Hypoglossal Nerve Palsy Following COVID-19 Vaccination in a Young Adult Complicated by Various Medicines

Authors: Tatsuhiko OkayasuRyuichi OhtaFumiko YamaneSatoshi AbeChiaki Sano

 September 15, 2022 (see history) DOI: 10.7759/cureus.29212 Cite this article as: Okayasu T, Ohta R, Yamane F, et al. (September 15, 2022) Hypoglossal Nerve Palsy Following COVID-19 Vaccination in a Young Adult Complicated by Various Medicines. Cureus 14(9): e29212. doi:10.7759/cureus.29212

Abstract

Mononeuritis multiplex is a rare form of cerebral nerve palsy caused by various factors. Coronavirus disease 2019 (COVID-19) vaccination could be an etiology of mononeuritis multiplex, which can affect various nerves. Post-COVID-19 and vaccination-related neurological impairments involve cranial nerves such as the facial, trigeminal, and vagal nerves. We report our experience with a 34-year-old man who developed hypoglossal nerve palsy following COVID-19 vaccination, complicated by progressive mononeuritis multiplex. Hypoglossal nerve palsy may occur following COVID-19 vaccination. The symptoms vary and may progress without treatment. Physicians should consider the possibility of mononeuritis multiplex after COVID-19 vaccination and provide prompt treatment for acute symptom progression.

Introduction

Mononeuritis multiplex is a rare form of cerebral nerve palsy caused by various factors, as the etiologies, infection, and autoimmunity are common. Herpes zoster and simplex are the predominant infections in the category of infection [1,2]. Among autoimmune causes, small-to-medium-sized vasculitis, such as an antineutrophil cytoplasmic antibody (ANCA)-related vasculitis and Sjogren’s syndrome, are common [1,2]. The progression of mononeuritis multiplex symptoms varies depending on the human body’s etiology and immunological reactions [3,4]. Severe cases may involve multi-extremity paralysis, which should be treated with intravenous immunoglobulin therapy, steroids, and plasma exchange, according to the etiology [2,5]. Thus, effective treatment requires the detection of etiology and rapid treatment.

COVID-19 and COVID-19 vaccinations are also potential etiologies of mononeuritis multiplex, which can affect various nerves. Based on previous reports, post-COVID-19 and vaccination-related neurological impairments involve cranial nerves such as the facial, trigeminal, and vagus nerves [6-8]. However, there are few reports of mononeuritis multiplex following COVID-19 vaccination. Here, we report a case of mononeuritis multiplex that spread from the right hypoglossal nerve to the right hand and leg. The progression was acute, and the patient required treatment with intravenous immunoglobulin and steroid pulse therapy. Various complications occurred during the clinical course, and the treatment course was complicated. Our case demonstrates the importance of a clinical diagnosis of mononeuritis multiplex with prompt treatment and approaches to reduce long-term complications.

Case Presentation

A 34-year-old man was admitted to our hospital with a chief complaint of dysphasia and difficulty speaking. Ten days before admission, the patient had received the third vaccination for COVID-19. He had a fever of >38 °C one day after vaccination. Seven days before admission, he experienced tingling on the right side of his tongue, followed by dysphagia and difficulty speaking. These symptoms progressed, and the patient noticed that the right side of his tongue had shrunk; therefore, he visited our hospital. He had a past medical history of varicella-zoster virus infection in the first branch of the left trigeminal nerve and had been treated with valaciclovir. The patient did not take any regular medication.

His vital signs at admission were as follows: blood pressure, 114/59 mmHg; pulse rate, 78 beats/min; body temperature, 36.9 °C, respiratory rate, 15 breaths/min; and oxygen saturation, 97% on room air. He was alert to time and place. Physical examination showed that the right half of his tongue was atrophied and shifted to the right during the prostration.

No other abnormal neurological findings were noted. There were no obvious abnormalities in the chest or abdomen and no skin eruptions. Physical examination revealed right hypoglossal nerve palsy; thus, viral infection, brain stroke, brain tumor, meningitis, ANCA-related vasculitis, and Guillain-Barre syndrome was suspected. Blood tests, head magnetic resonance imaging (MRI), head computed tomography (CT), and lumbar puncture were performed. The results were within normal limits (Table 1).

MarkerLevelReference
White blood cells6.83.5–9.1 × 103/μL
Neutrophils5144.0–72.0%
Lymphocytes32.918.0–59.0%
Monocytes80.0–12.0%
Eosinophils6.90.0–10.0%
Basophils1.20.0–3.0%
Red blood cells5.343.76–5.50 × 106/μL
Hemoglobin1611.3–15.2 g/dL
Hematocrit47.833.4–44.9%
Mean corpuscular volume89.579.0–100.0 fl
Platelets24.613.0–36.9 × 104/μL
Total protein6.96.5–8.3 g/dL
Albumin4.43.8–5.3 g/dL
Total bilirubin0.50.2–1.2 mg/dL
Aspartate aminotransferase188–38 IU/L
Alanine aminotransferase274–43 IU/L
Alkaline phosphatase80106–322 U/L
γ-Glutamyl transpeptidase50<48 IU/L
Lactate dehydrogenase165121–245 U/L
Blood urea nitrogen13.98–20 mg/dL
Creatinine0.660.40–1.10 mg/dL
eGFR≥90> 60.0 mL/min/1.73 m2
Serum Na137135–150 mEq/L
Serum K3.93.5–5.3 mEq/L
Serum Cl10198–110 mEq/L
Serum P3.12.7–4.6 mg/dL
Serum Mg21.8–2.3 mg/dL
CK11256–244 U/L
CRP0.07<0.30 mg/dL
Artery blood gas analysis  
pH7.4187.35–7.45 
PCO242.535.0–45.0 mmHg
PO289.375.0–100.0 mmHg
HCO326.920.0–26.0 mmol/L
Lactate1.20.5–1.6 mmol/L
Cerebrospinal fluid testing  
Colorclear 
Cell count10–5 /μL
Protein3615–45 mg/dL
Glucose5748–83 mg/dL
Chloride126.5113–128 mEq/L
Table 1: Initial laboratory data of the patient

eGFR: estimated glomerular filtration rate; CK: creatine kinase; CRP: C-reactive protein

A videoendoscopic examination of swallowing was performed to evaluate dysphagia, with no obvious problems associated with swallowing function. Since the difficulty in moving the tongue and the white coating was remarkable, the patient was referred to a dental and oral surgeon to rule out tongue cancer.

Because the patient had a history of herpes zoster, we also considered viral reactivation and prescribed acyclovir (1500 mg/day) and prednisolone (60 mg/day) from the second day of admission. However, lumbar pain and headache appeared on day four of admission, for which epidural hematoma after lumbar puncture was suspected. Plain lumbar magnetic MRI and head CT showed edematous findings around both kidneys, clinically suggesting the possibility of acute kidney injury due to acyclovir. As the patient tested negative for varicella virus, acyclovir was discontinued (Figure 2).

Edematous-findings-around-both-kidneys-(blue-arrows)
Figure 2: Edematous findings around both kidneys (blue arrows)

On the seventh day of illness, weakness of the right upper and lower extremities and a Romberg’s sign was observed. Plain MRI of the upper arm and nerve conduction velocity tests were performed to investigate the cause, with no positive findings. Blood tests were negative for syphilis, hepatitis, HIV, ANCA, antinuclear antibody, and IgG4. Therefore, a clinical diagnosis of mononeuritis multiplex after administering the COVID-19 vaccine was made. On day seven of admission, prednisolone (60 mg/day), intravenous immunoglobulin (0.4 g/kg/day for five days), and methylprednisolone (1 g/day for three days) were initiated after consultation with a neurology physician. On day nine of admission, muscle pain, and general malaise developed immediately after intravenous methylprednisolone administration. As intravenous methylprednisolone could be the cause, the administration was discontinued, and oral prednisolone (60 mg/day) was started. Subsequently, a tingling pain appeared on the right scalp. He was treated with valacyclovir (3 g/day for one week). Dysphagia and extremity weakness gradually improved after rehabilitation. On day 14, after admission, the patient was transferred to a university hospital for further investigation and advanced rehabilitation.

Discussion

This case showed the possibility of hypoglossal nerve palsy as a rare complication of COVID-19 vaccination, specific neurological complications following COVID-19 vaccination, and the rapid treatment of mononeuritis multiplex to prevent symptom progression.

The relationship between the COVID-19 vaccine and mononeuritis multiplex has been discussed in various studies. Several case reports have shown an increased risk of mononeuritis multiplex within a few days to months after COVID-19 vaccination [8,9]. A review of COVID-19 vaccination also showed that most symptoms related to mononeuritis multiplex were mild and disappeared naturally [10]. However, some cases show severe symptoms that affect the patient’s activities of daily life and require intensive treatment [7,11]. Our patient initially had mild symptoms and did not require treatment for his vital symptoms. However, within one week, the symptoms progressed drastically from the tongue to the extremities, causing difficulties in walking. The clinical course of mononeuritis multiplex varies, and some cases caused by vasculitis from autoimmune and infectious diseases may be progressive [5,12]. Precise follow-up and prompt treatment with intravenous immunoglobulins and steroids should be initiated to prevent disease progression.

Hypoglossal nerve palsy could be a rare symptom following COVID-19 vaccination and warrants further investigation in future studies. Among the complications of COVID-19 vaccination, various neurological complications were reported in 2020 [9,10]. Guillain-Barre syndrome is a well-known but rare complication of COVID-19 vaccination and appears a few weeks after vaccination [13]. Other cranial nerves may also be involved in the complications of COVID-19. Several case reports and reviews have reported facial palsy, the pain of the trigeminal and facial nerves, and diplopia of the oculomotor nerves [10,14]. However, hypoglossal nerve palsy is rare, and its pathophysiology remains unclear. In the present case, the initial finding was difficulty in tongue movement caused by palsy of the hypoglossal nerves, which led to systemic neurological symptoms. Clinicians should consider assessing single cranial symptoms following COVID-19 because of the possible spread of multiple nerve symptoms, causing a decreased quality of life.

The COVID-19 pandemic may persist in the future; therefore, preventable measures are vital. Vaccination is a critical measure for prevention. Although various complications have been reported, they are rare; therefore, vaccination should be promoted [15,16]. However, the possible symptoms following COVID-19 vaccination should be appropriately described, and help-seeking behaviors (HSB) to medical facilities should be facilitated, especially in rural contexts lacking healthcare resources [17-19]. The patient in the present case was younger, but the duration of his visit to the hospital was nearly two weeks. Early treatment could have prevented symptom progression [14]. When the same symptoms occur in older patients, HSB varies and is challenging, causing a greater delay in treatment. Citizens and healthcare professionals should be educated regarding responses to symptoms following vaccination, and information provision should be promoted [20].

Conclusions

Hypoglossal nerve palsy may be a symptom of COVID-19 vaccination. The symptoms vary and may progress without treatment. Physicians should consider the possibility of mononeuritis multiplex after COVID-19 vaccination and provide prompt treatment for acute symptom progression.


References

  1. Mutluay B, Koksal A, Karagoz N, et al.: Early detection of mononeuritis multiplex & diagnosis of systemic diseases thru electrophysiological work out with polyneuropathy as preceeding symptom. J Neurol Sci. 2015, 357:341. 10.1016/j.jns.2015.08.1212
  2. Ghazaei F, Sabet R, Raissi GR: Vasculitic mononeuritis multiplex may be misdiagnosed as carpal tunnel syndrome. Am J Phys Med Rehabil. 2017, 96:e44-7. 10.1097/PHM.0000000000000562
  3. Marques IB, Giovannoni G, Marta M: Mononeuritis multiplex as the first presentation of refractory sarcoidosis responsive to etanercept. BMC Neurol. 2014, 14:237. 10.1186/s12883-014-0237-5
  4. Tanemoto M, Hisahara S, Hirose B, et al.: Severe mononeuritis multiplex due to rheumatoid vasculitis in rheumatoid arthritis in sustained clinical remission for decades. Intern Med. 2020, 59:705-10. 10.2169/internalmedicine.3866-19
  5. Tokonami A, Ohta R, Katagiri N, Yoshioka N, Yamane F, Sano C: Autoimmune vasculitis causing acute bilateral lower limb paralysis. Cureus. 2022, 14:e27651. 10.7759/cureus.27651
  6. Enrique E-R, Javier B, Hernando R, Herney Andrés G: Mononeuritis multiplex associated with SARS-CoV2-COVID-19 infection: case report. Int J Neurol Neurother. 2020, 7:102. 10.23937/2378-3001/1410102
  7. Needham E, Newcombe V, Michell A, et al.: Mononeuritis multiplex: an unexpectedly frequent feature of severe COVID-19. J Neurol. 2021, 268:2685-9. 10.1007/s00415-020-10321-8
  8. Andalib S, Biller J, Di Napoli M, et al.: Peripheral nervous system manifestations associated with COVID-19. Curr Neurol Neurosci Rep. 2021, 21:9. 10.1007/s11910-021-01102-5
  9. Taga A, Lauria G: COVID-19 and the peripheral nervous system. A 2-year review from the pandemic to the vaccine era. J Peripher Nerv Syst. 2022, 27:4-30. 10.1111/jns.12482
  10. Finsterer J, Scorza FA, Scorza C, Fiorini A: COVID-19 associated cranial nerve neuropathy: A systematic review. Bosn J Basic Med Sci. 2022, 22:39-45. 10.17305/bjbms.2021.6341
  11. Oaklander AL, Mills AJ, Kelley M, Toran LS, Smith B, Dalakas MC, Nath A: Peripheral neuropathy evaluations of patients With prolonged long COVID. Neurol Neuroimmunol Neuroinflamm. 2022, 9:10.1212/NXI.0000000000001146
  12. Abdelhakim S, Klapholz JD, Roy B, Weiss SA, McGuone D, Corbin ZA: Mononeuritis multiplex as a rare and severe neurological complication of immune checkpoint inhibitors: a case report. J Med Case Rep. 2022, 16:81. 10.1186/s13256-022-03290-1
  13. Raahimi MM, Kane A, Moore CE, Alareed AW: Late onset of Guillain-Barré syndrome following SARS-CoV-2 infection: part of ‘long COVID-19 syndrome’?. BMJ Case Rep. 2021, 14:10.1136/bcr-2020-240178
  14. Hasan I, Saif-Ur-Rahman KM, Hayat S, et al.: Guillain-Barré syndrome associated with SARS-CoV-2 infection: A systematic review and individual participant data meta-analysis. J Peripher Nerv Syst. 2020, 25:335-43. 10.1111/jns.12419
  15. Machida M, Nakamura I, Kojima T, et al.: Acceptance of a COVID-19 vaccine in Japan during the COVID-19 pandemic. Vaccines (Basel). 2021, 9:10.3390/vaccines9030210
  16. García-Montero C, Fraile-Martínez O, Bravo C, et al.: An updated review of SARS-CoV-2 vaccines and the importance of effective vaccination programs in pandemic times. Vaccines (Basel). 2021, 9:10.3390/vaccines9050433
  17. Cornally N, McCarthy G: Help-seeking behaviour: a concept analysis. Int J Nurs Pract. 2011, 17:280-8. 10.1111/j.1440-172X.2011.01936.x
  18. Ohta R, Ryu Y, Sano C: Older people’s help-seeking behaviors in rural contexts: A systematic review. Int J Environ Res Public Health. 2022, 19:10.3390/ijerph19063233
  19. Shaw C, Brittain K, Tansey R, Williams K: How people decide to seek health care: a qualitative study. Int J Nurs Stud. 2008, 45:1516-24. 10.1016/j.ijnurstu.2007.11.005
  20. Ohta R, Ryu Y, Kitayuguchi J, Sano C, Könings KD: Educational intervention to improve citizen’s healthcare participation perception in rural Japanese communities: A pilot study. Int J Environ Res Public Health. 2021, 18:10.3390/ijerph18041782

Syncope and COVID-19 disease – A systematic review

Authors: Raquel Falcão de Freitas 1Sofia Cardoso Torres 2Francisco Javier Martín-Sánchez 3Adrián Valls Carbó 3Giuseppe Lauria 4José Pedro L Nunes

. 2021 Nov;235:102872. doi: 10.1016/j.autneu.2021.102872. Epub 2021 Aug 27.

Abstract

Background

Syncope is not a common manifestation of COVID-19, but it may occur in this context and it can be the presenting symptom in some cases. Different mechanisms may explain the pathophysiology behind COVID-19 related syncope. In this report, we aimed to examine the current frequency and etiology of syncope in COVID-19.

Methods

A systematic review across PubMed, ISI Web of Knowledge and SCOPUS was performed, according to PRISMA guidelines, in order to identify all relevant articles regarding both COVID-19 and syncope.

Results

We identified 136 publications, of which 99 were excluded. The frequency of syncope and pre-syncope across the selected studies was 4.2% (604/14,437). Unexplained syncope was the most common type (87.9% of the episodes), followed by reflex syncope (7.8% of the cases). Orthostatic hypotension was responsible for 2.2% of the cases and syncope of presumable cardiac cause also accounted for 2.2% of cases. Arterial hypertension was present in 52.0% of syncope patients. The use of angiotensin receptor blockers or angiotensin converting enzyme inhibitors were not associated with an increased incidence of syncope (chi-square test 1.07, p 0.30), unlike the use of beta-blockers (chi-square test 12.48, p < 0.01).

Conclusion

Syncope, although not considered a typical symptom of COVID-19, can be associated with it, particularly in early stages. Different causes of syncope were seen in this context. A reevaluation of blood pressure in patients with COVID-19 is suggested, including reassessment of antihypertensive therapy, especially in the case of beta-blockers rterial hypertension

1. Introduction

The ongoing Coronavirus pandemic has proved to be a challenging setback to the health of the world population ever since its first cases were announced in the city of Wuhan, China, around December 2019. As of the 1st of July 2021, there have been a total of approximately 181 million confirmed cases of COVID-19 (Coronavirus disease 2019) worldwide and 3.9 million deaths, translating to a fatality rate of 2% (

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel betacoronavirus and COVID-19 is the infectious disease caused by this novel virus. Its spike protein (glycoprotein S) determines the specificity of the virus for epithelial cells of the respiratory tract (. It is composed of a receptor binding domain that recognizes the ACE-2 (type 2 angiotensin converting enzyme) receptor specifically, allowing the entrance of the virus into its target cells (

Wang et al., 2020

). The ACE-2 receptor can be found on the surface of epithelial cells in the lungs, intestines, kidneys and blood vest is currently known that, although the novel SARS-CoV-2 virus can lead to significant disease in the respiratory system, it can also negatively affect several other vital organ systems. Significant damage, namely, to the cardiovascular, nervous and hematopoietic systems has been outlined and an impact in hemostasis has also been thoroughly discussed as blood hypercoagulability is common among hospitalized COVID-19 patient). Regarding the cardiovascular manifestations, heart failure, thromboembolism, myocarditis, arrhythmias, pericarditis and acute coronary syndromes have been described in this contex). On the other hand, the most common neurological symptoms reported in COVID-19 patients have been smell and taste disturbances, headache, myalgia, and altered mental status (yncope is largely defined as a transient loss of consciousness due to cerebral hypoperfusion

). It is characterized by a rapid onset, short duration and spontaneous, complete rec

). Presyncope, on the other hand, is the state that resembles the prodrome of syncope (with all its signs and symptoms such as pallor, sweating, nausea, palpitations) without being followed by a loss of consciousness (In the light of a severe systemic disease, non-traumatic transient loss of consciousness can have distinct etiologies, varying from the benign reflex syncope and syncope due to orthostatic hypotension to the increasingly serious cardiac). Apart from unexplained syncope, these three main groups stem from different mechanisms and, therefore, may require specialized treatment. Consequently, an accurate diagnosis becomes imperative.

Recently, some case reports and case-series have emerged reporting syncope as a possible symptom of COVID-19, whether it had developed at the onset or during the course of the d). It is important to mention that some of these reports outline its occurrence days before the main respiratory symptoms, or even as an isolated p). If a valid relationship between COVID-19 and syncope is established, a number of patients could be isolated in a timely manner, minimizing the contagious phase.

In the present report, we aimed to systematically review the recent published literature that describes syncope or presyncope as a symptom of COVID-19, having it been observed in the days before or after the diagnosis. We aimed to calculate its frequency and divide it into each different type of syncope observed.

As a secondary aim of the review, the investigation of the relationship between syncope and use of angiotensin receptor inhibitor drugs (ACEi), angiotensin receptor blockers (ARBs) and/or beta-blockers in the context of COVID-19 was carried out. This seemed to be important to investigate since arterial hypertension is a common comorbidity among COVID-19 patien, and the use of standard anti-hypertensive agents could influence the incidence of this symptom.

2. Methods

2.1 Eligibility criteria

Regarding our population of interest, we were in the search for studies that simultaneously described COVID-19 and syncope or presyncope presented as a possible symptom of the acute infection or occuring in a post-acute COVID-19 setting. Articles were excluded if they described falls in the context of COVID-19 that were not stated to be of syncopal origin; episodes of syncope not temporally related with SARS-CoV-2 infection (for example, occurring throughout the year prior to the infection) and episodes of syncope with another possible underlying cause mentioned in the study as relevant apart from COVID-19. We included case-series, case-reports, cross-sectional studies with prospective data collection, retrospective analyses and letters published in 2020 or 2021 for which it was possible to extract an exact number of patients with COVID-19 exhibiting syncope/presyncope.

We did not restrict articles to witnessed syncope nor exclude articles that did not describe the specific comorbidities, clinical characteristics or evolution exhibited by the pre/syncope cohort. This was because our primary outcome measure was to quantify the number of COVID-19 related pre/syncopal episodes published in the literature thus far.

We considered articles written in English, Spanish, French, Italian, or Portuguese. Articles written in German, Hungarian or Mandarin were excluded (since the authors are not familiar with these languages).

2.2 Search strategy

A comprehensive literature search was carried out with the purpose of identifying all reported articles relating syncope to COVID-19, according to the guidelines for Preferred Reporting Items for Systematic Reviews and Meta-Analys. This search was conducted on the databases Medline (PUBMED), ISI Web of Knowledge and SCOPUS.

The search query, which took place on the 9th of March 2021, included the following MeSH terms and keywords: “(“COVID-19” OR “COVID 19” OR “SARS-COV-2” OR “coronavirus” OR “2019 novel coronavirus”) AND (“syncope” OR “presyncope” OR “syncopal”). Additionally, we scanned the list of references from the included studies in this analysis and of systematic reviews pertaining to neurological symptoms in the context of COVID-19.

2.3 Selection process

Two investigators independently assessed whether the studies addressed the topic in question and if all the inclusion/exclusion criteria were met. Initially, this was done according to the “screening phase”, where only the title and the abstract were analyzed. After this process, 52 articles were considered eligible. This was followed by the “inclusion phase”, where the integral text was fully evaluated. Any doubtful situation was solved by consensus between the authors, after which, concerning study eligibility, 100% agreement between authors was seen in each step of the study assessment.

2.4 Data collection process and data items

From the selected articles, two authors worked independently to retrieve the following data: location, number of patients (with and without pre/syncope), age, sex and ethnicity when available, comorbidities (from patients with and without pre/syncope), chronic medications the patients were on regarding treatment of arterial hypertension and the description of the clinical course, including relevant laboratory findings and any auxiliary exams performed, such as computerized tomography scans and cardiac magnetic resonances. Any doubtful situation was solved by consensus between the authors.

2.5 Study quality assessment

Quality of the observational cohorts and cross-sectional studies and case-series was evaluated using the National Heart, Lung and Blood Institute study quality assessment t

) and is presented in Table 1Table 2. Any disagreements between the two main reviewers were discussed with a third evaluator.

Table 1Quality assessment tool for observational cohort and cross-sectional studies. Y – Yes; NR – Not Reported; NA – Not Applicable.

Oates et al.Chen et al.Canetta et al.Radmanesh et al.Chachkhiani et al.García-Moncó et al.Xiong et al.Romero-Sánchez et al.Chuang et al.Mizrahi et alMartin-Sanchez et al.Travi et al.Chou et al.
Was the research question or OBJECTIVE in this paper clearly stated?YYYYYYYYYYYYY
Was the study population clearly specified and defined?YYYYYYYYYYYYY
Was the participation rate of eligible persons at least 50%?YYYYYYYYYYYYY
Were all the subjects selected or recruited from the same or similar populations (including the same time period)? Were inclusion and exclusion criteria for being in the study prespecified and applied uniformly to all participants?YYYYYYYYYYYYY
Was a sample size justification, power description, or variance and effect estimates provided?NRNRNRNRNRNRNRNRNRNRNRNRNR
For the analyses in this paper, were the exposure(s) of interest measured prior to the outcome(s) being measured?NANANANANANANANANANANANANA
Was the timeframe sufficient so that one could reasonably expect to see an association between exposure and outcome if it existed?YYYYYYYYYYYYY
For exposures that can vary in amount or level, did the study examine different levels of the exposure as related to the outcome (e.g., categories of exposure, or exposure measured as continuous variable)?NANANANANANANANANANANANANA
Were the exposure measures (independent variables) clearly defined, valid, reliable, and implemented consistently across all study participants?YYYYYYYYYYYYY
Was the exposure(s) assessed more than once over time?NRNRNRNRNRNRNRNRNRYYNRNR
Were the outcome measures (dependent variables) clearly defined, valid, reliable, and implemented consistently across all study participants?YYYYYYYYYYYYY
Were the outcome assessors blinded to the exposure status of participants?NANANANANANANANANANANANANA
Was loss to follow-up after baseline 20% or less?NRNRNRNRNRNRNRNRNRNRNRNRNR
Were key potential confounding variables measured and adjusted statistically for their impact on the relationship between exposure(s) and outcome(s)?NRNRNRNRYNRNRNRNRYYYY
Quality ratingGoodFairGoodGoodGoodFairFairFairFairGoodGoodGoodGood

Table 2Quality assessment tool for case-series studies. Y – Yes; NR – Not reported; NA – Not applicable.

Ebrille et al.Birlutiu et al.Argenziano et al.Espinoza et al.Gonfiotti et al.
Was the study question or objective clearly stated?YYYYY
Was the study population clearly and fully described, including a case definition?YYYYY
Were the cases consecutive?NRNRYNRNR
Were the subjects comparable?YYYYY
Was the intervention clearly described?YYYYY
Were the outcome measures clearly defined, valid, reliable, and implemented consistently across all study participants?YYYYY
Was the length of follow-up adequate?NRYYNRY
Were the statistical methods well-described?NANAYNANA
Were the results well-described?YYYYY
Quality RatingFairGoodGoodFairGood

2.6 Outcome measures

The primary outcome measures assessed were the occurrence of syncope or presyncope either in the days prior or subsequent to a COVID-19 diagnosis and its relative frequency, divided into each type of syncope experienced.

We also assessed the association between the usage of ARBs or ACEi and beta blockers with the occurence of syncope as well as the association of syncope with mortality.

2.7 Effect measures

Concerning these latter data, a chi-square test was used, with a level of significance of 0.05. Statistical analysis was done using Stata, version 17.0, StataCorp, Texas, USA.

3. Results

3.1 Study selection

With the use of our keywords, we obtained 51 results from Medline (PUBMED), 28 from ISI Web of Knowledge, 50 from SCOPUS and 7 from scanning the references of the selected articles and adequate systematic reviews (Fig. 1) – with a total number of 37 articles selected for the purpose of the present study (Fig. 1). The complete set of selected studies is presented in Table 3. SARS-CoV-2 infection was diagnosed by real-time reverse transcriptase polymerase chain reaction (RT-PCR) or a chest X-ray or CT scan showing the characteristic bilateral interstitial pneumonia of COVID-19 in all cases, except in the report by Romero-Sánchez et al., in which a minority of patients were diagnosed by means of serological testing

Fig. 1
Fig. 1Flowchart showing literature search method. n = number of articles.View Large ImageDownload Hi-res imageDownload (PPT)

Table 3Summary of included articles. Pts – patients; ARBs – angiotensin receptor blockers; PPM – permanent pacemaker implantation; ECG – electrocardiogram; ICD – implantable cardioverter-defibrillator; AV – atrioventricular; ACE-I – angiotensin-converting-enzyme inhibitors; CMR – cardiac magnetic resonance; CSF – cerebrospinal fluid; CT -computed tomography; MRI – magnetic resonance imaging; RT-PCR – real time polymerase chain reaction; CRP – C-Reactive Protein, NT-proBNP – N-terminal type B natriuretic peptide; POTS – Postural Orthostatic Tachycardia Syndrome; BP – blood pressure. 

1000 Peer Reviewed Studies Questioning Covid-19 Vaccine Safety

Peer Reviewed Medical Papers Submitted To Various Medical Journals, Evidencing A Multitude Of Adverse Events In Covid-19 Vaccine Recipients.

The list includes studies published as of January 20, 2022 concerning the potential adverse reaction from COVID-19 vaccines, such as myocarditis, thrombosis, thrombocytopenia, vasculitis, cardiac, Bell’s Palsy, immune-mediated disease, and many more.

  1. Myocarditis after mRNA vaccination against SARS-CoV-2, a case series: https://www.sciencedirect.com/science/article/pii/S2666602221000409
  2. Myocarditis after immunization with COVID-19 mRNA vaccines in members of the US military. This article reports that in “23 male patients, including 22 previously healthy military members, myocarditis was identified within 4 days after receipt of the vaccine”: https://jamanetwork.com/journals/jamacardiology/fullarticle/2781601
  3. Association of myocarditis with the BNT162b2 messenger RNA COVID-19 vaccine in a case series of children: https://pubmed.ncbi.nlm.nih.gov/34374740/
  4. Acute symptomatic myocarditis in seven adolescents after Pfizer-BioNTech COVID-19 vaccination: https://pediatrics.aappublications.org/content/early/2021/06/04/peds.2021-052478
  5. Myocarditis and pericarditis after vaccination with COVID-19 mRNA: practical considerations for care providers: https://www.sciencedirect.com/science/article/pii/S0828282X21006243
  6. Myocarditis, pericarditis and cardiomyopathy after COVID-19 vaccination: https://www.sciencedirect.com/science/article/pii/S1443950621011562
  7. Myocarditis with COVID-19 mRNA vaccines: https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.121.056135
  8. Myocarditis and pericarditis after COVID-19 vaccination: https://jamanetwork.com/journals/jama/fullarticle/2782900
  9. Myocarditis temporally associated with COVID-19 vaccination: https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.121.055891.
  10. COVID-19 Vaccination Associated with Myocarditis in Adolescents: https://pediatrics.aappublications.org/content/pediatrics/early/2021/08/12/peds.2021-053427.full.pdf
  11. Acute myocarditis after administration of BNT162b2 vaccine against COVID-19: https://pubmed.ncbi.nlm.nih.gov/33994339/
  12. Temporal association between COVID-19 vaccine Ad26.COV2.S and acute myocarditis: case report and review of the literature: https://www.sciencedirect.com/science/article/pii/S1553838921005789
  13. COVID-19 vaccine-induced myocarditis: a case report with review of the literature: https://www.sciencedirect.com/science/article/pii/S1871402121002253
  14. Potential association between COVID-19 vaccine and myocarditis: clinical and CMR findings: https://www.sciencedirect.com/science/article/pii/S1936878X2100485X
  15. Recurrence of acute myocarditis temporally associated with receipt of coronavirus mRNA disease vaccine 2019 (COVID-19) in a male adolescent: https://www.sciencedirect.com/science/article/pii/S002234762100617X
  16. Fulminant myocarditis and systemic hyper inflammation temporally associated with BNT162b2 COVID-19 mRNA vaccination in two patients: https://www.sciencedirect.com/science/article/pii/S0167527321012286.
  17. Acute myocarditis after administration of BNT162b2 vaccine: https://www.sciencedirect.com/science/article/pii/S2214250921001530
  18. Lymphohistocytic myocarditis after vaccination with COVID-19 Ad26.COV2.S viral vector: https://www.sciencedirect.com/science/article/pii/S2352906721001573
  19. Myocarditis following vaccination with BNT162b2 in a healthy male: https://www.sciencedirect.com/science/article/pii/S0735675721005362
  20. Acute myocarditis after Comirnaty (Pfizer) vaccination in a healthy male with previous SARS-CoV-2 infection: https://www.sciencedirect.com/science/article/pii/S1930043321005549
  21. Acute myocarditis after vaccination with SARS-CoV-2 mRNA-1273 mRNA: https://www.sciencedirect.com/science/article/pii/S2589790X21001931
  22. Acute myocarditis after SARS-CoV-2 vaccination in a 24-year-old man: https://www.sciencedirect.com/science/article/pii/S0870255121003243
  23. A series of patients with myocarditis after vaccination against SARS-CoV-2 with mRNA-1279 and BNT162b2: https://www.sciencedirect.com/science/article/pii/S1936878X21004861
  24. COVID-19 mRNA vaccination and myocarditis: https://pubmed.ncbi.nlm.nih.gov/34268277/
  25. COVID-19 vaccine and myocarditis: https://pubmed.ncbi.nlm.nih.gov/34399967/
  26. Epidemiology and clinical features of myocarditis/pericarditis before the introduction of COVID-19 mRNA vaccine in Korean children: a multicenter study https://search.bvsalud.org/global-literature-on-novel-coronavirus-2019-ncov/resourc e/en/covidwho-1360706.
  27. COVID-19 vaccines and myocarditis: https://pubmed.ncbi.nlm.nih.gov/34246566/
  28. Myocarditis and other cardiovascular complications of COVID-19 mRNA-based COVID-19 vaccines https://www.cureus.com/articles/61030-myocarditis-and-other-cardiovascular-complications-of-the-mrna-based-covid-19-vaccines
  29. Myocarditis and other cardiovascular complications of COVID-19 mRNA-based COVID-19 vaccines https://www.cureus.com/articles/61030-myocarditis-and-other-cardiovascular-complications-of-the-mrna-based-covid-19-vaccines
  30. Myocarditis, pericarditis, and cardiomyopathy after COVID-19 vaccination: https://pubmed.ncbi.nlm.nih.gov/34340927/
  31. Myocarditis with covid-19 mRNA vaccines: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.056135
  32. Association of myocarditis with COVID-19 mRNA vaccine in children: https://media.jamanetwork.com/news-item/association-of-myocarditis-with-mrna-co vid-19-vaccine-in-children/
  33. Association of myocarditis with COVID-19 messenger RNA vaccine BNT162b2 in a case series of children: https://jamanetwork.com/journals/jamacardiology/fullarticle/2783052
  34. Myocarditis after immunization with COVID-19 mRNA vaccines in members of the U.S. military: https://jamanetwork.com/journals/jamacardiology/fullarticle/2781601%5C
  35. Myocarditis occurring after immunization with COVID-19 mRNA-based COVID-19 vaccines: https://jamanetwork.com/journals/jamacardiology/fullarticle/2781600
  36. Myocarditis following immunization with Covid-19 mRNA: https://www.nejm.org/doi/full/10.1056/NEJMc2109975
  37. Patients with acute myocarditis after vaccination withCOVID-19 mRNA: https://jamanetwork.com/journals/jamacardiology/fullarticle/2781602
  38. Myocarditis associated with vaccination with COVID-19 mRNA: https://pubs.rsna.org/doi/10.1148/radiol.2021211430
  39. Symptomatic Acute Myocarditis in 7 Adolescents after Pfizer-BioNTech COVID-19 Vaccination: https://pediatrics.aappublications.org/content/148/3/e2021052478
  40. Cardiovascular magnetic resonance imaging findings in young adult patients with acute myocarditis after COVID-19 mRNA vaccination: a case series: https://jcmr-online.biomedcentral.com/articles/10.1186/s12968-021-00795-4
  41. Clinical Guidance for Young People with Myocarditis and Pericarditis after Vaccination with COVID-19 mRNA: https://www.cps.ca/en/documents/position/clinical-guidance-for-youth-with-myocarditis-and-pericarditis
  42. Cardiac imaging of acute myocarditis after vaccination with COVID-19 mRNA: https://pubmed.ncbi.nlm.nih.gov/34402228/
  43. Case report: acute myocarditis after second dose of mRNA-1273 SARS-CoV-2 mRNA vaccine: https://academic.oup.com/ehjcr/article/5/8/ytab319/6339567
  44. Myocarditis / pericarditis associated with COVID-19 vaccine: https://science.gc.ca/eic/site/063.nsf/eng/h_98291.html
  45. The new COVID-19 mRNA vaccine platform and myocarditis: clues to the possible underlying mechanism: https://pubmed.ncbi.nlm.nih.gov/34312010/
  46. Myocarditis associated with COVID-19 vaccination: echocardiographic, cardiac tomography, and magnetic resonance imaging findings: https://www.ahajournals.org/doi/10.1161/CIRCIMAGING.121.013236
  47. In-depth evaluation of a case of presumed myocarditis after the second dose of COVID-19 mRNA vaccine: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.056038
  48. Occurrence of acute infarct-like myocarditis after COVID-19 vaccination: just an accidental coincidence or rather a vaccination-associated autoimmune myocarditis?: https://pubmed.ncbi.nlm.nih.gov/34333695/

This list is not meant to be all inclusive of all peer-reviewed potential harms from mRNA vaccines. To access any of the 1,000 Vaccine Harms published in Medical journals Click The Link Below:

https://www.informedchoiceaustralia.com/post/1000-peer-reviewed-studies-questioning-covid-19-vaccine-safety

OR VIEW AND DOWNLOAD FULL LIST PDF

Updated_Peer_Reviewed_medical_papers_submitted_to_various_medical.pdfDownload PDF • 1.01MB

How does coronavirus kill? Clinicians trace a ferocious rampage through the body, from brain to toes

Authors: By Meredith WadmanJennifer Couzin-FrankelJocelyn KaiserCatherine MatacicApr. 17, 2020 , 6:45 PM

On rounds in a 20-bed intensive care unit one recent day, physician Joshua Denson assessed two patients with seizures, many with respiratory failure and others whose kidneys were on a dangerous downhill slide. Days earlier, his rounds had been interrupted as his team tried, and failed, to resuscitate a young woman whose heart had stopped. All shared one thing, says Denson, a pulmonary and critical care physician at the Tulane University School of Medicine. “They are all COVID positive.”

As the number of confirmed cases of COVID-19 surges past 2.2 million globally and deaths surpass 150,000, clinicians and pathologists are struggling to understand the damage wrought by the coronavirus as it tears through the body. They are realizing that although the lungs are ground zero, its reach can extend to many organs including the heart and blood vessels, kidneys, gut, and brain.

“[The disease] can attack almost anything in the body with devastating consequences,” says cardiologist Harlan Krumholz of Yale University and Yale-New Haven Hospital, who is leading multiple efforts to gather clinical data on COVID-19. “Its ferocity is breathtaking and humbling.”

Understanding the rampage could help the doctors on the front lines treat the fraction of infected people who become desperately and sometimes mysteriously ill. Does a dangerous, newly observed tendency to blood clotting transform some mild cases into life-threatening emergencies? Is an overzealous immune response behind the worst cases, suggesting treatment with immune-suppressing drugs could help? What explains the startlingly low blood oxygen that some physicians are reporting in patients who nonetheless are not gasping for breath? “Taking a systems approach may be beneficial as we start thinking about therapies,” says Nilam Mangalmurti, a pulmonary intensivist at the Hospital of the University of Pennsylvania (HUP).

What follows is a snapshot of the fast-evolving understanding of how the virus attacks cells around the body, especially in the roughly 5% of patients who become critically ill. Despite the more than 1000 papers now spilling into journals and onto preprint servers every week, a clear picture is elusive, as the virus acts like no pathogen humanity has ever seen. Without larger, prospective controlled studies that are only now being launched, scientists must pull information from small studies and case reports, often published at warp speed and not yet peer reviewed. “We need to keep a very open mind as this phenomenon goes forward,” says Nancy Reau, a liver transplant physician who has been treating COVID-19 patients at Rush University Medical Center. “We are still learning.”

The infection begins

When an infected person expels virus-laden droplets and someone else inhales them, the novel coronavirus, called SARS-CoV-2, enters the nose and throat. It finds a welcome home in the lining of the nose, according to a preprint from scientists at the Wellcome Sanger Institute and elsewhere. They found that cells there are rich in a cell-surface receptor called angiotensin-converting enzyme 2 (ACE2). Throughout the body, the presence of ACE2, which normally helps regulate blood pressure, marks tissues vulnerable to infection, because the virus requires that receptor to enter a cell. Once inside, the virus hijacks the cell’s machinery, making myriad copies of itself and invading new cells.

As the virus multiplies, an infected person may shed copious amounts of it, especially during the first week or so. Symptoms may be absent at this point. Or the virus’ new victim may develop a fever, dry cough, sore throat, loss of smell and taste, or head and body aches.

If the immune system doesn’t beat back SARS-CoV-2 during this initial phase, the virus then marches down the windpipe to attack the lungs, where it can turn deadly. The thinner, distant branches of the lung’s respiratory tree end in tiny air sacs called alveoli, each lined by a single layer of cells that are also rich in ACE2 receptors.

Normally, oxygen crosses the alveoli into the capillaries, tiny blood vessels that lie beside the air sacs; the oxygen is then carried to the rest of the body. But as the immune system wars with the invader, the battle itself disrupts this healthy oxygen transfer. Front-line white blood cells release inflammatory molecules called chemokines, which in turn summon more immune cells that target and kill virus-infected cells, leaving a stew of fluid and dead cells—pus—behind. This is the underlying pathology of pneumonia, with its corresponding symptoms: coughing; fever; and rapid, shallow respiration (see graphic). Some COVID-19 patients recover, sometimes with no more support than oxygen breathed in through nasal prongs.

But others deteriorate, often quite suddenly, developing a condition called acute respiratory distress syndrome (ARDS). Oxygen levels in their blood plummet and they struggle ever harder to breathe. On x-rays and computed tomography scans, their lungs are riddled with white opacities where black space—air—should be. Commonly, these patients end up on ventilators. Many die. Autopsies show their alveoli became stuffed with fluid, white blood cells, mucus, and the detritus of destroyed lung cells.

For More Information: https://www.sciencemag.org/news/2020/04/how-does-coronavirus-kill-clinicians-trace-ferocious-rampage-through-body-brain-toes

Dysautonomia

Authors: Cleveland Clinic

What is dysautonomia?

Dysautonomia is a general term for a group of disorders that share a common problem – that is, an autonomic nervous system (ANS) that doesn’t function as it should. The ANS is the part of the nervous system that controls involuntary body functions (functions you don’t consciously control) like your heart rate, blood pressure, breathing, digestion, body and skin temperature, hormonal function, bladder function, sexual function and many other functions.

When the ANS doesn’t work the way it should, it can cause heart and blood pressure problems, breathing trouble, loss of bladder control and many other problems.

Who might get dysautonomia?

Dysautonomia, also called autonomic dysfunction or autonomic neuropathy, is relatively common. Worldwide, it affects more than 70 million people. It can be present at birth or appear gradually or suddenly at any age. Dysautonomia can be mild to serious in severity and even fatal (rarely). It affects women and men equally.

Dysautonomia can occur as its own disorder, without the presence of other diseases. This is called primary dysautonomia. It can also occur as a condition of another disease. This is called secondary dysautonomia.

Examples of diseases in which secondary dysautonomia can occur include:

For More Information: https://my.clevelandclinic.org/health/diseases/6004-dysautonomia

Covid-19 Story Tip: Brain Fog, Fatigue, Dizziness … Post-COVID POTS Is Real

Authors: Tae Chung, M.D., assistant professor of physical medicine and rehabilitation and neurology at the Johns Hopkins University School of Medicine and director of the Johns Hopkins POTS Program

For almost one year, COVID-19 has impacted the world and taken the lives of many people. While some survivors have fully recovered from this illness, others are still experiencing lingering effects, such as chronic fatigue, brain fog, dizziness and increased heart rate. These survivors have been called “long-haulers,” and experts say some of the symptoms they are experiencing are thought to be caused by postural orthostatic tachycardia syndrome (POTS), a blood circulation disorder.

Some patients may, at first, believe their symptoms are “all in their head,” but Tae Chung, M.D., assistant professor of physical medicine and rehabilitation and neurology at the Johns Hopkins University School of Medicine and director of the Johns Hopkins POTS Program, says “POTS is very real.”

While experts are still researching the long-term side effects of COVID-19, it is clear to experts that some survivors are experiencing the classic signs of POTS as a result of their COVID-19 diagnosis.

Chung says POTS is related to autonomic nerve dysfunction. He explains that the autonomic nervous system is responsible for involuntary control of many of our body functions, such as sweating, pupil movement, bowel movement and blood flow. Many POTS symptoms are thought to be related to inadequate control of blood flow, causing brain fog and dizziness. Chung suspects that COVID-19 may be associated with chronic inflammation in the autonomic nervous system, causing POTS.

For More Information: https://www.hopkinsmedicine.org/news/newsroom/news-releases/covid-19-story-tip-brain-fog-fatigue-dizziness–post-covid-pots-is-real

Extrapulmonary manifestations of COVID-19

Authors: Aakriti GuptaMahesh V. Madhavan[…]Donald W. Landry

Although COVID-19 is most well known for causing substantial respiratory pathology, it can also result in several extrapulmonary manifestations. These conditions include thrombotic complications, myocardial dysfunction and arrhythmia, acute coronary syndromes, acute kidney injury, gastrointestinal symptoms, hepatocellular injury, hyperglycemia and ketosis, neurologic illnesses, ocular symptoms, and dermatologic complications. Given that ACE2, the entry receptor for the causative coronavirus SARS-CoV-2, is expressed in multiple extrapulmonary tissues, direct viral tissue damage is a plausible mechanism of injury. In addition, endothelial damage and thromboinflammation, dysregulation of immune responses, and maladaptation of ACE2-related pathways might all contribute to these extrapulmonary manifestations of COVID-19. Here we review the extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.

For More Information: https://www.nature.com/articles/s41591-020-0968-3

Long covid: How to define it and how to manage it

Authors: Nikki Nabavi, editorial scholar

“Profound fatigue” was a common symptom in most people with long covid, she said, but added that a wide range of other symptoms included cough, breathlessness, muscle and body aches, and chest heaviness or pressure, but also skin rashes, palpitations, fever, headache, diarrhoea, and pins and needles. “A very common feature is the relapsing, remitting nature of the illness, where you feel as though you’ve recovered, then it hits you back,” she said.

Nick Peters added to this definition by highlighting a “distinction between very sick people who have recovered to an extent and [and have been] left with some impact of their severe sickness, versus those who had a relatively mild sickness from the start, in whom it is ongoing.”

Alwan described the fluctuations of her own illness: “It’s a constant cycle of disappointment, not just to you but people around you, who really want you to recover.”

Paul Garner, who also has long covid, described it as a “very bizarre disease” that had left him feeling “repeatedly battered the first two months” and then experiencing lesser episodes in the subsequent four months with continual fatigue. “Navigating help is really difficult,” he said.

Tim Spector said that his team at the Covid Symptom Study had identified six clusters of symptoms for covid-19,1 a couple of which were associated with longer term symptoms, indicating a possible way of predicting early on what might occur. “If you’ve got a persistent cough, hoarse voice, headache, diarrhoea, skipping meals, and shortness of breath in the first week, you are two to three times more likely to get longer term symptoms,” he said.

He said that patterns in the team’s data suggested that long covid was about twice as common in women as in men and that the average age of someone presenting with it was about four years older than people who had what might be termed as “short covid.”

But Spector added, “We do seem to be getting different symptom clusters in different ages, so it could be that there is a different type in younger people compared with the over 65s. As we get more data we should be able to break it into these groups and work out what is going on … which could be very interesting and help us to get early interventions for those at-risk groups.”

Peters said that the data showed fatigue was the most common trait in people who had symptoms beyond three weeks. He also said that around 80% of people who had symptoms lasting more than three weeks reported “having had clear good days and bad days.”

For More Information: https://www.bmj.com/content/370/bmj.m3489