Long-term consequences of COVID-19 in patients with inflammatory rheumatic diseases

Studies on the long-term consequences of COVID-19 (long-COVID) in patients with inflammatory rheumatic diseases (iRD) are scarce. Where available data do exist, they tend to be heterogeneous and largely inconclusive. In addition, it is not known whether correctly classifying patients with iRD as long-COVID cases is complicated by increased background noise due to the occurrence of persistent symptoms that could be attributed to either long-COVID or iRD.

A team in the Netherlands aimed to compare the risk of developing long-COVID after infection with the Omicron variant in iRD patients versus age- and sex-matched healthy controls. Data were collected from participants enrolled in a prospective cohort study. In line with WHO guidelines, long-COVID cases were defined as participants who reported persistent symptoms that lasted at least 8 weeks, started after the onset and within 3 months of a confirmed SARS-CoV-2 infection, and could not be explained by an alternative diagnosis.

A total of 1,974 iRD patients and 733 healthy controls participated, of whom 24% and 30% had an Omicron infection, respectively. Questionnaire data revealed that more patients compared to controls fulfilled long-COVID criteria; 21% versus 13% respectively – but this was attenuated after adjusting for potential confounders.

Post-hoc modeling showed that higher body mass index and worse severity in the acute infection phase were significantly associated with higher odds of developing long-COVID. Fatigue and loss of fitness were the most frequently reported symptoms of long-COVID in both groups, and recovery time from long-COVID was also similar.

Importantly, more iRD patients than healthy controls without a history of COVID-19 reported symptoms that are also observed in long-COVID; this could in part also be explained by clinical manifestations of underlying rheumatic diseases. Based on these findings, the authors concluded that people with iRD are not more susceptible to long-COVID than those in the general population.

In a session, COVID 19: A pandemic with a long tail, Ørbo and colleagues shared new data from Nor-vaC – a prospective cohort study that includes immune-mediated inflammatory disease (IMID) patients on immunosuppressive therapies.1 The group examined whether post-vaccination anti-Spike antibody levels were predictive of breakthrough infection and the clinical outcome of COVID-19.

To do this, they used data from 1,051 patients who provided post-vaccination samples and responded to follow-up questionnaires after three vaccine doses. Immunosuppressive medication included tumor necrosis factor inhibitors, methotrexate, interleukin inhibitors, janus kinase inhibitors, vedolizumab, and other medication. Hospital records, the Norwegian Patient Registry, and the Norwegian Death Cause Registry provided information on hospital admissions and cause of death.

Results showed that – while half of patients reported COVID-19 – few had life-threatening illness. Patients with the highest post-vaccination anti-Spike levels had a lower risk of COVID-19 infection, supporting the role of repeated vaccination in IMID patients on immunosuppressive therapies. The presence of comorbidities or ulcerative colitis increased the risk of breakthrough infections.

These results underline the good prognosis for Omicron infections in vaccinated IMID patients. Though it is possible that patients who knew they had low anti-Spike levels may have shielded during periods of high transmission, the absence of severe infections and deaths in this large cohort indicates that low antibody levels did not greatly increase risk of severe COVID-19.

Finally, Andreoli and colleagues report on the safety of COVID-19 vaccines during pregnancy and breastfeeding in women with autoimmune diseases, using data from 9,201 participants in the COVAD study. This international study in partnership with patient support groups focused on answering meaningful questions and addressing gaps in the literature about the uptake of COVID-19 vaccination in people living with autoimmune diseases.

Overall, 40 pregnant and 52 breastfeeding patients were identified, with vaccination rates of 100% and 96.2%, respectively. Adverse events of all severities were reported significantly more frequently by pregnant than non-pregnant patients, but there was no difference in comparison with pregnant healthy controls. There was also no difference observed between breastfeeding patients and healthy controls.

Post-vaccination disease flares were reported by 17.5% of pregnant and 20% of breastfeeding patients, and by 18% of age- and disease-matched control patients. All disease flares were managed with glucocorticoids, and one in five women required initiation or a change in their immunosuppressive treatment.

This study provides the first insights into the safety of COVID-19 vaccination during the antenatal period in women with autoimmune disease. While adverse events were more commonly reported by pregnant patients with autoimmune disease than those breastfeeding, these were no higher than among pregnant healthy controls without an autoimmune disease.

These observations are reassuring, and likely to strengthen physician-patient communication and overcome vaccine hesitancy. "The benefits for the mother and fetus by passive immunization are likely to overweigh the potential risks of adverse events and disease flares," said Laura Andreoli from the University of Brescia in Italy.