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 Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 2  |  Issue : 3  |  Page : 105-111

COVID-19 vaccine-related immunological adverse event presented as reversible autoimmune disease with rheumatological feature and pulmonary infiltrates


Respiratory Medicine and Tuberculosis, MIMSR Medical College, Latur, Maharshtra, India

Date of Submission15-Feb-2022
Date of Acceptance08-Mar-2022
Date of Web Publication17-Aug-2022

Correspondence Address:
Dr. Shital Patil
MIMSR Medical College, Latur, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jalh.jalh_5_22

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  Abstract 


Rheumatological manifestation with acute febrile respiratory illness known to occur after coronavirus disease 2019 (COVID-19) pneumonia and presenting as long COVID disease, its occurrence with COVID vaccination is not very well associated or described in the literature. In this case report, a 45-year-old female presented with constitutional symptoms, persistent fever, and lung parenchymal infiltrates, without mycobacterial microscopic or genome documentation, received empirical antituberculosis (TB) treatment with the progression of disease with little clinical or radiological response. Bronchoscopy workup was inconclusive and tropical screen for bacterial, fungal, TB, and malignancy was negative. Vasculitis workup was inconclusive and rheumatological workup documented highly raised antinuclear antibodies titers. We have started her on steroid and hydroxychloroquine and clinical response documented with near-complete resolution of shadows in 12 weeks. Rheumatological syndrome which is a rare vaccine-related adverse event, reversible and easily treatable with routinely available medicines and importantly it is having excellent prognosis. Minimal systemic adverse events are known to occur with all viral vector vaccines, but its occurrence is rare and it should not impact on routine vaccinations as vaccination is a key step in this pandemic to protect humankind.

Keywords: Antinuclear antibodies test, bronchoscopy, coronavirus disease 2019 pneumonia, febrile respiratory illness, rheumatological syndrome


How to cite this article:
Patil S, Narwade G. COVID-19 vaccine-related immunological adverse event presented as reversible autoimmune disease with rheumatological feature and pulmonary infiltrates. J Adv Lung Health 2022;2:105-11

How to cite this URL:
Patil S, Narwade G. COVID-19 vaccine-related immunological adverse event presented as reversible autoimmune disease with rheumatological feature and pulmonary infiltrates. J Adv Lung Health [serial online] 2022 [cited 2022 Sep 25];2:105-11. Available from: http://www.jalh.com/text.asp?2022/2/3/105/353873




  Introduction Top


Vaccines as triggers of autoimmunity are a controversial subject. Many vaccine-related immunological adverse events have been described, for example, evidence for an increased risk of Guillain‒Barre syndrome following influenza vaccine, an association between systemic lupus erythematosus and the papilloma vaccine and episodes of immune demyelination after hepatitis B vaccine were all previously suggested.[1],[2] Although direct causation is debatable, the association is plausible. Detecting immunological adverse reactions to the novel severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) vaccines is of great public and scientific interest. In this case report, we have documented reversible nature of rheumatological syndrome with febrile respiratory illness associated with coronavirus disease (COVID) vaccine.


  Case Report Top


Forty-five-year-old female, housewife, no addiction history, normotensive, nondiabetic, referred to our center by family physician for persistent fever, cough, and anorexia for 3 months of duration, received symptomatic treatment with antibiotics and antipyretics with no relief and her symptoms worsened during mentioned period, and labeled her as perimenopausal symptoms, received supplementary treatment without any response. She was further evaluated for tuberculosis (TB) and treated empirically for TB also without documentation of acid-fast bacilli (AFB) or Mycobacterium TB (MTB) genome (sputum microscopy for AFB negative with sputum for GeneXpert MTB/RIF negative), shown progression of anorexia with no responses to anti-tuberculosis treatment (ATT).

Further clinical details

  1. Fever-intermittent, high grade without chills and rigors associated with minimal body ache and headache
  2. Cough-dry, intermittent, with minimal white sputum production
  3. Loss of appetite and weight loss over period of 3 months
  4. Multiple small joints pain for 3 months
  5. Weakness and myalgia with fatigability
  6. Shortness of breath on exertion.


Clinical examination documented as

Heart rate was 100/min, respiratory rate: 26/bpm, blood pressure -110/70 mmHg PsO2: 90%–94% at room air resting, and 88%–90% at room air on exertion.

Respiratory system examination revealed-bilateral breath sounds diminished bilateral bases, bilateral crepitation's on both lung fields.

Nervous system examination-higher functions normal, no neurological abnormality, cranial nerves normal, recent and past memory normal recall.

Cardiovascular and gastrointestinal systems were normal.

We further asked for more history regarding the progression of disease over the past 3 months, and her husband was told regarding COVID vaccination (Covishield) taken 1 month before the onset of symptoms. The patient disclosed that she was apparently asymptomatic before COVID vaccination (Covishield), and having a history of mild fever after thefirst dose of vaccination which was resolved after 1 week of vaccination, and she took second dose of vaccine after 2 months developed low-grade fever after 2nd week of vaccination, which was progressed over 4 weeks to have moderate to high grade, started on typical respiratory symptoms as cough with shortness of breath which was progressed over period of 3 months to present in intensive care setting.

Laboratory examination documented as

Hemoglobin was 9.8 gm%, total white blood cells- 20,000/mm3, polymorphs-85%, and platelet count- 490000/uL C-reactive protein was 208 mg/L (0–6 mg/L), random blood sugar level-134 mg%, HbA1C-5.60%, lactate dehydrogenase (LDH)-980 IU/L (70–470 IU/L), and uric acid-3.4 mg (3.5–7.5 mg/dL). Serum electrolytes: sodium-138 meq/L (135–145 meq/L), potassium-3.9 meq/L (3.5–5.5 meq/L), ionic calcium-1.32 meq/L (1.09–1.36 meq/L),

D-dimer-980 ng/ml (<500 ng/ml), and interleukin- 6-1.75 pg/ml (0.00–7.00 pg/ml).

Rheumatoid arthritis factor was negative. anti cyclic citrullinated peptide (Anti-CCP) was negative. Thyroid functions were normal. Liver and kidney functions were normal, sputum examination for AFB was negative, and TB GeneXpert MTB/RIF was negative for MTB genome.

COVID-19 reverse transcription–polymerase chain reaction (RT-PCR) test and results documented were negative for SARS-CoV-2.

As clinical findings, chest X-ray suggestive of bilateral lung pathology [Figure 1], electrocardiogram documented normal sinus rhythm [Figure 2], we performed high-resolution computed tomography (HRCT) thorax.
Figure 1: Chest X-ray posteroanterior

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Figure 2: Electrocardiogram

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High-resolution computed tomography thorax documented

Predominant abnromality in left upper lobe as ground-glass opacifications (GGOs) with consolidation [Figure 3], in middle and lower lobe GGOs and consolidation with increased interstitial opacities [Figure 4] and [Figure 5], in left upper and lingula and right lower lobe GGOs [Figure 4], [Figure 5], [Figure 6], and bilateral pleural effusion [Figure 7] and [Figure 8].
Figure 3: High-resolution computed tomography thorax showing left upper lobe GGOs

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Figure 4: High-resolution computed tomography thorax showing upper lobe consolidations

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Figure 5: High-resolution computed tomography thorax showing increased interstitial opacities in left lower lobe

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Figure 6: High-resolution computed tomography thorax showing left upper lobe, lingula and right lower lobe GGOs

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Figure 7: High-resolution computed tomography thorax showing bilateral pleural effusion

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Figure 8: High-resolution computed tomography thorax showing left pleural effusion

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As HRCT was showing lung parenchymal abnormality with predominant acinonodular opacities bilaterally, we have performed fiberoptic video bronchoscopy as sputum examination was inconclusive.

Bronchoscopic examination revealed hyperemic mucosa at lower trachea, carina with purulent secretions coming out from bilateral main stem bronchial lumens, increased rugosity in segmental bronchial openings, without any endobronchial, submucosal, and peribronchial visible abnormality. Bronchoalveolar lavage (BAL) was collected after 100 ml saline instillation and four aliquots were sent for cytology, GeneXpert, bacterial, and fungal culture.

BAL cytology was suggestive of acute inflammation negative for malignant cell. BAL AFB was negative. BAL GeneXpert MTB/RIF was negative. BAL bacterial culture-there was no growth. BAL fungal culture-there was no growth.

As tropical workup and lung malignancy workup were negative in the presence of positive bronchus sign on HRCT thorax, we have analyzed further for rheumatological and vasculitis workup.

Vasculitis workup documented insignificant and titers of MPO (Myeloperoxidase) Test (P-ANCA) was 0.88 RU/ml (normal range 0–20 RU/ml) and PR3 (proteinase-3) test (C-ANCA) was 0.86 RU/ml (normal range 0–20 RU/ml). Antinuclear antibodies (ANA) test documnted speckled and nucleolar pattern, with 1:1000 titer and dsDNA analysis were negative. ANA BLOT was negative (dsDNA, nucleosomes, histones, SmD1, PCNA, P0, SS-A/Ro60kD, SS-A/Ro52kD, SS-B/La, CENP-B, Scl-70, U1 snRNP, AMA M2, Jo-1, Pm-Scl, Ku, and Mi-2 in serum).

Cardiac workup as-

NT-Pro-BNP-115 Pg/ml (<125 pg/ml exclusion of nonacute heart failure) Troponin-I-10 ng/ml (normal <19 ng/ml) CPK-MB-9 ng/ml (normal <25 IU/L).

2-D echocardiography (2-D-Echo) has documnted normal left ventricular systolic function, type I left ventricular diastolic dysfunction, normal chambers, normal valves, no regional wall motion abnormality, with no evidance of pulmonary hypertension.

The patient was having febrile respiratory illness with leukocytosis and minimal bilateral pleural effusion, we have done ultrasonography (USG) thorax for possible aspiration, but it was found difficult to aspirate to differentiate infective etiology or culture if possible. As the patient was having minimal dry cough, without any expectoration, nil sputum in spite of induction with saline nebulization, sputum microbiology, and culture was not done, we have sent one postinduction sample which was labeled as inadequate by microbiologist.

Treatment was initiated with higher antibiotics as injection meropenem 1 g intravenous (IV) TDS, injection teicoplanin 400 mg IV OD, injection methylprednisolone 40 mg IV TDS, antipyretics for fever control, adequate oral liquids with IV fluids, and maintained hydration with kidney functions and liver functions tests monitoring. After 1-week, HRCT thorax and other laboratory investigations were repeated.

HRCT thorax suggestive of minimal GGOs bilaterally, no consolidation [Figure 9] and [Figure 10], with complete resolution of bilateral pleural effusion [Figure 11] and [Figure 12].
Figure 9: High-resolution computed tomography thorax showing minimal GGOs upper lobe

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Figure 10: High-resolution computed tomography thorax showing minimal GGOs upper lobe without consolidations (resolving)

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Figure 11: High-resolution computed tomography thorax mediastinal window showing resolving pleural effusion

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Figure 12: High-resolution computed tomography thorax showing near complete resolution of plerual effusion

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After 1 week, injectable methylprednisolone has been shifted to oral and dose decreased from 40 mg TDS to oral 48 mg and tapered over 12 weeks. We have added hydroxychloroquine 400 BD for 1 month then 400 OD for 12 weeks.

Repeated chest X-ray posteroanterior after 12 weeks of treatment, showing near-normal lung parenchyma with both costophrenic angles clear [Figure 13].
Figure 13: High-resolution computed tomography thorax

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After 3 months, we have repeated ANA titer, liver and kidney functions, with routine hemogram and other tests and documented all parameters in normal range.

ANA test was negative.

We have continued hydroxychloroquine 200 mg OD for more 3 months and then stopped all medicines thereafter. We are following for any rheumatological symptoms in the past 6 months and documented as symptoms with pathology near-complete reversed with all vital parameters in normal.


  Discussion Top


At the end of 2019, COVID-19 wasfirst reported in Wuhan, China, triggered by SARS-CoV-2, and has swiftly spread worldwide. COVID-19 pandemic caused by SARS-CoV-2 has led to an unprecedented setback for the global economy and health. Vaccination is one of the most effective interventions to substantially reduce severe disease and death due to SARS-CoV-2 infection. To date, treatments for COVID-19 are mainly targeted symptomatic treatment and supportive therapy. Currently, one of the most effective strategies for mitigating the COVID-19 pandemic is global vaccination that can create an immune barrier among the population to attenuate the speed and scope of SARS-CoV-2 transmission.

The two most common COVID-19 vaccine platforms currently in use, including mRNA (i.e., Pfizer-BioNTech and Moderna) and adenovirus vector (i.e., Johnson and Johnson and AstraZeneca), elicit robust humoral responses and have shown safety in the majority of populations vaccinated.[3]

However, as vaccination programs are being rolled out globally, many COVID-19 vaccine-related side effects have been recently reported,[4],[5] ranging from mild local symptoms (e.g., pain at the injection site) to systemic symptoms (e.g., fever and/or headache).[6] Localized pain, fatigue, headache, and muscle ache are the most prevalent adverse effects in patients with autoimmune and inflammatory rheumatic diseases following six COVID-19 vaccines.[7] Previous studies indicated that human papillomavirus, hepatitis B, and influenza vaccines may trigger the onset or exacerbations of autoimmune diseases by molecular mimicry inducing autoimmunity.[2],[8]

Once mRNA vaccine is injected, the mRNA enters muscle cells, and the ribosomes perform cellular translation producing the spike protein, a viral receptor-binding domain that recognizes and binds to the host receptor angiotensin-converting enzyme 2. Subsequently, a robust CD8+ and CD4+ T-cell-mediated response are triggered and eventually induces the production of neutralizing antibodies and memory T and B-cells.[9] As for adenoviral vector vaccines, SARS-CoV-2 antigens were delivered by viral vector to invade the cell. The virus vector is physically or chemically weakened and therefore does not cause disease.[10] Within the host cell, the SARS-CoV-2 spike protein antigen is expressed and triggers T-cell-mediated immune response.[11],[12] There are two leading viral vector vaccines currently in use including Janssen adenovirus-based vaccine and AstraZeneca adenovirus-based vaccine (ChAdOx1 nCoV-19). There are currently 17 nonreplicating and two replicating viral vector candidate SARS-CoV-2 vaccines in clinical development.[13] The former has been approved by regulatory authorities around the world for emergency use.[14]

New-onset autoimmune manifestations following COVID-19 vaccination are being reported extensively[15],[16],[17] The main mechanisms through which COVID-19 vaccine triggers autoimmunity include molecular mimicry, the production of particular autoantibodies, and the role of certain vaccine adjuvants. Previous studies have revealed that SARS-CoV-2 infection could trigger autoimmunity,[18] but the association between COVID-19 vaccine and autoimmune phenomena remains nebulous [Table 1]. The respiratory system presented as thefirst organ invaded by SARS-CoV-2, which may be involved in the cross-reactions between the immune response after SARS-CoV-2 infection and pulmonary surfactant proteins, because the SARS-CoV-2 spike glycoprotein and lung surfactant proteins shared 13 of 24 pentapeptides.[19] In addition, the cross-reaction between SARS-CoV-2 proteins and a variety of tissue antigens could lead to autoimmunity against connective tissue and the cardiovascular, gastrointestinal, and nervous systems.[20] Infections act as environmental triggers to cause autoimmune diseases triggered by vaccines, whereas microbial antigens can elicit cross-reactive immune responses against self-antigens.[8] The immune cross-reactivity triggered by the similarity between certain vaccine components and specific human proteins could render the immune system against pathogenic antigens to attack similar proteins in susceptible population and lead to autoimmune diseases, a process known as molecular mimicry. Influenza, hepatitis B, and human papillomavirus vaccines have been suspected to trigger autoimmunity through molecular mimicry.[2],[20] In addition, only a minority of vaccinated subjects subsequently developed autoimmune phenomena, indicating a genetic predisposition to vaccine-induced autoimmunity.[21]
Table 1: Different new-onset autoimmune phenomena following diverse COVID-19 vaccines[[21]

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In the presnt case report, we have documented as reversible nature of rheumatological syndrome and shown excellent response to steroids and hydroxychloroquine.

Key learning points from this case report are

  1. Rheumatological syndrome is known to occur after COVID pneumonia and now data are available its association with COVID vaccination
  2. Although rheumatological syndrome that occurs with COVID-19 pneumonia is not totally reversible or many cases showing persistent nature, we have documented reversible nature as its association with COVID vaccination in our case
  3. Febrile respiratory illness is a typical manifestation of infective etiology in tropical seating like India ranging from bacterial, atypical organisms, viral, and TB. In COVID-19 pneumonia, typical presentation as “acute febrile respiratory illness” is relatively less common, and it has been well documented after vaccination
  4. Persistent constitutional symptoms and poor response to anti-TB treatment is a clinical clue toward to rule out other etiological factors for similar syndromic presentation. Bilateral pleural effusion with parenchymal infiltrates is radiological clue toward viral or immunological nature of disease
  5. Although ANA test is not confirmatory and specific to rule out rheumatological syndrome, its high titer signifies toward immune nature of disease. ANA blot panel is more specific to label in exact nature of autoimmune disease
  6. Steroids are cornerstone of the treatment of rheumatological syndrome with lung involvement and shown excellent response to steroids with hydroxychloroquine. Echocardiography is must in all cases to rule out cardiac dysfunction before initiation of treatment
  7. We recommend all cases with febrile respiratory illness with a history of COVID vaccination should undergo prompt evaluation to rule out rheumatological nature of disease
  8. Rheumatological syndrome which is a rare vaccine-related adverse event, and importantly, it is reversible and managed with routinely available medicines and is having excellent prognosis
  9. Minimal systemic adverse events are known to occur with all viral vector vaccines, but its occurrence is rare and it should not impact on routine vaccinations as vaccination is a key step in this pandemic to protect humankind.


Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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McMahon DE, Amerson E, Rosenbach M, Lipoff JB, Moustafa D, Tyagi A, et al. Cutaneous reactions reported after Moderna and Pfizer COVID-19 vaccination: A registry-based study of 414 cases. J Am Acad Dermatol 2021;85:46-55.  Back to cited text no. 6
    
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Esquivel-Valerio JA, Skinner-Taylor CM, Moreno-Arquieta IA, Cardenas-de la Garza JA, Garcia-Arellano G, Gonzalez-Garcia PL, et al. Adverse events of six COVID-19 vaccines in patients with autoimmune rheumatic diseases: A cross-sectional study. Rheumatol Int 2021;41:2105-8.  Back to cited text no. 7
    
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Wraith DC, Goldman M, Lambert PH. Vaccination and autoimmune disease: What is the evidence? Lancet 2003;362:1659-66.  Back to cited text no. 8
    
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Wack S, Patton T, Ferris LK. COVID-19 vaccine safety and efficacy in patients with immune-mediated inflammatory disease: Review of available evidence. J Am Acad Dermatol 2021;85:1274-84.  Back to cited text no. 9
    
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WHO COVID-19 Vaccine Tracker and Landscape 2021. Available from: https://www.WHO.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines. [Last accessed on 2022 Jan 17].  Back to cited text no. 13
    
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Cabanillas B, Novak N. Allergy to COVID-19 vaccines: A current update. Allergol Int 2021;70:313-8.  Back to cited text no. 15
    
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Cabanillas B, Akdis CA, Novak N. COVID-19 vaccine anaphylaxis: IgE, complement or what else? A reply to: “COVID-19 vaccine anaphylaxis: PEG or not?” Allergy 2021;76:1938-40.  Back to cited text no. 16
    
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Ehrenfeld M, Tincani A, Andreoli L, Cattalini M, Greenbaum A, Kanduc D, et al. Covid-19 and autoimmunity. Autoimmun Rev 2020;19:102597.  Back to cited text no. 18
    
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Vojdani A, Kharrazian D. Potential antigenic cross-reactivity between SARS-CoV-2 and human tissue with a possible link to an increase in autoimmune diseases. Clin Immunol 2020;217:108480.  Back to cited text no. 20
    
21.
Chen Y, Xu Z, Wang P, Li XM, Shuai ZW, Ye DQ,et al. New-onset autoimmune phenomena post-COVID-19 vaccination. Immunology. 2022;165:386-401. doi: 10.1111/imm.13443. Epub 2022 Jan 7. PMID: 34957554.  Back to cited text no. 21
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12], [Figure 13]
 
 
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