Risk Factors for Infection, Predictors of Severe Disease, and Antibody Response to COVID-19 in Patients With Inflammatory Rheumatic Diseases in Portugal—A Multicenter, Nationwide Study

  1. Ana Rita Cruz-Machado
  2. Sofia C. Barreira
  3. Matilde Bandeira
  4. Marc Veldhoen
  5. Andreia Gomes
  6. Marta Serrano
  7. Catarina Duarte
  8. Maria Rato
  9. Bruno Miguel Fernandes
  10. Salomé Garcia
  11. Filipe Pinheiro
  12. Miguel Bernardes
  13. Nathalie Madeira
  14. Cláudia Miguel
  15. Rita Torres
  16. Ana Bento Silva
  17. Jorge Pestana
  18. Diogo Almeida
  19. Carolina Mazeda
  20. Filipe Cunha Santos
  21. Patrícia Pinto
  22. Marlene Sousa
  23. Hugo Parente
  24. Graça Sequeira
  25. Maria José Santos
  26. João Eurico Fonseca
  27. Vasco C. Romão

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Abstract

To identify risk factors for SARS-CoV-2 infection and for severe/critical COVID-19, and to assess the humoral response after COVID-19 in these patients.

Methods

Nationwide study of adult patients with inflammatory RMDs prospectively followed in the Rheumatic Diseases Portuguese Register—Reuma.pt—during the first 6 months of the pandemic. We compared patients with COVID-19 with those who did not develop the disease and patients with mild/moderate disease with those exhibiting severe/critical COVID-19. IgG antibodies against SARS-CoV-2 were measured ≥3 months after infection and results were compared with matched controls.

Results

162 cases of COVID-19 were registered in a total of 6,363 appointments. Patients treated with TNF inhibitors (TNFi; OR = 0.160, 95% CI 0.099–0.260, P < 0.001) and tocilizumab (OR 0.147, 95% CI 0.053–0.408, P < 0.001) had reduced odds of infection. Further, TNFi tended to be protective of severe and critical disease. Older age, major comorbidities, and rituximab were associated with an increased risk of infection and worse prognosis. Most patients with inflammatory RMDs (86.2%) developed a robust antibody response. Seroconversion was associated with symptomatic disease (OR 13.46, 95% CI 2.21–81.85, P = 0.005) and tended to be blunted by TNFi (OR 0.17, 95% CI 0.03–1.05; P = 0.057).

Conclusions

TNFi and tocilizumab reduced the risk of infection by SARS-CoV-2. Treatment with TNFi also tended to reduce rates of severe disease and seroconversion. Older age, general comorbidities and rituximab were associated with increased risk for infection and worse prognosis, in line with previous reports. Most patients with RMDs developed a proper antibody response after COVID-19, particularly if they had symptomatic disease.

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  1. Version published to 10.3389/fmed.2022.901817
  2. ScreenIT

    SciScore for 10.1101/2021.10.01.21264428: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: This study was approved by the Ethics Committee of the Lisbon Academic Medical Centre and all patients signed informed consent.
    Consent: This study was approved by the Ethics Committee of the Lisbon Academic Medical Centre and all patients signed informed consent.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Considering that SARS-CoV-2 neutralizing antibodies that inhibit viral replication in vitro mainly target the receptor-binding domain (RBD) of the virus spike protein (19),(20),(21), we quantified IgG antibodies recognizing the RBD using ELISA (through the assay developed by Florian Krammer et al, a format that received FDA emergency approval in April 2020 and is described in detail elsewhere)(22)(8).
    quantified IgG
    suggested: None

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Our study has some limitations, namely concerning the relatively small sample of COVID-19+ patients included. As such, the aforementioned findings must be interpreted with caution. Genetic or environmental factors specific to the Portuguese population might also preclude external generalization. Also, we did not take into consideration potential different social behaviours of COVID-19+ and COVID-19-patients while assessing risk factors for infection. Finally, ours is not a population-based study, thus we cannot affirm the total number of patients with RMDs affected by COVID-19 in the whole country during the first 6 months of the pandemic. In conclusion, we conducted a multicentre, nationwide, comprehensive evaluation of COVID-19 in patients with RMDs, aiming to assess risk factors for infection, predictors of severe/critical disease and antibody response. We found that TNFi reduced the risk for infection, the odds for severe forms of the disease, and the likelihood of seroconversion. Tocilizumab also reduced the risk for COVID-19. These findings warrant further confirmation in independent cohorts. On the other hand, older age, general comorbidities and rituximab are associated with increased risk for infection and worse prognosis, in line with previous reports. At last, most patients with inflammatory RMDs seem to be able to develop a proper antibody response after COVID-19, particularly if they had experienced symptomatic disease. Our findings are overall reassuring for pat...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

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  3. Version published to 10.1101/2021.10.01.21264428v1 on medRxiv