At present, over 56.56 million people worldwide have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen that causes coronavirus disease 2019 (COVID-19), which has caused over 1.35 million deaths. On the other hand, over 39.35 million people have recovered from the infection. The question currently baffling researchers is the longevity or duration of immunity against reinfection among those recovered.
US-based scientists – from the La Jolla Institute for Immunology, University of California, San Diego and Icahn School of Medicine at Mount Sinai – have released a study on preprint server bioRxiv*, titled “Immunological memory to SARS-CoV-2 assessed for greater than six months after infection,” contributing to the enormous research effort currently underway in this area.
As the researchers note, to understand the efficacy of vaccines currently in development, it is important to know the longevity of immunological memory against SARS-CoV-2. This would also help develop better diagnostic methods for the infection, they added.
Overall, the future course of the pandemic could be more accurately predicted if the individual immune reaction to SARS-CoV-2 infection can be quantified and its longevity defined.
The viral infection is known to release SARS-CoV-2-specific antibodies and stimulate the CD4+ T cells and CD8+ T cells. This T cell response leads to less severe disease, and thus, “CD4+ T cell and CD8+ T cell responses may be important for control and resolution of primary SARS-CoV-2 infection,” write the researchers.
The neutralizing antibodies against the infection are capable of protecting against secondary infection with SARS-CoV-2. When these neutralizing antibodies were given passively – through convalescent plasma transfusion, for example – infection severity was found to be much less severe in lab animals. However, in humans, if this passive transfer of neutralizing antibodies provided after the infection had already started, the infection severity could not be significantly controlled. This means that the T cells within the infected person play a significant role in protecting against secondary infection rather than the antibodies alone, write the researchers.
Circulating memory T cells and memory B cells may take several days to reactivate when exposed to the infection again, and this reactivation can trigger “recall T cell responses and/or anamnestic antibody responses,” write the researchers.
“COVID-19 vaccine development is closely tied to the topic of immunological memory.” This study was undertaken to assess the immune memory of the “three branches of adaptive immunity (CD4+ T cell, CD8+ T cell, and humoral immunity),” they add.
This study analyzed the immune memory against SARS-CoV-2 in 185 recovered COVID-19 cases for over 6 months after recovery from the infection. 43 percent of the participants were male, and 57 percent were female. The participants had a wide range of severity of disease, from asymptomatic to severe. They were recruited from multiple sites. Of the patients, 7 percent had needed hospitalization and some needed intensive care unit (ICU) care.
Adults with confirmed infection were included and their disease was scored from 0 to 10 using a numerical scoring system based on the NIH ordinal scale. The team explains that “asymptomatic” cases had a score of 1, those with “mild symptoms” has scores of 2 or 3, those with “moderate symptoms or disease” had scores of 4 or 5 and those with “severe disease” had scores 6 and over. Those over scores of 4 had needed hospitalization.
Blood samples were collected for antibody analysis as well as for SARS-CoV-2-specific CD4+ T cells and CD8+ T cell assays and memory B cell assays. Spike receptor-binding domain (RBD) IgG was also measured. SARS-CoV-2-specific memory B cells were identified using fluorescently labeled multimerized probes.
Most of the participants provided blood samples at 6 days post-onset-of-symptoms and then against at 240 days post-onset-of-symptoms. A total of 41 samples were obtained at over 6 months post-onset-of-symptoms (178 days or longer). A total of 38 participants provided samples at 2 to 4 points over the study period.
The study results
Overall, the study results showed that specific antibody responses against the spike protein on the virus (called the Spike IgG) were stable in convalescent patients for over 6 months. Spike protein-specific memory B cells were also abundantly present at 6 months. The number of these memory B cells was also found to be higher at 6 months post-infection recovery than at 1 month post-recovery. SARS-CoV-2-specific CD4+ T cells and CD8+ T cells had a half-life of 3 to 5 months and showed a declining trend thereafter.
- 98 percent were seropositive for spike IgG at 1 month post-onset-of-symptoms (days 20 to 50)
- 90 percent were seropositive for spike IgG at 6 to 8 months (post-onset-of-symptoms over 178 days)
- SARS-CoV-2 RBD IgG titers had a half-life of 83 days
- 88 percent were seropositive for RBD IgG at 6 to 8 months (post-onset-of-symptoms over 178 days)
- The percentage of subjects seropositive for SARS-CoV-2 neutralizing antibodies (titer > 20) at 6 to 8 months post-onset-of-symptoms was 90 percent
- Circulating RBD IgA had a half-life of 27 days
Memory B cells:
Spike-specific memory B cells in SARS-CoV-2 unexposed donors were rare. Spike-specific memory B cell rose from the first measurement at days 36 to 163 on the second measurement at days 111 to 240. Authors wrote, “Overall, based on the observations here, development of B cell memory to SARS-CoV-2 appeared to be robust and likely long-lasting.”
Memory T cells:
SARS-CoV-2 memory CD8+ T cells in 155 subjects were identified. At days 20 to 50 post symptom onset, the SARS-CoV2 memory CD8+ T cells were found in 61 percent of participants. The proportion of subjects with SARS-CoV-2 memory CD8+ T cells at post 6 months after symptom onset was 50 percent.
SARS-CoV-2 memory CD4+ T cell response was robust, say the researchers. At days 20 to 50 post symptom onset, the SARS-CoV2 memory CD4+ T cells were found in 94 percent of participants. The proportion of subjects with SARS-CoV-2 memory CD4+ T cells at post 6 months after symptom onset was 89 percent.
Conclusions and implications
The authors of the study concluded that each component of SARS-CoV-2 immune memory, including the antibody, memory B cell, CD4+ T cell and CD8+ T cell memory to SARS-CoV-2, showed a robust presence months after recovery from the infection. They write, “immune memory consisting of at least three immunological compartments was measurable in ~90% of subjects > 5 months PSO (post symptom onset), indicating that durable immunity against 2o (secondary) COVID-19 disease is a possibility in most individuals.”
bioRxiv 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.
- Jennifer M. Dan, Jose Mateus, Yu Kato, Kathryn M. Hastie, Caterina E. Faliti, Sydney I. Ramirez, April Frazier, Esther Dawen Yu, Alba Grifoni, Stephen A. Rawlings, Bjoern Peters, Florian Krammer, Viviana Simon, Erica Ollmann Saphire, Davey M. Smith, Daniela Weiskopf, Alessandro Sette, Shane Crotty. Immunological memory to SARS-CoV-2 assessed for greater than six months after infection. bioRxiv. Nov 16, 2020. doi: https://doi.org/10.1101/2020.11.15.383323, https://www.biorxiv.org/content/10.1101/2020.11.15.383323v1