COVID-19: A Global Public Health Issue and Role of T cells in Controlling SARS-CoV-2 Infections

SARS-CoV-2 infection causes the severe and life-threatening viral disease, COVID-19, creating a global public health issue. Studies to date estimate that the risk of mortality is up to 500% higher in patients 65 years of age or greater than in those aged 30 to 59 years. Other risk factors for severe COVID-19 include chronic lung or heart disease, hypertension, diabetes and underlying immune compromise.

Early evidence suggests that T cells play an important role in the body’s fight against COVID-19 and demonstrates that COVID-19 leads to depletion of endogenous T cells leading to acute immune deficiency, making infected individuals susceptible to developing, overwhelming and sometimes fatal pneumonia. Beyond the lungs, COVID-19 is a multi-organ disease that affects the heart, kidneys, brain, liver, and gastrointestinal tract, as well as causing blood clots. Over 80% of hospitalized patients with COVID-19 are lymphopenic, with reduced CD8+ and CD4+ T cell counts. These reductions in T cell counts correlate negatively with survival. Reduced T cell counts have been observed to be prevalent in older COVID-19 patients and those with severe illness, regardless of age. As further data on the immunogenicity of SARS-CoV-2 continues to emerge, the important protective role of SARS-CoV-2-specific T cells is increasingly being recognized.

Prevention of SARS-CoV-2 infection and clinical management of COVID-19 disease continue to evolve, and guidelines are updated regularly (e.g., https://www.covid19treatmentguidelines.nih.gov ; https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/). Vaccines are the most effective way to prevent infection, and monoclonal antibodies may be used for pre-exposure prophylaxis in individuals who may not be candidates for active immunization. Recommendations for COVID-19 treatment regimens are based on clinical severity and time from development of symptoms, and include immunomodulatory agents (e.g., corticosteroids, JAK inhibitors and IL-6 inhibitors), as well as antiviral agents (e.g., nirmatrelvir, remdesivir, molnupiravir) in addition to supportive care measures. Like other RNA viruses, SARS-CoV-2 is constantly evolving through random mutations, which can impact the efficacy of available preventive and therapeutic interventions. There is therefore still a need to develop alternative therapeutics that can maintain efficacy in the face of viral evolution. Novel therapeutics, including ALVR109, an allogeneic, off-the-shelf, SARS-CoV-2-specific T cell (VST) therapy candidate for COVID-19, may be of benefit to address this urgent unmet medical need. We are making ALVR109 available to physicians in response to compassionate use requests.