since any viral illness poses more of a health risk to a person with mitochondrial disease than to an otherwise healthy person. While it is simply not possible to make a blanket vaccination recommendation for all mitochondrial disease patients at this time, there is no evidence that the COVID-19 vaccines discussed above pose a risk of injury, or are less effective, in any known disease state or risk group. Any decision regarding vaccination should be made after thorough discussion with your doctor of the risks and benefits.
UMDF, in consultation with its SMAB, will continue to monitor the situation and post additional guidance when appropriate. We are also planning to dedicate another webinar of Ask the Mito Doc to this topic on February 16, 2021, or sooner if any major changes in the pandemic emerge.