Severe COVID-19 recovered patients do not display long-lasting adaptive immune responses, finds study

A team of scientists from the University of Valencia and INCLIVA Health Research Institute, Spain, has recently investigated the durability of immune responses specifically developed against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of coronavirus disease 2019 (COVID-19). The study findings reveal that severe COVID-19 patients develop detectable T cell-mediated responses about 3 months after the onset of symptoms. Moreover, the study reveals that the levels of IgG-specific anti-SARS-CoV-2 antibodies decline over time in these patients. The study is currently available on the medRxiv* preprint server.

Study: Adaptive immune responses to SARS-CoV-2 in recovered severe COVID-19 patients. Image Credit: Corona Borealis Studio / Shutterstock
Study: Adaptive immune responses to SARS-CoV-2 in recovered severe COVID-19 patients. Image Credit: Corona Borealis Studio / Shutterstock

Background

Since the emergence of the COVID-19 pandemic, many studies have been conducted to thoroughly investigate the pattern and durability of SARS-CoV-specific adaptive immune responses in COVID-19 recovered patients. These studies are particularly important to determine whether SARS-CoV-2-specific immunity developed due to natural infection or vaccination can provide long-term protection against reinfection.

According to the available literature, neutralizing antibodies developed against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein have the highest potency to provide protection. Similarly, CD4+ and CD8+ T cells targeting the spike, membrane, and nucleocapsid proteins of SARS-CoV-2 have been found predominantly in convalescent COVID-19 patients.

Current study

The current study was designed to evaluate the specificity and durability of anti- SARS-CoV-2 immune responses in 58 COVID-19 recovered patients who had been hospitalized because of severe COVID-19-related complications. The SARS-CoV-2-specific immune responses were measured for a period of up to 6 months after the onset of symptoms. Specifically, IgG-specific antibodies developed against the spike RBD and SARS-CoV-2-reactive IFNγ-producing CD4+ and CD8+ T cells were estimated as a measure of adaptive immune responses.   

Important observations

The patients enrolled in the study had a severe form of COVID-19 with bilateral pneumonia. About 60% of all patients had comorbidities, including diabetes, hypertension, asthma, chronic lung disease, dyslipidemia, or cancer.

T cell-mediated immune response

About 29% and 10% of enrolled COVID-19 recovered patients showed detectable levels of SARS-CoV-2 spike/membrane protein-reactive CD4+ and CD8+ T cells, respectively, on an average 84 days after the onset of symptoms.

IgG antibody response

The serum samples obtained from 35 patients were analyzed for IgG-specific antibodies developed against the RBD of the viral spike protein. Of these patients, about 60% exhibited detectable levels of SARS-CoV-2-specific antibodies on an average 118 days after the onset of symptoms. However, the levels of SARS-CoV-2-specific antibodies were found to decline over time in all COVID-19 recovered patients.   

Of all patients who exhibited SARS-CoV-2-specific antibody responses, about 48% displayed T cell-mediated immune responses against SARS-CoV-2. About 35% of patients who could not develop SARS-CoV-2-specific antibody response had detectable levels of CD4+ T cells in the serum. However, no correlation was observed between the antibody-mediated and T cell-mediated immune responses.

Regarding demographic, clinical, and biological characteristics, no significant difference in T cell response was observed between patients who had been admitted to the intensive care unit (ICU) or other hospital wards. In contrast, the likelihood of developing detectable T cell responses was considerably low in patients with comorbidities.

Unlike T cell response, the presence of comorbidities did not influence the possibility of developing SARS-CoV-2-specific antibody response. However, COVID-19 recovered patients who had been admitted to ICU were more likely to develop antibody responses against SARS-CoV-2.

Study significance

According to the study findings, only a limited number of COVID-19 recovered patients develop T cell responses against SARS-CoV-2. Moreover, the T cell responses become undetectable after 130 days of COVID-19 diagnosis.

A comparatively higher number of patients exhibit SARS-CoV-2-specific antibody response within 2 to 5 months after COVID-19 diagnosis. However, the antibody response shows a declining trend over time.

Interestingly, the presence of comorbidities is found to influence the T cell response but not the antibody response; whereas, disease severity is found to influence the antibody response but not the T cell response.

Another interesting observation is that no association has been observed between the systemic inflammatory response and SARS-CoV-2-specific antibody or T cell response in COVID-19 recovered patients.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Dr. Sanchari Sinha Dutta

Written by

Dr. Sanchari Sinha Dutta

Dr. Sanchari Sinha Dutta is a science communicator who believes in spreading the power of science in every corner of the world. She has a Bachelor of Science (B.Sc.) degree and a Master's of Science (M.Sc.) in biology and human physiology. Following her Master's degree, Sanchari went on to study a Ph.D. in human physiology. She has authored more than 10 original research articles, all of which have been published in world renowned international journals.

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