SINGAPORE—Almost five years after the onset of the COVID-19 pandemic, the reverberations of this global scourge continue to be felt across the world of medicine, including in the field of rheumatology.
At the 26th Congress of the Asia Pacific League of Associations for Rheumatology (APLAR) in August 2024, Ernest Choy, MD, FRCP, head of rheumatology and translational research in the Division of Infection and Immunity and director of the Cardiff Regional Experimental Arthritis Treatment and Evaluation Centre at Cardiff University School of Medicine, Wales, U.K., delivered a talk titled, The Long-Term Impact of COVID Infections on Patients with Rheumatic Diseases. He described the current evidence regarding the persistent effects of infection with the SARS-CoV-2 virus.
Disease Variability
Dr. Choy began with a key lesson from the pandemic: Even when a single, clearly identifiable entity—in this case, the SARS-CoV-2 virus—is the cause of a disease, the spectrum of clinical phenotypes for that disease can vary widely. From mild, asymptomatic infections to severe, life-threatening COVID-19 cases, clinicians have observed a vast heterogeneity of outcomes across millions of patients.
Dr. Choy outlined the many factors that influence the course of disease for individuals. These variables include:
- Viral factors, such as the specific variant, the portal of entry into the body and the inoculation dose of the virus;
- Host factors, including genetic susceptibility to severe disease, immunocompromised status and frailty; and
- The absence or presence of irreversible tissue damage.
A study co-authored by Dr. Choy helps hammer home the importance of host factors with regard to the implications of COVID-19 infection. In this retrospective, population-based cohort study using linked, anonymized electronic health data from SAIL Databank in the U.K., researchers looked at more than 1,900 people with inflammatory arthritis and more than 160,000 people without inflammatory arthritis who tested positive for COVID-19. Post infection, significantly more people with inflammatory arthritis were hospitalized and the 28-day mortality rate was significantly higher in this group than the general population—24.4% vs. 16.9% for hospitalizations and 11.2% vs. 3.2% for mortality, respectively. However, the main drivers of increased mortality were medical co-morbidities and increased age among patients with inflammatory arthritis. After the study controlled for these confounders, the mortality rate was no longer different between individuals with and without inflammatory arthritis.1
Clinicians should be aware of the potential of worsened bone health in patients following COVID-19 infection.
Long-Term Complications
Next, Dr. Choy discussed the emergence of new clinical entities that may be linked to a patient’s prior COVID-19 infection.
He noted a paper on COVID-19 associated arthritis, which has variably been reported as either COVID-19 viral arthritis and COVID-19 reactive arthritis. In the paper, the authors found 33 cases of COVID-19-associated arthritis described in the medical literature, and the majority of these cases were in adults, included peripheral joint involvement, responded well to treatment and were self-limited. However, the authors noted that it’s not possible to exclude other potential etiologies as the cause of arthritis in these patients and that the causality between SARS-CoV-2 infection and the onset of arthritis still needs to be proved because substantial mechanistic and epidemiological data are lacking.2
Another possible complication of COVID-19 explored in the research literature is COVID-19-associated bone loss. In a paper, Harris et al. noted that in vitro and preclinical studies suggest that SARS-CoV-2 may directly infect bone marrow cells, leading to alterations in bone structure and osteoclast numbers. Additionally, the virus can trigger a cytokine storm, which can stimulate osteoclast activity and lead to bone loss. Additional clinical findings after viral infection—hypocalcemia, altered bone turnover markers and a high prevalence of vertebral fractures—further suggest that clinicians should be aware of the potential of worsened bone health in patients following COVID-19 infection.3
Antibodies: Dr. Choy described the reported appearance of a range of autoantibodies in patients with prior COVID-19 infection. In 2020 study, Zuo et al. measured eight types of antiphospholipid antibodies in the serum of patients hospitalized with COVID-19, finding that >50% of these patients tested positive for at least one of these antibodies. They also found that higher titers of these antibodies associated with neutrophil extracellular traps (NETs), higher platelet count, severe respiratory disease and lower glomerular filtration rate in these patients.4
Although these findings have been reproduced in other studies, Dr. Choy noted that an increased risk of antiphospholipid syndrome has not been demonstrated in these patients. Thus, more work is needed to understand the implications of antibody formation after COVID-19 infection.
Long COVID
In the final portion of the talk, Dr. Choy discussed the challenging topic of long COVID. One difficulty clinicians have encountered in understanding this phenomenon is that post-COVID symptoms can be vague, as well as common. Many patients experience fatigue, myalgias, brain fog and a host of other symptoms post infection.
To date, case definitions and the absence of control groups have muddied the waters when it comes to understanding long COVID. Dr. Choy advocates for more years of follow-up for patients and rigorous research methodologies to be applied to this important topic.
Dr. Choy referenced an interesting article from Stein et al. in which autopsies were conducted on 44 patients who died with COVID-19. With extensive tissue sampling, including the central nervous system, the authors demonstrated that SARS-CoV-2 was widely distributed at time of death, predominantly in patients who passed away from severe COVID-19. The researchers also detected persistent SARS-CoV-2 RNA in multiple organs, including the brain, as late as 230 days after symptom onset in one case. These findings provide a rationale for additional work to define the mechanisms of SARS-CoV-2 persistence that may contribute to post-acute sequelae of the infection.4,5
In Sum
Throughout the presentation, the audience was treated to an extremely helpful summary of the most pressing topics related to COVID-19 in the patients with rheumatologic diseases. COVID-19 is not going anywhere, which is why it remains important to follow the story of this fascinating disease.
Jason Liebowitz, MD, is an assistant professor of medicine in the Division of Rheumatology at Columbia University Vagelos College of Physicians and Surgeons, New York.
References
- Cooksey R, Underwood J, Brophy S, et al. Shielding reduced incidence of COVID-19 in patients with inflammatory arthritis but vulnerability is associated with increased mortality. Rheumatology (Oxford). 2022 Jun 28;61(SI2):SI120–SI128.
- Farisogullari B, Pinto AS, Machado PM. COVID-19-associated arthritis: An emerging new entity? RMD Open. 2022 Sep;8(2):e002026.
- Harris A, Creecy A, Awosanya OD, et al. SARS-CoV-2 and its multifaceted impact on bone health: Mechanisms and clinical evidence. Curr Osteoporos Rep. 2024 Feb;22(1):135–145.
- Zuo Y, Estes SK, Ali RA, et al. Prothrombotic autoantibodies in serum from patients hospitalized with COVID-19. Sci Transl Med. 2020;12(570):eabd3876.
- Stein SR, Ramelli SC, Grazioli A, et al. SARS-CoV-2 infection and persistence in the human body and brain at autopsy. Nature. 2022 Dec;612(7941):758–763.
