A review of the immunology of COVID-19 was published in March 2022 in Science by Miriam Merad, MD, PhD, Mount Sinai Professor in Cancer Immunology and Director of the Precision Immunology Institute at the Icahn School of Medicine at Mount Sinai, and an international team of scientists. Here are excerpts:
Variants of Concern
As the virus evolves and new variants emerge, there have been concerns that such variants could increase pathogenesis by escaping from immunity generated through previous infection or vaccination or by inducing more severe disease. Some variants of concern, such as 1.351 (Beta), P.1 (Gamma), and the recently described B.1.1.529 (Omicron), have mutations that render them less susceptible to vaccine-mediated and infection-acquired immunity. It is less apparent whether some variants induce more severe disease upon primary infection than others, though strains such as B.1.1.7 (Alpha) and B.1.617.2 (Delta) are known to spread more efficiently, making it difficult to distinguish increased infection rates from increased severity. As new variants emerge, it will be important to direct continued research efforts into identifying how such variants escape from either innate or adaptive immune responses.
Immunology of Long COVID
It is now clear that COVID-19 can lead to long-term disease—often referred to as Long COVID syndrome or post-acute sequelae of SARS-CoV-2infection (PASC)—in a significant proportion of survivors. Although there is no universal consensus in the definition of PASC, the Centers for Disease Control and Prevention defines it as a wide range of new, returning, or ongoing health problems that people experience four or more weeks after first being infected with SARS-CoV-2. By contrast, the World Health Organization defines it as a condition that occurs in people with confirmed or probable SARS-CoV-2infection, usually three months from the onset of COVID-19 with symptoms and that last for at least two months and cannot be explained by an alternative diagnosis.
A systematic review of 57 peer-reviewed studies with 250,351 survivors of COVID-19 who met their inclusion criteria for PASC showed that the median age of patients was 54.4 years, 56 percent were male, and 79 percent were hospitalized during acute COVID-19. At six months, 54 percent of survivors suffered at least one PASC symptom. However, non-hospitalized COVID-19 survivors who developed PASC were primarily middle-aged women.
In a survey of 445 non-hospitalized Danish COVID-19 patients, persistent symptoms—most commonly fatigue and difficulty with memory and concentration—were reported by 36 percent of symptomatic participants with a follow-up of more than four weeks. Risk factors for persistent symptoms included female sex (44 percent for women and 24 percent for men) and body mass index. The immunobiology of PASC is currently under investigation. Leading hypotheses include:
- persistent virus or viral antigens and RNA in tissues that drive chronic inflammation;
- the triggering of autoimmunity after acute viral infection;
- a disruption of the gut microbiota, potentially driven by virus persistence in the intestine;
- and unrepaired tissue damage.
Concluding remarks and future directions
The COVID-19 pandemic has wrought massive disruption and resulted in the loss of countless lives; however, there have been silver linings. The particularly rapid development of highly efficacious vaccines is foremost among these and has established a playbook for the response to future pandemics.
One comforting prospect is the degree to which advances in our understanding and treatment of COVID-19 have been aided by an unprecedented degree of scientific cooperation. Free sharing of data has allowed us to rapidly glean critical insights into the role of the immune system in contributing to both protection and pathogenesis in COVID-19. Such insights will undoubtedly help us prepare for the next pandemic, just as decades of previous immunological research led to our current COVID-19 vaccines. However, many challenges remain, and our progress in ending this pandemic is threatened by inequitable distribution of vaccines and the rise of variants that are less susceptible to vaccination and prior-infection-mediated immunity.
As infections continue to occur, there remains a need for new therapeutics and hence a need for a better understanding of the pathophysiology of COVID-19. In addition to treating acute infections, there is a dire need to better understand and develop treatments for individuals with Long COVID. Another threat is the amount of misinformation and erroneous theories about the pandemic, vaccines, and therapeutic efforts that have been circulating in social media, some unfortunately introduced by scientists.
More than ever, interdisciplinary and integrative approaches to scientific collaboration and fighting misinformation are necessary to tackle these and other challenges that lie ahead.
Read more insights from Leadership