After the end of the COVID-19 public health emergency, we analysed the relationship between Systemic Lupus Erythematosous (SLE) and COVID-19 from the virologist’s perspective based on recent findings. SLE and COVID-19 co-morbidity present unique challenges, as individuals with SLE may be at increased risk for severe COVID-19 illness due to immune system abnormalities and ongoing therapies. Effective management of both diseases requires careful monitoring, adherence to vaccination programs, preventive measures and approved and patient-tailored therapies. This review covers various aspects, including the clinical outcome of SLE patients infected by SARS-CoV-2, the impact of this infection on SLE onset or flare-ups and the benefits of vaccination for this population. Furthermore, this review presents the most recent recommendations on clinical management of COVID-19 in rheumatic patients, including those with SLE, discussing the currently available therapeutic options. Finally, we explore the most effective tools for SARS-CoV-2 diagnosis in autoimmune conditions and examine prognostic biomarkers in COVID-19 rheumatic patients with potential implications on their clinical oversight. By adopting a comprehensive approach, we address these complexities from the virologist’s perspective, aiming to improve health care for this vulnerable population.
StrangfeldASchäferMGianfrancescoMA, et al.Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 global rheumatology alliance physician-reported registry. Ann Rheum Dis2021; 80: 930–942.
3.
SaadounDVieiraMVautierM, et al.SARS-CoV-2 outbreak in immune-mediated inflammatory diseases: the Euro-COVIMID multicentre cross-sectional study. Lancet Rheumatol2021; 3: e481–e488.
4.
AkiyamaSHamdehSMicicD, et al.Prevalence and clinical outcomes of COVID-19 in patients with autoimmune diseases: a systematic review and meta-analysis. Ann Rheum Dis2021; 80: 384–391.
5.
QianGWangXPatelNJ, et al.Outcomes with and without outpatient SARS-CoV-2 treatment for patients with COVID-19 and systemic autoimmune rheumatic diseases: a retrospective cohort study. Lancet Rheumatol2023; 5: e139–e150.
6.
DiovertiVSalto-AlejandreSHaidarG. Immunocompromised patients with protracted COVID-19: a review of ‘long persisters. Curr Transplant Rep2022; 9: 209–218.
7.
PappaMPanagiotopoulosAThomasK, et al.Systemic lupus erythematosus and COVID-19. Curr Rheumatol Rep2023; 25: 192–203.
8.
LawJSorrentoCSaxenaA. Vaccination updates and special considerations for systemic lupus erythematosus patients. Curr Opin Rheumatol2024; 36: 148–153.
9.
ObrișcăBVornicuAJurubițăR, et al.Characteristics of SARS-CoV-2 infection in an actively monitored cohort of patients with lupus nephritis. Biomedicines2022; 10: 2423.
10.
KouranlooKDeyMElwellH, et al.A systematic review of the incidence, management and prognosis of new-onset autoimmune connective tissue diseases after COVID-19. Rheumatol Int2023; 43: 1221–1243.
11.
SakthiswaryRChuahHYChiangKS, et al.COVID-19 in systemic lupus erythematosus: a pooled analysis and systematic review of case reports and series. Lupus2021; 30: 1946–1954.
12.
Lawson-ToveySStrangfeldAHyrichKL, et al.EULAR COVID-19 registry: lessons learnt and future considerations. Ann Rheum Dis2021; 80: 1110–1115.
13.
OverbeckVTaylorBPTurcinovicJ, et al.Successful treatment of SARS-CoV-2 in an immunocompromised patient with persistent infection for 245 days: a case report. Heliyon2024; 10: e23699.
14.
MudgeHRHoneyJRTachoukaftS, et al.Summarizing evidence of associations of COVID-19 with a future diagnosis of inflammatory rheumatic and musculoskeletal diseases: a rapid review. Arthritis Care Res2024; 76: 40–48.
15.
ZamaniBMoeini TabaS-MShayestehpourM. Systemic lupus erythematosus manifestation following COVID-19: a case report. J Med Case Rep2021; 15: 29.
16.
MagnussonKKristoffersenDTDell’IsolaA, et al.Post-covid medical complaints following infection with SARS-CoV-2 omicron vs delta variants. Nat Commun2022; 13: 7363.
17.
AssarSPournazariMSoufivandP, et al.Systemic lupus erythematosus after coronavirus disease-2019 (COVID-19) infection: case-based review. Egypt Rheumatol2022; 44: 145–149.
18.
Cahuapaza-GutierrezNL. Systemic lupus erythematosus following COVID-19 vaccination. A systematic review of case reports and case series. Lupus2024: 9612033241232054.
19.
DasSParulSMSamantaM. Autoimmune diseases post-COVID 19 infection in children in intensive care unit: a case series. Int J Rheum Dis2023; 26: 2288–2293.
CurtisJRJohnsonSRAnthonyDD, et al.American college of rheumatology guidance for COVID-19 vaccination in patients with rheumatic and musculoskeletal diseases: version 5. Arthritis Rheumatol2023; 75: E1–E16, Hoboken NJ.
ColmegnaIValerioVAmiableN, et al.COVID-19 vaccine in immunosuppressed adults with autoimmune rheumatic diseases (COVIAAD): safety, immunogenicity and antibody persistence at 12 months following moderna spikevax primary series. RMD Open2023; 9: e003400.
30.
BieberABrikmanSNovackL, et al.Fourth dose of BNT162b2 vaccine for patients with autoimmune rheumatic diseases in a nationwide setting. Rheumatol Oxf Engl2023; 62: 3332–3338.
31.
AikawaNEKupaLVKSilvaCA, et al.Strong response after fourth dose of mRNA COVID-19 vaccine in autoimmune rheumatic diseases patients with poor response to inactivated vaccine. Rheumatol Oxf Engl2022; 62: 480–485.
32.
BjørlykkeKHØrboHSTveterAT, et al.Four SARS-CoV-2 vaccine doses or hybrid immunity in patients on immunosuppressive therapies: a Norwegian cohort study. Lancet Rheumatol2023; 5: e36–e46.
33.
HitchonCAMesaCBernsteinCN, et al.Immunogenicity and safety of mixed COVID-19 vaccine regimens in patients with immune-mediated inflammatory diseases: a single-centre prospective cohort study. BMJ Open2023; 13: e071397.
34.
HanbergJSFuXWangX, et al.Effectiveness of a fourth dose of COVID-19 mRNA vaccine in patients with systemic autoimmune rheumatic diseases using disease-modifying antirheumatic drugs: an emulated target trial. Lancet Rheumatol2024; 6: e21–e30.
35.
FraenkelLBathonJMEnglandBR, et al.2021 American college of rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol2021; 73: 1108–1123.
36.
FurerVRondaanCHeijstekMW, et al.2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis2020; 79: 39–52.
37.
AurouxMLaurentBCosteB, et al.Serological response to SARS-CoV-2 vaccination in patients with inflammatory rheumatic disease treated with disease modifying anti-rheumatic drugs: a cohort study and a meta-analysis. Joint Bone Spine2022; 89: 105380.
38.
ParsonsCRubioJBoulougouraA, et al.Predictors of a weak antibody response to COVID-19 mRNA vaccine in systemic lupus erythematosus. Rheumatol Int2023; 43: 1621–1627.
39.
PetriMJoyceDHaagK, et al.Effect of systemic lupus erythematosus and immunosuppressive agents on COVID-19 vaccination antibody response. Arthritis Care Res2023; 75: 1878–1885.
40.
ThomasΚGrigoropoulosIAlexopoulouP, et al.Sustained cell-mediated but not humoral responses in rituximab-treated rheumatic patients after vaccination against SARS-CoV-2. Rheumatol Oxf Engl2024; 63: 534–541.
41.
CurtisJRJohnsonSRAnthonyDD, et al.American college of rheumatology guidance for COVID-19 vaccination in patients with rheumatic and musculoskeletal diseases: version 4. Arthritis Rheumatol2022; 74: e21–e36.
42.
GiannopoulouNGuptaLAndreoliL, et al.COVID-19 vaccine safety during pregnancy in women with systemic lupus erythematosus. Autoimmun Rev2023; 22: 103292.
43.
AnZFigueroa-ParraGZhouX, et al.Immune responses and disease biomarker long-term changes following COVID-19 mRNA vaccination in a cohort of rheumatic disease patients. Front Immunol2023; 14: 1224702.
44.
WardILRobertsonCAgrawalU, et al.Risk of COVID-19 death in adults who received booster COVID-19 vaccinations in England. Nat Commun2024; 15: 398.
Najjar-DebbinyRGronichNWeberG, et al.Effectiveness of paxlovid in reducing severe coronavirus disease 2019 and mortality in high-risk patients. Clin Infect Dis2023; 76: e342–e349.
HaddadAJHachemRYMoussaM, et al.Comparing molnupiravir to nirmatrelvir/ritonavir (paxlovid) in the treatment of mild-to-moderate COVID-19 in immunocompromised cancer patients. Cancers2024; 16: 1055.
52.
TianFFengQChenZ. Efficacy and safety of molnupiravir treatment for COVID-19: a systematic review and meta-analysis of randomized controlled trials. Int J Antimicrob Agents2023; 62: 106870.
53.
HuangCLuT-LLinL. Real-world clinical outcomes of molnupiravir for the treatment of mild to moderate COVID-19 in adult patients during the dominance of the omicron variant: a meta-analysis. Antibiotics (Basel)2023; 12: 393.
54.
HammondJLeister-TebbeHGardnerA, et al.Oral nirmatrelvir for high-risk, nonhospitalized adults with COVID-19. N Engl J Med2022; 386: 1397–1408.
55.
MozaffariEChandakAGottliebRL, et al.Remdesivir reduced mortality in immunocompromised patients hospitalized for COVID-19 across variant waves: findings from routine clinical practice. Clin Infect Dis2023; 77: 1626–1634.
56.
KastenMJLahrBDParisapoguA, et al.COVID-19 outcome is not affected by anti-CD20 or high-titer convalescent plasma in immunosuppressed patients. Sci Rep2023; 13: 21249.
LandewéRBMKroonFPBAlunnoA, et al.EULAR recommendations for the management and vaccination of people with rheumatic and musculoskeletal diseases in the context of SARS-CoV-2: the november 2021 update. Ann Rheum Dis2022; 81: 1628–1639.
63.
YamamotoNTsuchiyaYFukudaM, et al.A case report of drug interactions between nirmatrelvir/ritonavir and tacrolimus in a patient with systemic lupus erythematosus. Cureus2024; 16: e52506.
64.
LemaitreFBuddeKVan GelderT, et al.Therapeutic drug monitoring and dosage adjustments of immunosuppressive drugs when combined with nirmatrelvir/ritonavir in patients with COVID-19. Ther Drug Monit2023; 45: 191–199.
TarhiniHRecoingABridier-NahmiasA, et al.Long-term severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectiousness among three immunocompromised patients: from prolonged viral shedding to SARS-CoV-2 superinfection. J Infect Dis2021; 223: 1522–1527.
67.
ThorntonCSHuntleyKBerengerBM, et al.Prolonged SARS-CoV-2 infection following rituximab treatment: clinical course and response to therapeutic interventions correlated with quantitative viral cultures and cycle threshold values. Antimicrob Resist Infect Control2022; 11: 28.
68.
NakamuraKGotoTShiraishiK, et al.Clinical and virological features of SARS-CoV-2 omicron variant-infected immunocompromised patients receiving immunosuppressive medications. BMC Infect Dis2024; 24: 736.
69.
JacobsJLBainWNaqviA, et al.Severe acute respiratory syndrome coronavirus 2 viremia is associated with coronavirus disease 2019 severity and predicts clinical outcomes. Clin Infect Dis2022; 74: 1525–1533.
70.
MoriALavezzariDPomariE, et al.sgRNAs: a SARS-CoV-2 emerging issue. Asp Mol Med2023; 1: 100008.
71.
ChenZNgRWYLuiG, et al.Quantitative and qualitative subgenomic RNA profiles of SARS-CoV-2 in respiratory samples: a comparison between Omicron BA.2 and non-VOC-D614G. Virol Sin2024; 39: 218–227.
72.
RaglowZSurieDChappellJD, et al.SARS-CoV-2 shedding and evolution in patients who were immunocompromised during the omicron period: a multicentre, prospective analysis. Lancet Microbe2024; 5: e235–e246.
GeorgievTAngelovAK. Complexities of diagnosis and management of COVID-19 in autoimmune diseases: potential benefits and detriments of immunosuppression. World J Clin Cases2020; 8: 3669–3678.
ElefanteETaniCZucchiD, et al.Are patients with systemic lupus erythematosus more prone to result false-positive for SARS-CoV2 serology?Clin Exp Rheumatol2020; 38: 577.
77.
MaXLiZWhelanMG, et al.Serology assays used in SARS-CoV-2 seroprevalence surveys worldwide: a systematic review and meta-analysis of assay features, testing algorithms, and performance. Vaccines2022; 10: 2000.
78.
NicolaiETomassettiFPignalosaS, et al.The evolution of serological assays during two years of the COVID-19 pandemic: from an easy-to-use screening tool for identifying current infections to laboratory algorithms for discovering immune protection and optimizing vaccine administration. COVID2024; 4: 1272–1290.
79.
FDA-NIH Biomarker Working Group. Prognostic biomarker. In: BEST (biomarkers, EndpointS, and other tools) resource. Maryland: Food and Drug Administration (US), 2016. https://www.ncbi.nlm.nih.gov/books/NBK402289/ (accessed 6 May 2024).
80.
HIFernandez-RuizRMuskardinTLW, et al.Interferon pathway lupus risk alleles modulate risk of death from acute COVID-19. Transl Res J Lab Clin Med2022; 244: 47–55.
81.
JeongHBaekARParkSW, et al.Rheumatoid factor is associated with severe COVID-19. Int J Rheum Dis2023; 26: 850–861.
82.
MosavatAMirhosseiniAShariatiA, et al.SARS-CoV-2 infection and increasing autoimmune disorders among ICU-hospitalized COVID-19 patients. Int J Rheum Dis2023; 26: 2151–2156.
83.
BakshiJDAtyeoCZurY, et al.Humoral immunity to an endemic coronavirus is associated with postacute sequelae of COVID-19 in individuals with rheumatic diseases. Sci Transl Med2023; 15: eadf6598.
84.
BakshiTLiluashviliELipartiaE, et al.Correlation between SARS-CoV-2 infection and autoimmune rheumatic diseases: a comprehensive analysis of blood biomarkers in COVID-19 patients. Eur Rev Med Pharmacol Sci2023; 27: 12134–12140.
85.
SacchiMCTamiazzoSStobbioneP, et al.SARS-CoV-2 infection as a trigger of autoimmune response. Clin Transl Sci2021; 14: 898–907.
86.
TaeschlerPCerviaCZurbuchenY, et al.Autoantibodies in COVID-19 correlate with antiviral humoral responses and distinct immune signatures. Allergy2022; 77: 2415–2430.
87.
TahaSISamaanSFIbrahimRA, et al.Post-COVID-19 arthritis: is it hyperinflammation or autoimmunity?Eur Cytokine Netw2021; 32: 83–88.
88.
AhmedSMehtaPPaulA, et al.Postvaccination antibody titres predict protection against COVID-19 in patients with autoimmune diseases: survival analysis in a prospective cohort. Ann Rheum Dis2022; 81: 868–874.
89.
AvouacJMiceli-RichardCCombierA, et al.Risk factors of impaired humoral response to COVID-19 vaccination in rituximab-treated patients. Rheumatol Oxf Engl2022; 61: SI163–SI168.
90.
StefanskiA-LRincon-ArevaloHSchrezenmeierE, et al.B cell numbers predict humoral and cellular response upon SARS-CoV-2 vaccination among patients treated with rituximab. Arthritis Rheumatol2022; 74: 934–947.
91.
HuHTangNZhangF, et al.Bioinformatics and system biology approach to identify the influences of COVID-19 on rheumatoid arthritis. Front Immunol2022; 13: 860676.
92.
WuYLiYZhouY, et al.Bioinformatics and systems-biology approach to identify common pathogenic mechanisms for COVID-19 and systemic lupus erythematosus. Autoimmunity2024; 57: 2304826.
93.
ZhengQLinRChenY, et al.SARS-CoV-2 induces ‘cytokine storm’ hyperinflammatory responses in RA patients through pyroptosis. Front Immunol2022; 13: 1058884.
94.
GaoZZhaiXYanG, et al.Bioinformatics analyses of gene expression profile to identify pathogenic mechanisms for COVID-19 infection and cutaneous lupus erythematosus. Front Immunol2023; 14: 1268912.
95.
ZhengQWangDLinR, et al.IFI44 is an immune evasion biomarker for SARS-CoV-2 and staphylococcus aureus infection in patients with RA. Front Immunol2022; 13: 1013322.
96.
ZengHZhuangYLiX, et al.Exploring the potential common denominator pathogenesis of system lupus erythematosus with COVID-19 based on comprehensive bioinformatics analysis. Front Immunol2023; 14: 1179664.
97.
LuoHZhouX. Bioinformatics analysis of potential common pathogenic mechanisms for COVID-19 infection and primary Sjogren’s syndrome. Front Immunol2022; 13: 938837.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
