No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Severe Rhabdomyolysis After COVID-19 Vaccine
The identification of rhabdomyolysis as a potential fatal adverse reaction to recent COVID‐19 vaccines is essential. As the symptoms of rhabdomyolysis are not specific, the threshold to actively search for this complication should be low. image
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or COVID-19 pandemic has taken away the lives of many people (>4 million per WHO) around the world as of July 2021. With the advancement of the vaccine against COVID-19, in less than a year since the start of the pandemic, the infection rate has come under control in certain regions but is still rising in many more. However, with time, we are also learning a lot more about the adverse events related to the vaccine. This report documents the first fatal case of rhabdomyolysis potentially associated with the COVID-19 vaccine and supports the possibility that autoimmunity is a major risk factor for covid vaccine-related rhabdomyolysis.
SARS-CoV-2 entered the world by storm when it made its appearance at the end of 2019 in Wuhan, China. The severity can range from asymptomatic infection, which occurs in approximately 33% of infected patients, to death. Worldwide deaths due to SARS-CoV-2 are currently approximated at 3.8 million people with close to 600,000 deaths in the United States alone, reiterating the significant impact this virus has on the population. SARS-CoV-2 can affect systems of the body such as respiratory, gastrointestinal tract, neurological, cardiac, renal, and even skeletal muscle tissue. A few cases of rhabdomyolysis are reported in SARS-CoV-2 infection, but the significant level of creatinine kinase in the hundreds of thousands is rare. Our case demonstrates the rarity of SARS-CoV-2 manifestation in a 33-year-old African American male with severe rhabdomyolysis with a creatinine kinase on the admission of 362,445 IU/L. The patient was treated aggressively with intravenous fluids, monitoring electrolytes, renal function, and respiratory status closely. His management includes liberal administration of fluid to treat his rhabdomyolysis, without compromising his respiratory status. He was subsequently discharged home after seven days of hospitalization. We strive to share this information in hopes to share our management for future similar cases.
Rhabdomyolysis has been described as a complication of coronavirus disease 2019 (COVID-19) infection, but few cases of rhabdomyolysis associated with COVID-19 vaccination have been reported. We described a case of an 80-year-old male who developed rhabdomyolysis two days after receiving his second dose of the Moderna COVID-19 vaccine. He presented with severe weakness, myalgias, and an initial creatinine kinase (CK) of 6,546 IU/L that improved with intravenous fluids. Common causes of rhabdomyolysis were excluded including statin use, strenuous exercise, and trauma. With the increasing immunization efforts against COVID-19, physicians should consider the possibility of rhabdomyolysis when a patient presents with neuromuscular complaints following vaccination.
We sought to determine whether immune reactivity occurs between anti-SARS-CoV-2 protein antibodies and human tissue antigens, and whether molecular mimicry between COVID-19 viral proteins and human tissues could be the cause. We applied both human monoclonal anti-SARS-Cov-2 antibodies (spike protein, nucleoprotein) and rabbit polyclonal anti-SARS-Cov-2 antibodies (envelope protein, membrane protein) to 55 different tissue antigens. We found that SARS-CoV-2 antibodies had reactions with 28 out of 55 tissue antigens, representing a diversity of tissue groups that included barrier proteins, gastrointestinal, thyroid and neural tissues, and more. We also did selective epitope mapping using BLAST and showed similarities and homology between spike, nucleoprotein, and many other SARS-CoV-2 proteins with the human tissue antigens mitochondria M2, F-actin and TPO. This extensive immune cross-reactivity between SARS-CoV-2 antibodies and different antigen groups may play a role in the multi-system disease process of COVID-19, influence the severity of the disease, precipitate the onset of autoimmunity in susceptible subgroups, and potentially exacerbate autoimmunity in subjects that have pre-existing autoimmune diseases. Very recently, human monoclonal antibodies were approved for use on patients with COVID-19. The human monoclonal antibodies used in this study are almost identical with these approved antibodies. Thus, our results can establish the potential risk for autoimmunity and multi-system disorders with COVID-19 that may come from cross-reactivity between our own human tissues and this dreaded virus, and thus ensure that the badly-needed vaccines and treatments being developed for it are truly safe to use against this disease.
Background
Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle–encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19.
Methods
This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2.
Results
Download a PDF of the Research Summary.
The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001). Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe Covid-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups.
Conclusions
The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.)
Rhabdomyolysis is caused by the breakdown and necrosis of muscle tissue and the release of intracellular content into the blood stream. There are multiple and diverse causes of rhabdomyolysis but central to the pathophysiology is the destruction of the sarcolemmal membrane and release of intracellular components into the systemic circulation. The clinical presentation may vary, ranging from an asymptomatic increase in serum levels of enzymes released from damaged muscles to worrisome conditions such as volume depletion, metabolic and electrolyte abnormalities, and acute kidney injury (AKI). The diagnosis is confirmed when the serum creatine kinase (CK) level is > 1000 U/L or at least 5x the upper limit of normal. Other important tests to request include serum myoglobin, urinalysis (to check for myoglobinuria), and a full metabolic panel including serum creatinine and electrolytes. Prompt recognition of rhabdomyolysis is important in order to allow for timely and appropriate treatment. A McMahon score, calculated on admission, of 6 or greater is predictive of AKI requiring renal replacement therapy. Treatment of the underlying cause of the muscle insult is the first component of rhabdomyolysis management. Early and aggressive fluid replacement using crystalloid solution is the cornerstone for preventing and treating AKI due to rhabdomyolysis. Electrolyte imbalances must be treated with standard medical management. There is, however, no established benefit of using mannitol or giving bicarbonate infusion. In general, the prognosis of rhabdomyolysis is excellent when treated early and aggressively.
The role of various environmental factors in the pathogenesis of immune mediated diseases is well established. Of which, factors entailing an immune adjuvant activity such as infectious agents, silicone, aluminium salts and others were associated with defined and non-defined immune mediated diseases both in animal models and in humans. In recent years, four conditions: siliconosis, the Gulf war syndrome (GWS), the macrophagic myofasciitis syndrome (MMF) and post-vaccination phenomena were linked with previous exposure to an adjuvant. Furthermore, these four diseases share a similar complex of signs and symptoms which further support a common denominator.Thus, we review herein the current data regarding the role of adjuvants in the pathogenesis of immune mediated diseases as well as the amassed data regarding each of these four conditions. Relating to the current knowledge we would like to suggest to include these comparable conditions under a common syndrome entitled ASIA, "Autoimmune (Auto-inflammatory) Syndrome Induced by Adjuvants".
Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine
- F P Polack
- S J Thomas
- N Kitchin
Polack FP, Thomas SJ, Kitchin N, et al. Safety and
efficacy of the BNT162b2 mRNA Covid-19 vaccine.
N Engl J Med. 2020;384:1576-77. [PMID: 33596348]
doi:10.1056/NEJMc2036242
The danger hypothesis applied to idiosyncratic drug reactions
- S Béatrice
- J Uetrecht
Béatrice S, Uetrecht J. The danger hypothesis applied
to idiosyncratic drug reactions. Curr Opin Allergy
Clin Immunol. 2003;3:235-42. [PMID: 12865765]
doi:10.1097/00130832-200308000-00001
RECOVAC repeated vaccination study
- Jsf Sanders
Sanders JSF. RECOVAC repeated vaccination study. Accessed
at https://clinicaltrials.gov/ct2/show/NCT05030974 on 26
May 2022.