Penn Rheumatology Investigators Report on the Immunology and Epidemiology of SARS-CoV2 infection, and the Efficacy of mRNA Vaccination for COVID-19

Throughout the pandemic Penn Rheumatology has been a leader in clinical research to help understand the impact of COVID-19 on patients with rheumatic disease. To date, reports of these investigations have appeared in more than a dozen high-impact general medical and rheumatology journals — including Nature, Science, and JAMA Internal Medicine.

Immunology of COVID-19

During the COVID-19 pandemic, the Penn Division of Rheumatology at Penn led national efforts to understand the immunological consequences of SARS-CoV-2 infection and vaccine responses in both healthy and immunosuppressed patients.

In a report published in Nature Communications in September Sokratis Apostolidis, MD, a Penn Rheumatology fellow, and colleagues showed that patients with COVID-19 develop de novo autoantibodies during the course of their infection, including autoantibodies commonly seen in primary systemic rheumatic diseases.¹

In a separate, elegant series of studies involving fresh samples from patient with severe COVID-19, Dr. Apostolidis demonstrated that hyperinflammation was associated with platelet dysregulation and thrombotic events and identified pathways that mitigate platelet hyperactivation and can be targeted therapeutically².

Jonathan J. Miner, MD, PhD, a new faculty member in Penn Rheumatology, co- authored an article in Cell Reports in late 2020 that demonstrated that SARS-CoV-2 does not replicate in the human cornea, in contrast to Zika and HSV viruses that have the ability to replicate with different efficiencies.³

mRNA Vaccination and Rheumatology

The Division of Rheumatology at Penn took center stage in the efforts to profile immune responses after mRNA vaccination, which has shown great success in preventing morbidity and mortality from SARS-CoV-2. Work originating in the laboratories of Drs. Apostolidis, Miner, and Su have substantially contributed to our understanding of the human immunology responses to SARS-CoV-2 and vaccination.

A seminal study published in Science by a large collaborative group at Penn, including Penn Rheumatology faculty, showed that SARS-CoV-2 mRNA vaccination induces durable, long-term immunity that is resilient against emerging variants in healthy individuals.⁴

In work published in Nature Medicine investigating patients on CD20-based B cell depleting therapies, Dr. Apostolidis showed that mRNA vaccination against SARS-CoV-2 generates robust T cell responses even in the absence of humoral responses, highlighting the importance of vaccination in these immunologically vulnerable patient populations.⁵

Epidemiology of COVID-19

Throughout the pandemic, Penn Rheumatology faculty members applied clinical epidemiologic principles and advanced research methods to address important patient-oriented research questions.

In 2020, for example, Joshua Baker, MD, MSCE used publicly available cell phone location and weather data to show that reductions in time spent in stores and workplaces was tied to lower rates of COVID-19 and that COVID-19 transmission remained high at warmer temperatures, helping guide interventions to slow the pandemic's spread.^6-8

Penn researchers also partnered with ArthritisPower and the Vasculitis Patient-Powered Research Network to launch the Autoimmune COVID-19 Project, a longitudinal study of several thousand patients with rheumatic disease. Using these data, Michael George, MD, MSCE and Shubhasree Banerjee, MD, found early evidence that during the early phase of the pandemic patients frequently missed follow-up visits and routine testing and stopped using their medications.^9,10

Studying a large community rheumatology practice network, Dr. George then demonstrated that telehealth helped partially replace missed office visits, but that vulnerable populations, including older patients, racial/ethnic minorities, and patients of lower socioeconomic status, were more likely to miss visits entirely.¹¹

Penn investigators also contributed to reports that found that many patients stopped immunosuppressive medications because of concerns about COVID-19.^9,12 Tiffany Dharia, MD, a Penn medical resident and future rheumatologist, then worked with Penn Rheumatology and the Autoimmune COVID-19 Project to show that these pandemic-related treatment interruptions can lead to severe flares of rheumatic disease.¹³

References:

1. Chang, SE, et al. New-onset IgG autoantibodies in hospitalized patients with COVID-19. Nat Commun12, 5417 (2021). https://doi.org/10.1038/s41467-021-25509-3.
2. Apostolidis SA, et al. Signaling through FcγRIIA and the C5a-C5aR pathway mediates platelet hyperactivation in COVID-19. bioRxiv Prepr. Serv. Biol. 2021 doi:10.1101/2021.05.01.442279.
3. Miner, JJ. et al. HSV-1 and Zika Virus but Not SARS-CoV-2 Replicate in the Human Cornea and Are Restricted by Corneal Type III Interferon. Cell Rep.2020;33:108339.
4. Goel, R. R. et al. mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern. Science. 2021;374, eabm0829.
5. Apostolidis, SA, et al. Cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy. Nat. Med. 2021;27:1990 — 2001.
6. Sehra ST… Baker JF. Cell Phone Activity in Categories of Places and Associations With Growth in Cases of COVID-19 in the US. JAMA Intern Med 2020.1;180:1614-1620.
7. Sehra ST… Baker JF. Association of cell phone location data and trends in COVID-19 infections during loosening of stay-at-home restrictions. J Travel Med. 2020 Dec 23;27(8):taaa177.
8. Sehra ST … Baker JF. Maximum daily temperature, precipitation, ultraviolet light, and rates of transmission of severe acute respiratory syndrome coronavirus 2 in the United States. Clin. Infect. Dis. 2020;71, 2482 — 2487.
9. George M, et al. Concerns, Healthcare Use, and Treatment Interruptions in Patients With Common Autoimmune Rheumatic Diseases During the COVID-19 Pandemic. J Rheumatol. 2021;48:603-607.
10. Banerjee S, George M, et al. Effects of the COVID-19 Pandemic on Patients Living With Vasculitis. ACR Open Rheumatol. 2021;3:17-24.
11. George MD, et al. Social Distancing, Health Care Disruptions, Telemedicine Use, and Treatment Interruption During the COVID-19 Pandemic in Patients With or Without Autoimmune Rheumatic Disease. ACR Open Rheumatol. 2021;3:381-389.
12. Michaud K … Ogdie A, et al. Experiences of Patients With Rheumatic Diseases in the United States During Early Days of the COVID-19 Pandemic. ACR Open Rheumatol. 2020;2:335-343.
13. Dharia T … George MD, et al. Medication interruptions and subsequent disease flares during the COVID-19 pandemic: a longitudinal online study of patients with rheumatic disease. Arthritis Care Res. Accepted Author Manuscript. https://doi.org/10.1002/acr.24837