A team of scientists from the University of Washington, USA, and the Karolinska Institute, Sweden, has comprehensively studied the antibody-mediated immune responses in patients diagnosed with coronavirus disease 2019 (COVID-19). Their findings reveal that moderately or severely affected COVID-19 patients exhibit robust antibody responses in the blood and airways, whereas asymptomatic or mildly symptomatic COVID-19 patients develop significantly lower antibody responses. The study is currently available on the medRxiv* preprint server.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of the COVID-19 pandemic, is a highly infectious and lethal member of the human coronavirus family. The virus rapidly spread from person to person primarily via respiratory droplets and triggers a wide variety of symptoms, ranging from mild fever, dry cough, weakness to severe breathlessness, chest pain, cognitive impairment, and multiorgan failure. Although the majority of COVID-19 patients remain asymptomatic or mildly symptomatic, older adults and people with comorbidities are highly susceptible to develop life-threatening COVID-19.
Because COVID-19 is a newly emerged disease, a thorough understanding of SARS-CoV-2 specific acute and long-term immune responses is required to determine the effectiveness and outcomes of upcoming vaccines. In the current study, the scientists aimed to investigate whether SARS-CoV-2 specific adaptive immune responses vary with different disease severities. Specifically, they compared the antibody responses between patients who were mildly, moderately, or severely affected with COVID-19.
Current study design
A total of 147 COVID-19 patients with varying levels of disease severity were enrolled for the study. The blood and airway samples were collected from the patients during the acute infection phase and recovery phase. Based on the disease severity, the patients were categorized as mild, moderate, severe, and fatal.
To determine the robustness of adaptive immunity, the levels of immunoglobulin G (IgG) and immunoglobulin A (IgA) in the blood and airway samples were analyzed together with the levels of SARS-CoV-2 specific memory B cells.
The scientists observed that patients with moderate to severe COVID-19 exhibited robust IgG- and IgA-specific circulating antibody responses against the viral nucleocapsid protein, spike protein, and receptor-binding domain. In contrast, mildly affected COVID-19 patients displayed significantly lower antibody responses. The scientists believe that relatively earlier inclusion of mildly affected patients (after 11 days of symptom onset) than moderately affected (after 13 days of symptom onset) and severely affected (after 21.5 days of symptom onset) patients might be one of the reasons behind the differences in antibody responses.
Interestingly, they observed that while a high level of IgG antibody response was maintained in moderate to severe COVID-19 patients during the recovery phase, the levels of IgG also increased in mildly affected COVID-19 patients. However, the IgA-specific antibody responses declined significantly in most of the patients during the recovery phase.
Importantly, a positive correlation between the antibody response and disease severity was observed during the acute and recovery phases. This indicates that patients affected moderately or severely with COVID-19 exhibit the highest antibody responses.
The estimation of receptor binding domain-specific IgG and IgA levels in the upper and lower airway samples also showed a similar trend. Compared to mild COVID-19 patients, significantly higher antibody response was observed in respiratory samples collected from moderate or severe COVID-19 patients. However, the overall antibody response declined significantly during the recovery phase. Interestingly, the robustness of the antibody response was found to be significantly higher in the upper airway samples compared to that in the lower airway samples.
By estimating the levels of spike protein- and receptor binding domain-specific memory B cells in the blood, the scientists observed that both mild and moderate/severe COVID-19 patients exhibited comparable levels of circulating spike protein-specific memory B cells during the recovery phase. Moreover, they found that these memory B cells were predominantly IgG+.
The study provides a comparative analysis of the antibody responses in patients who are mildly, moderately, or severely affected with COVID-19. The study findings reveal that the robustness of antibody response depends on the severity of the disease. The more severe the disease, the more robust the antibody response. The presence of antigen-specific memory B cells in both mildly and moderately/severely affected COVID-19 patients during the recovery phase provides valuable information regarding the development of adaptive immunity.
Another important finding of the study is that while the circulating IgG levels remain high in all COVID-19 patients during the recovery phase, the levels of IgA decline with time. This indicates that COVID-19 recovered patients may not have sufficient airway antibodies to prevent the viral entry upon re-exposure.
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.