BREAKING! COVID-19 News: Study Finds That Recovered Patients Of Severe COVID-19 Do Not Have Long-Lasting Adaptive Immune Responses

COVID-19 News: Spanish researchers from the University of Valencia and INCLIVA Health Research Institute have discovered in a new study that Severe COVID-19 recovered patients do not display long-lasting adaptive immune responses.


 
The study has recently investigated the durability of immune responses specifically developed against SARS-CoV-2, the causative pathogen of 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. However the study also revealed that the levels of IgG-specific anti-SARS-CoV-2 antibodies decline over time in these patients.
 
According to the study team, there is an imperative need to determine the durability of adaptive immunity to SARS-CoV-2. The team enumerated SARS-CoV-2-reactive CD4+ and CD8+ T cells targeting S1 and M proteins and measured RBD-specific serum IgG over a period of 2-6 months after symptoms onset in a cohort of subjects who had recovered from severe clinical forms of COVID-19.
 
The study team recruited 58 patients (38 males and 20 females; median age, 62.5 years), who had been hospitalized with bilateral pneumonia, 60% with one or more comorbidities. IgG antibodies binding to SARS-CoV-2 RBD were measured by ELISA. SARSCoV-2-reactive CD69+ -expressing-IFNγ-producing-CD4+ and CD8+ T cells were enumerated in heparinized whole blood by flow cytometry for ICS.
 
The study findings showed that detectable SARS-CoV-2-S1/M-reactive CD69+ -IFN-γ CD4+ and CD8+ T cells were displayed in 17 (29.3%) and 6 (10.3%) subjects respectively, at a median of 84 days after onset of symptoms (range, 58-191 days). Concurrent comorbidities increased the risk (OR, 3.15; 95% CI, 1.03-9.61; P=0.04) of undetectable T-cell responses in models adjusted for age, sex and hospitalization ward. Twenty-one out of the 35 patients (60%) had detectable RBD-specific serum IgGs at a median of 118 days (range, 60 to 145 days) after symptoms onset. SARS-CoV-2 RBD specific IgG serum levels were found to drop significantly over time.
 
The study findings concluded that a relatively limited number of subjects who developed severe forms of COVID-19 had detectable SARS-CoV-2-S1/M IFNγ CD4+ and CD8+ T cells at midterm after clinical diagnosis. The findings also indicated that serum levels of RBD specific IgGs decline over time, becoming undetectable in some patients.
 
The study findings were published on a preprint server and are currently being peer reviewed. https://www.medrxiv.org/content/10.1101/2021.01.05.20249027v1
 
Ever since the debut 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.
 
From current available research, 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.
 
This 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. 
 
The hospitalized 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.
 
The study found that 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.
 
Also 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.   
 
Interestingly 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.
 
However 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.
 
Also 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.
 
The significance of the study findings is that 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.
 
Also 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.
 
An interesting observation was that 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.
Also 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.
 
In summary, the study findings have shown that a relatively low number of subjects who developed severe forms of COVID-19 had detectable SARS-CoV-2-S1/M IFNγ CD4+ and CD8+ T cells at medium term after clinical diagnosis (up to 6 months), particularly those with  concurrent comorbidities. Our data also indicated that serum levels of RBD-specific IgGs decline over time, becoming undetectable in some patients. Elucidating whether individuals lacking these specific adaptive immune responses are susceptible to reinfection is beyond the scope of the current study and needs to be addressed in future research.
 
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