Dysautonomia can also cause: Abnormal heart rate (too fast, too slow or irregular). Tanya studied Marketing and Business Administration at the University of Florida. These include strokes, cranial neuropathies including Bell palsy, tinnitus and trigeminal neuralgia, peripheral neuropathies, dysautonomia, acute disseminated encephalomyelitis, transverse myelitis, and AIDP.44 Case reports are also starting to emerge in the published literature45,46 and the popular press. They are thought to be immune-mediated and early recognition and treatment with immunomodulatory therapies might be warranted. 2023. ), Rochester, MN. Additional analyses contrasting non-hospitalized and hospitalized individuals were conducted on test-confirmed COVID-19 patients. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. A severe allergic Some vaccines have been known to trigger tinnitus. . Do not be redundant. Hes been awarded the Florida Medical Communicators Award two years in a row as well as 4 Emmy Awards for investigative and live on-air anchoring. The condition is a known symptom of a COVID-19 infection. However, the CDC said it "did not find any data suggesting a link between Covid-19 vaccines and tinnitus". 'Healthy' doctor died after rare severe reaction to AstraZeneca COVID jab. WebThe initial symptoms of GBS included myalgia (12/39), paraparesis (5/39), quadriparesis (22/39), paresthesia (28/39), and facial palsy (23/39), and symptoms of dysautonomia also were observed during hospitalizations (3/39). Her most recent leadership appointment is with The Florida Bars Citizens Advisory Committee. In 2019, Angela joined the TDP board and chaired the Under The Umbrella Gala - which was her creation. Some vaccines have been known to trigger tinnitus. A small study of patients with rheumatic and musculoskeletal diseases found a blunted antibody response to 2 doses of SARS-CoV-2 mRNA vaccine in those treated with glucocorticoids (82% seroconversion), mycophenolate (73% seroconversion), or rituximab (26% seroconversion).e12. However, along with the optimal timing of vaccination, there are additional considerations for many groups, prompting national societies to offer statements in support of vaccine administration. Your organization or institution (if applicable), e.g. Mr. Ward is a former President of the Pinellas Real Estate Law Council and Past Chairman of the Greater Clearwater Chamber of Commerce, the Pinellas County United Way and the United Way of Tampa Bay. He co-founded The Dysautonomia Project with Kelly in 2014 and has served as its president and currently serves as Treasurer. Prevalence data on acute neurologic effects of COVID-19 are limited. Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment. Thats an estimated 38 million Americans with Long COVID dysautonomia, and millions more around the world, says Lauren Stiles, President of Dysautonomia International and Research Assistant Professor of Neurology at Stony Brook University. How are Women Emotionally Affected After a Hysterectomy? Most side effects were mild to moderate. Posted in: Medical Research News | Medical Condition News | Disease/Infection News, Tags: Anxiety, Asthma, Autoimmune Disease, Autoimmunity, Autonomic Nervous System, Brain, Brain Fog, Coronavirus, Coronavirus Disease COVID-19, covid-19, Depression, Disability, Exercise, Exhaustion, Fatigue, Food, Frequency, Headache, Hypotension, Inflammation, Nervous System, Neurology, Neuropathic Pain, Obesity, Orthostatic Hypotension, Pain, Research, Respiratory, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Smoking, Syndrome, Vaping. Given the challenges facing underrepresented and underserved groups, strategies to increase vaccine access and advocacy within these communities remain critical. higgs-boson@gmail.com. "Study finds 67% of individuals with long COVID are developing dysautonomia". Five patients reported Web page addresses and e-mail addresses turn into links automatically. Her daughter is still currently a research patient at the NIH hoping to shed light on the autonomic nervous system for others. WebMODERNA COVID-19 VACCINE, BIVALENT . She is the mother of three daughters, one of whom has POTS. Researchers have also Clearly, there is evidence that SARS-CoV-2 infection poses risk to patients with neurologic disease. He and Kelly are passionate about building and strengthening marriages and currently serve as leaders in a marrieds ministry at church. Under her leadership, the organization expanded its donor base, increased its budget through diversified revenues, and ultimately improved the lives of 300% more children. Management includes noninvasive therapies, behavioral approaches, and pharmacologic regimens. A "fit and healthy" doctor who was one of the first people to be given the AstraZeneca COVID vaccination died after a "rare" severe reaction to the jab, a coroner has ruled. The benefits of COVID-19 vaccination continue to outweigh any potential risks. "Identifying dysautonomia in Long COVID is important because the autonomic nervous system plays a critical role in regulating immune function, inflammation, coagulation pathways, fatigue, exercise intolerance, cognition, and other factors that appear to play a role in Long COVID. She is past President of the Osceola High School Athletic Boosters, where she oversaw the Christina Tournant Memorial Scholarship. In this statement on behalf of the Quality Committee of the American Academy of Neurology, we review the current literature, focusing on COVID-19 infection in adults with neurologic disease, in order to elucidate risks and benefits of vaccination in these individuals. No grade 4 local reactions were reported. Please take all of these words into consideration and if you are a physician please do more work into it go to The dishonomia institute learn more about this because there's so much information that is free online for these conditions it is an umbrella term so there are many conditions under the dysautonomia umbrella including pots the condition that I suffer from. Doctors are warning of the possibility of a surge in cases of a debilitating nervous-system disorder that may be associated with long COVID. The death of a psychologist after his Oxford-AstraZeneca Covid-19 jab was due to "unintended complications of the vaccine", an inquest has ruled. He has been reporting and anchoring for more than 50 years, 34 of those years in the Tampa Bay area, interviewing literally thousands of newsmakers, politicians, subject matter experts, and even 6 presidents, and numerous presidential candidates. Coronavirus components persist in one patients small intestine, 92 days after the start of their Covid symptoms. These issues are becoming increasingly relevant and challenging as a greater share of the population becomes vaccinated, leading to lifting of state- and locally mandated safety measures and recommendations regarding the return to normal activities for the fully vaccinated.e31 Some providers may choose to measure postvaccination antibody levels against the SARS-CoV-2 spike protein to assess vaccine response and aid in counseling these patients, although the clinical significance of such testing with regard to COVID-19 risk remains uncertain. We also review the potential risks associated with vaccination using data from the existing COVID-19 vaccination trials and known history of responses to vaccines for other diseases. However, the risk of viral infection is also highest in this demographic and the Alzheimer's Association is recommending vaccination for elderly individuals and their caregivers.e32 More research is required to determine whether individuals with neurodegenerative cognitive disease are at risk for accelerated decline after COVID-19. The researchers examined53 distinct symptoms over eight different symptom areas to analyze PASC heterogeneity. Further studies are needed regarding how best to evaluate postvaccination immunity in this patient population and whether additional measures (such as booster vaccines) may be useful. (accessed May 01, 2023). News-Medical, viewed 01 May 2023, https://www.news-medical.net/news/20220501/Study-finds-6725-of-individuals-with-long-COVID-are-developing-dysautonomia.aspx. Post retirement Susan traveled the country conducting agency audits for Big Brothers Big Sisters of America. L.K. In this interview conducted at Pittcon 2023 in Philadelphia, Pennsylvania, we spoke to Ron Heeran, a speaker at the 2023 James L. Waters Symposium. CDC is providing timely updates on the following adverse events of interest: Anaphylaxis For more than a decade, she was the Chief Executive Officer of Big Brothers Big Sisters of Pinellas County. Based on COVID-19 vaccine data from the general population and extrapolations from other vaccines studied in patients with neurologic disease, statements from the American Academy of Neuromuscular and Electrodiagnostic Medicine and the National Multiple Sclerosis Society support vaccination.47,48 As discussed further below, a single study has now reported no increased risk of complications in patients with MS receiving the Pfizer COVID-19 vaccine.49. 29 Apr 2023 18:05:56 After leading a highly successful merger with Big Brothers Big Sisters of Tampa Bay, she retired in 2014. Nate and Kelly Freeman founded Network People, Inc. in 1996, a company that specializes in IT security/management and website digital marketing. Understanding the Role of Epigenetics in Cancer, Understanding Chronic Cough: Causes, Symptoms, and Diagnosis, Circumcised vs. Uncircumcised; Differences in the Penile Microbiome, Obesity management: a women's health approach, AI analysis software for Zebrafish you must know, Excessive digital technology use is associated with reduced sleep quality regardless of environmental and genetic factors, study finds, Activating well-being goals in grocery stores: innovative strategies for encouraging healthy food purchases. Good News Beth serves as Secretary of TDP and on the board of directors in order to help create hope for dysautonomia patients, and their families, so they won't have to go through the despair and isolation that her family has suffered. Careful surveillance will be required to determine whether there are age-related vaccination risks, but in the absence of clear data indicating increased risk, the clear impetus is to vaccinate that portion of the population that has constituted 80% of US deaths due to COVID-19 to date. Despite limited data specific to COVID-19 vaccination, prior studies have been helpful in elucidating the effect of immunomodulatory and immunosuppressive therapies on vaccine response. 11/17 Small fiber neuropathy underlying dysautonomia in COVID19 and in postSARSCoV2 vaccination and longCOVID syndromes. If you are responding to a comment that was written about an article you originally authored: Dr. Bryant is an Assistant Professor at the University of Tampa, Department of Nursing, and a pediatric Nurse Practitioner with over 12 years' experience. in 1973 from the University of Florida. WebMODERNA COVID-19 VACCINE, BIVALENT . Results:Six patients were identified with signs and symptoms suggestive of dysautonomia who underwent autonomic testing. AIDP is the most common neurologic syndrome and has been described in case reports following vaccination for influenza, polio, rabies, meningococcus, measles, mumps, and tetanus.50 Vaccination for H1N1 in 1976 was associated with an increased risk of AIDP of 1 additional case per 100,000 vaccinated individuals.51 These cases occurred between 1 and 6 weeks following immunization. For patients with MS, there appears to be preserved immunity postvaccination for those taking interferons.e6,e8 Dimethyl fumarate was similarly found to have no effect on vaccine response, although only in a single study.e13 Glatiramer acetate, teriflunomide, and natalizumab have demonstrated mixed results, with mildly attenuated immune responses in some but not all studies.e14-e20 Based on mechanism of action and the at most modest effect on vaccine response in prior studies, the above therapies are not expected to substantially decrease the efficacy of COVID-19 vaccines. She also endorsed palpitations, especially when getting up from a seated or lying position as well as with mild exertion. When possible, it is generally prudent to complete vaccinations 24 weeks prior to initiating the above therapies, but treatment with these therapies does not preclude vaccination except for live-attenuated vaccines. ), Charlottesville; The University of Miami Miller School of Medicine (I.H. In this statement, written on behalf of the Quality Committee and approved by the Board of Directors of the American Academy of Neurology, we review the risk of COVID-19 in adults with neurologic disorders. Since the vaccines are not an attenuated version of the COVID-19 virus, there is not a risk of getting infected by the vaccine. The Johnson & Johnson vaccine (along with vaccines using similar technology available outside the United States) utilizes an adenovirus vector to deliver nucleic acids encoding the SARS-CoV-2 spike protein but the adenovirus has been genetically engineered to prevent replication. Owned and operated by AZoNetwork, 2000-2023. Common Side Effects of COVID Vaccines After getting vaccinated for COVID-19, you might experience some temporary symptoms similar to those you might notice Infection and immunization in individuals with neuromuscular disorders, COVID-19 vaccination in patients with multiple sclerosis: what we have learnt by February 2021, Guillain-Barr syndrome following vaccination in the national influenza immunization program, United States, 1976-1977, Guillain-Barr syndrome, influenza vaccination, and antecedent respiratory and gastrointestinal infections: a case-centered analysis in the vaccine safety datalink, 2009-2011, Guillain-Barr syndrome following influenza vaccination, The Guillain-Barr syndrome and the 1992-1993 and 1993-1994 influenza vaccines, Seasonal influenza vaccine and Guillain-Barr syndrome: a self-controlled case series study, Guillain-Barr syndrome, influenza, and influenza vaccination: the epidemiologic evidence, Guillain-Barr syndrome after exposure to influenza virus, Recurrences, vaccinations and longterm symptoms in GBS and CIDP, Recurrent Guillain-Barr syndrome following vaccination, Neurological events following immunizations, Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), who.int/publications/m/item/weekly-operational-update-on-covid-19, fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/pfizer-biontech-covid-19-vaccine, fda.gov/news-events/press-announcements/fda-issues-emergency-use-authorization-third-covid-19-vaccine, hematology.org/covid-19/vaccine-induced-immune-thrombotic-thrombocytopenia, nationalmssociety.org/coronavirus-covid-19-information/multiple-sclerosis-and-coronavirus/covid-19-vaccine-guidance, Effect of COVID-19 on Patients With Neurologic Disorders, COVID-19 Vaccines Currently Approved for Use in the United States, Additional Considerations From Prior Vaccine Experience, Neurology: Neuroimmunology & Neuroinflammation. Individuals with a history of severe allergic reactions should discuss vaccine options including the various components found in each vaccine formulation with their physicians. Recently, the first mRNA vaccine was approved for administration in children over 12 years of age; however, this review focuses on the ramifications of COVID-19 and evidence regarding safety of vaccination in the adult population, as the riskbenefit ratio is likely different between the 2 groups. ), Baltimore, MD; The University of Virginia Medical Center (K.K. Neurologic complications have been reported in 30%60% of patients with COVID-19 and typically fall into 3 broad categories: those that are caused acutely by the virus' systemic effects on the body itself, those that result from direct invasion of the nervous system, and those with long-term sequelae after an individual has recovered from the acute illness. Evaluating the association between Mediterranean Diet adherence and type 2 diabetes using nutritional biomarkers. Local reactions in persons ages 6-23 months, Moderna mRNA-1273 COVID-19 vaccine and placebo Key Points. The autoantibody theory might explain some of the delay in the onset of severe symptoms in COVID-19. Vaccination presents an opportunity to decrease transmission and reduce severity of infection within vulnerable populations. Reactions reported after getting a booster shot are similar to those after the two-dose or single-dose primary shots. The most prevalent symptoms were brain fog, exhaustion, shortness of breath with exercise, headache, palpitations, body pains, tachycardia, and lightheadedness, consistent with previous research that found many of the same symptoms in individuals with PASC. Meta-analysis shows phytosterol-fortified foods effectively lower LDL cholesterol levels. At this point there are no indications the COVID-19 vaccine recommendations should be altered for people with POTS or other autonomic disorders. In 2015, she was appointed to the Juvenile Welfare Board by Governor Rick Scott and currently serves as Immediate Past Board Chair. Retrieved on May 01, 2023 from https://www.news-medical.net/news/20220501/Study-finds-6725-of-individuals-with-long-COVID-are-developing-dysautonomia.aspx. Nate serves on the board of the Joseph F. Cornelius Foundation as Treasurer. He has served his community as an Episcopal priest for over 40 years. Submissions should not have more than 5 authors. These complications are rare when compared to the large number of vaccinated individuals; however, it is too early to know the true incidence and risk factors for these complications. Due to the rapid development of the pandemic and COVID-19 vaccination, the current evidence base is limited in regard to patients with neurologic disease. Overall, the median onset of local reactions in the vaccine group was 1 day after either dose, with a median duration of 2 days. The approval of 3 vaccines (PfizerBioNTech, Moderna, and Johnson & Johnson) by the US Food and Drug Administration (FDA) for emergency use results in the potential to significantly reduce the incidence of symptomatic disease in these vulnerable populations.3,-,5 However, the rapidity of approval, and history of prior vaccination regimens resulting in neurologic and other complications,6 creates concern surrounding widespread vaccination. She also served on the Board of Directors for the Early Learning Coalition of Pinellas County, Sixth Judicial Circuit Florida Bar Grievance Committee, and United Way Suncoasts Community Impact Committee. However, the CDC said it "did not find any data suggesting a link between Covid-19 No comments have been published for this article. Both the American Academy of Neuromuscular and Electrodiagnostic Medicine and the National Multiple Sclerosis Society are in favor of vaccination for patients with neuromuscular disease and MS, regardless of immunosuppressive status. Vaccine administration for the majority of patients with stroke and cardiovascular disease is also supported by the American Heart Association,e33 as infection with COVID-19 can exacerbate neurologic sequelae of prior strokes. The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical. The She became involved in dysautonomia awareness efforts as a result of her struggle to find a diagnosis and treatment for her daughter. Study highlights the importance of bivalent mRNA booster vaccination in populations at high risk of severe COVID-19, An exploration of the pathophysiological factors and abnormalities of coagulation of long-COVID, Adapting for endemic not pandemic: Time to reassess universal masking in healthcare, Novel self-amplifying RNA vaccine confers durable protection against COVID-19, reduces viral shedding in primate study, Study indicates that SARS-CoV-2 has evolved to gain increased replicative fitness and become well-adapted in epithelial cells of human airways, So I have dysautonomia I have pots it was not due to anything other than, High-protein diet counters adaptive thermogenesis in prediabetic individuals. All patients reported symptoms of postural lightheadedness and near-syncope, fatigue, and activity Your role and/or occupation, e.g. The condition is a known symptom of a COVID-19 infection. 29 Apr 2023 18:05:56 It must be noted, of course, that the currently available COVID-19 vaccines utilize largely novel technologies, complicating precise extrapolations from prior experience. An autonomic nervous system illness, postural orthostatic tachycardia syndrome (POTS), strongly connected with a prior viral infection, is the most prevalent autonomic diagnosis correlated with PASC. Some of us already got our stuff together we are doing really good medically and we figured out what works for our dish autonomy of personally but if we were to get covid which I did oh my God I cannot even explain how bad it was I cannot even explain how bad it was I'm not even kidding. The immune theory suggests that Covid-19 turns the immune system against the body. John joined the board of TDP in January 2022 to help the organization connect with key supporters in the community to further TDPs mission. After gaining experience in New York City, he returned to St. Petersburg with a goal to innovate architecture for this generation in the Tampa Bay area. Emerging SARS-CoV-2 vaccines offer substantial protection from symptomatic infection, but both patients and providers may have concerns regarding theoretical risks of vaccination, including vaccine safety and efficacy in the context of immunotherapy and the potential for precipitating or exacerbating neurologic symptoms. Methotrexate acts by inhibiting lymphocyte activation and results in a decreased response to pneumococcal vaccine.e26 Similarly, azathioprine, mycophenolate mofetil, and systemic corticosteroids generally have been associated with decreased immunologic response to vaccines.e27 The anti-interleukin-6 monoclonal antibody tocilizumab has thus far not been shown to attenuate humoral responses to vaccination, at least after short durations of therapy.e28-e30 However, the possibility of decreased vaccine response must still be considered. For instance, a recent autopsy study of 41 consecutive patients who died of SARS-CoV-2 infection found low to very low viral RNA levels in some of the brains by qRT-PCR, but viral proteins were not detected, and the level of detectable RNA did not correlate with histopathologic alterations.14 Other studies have not been able to detect viral RNA or protein in the brain.11,15 Based on rodent studies with other coronaviruses, researchers have speculated that the virus might be able to enter the CNS via retrograde dissemination. She has served as TDPs president and is the immediate past president of the Joseph F. Cornelius Family Foundation; past president of the Junior League of Clearwater/Dunedin; past president of Suncoast Family YMCA; past president of St. Paul School Parents Association; past president of Tri Delta Clearwater Alumnae Association. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. (Exception: original author replies can include all original authors of the article). A. Nath is the Clinical Director of NINDS at NIH. Furthermore, many studies of vaccine response have evaluated only humoral (antibody-mediated) immunity, without consideration of cell-mediated T-lymphocyte responses. The 2009 H1N1 epidemic showed that individuals were actually more likely to experience AIDP after viral infection than after administration of the vaccine,52 and subsequent influenza vaccines have been considered safe with an excess risk of about 0.1 case per 100,000 vaccinations.53,-,59 Case reports of AIDP have been reported with a number of vaccines such as hepatitis A, Japanese encephalitis, smallpox, yellow fever, and meningococcus.60 Current guidelines by the advisory committee on immunization practices of the Centers for Disease Control & Prevention list AIDP within 6 weeks of previous influenza as a precaution for immunization against influenza. Beyond this concern, much of our knowledge about the safety and efficacy of vaccination in neurologic patients comes from the results of previous vaccine studies and our understanding of the mechanisms of action of commonly used immunotherapies. Long-term health problems such as fatigue, palpitations, syncope, and dizziness are well-known in patients after COVID-19 (post-acute sequelae of coronavirus It was interesting to see that the diagnosis of celiac disease (the autoimmune reaction to wheat which, among other things, causes malabsorption of nutrients) commonly thought of a genetic disorder was increased. The coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) has resulted in over 3 million deaths worldwide1 and nearly 600,000 in the United States alone. A longtime Pinellas resident, Susan has served in numerous public service and volunteer capacities. His background in short and long form interviewing made him a natural choice for leading the video discussions on our website. These symptoms persisted unabated for the next seven days. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. ), FL; Nationwide Children's Hospital (A.D.P. WebThe Dysautonomia Project's Statement on COVID-19 Vaccinations (March 2021) At this point there are no indications the COVID-19 vaccine recommendations should be altered More guidelines and information on Disputes & Debates, Prospective Long-term Follow-up of Focused Ultrasound Unilateral Subthalamotomy for Parkinson Disease, Neurology | Print ISSN:0028-3878 Patients treated with immunotherapies known or suspected to attenuate vaccine response must be counseled about the ongoing potential for SARS-CoV-2 infection, an issue of increasing relevance as state and local safety mandates are lifted. Her daughter spent more than 60 days in 2 hospitals trying to figure out what was wrong with her, and why she was so desperately ailing. Global registries will be crucial for determining whether SARS-CoV-2 infection, like other viral infections, will be associated with increased incidence of psychiatric disease, dementia, thrombosis, or demyelination later in life. This article was reviewed and approved for publication by the Quality Committee and board members of the American Academy of Neurology on March 12, 2021. "Study finds 67% of individuals with long COVID are developing dysautonomia". She Co-Founded the St. Petersburg Road Runners Club in 2006, served as advisor on youth programs for Motion Sports Management, and has experience organizing and directing community, athletic and fundraising events. An Estimated 38 Million Americans Have Developed an Autonomic Nervous System Disorder Following COVID-19 Infection According to Experts, Signaling Healthcare Crisis -. As neurologic disorders are common,2 the effect of SARS-CoV-2 on patients with neurologic illnesses poses a substantial public health risk. The following individuals are members of the Quality Committee of the American Academy of Neurology that read and formally approved this statement: Christine B. Baca, MD (University of Colorado); Sarah M. Benish, MD (University of Minnesota Physicians); Jeffrey R. Buchhalter, MD; Calli L. Cook, DNP, FNP-C (Emory Healthcare); Allen L. Gee, MD, PhD (Frontier Neurosciences); Ihtsham Haq, MD (University of Miami Miller School of Medicine); Lyell K. Jones, MD (The Mayo Clinic); Adam Kelly, MD (University of Rochester); Kevin Kessler, MD (University of Virginia Medical Center); Elisabeth B. Marsh, MD (Johns Hopkins University School of Medicine); Anup D. Patel, MD (Nationwide Children's Hospital); Michael Phipps, MD, MHS (University of Maryland School of Medicine); Sonja Potrebic, MD, PhD (Southern California Permanente Medical Group); Alexander D. Rae-Grant, MD (Cleveland Clinic); Jose G. Romano, MD (University of Miami Miller School of Medicine); Amy E. Sanders, MD (Ayer Neuroscience Institute); and Adam Webb, MD (Emory University School of Medicine). Alexandra is pleased to contribute to this worthy cause by using her past experience in non-profit work and is greatly encouraged by the strides made since TDPs inception. Although limited, the currently available data report low rates of neurologic complications postvaccination, particularly when weighed against the severity of morbidity and mortality resulting from the infection in populations of people with neurologic illness. A similar platform has been used in a prior Ebola virus vaccine approved for use in the European Union.38 Because none of the currently approved vaccines utilize live-attenuated SARS-CoV-2 virus, none has the potential to cause SARS-CoV-2 infection.
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