What is the association of SARS-CoV-2 vaccination with the risk of PASC in patients with SARDs?

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Findings of a new study posted on medRxiv* preprint server depicted that fully vaccinated patients with systemic autoimmune rheumatic diseases (SARDs) harbor a lower propensity to developing long COVID symptoms compared to SARDs patients who are not fully vaccinated.

Study: Impact of vaccination on post-acute sequelae of SARS CoV-2 infection in patients with rheumatic diseases. Image Credit: V_Lisovoy/Shutterstock
Study: Impact of vaccination on post-acute sequelae of SARS CoV-2 infection in patients with rheumatic diseases. Image Credit: V_Lisovoy/Shutterstock

These results emphasize the importance of coronavirus disease 2019 (COVID-19) vaccination and illustrate the impact of immune responses during the acute phase of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the post-acute sequelae of COVID-19 (PASC) among SARD patients.


Post-acute sequelae of COVID-19, also referred to as long COVID or PASC, depends on the duration of persistence of symptoms in the acute phase of the viral infection. Some of these symptoms persist for at least a month after the acute infection, while others linger longer – a minimum of three months. Meanwhile, PASC affects 20-50% of COVID-19 patients.

The probability of developing PASC is influenced by the severity of the acute infection. Individuals with systemic autoimmune rheumatic diseases (SARDs) are at an increased risk of developing severe COVID-19. Additionally, due to the compromised immunity, this group of patients is likely to respond inadequately to vaccines, further accentuating their chances of developing PASC. 

Symptoms of PASC include – fatigue, arthralgias, myalgias, anosmia, palpitations, cough, dyspnea, and impaired executive function. Altered immunity, together with immunosuppressive therapies, predisposes patients of SARD to develop severe acute COVID-19. However, the impact of vaccination status among SARD patients on the risk of developing PASC remains unclear.

The study

This prospective study explored the impacts of vaccination status in reducing the risk of PASC in SARD patients.

The study was conducted in a multicenter healthcare facility (Mass General Brigham, MGB), including two tertiary hospitals, twelve community hospitals, and the associated outpatient centers in Massachusetts. A nasopharyngeal swab test or polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infected individuals at least 18 years of age were selected between March 2020 to July 2022. All selected patients also had been diagnosed with rheumatic disease. SARD diagnoses were also reconfirmed.

Patients were deemed fully vaccinated if the date of diagnosis of SARS-CoV-2 infection was at least two weeks after completing the recommended vaccination schedule – as prescribed by the Centers for Disease Control and Prevention (CDC), United States. The CDC recommendations suggest – two doses of any messenger ribonucleic acid (mRNA) COVID-19 vaccine; two doses of mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech), or a single dose of Ad26.COV2.S vaccine (Johnson & Johnson- Janssen). 

All the other patients were considered partially vaccinated or unvaccinated on the date of SARS-CoV-2 infection diagnosis (index date). SARDs were categorized as vasculitis, inflammatory arthritis, connective tissue disease, or other.

The participants were enrolled 28 days post a confirmed COVID-19 positive test result. Patients who had completed 90 days of the survey post-COVID-19 diagnosis were analyzed for the definition of SARD according to the WHO. 


Out of the 280 patients analyzed, 41% had breakthrough SAR-CoV-2 infection, and the remaining (59%) had non-breakthrough SARS-CoV-2 infection (partially vaccinated or unvaccinated at the index date). Both these groups had similar demographics – gender, age, ethnicity, race, SARD category, and smoking status. 

Most participants in both groups were females; the mean ages were comparable. Most of the patients had never smoked and were Whites. Further, the comorbidities were identical between the groups, except for obesity, which was more common in the non-breakthrough infection group. 

Among SARD categories, inflammatory arthritis was the most common. Disease-modifying anti-rheumatic drugs (DMARDs), most frequently used during COVID-19 were – hydroxychloroquine, methotrexate, and mycophenolate. The most common targeted synthetic and biologic DMARDs were tumor necrosis factor (TNF) inhibitors, Janus-kinase inhibitors (JAK inhibitors), and anti-CD20 monoclonal antibodies.

Infections during the SARS-CoV-2 Omicron variant dominance (since December 2021), were more common among breakthrough COVID-19 infection patients. Further, patients with breakthrough infection suffered more from sore throat and nasal congestion or rhinorrhea and were given monoclonal antibodies or nirmatrelvir/ritonavir more often compared to those with non-breakthrough infection. Of note, the latter group mostly experienced joint pain, anosmia, and dysgeusia. Furthermore, non-breakthrough infection patients appeared to be hospitalized more frequently than breakthrough infection patients.

Both on day 28 and day 90, patients with breakthrough infections were found to be less likely to suffer from PASC. The time spent after the resolution of symptoms was 28.9 days more for the breakthrough group. In addition, this group had more days devoid of symptoms during the follow-up period. 

Of note, the results of the questionnaire revealed less severe fatigue and pain in patients with breakthrough infections. The health-related quality of life and functional status scores were equivalent among the groups.

Patient-reported PASC – relating the overall health status, pain, functional status, fatigue, frequency of flares of the underlying SARD, and the timing of flares of SARD was also comparable amongst the groups.


Fully vaccinated SARD patients are at a lower risk for severe COVID-19 outcomes and harbor a lower predilection to developing PASC. Although vaccinated SARD patients are more prone to breakthrough infections, the risk of severe outcomes, as well as long COVID, are lower than those in unvaccinated SARD patients. However, the incidence of PASC persists in SARD patients despite vaccination; its severity, too, remains unaffected by the vaccination status.

Journal reference:
Nidhi Saha

Written by

Nidhi Saha

I am a medical content writer and editor. My interests lie in public health awareness and medical communication. I have worked as a clinical dentist and as a consultant research writer in an Indian medical publishing house. It is my constant endeavor is to update knowledge on newer treatment modalities relating to various medical fields. I have also aided in proofreading and publication of manuscripts in accredited medical journals. I like to sketch, read and listen to music in my leisure time.


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