A panel of experts discussed the immune response to COVID-19, during a virtual congressional briefing, held on Thursday, May 13, 2021. The panel included leaders and experts from the National Institutes of Health (NIH), Yale University, Fred Hutchinson Cancer Research Center, Survivor Corps, and Adaptive Biotechnologies. The event, co-hosted by Adaptive Biotechnologies and the Personalized Medicine Coalition, was organized with support from the co-chairs of the US Congressional Personalized Medicine Caucus — Senator Tim Scott (R-SC), Senator Kyrsten Sinema (D-AZ), Rep. Eric Swalwell (D-CA) and Rep. Tom Emmer (R-MN).

Members of the panel included Lance Baldo, MD, chief medical officer at Adaptive Biotechnologies; Diana Berrent, founder at Survivor Corps; Akiko Iwasaki, PhD, professor of Immunobiology and Molecular, Cellular and Developmental Biology and professor of Epidemiology (Microbial Diseases) at Yale School of Medicine and Howard Hughes Medical Institute; James Kublin, MD, MPH, principal staff scientist of the Vaccine and Infectious Disease Division at Fred Hutchinson Cancer Research Center; and Norman E. “Ned” Sharpless, MD, director at the National Cancer Institute. The event was moderated by Cynthia Bens, senior vice president of public policy at Personalized Medicine Coalition.

“Long COVID”

Discussions at the briefing were focused on the role of T cells in the diagnosis and treatment of infection caused by COVID-19. Panelists addressed critical questions about new diagnostic technologies, vaccine and treatment development, and the long-term impact of COVID-19 on individuals who have recovered from the disease. Although the majority of patients fully recover from COVID-19 within a few weeks, some of them experience persistent symptoms. These individuals are commonly considered to be “COVID-19 long-haulers,” and have a condition known as “long COVID.”

Persistent symptoms of “long COVID” often include brain symptoms, fatigue, headaches, dizziness, and shortness of breath (Figure 1). According to the Centers for Disease Control and Prevention (CDC), symptoms of “long COVID” also include a loss of smell or taste, heart palpitations, chest pain, cough, joint or muscle pain, depression or anxiety, fever, or symptoms that get worse after physical or mental activities.¹

In a study of 143 hospitalized patients who were followed up after discharge, 87% had at least 1 symptom nearly 2 months later and more than half of patients still had fatigue.²

Figure 1: Percentage of Patients With “Long-COVID” Symptoms

*Source: Recreated with data from Agostino Gemelli University, Italy/BBC.*

Highlights of the Briefing

T cells play a critical role in the diagnosis of COVID-19 and our immune response to the virus, with T cells monitoring the immune systems and helping B cells make antibodies.
The T-cell response is important in determining vaccine efficacy for viral variants.
There is scientific evidence for the use of new technology to detect recent or prior COVID-19 infection, including a new T cell-based clinical test called T-Detect^TM COVID.
Infection from COVID-19 results in multiple-organ involvement. Because the effect of the virus differs among individuals, a pathway for recovery must be considered using a personalized approach.
COVID-19 is characterized as a vascular disease because the replication of the virus can damage the vasculature and lead to multiple-organ dysfunction, including the eyes, erectile dysfunction, hearing loss, and tooth loss.
COVID-19 outcomes vary among individuals, from no symptoms to acute hospitalization, death, or recovery, as well as “long COVID.” More COVID-19 care centers are needed, along with a template for a tiered-system of handling the long-term effects of the disease.
Vaccine development is a complicated process; however, the current vaccines have been well-evaluated and are safe and effective among a majority of the world’s population. Issues including how long immunity will last or the probability of future harm from the vaccine are currently unknown. The immunity induced by the vaccines is much higher than the immunity by infection from the virus. Booster doses of the vaccines may be needed in the future, but there are currently not enough data to make definitive statements.
Everyone should get vaccinated. The best way of avoiding long-term COVID is to avoid COVID-19. The mechanism leading to long-term COVID is currently unknown. It may be caused by persistent, undetectable viral infection or by an autoimmune response to the virus.
All aspects of the disease sequelae should be handled. Some individuals have reported transient improvement of “long-COVID” symptoms after receiving a vaccine.

Rheumatic and neuromuscular effects of long COVID-19 on muscles, nerves, joints, soft tissues, and bones have been reported among those who recovered from SARS-CoV-2 infection.⁴

The subset of patients developing “long COVID” is growing, with a new study reporting that patients did not feel sick after testing positive for the virus but later developed long-term symptoms.³ In the study, the researchers analyzed the medical records of 1407 individuals in California who tested positive for SARS-CoV-2. However, more than 60 days later, 27% (n=382) of patients, presented with post-COVID-19 symptoms, such as shortness of breath, chest pain, cough, and abdominal pain.

The panelists also noted that the health care system must be prepared to manage this new patient population, who may require expertise from clinicians of different specialties to manage their health and well-being.

Recent CDC guidelines have relaxed the use of masks for fully vaccinated individuals.⁵ However, these guidelines must be evaluated with caution, especially its impact on unvaccinated children and immunocompromised individuals.

Interview With Panelist James Kublin, MD, MPH

We interviewed one of the panelists Dr James Kublin regarding his perspectives on the issues raised at the briefing.

“There is still so much to learn about the long-term consequences of COVID-19 and how they are manifested by rheumatic and neuromuscular symptoms. Several research efforts are underway, including those by the NIH that are focused on post-acute sequelae of SARS-CoV-2 infection (PASC). The symptoms of PASC include a diverse array of physiological conditions, ranging from fatigue or muscle weakness, sleep difficulties, and anxiety or depression, to those patients who were more severely ill during their hospital stay resulting in more severe conditions such as impaired pulmonary diffusion capacities and abnormal chest imaging,” he noted.

“Unfortunately, we are seeing more evidence for autoimmunity being an etiologic factor behind the effects of long COVID-19 on muscles, nerves, joints, soft tissue, and bone. Rheumatologists, as cardiovascular specialists, need to be prepared to treat PASC as part of a multifactorial condition that may require expertise outside of their immediate field,” Dr Kublin added.

On the topic of patients developing “long COVID,” he stated, “Recent reports highlight the need for ongoing surveillance of these PASC conditions, and public and private health care systems are attempting to increase awareness of the importance of this surveillance. The manifestations of PASC across multiple specialties highlight the need for a transdisciplinary approach to capture the constellation of symptoms, the systematic approaches that will be required to dissect the mechanisms behind these likely autoimmune phenomena, and the design of interventions that may improve outcomes. Ultimately, at this point in time, we’re doing our best to prepare for more conclusive evidence that will guide how specialists contribute to such a broad, general disease.”

Overall, rheumatologists will have a major role to play in managing the post-infection symptoms and health issues associated with “long COVID.”

References

Centers for Disease Control and Prevention (CDC). Post-COVID conditions. Long COVID. Updated April 8, 2021. Accessed June 22, 2021. https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects.html
Carfì A, Bernabei R, Landi F; et al; Gemelli Against COVID-19 Post-Acute Care Study Group. Persistent symptoms in patients after acute COVID-19. JAMA. 2020;324(6):603-605. doi:10.1001/jama.2020.12603
Huang Y, Pinto MD, Borelli JL, et al. COVID symptoms, symptom clusters, and predictors for becoming a long-hauler: looking for clarity in the haze of the pandemic. MedRxiv. Published online March 5, 2021. doi:10.1101/2021.03.03.21252086
Ramani SL, Samet J, Franz CK, et al. Musculoskeletal involvement of COVID-19: review of imaging. Skeletal Radiol. Published online February 18, 2021. doi:10.1007/s00256-021-03734-7
Centers for Disease Control and Prevention (CDC). When you’ve been fully vaccinated. Updated June 11, 2021. Accessed June 23, 2021. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/fully-vaccinated.html

Highlights of Virtual Congressional Briefing: Understanding the Immune Response to COVID-19