The results of this study indicate that in the case of natural infection, the seroprevalence in people ≥40 years of age with underlying diseases in Wuhan was 6.30% (95% CI [5.09-7.52]), while it was 6.12% in people without underlying diseases (95% CI [5.33-6.91]), suggesting that the common underlying diseases as previously mentioned had no significant effect on the positive antibody conversion rate (P>0.05). There were 219 participants who had three consecutive serum samples. Regardless of whether underlying disease was present, the IgG titer decreased significantly over time, and the neutralizing antibody titer remained relatively stable within the 9 months. There was no significant difference in the decline rate of IgG between people with and without underlying diseases. In patients with underlying diseases, the mean IgG titers of asymptomatic infections at the second follow-up were still lower than those of symptomatic infections, suggesting that the presence or absence of symptoms after infection is related to the intensity of immune efficacy.
There have been a few studies on underlying diseases and SARS-CoV-2. These studies have proven that underlying disease is a risk factor for severe disease, but it is unknown whether they are risk factors for SARS-CoV-2 infection. Our study is the first serological study of dynamic follow-up of people 40 years of age and older with underlying diseases and in a state of natural infection. We continued to follow up on the rate of positive antibodies and their dynamic changes within the 9 months. At the same time, we also conducted tests on participants’ antiviral immunoglobulin and neutralizing antibodies, comprehensively assessed the immune response and efficacy, and improved understanding of the seroconversion of people with underlying diseases after natural infection with SARS-CoV-2. To the best of our knowledge, there are few long-term studies with such large samples of people with natural infections and all-round testing of participants’ antiviral immunoglobulins and neutralizing antibodies simultaneously. In this way, it is possible to evaluate the characteristics of the immune response to SARS-CoV-2 infection in the common underlying disease population more objectively.
We also used logistic regression (stepwise regression) regulations to avoid the collinearity problem between various factors. After adjustment, the risk of SARS-CoV-2 infection in retirees was 2.71 times that of other occupations in the group with underlying diseases, which may be related to the fact that most retirees are elderly. Wei-Jie Guan et al. conducted a study of 1,590 confirmed COVID-19 patients with an average age of nearly 50 years in 575 hospitals in 31 provinces, autonomous regions, and municipalities in mainland China. The results showed that COVID-19 patients with at least one comorbidity were associated with higher severity of the disease. Complications mainly included hypertension, diabetes, cerebrovascular disease, and chronic obstructive pulmonary disease. These results align with our research, suggesting that retirees with underlying disease were at higher risk of infection. As a special population, health workers have higher exposure risks and were more likely to be infected with SARS-CoV-2 (OR=17.76, 95%, CI: 3.32-94.95). The confidence interval range was larger because the number of qualified medical personnel included in the statistical analysis was small. However, it still provided a certain amount of practical reference value. In a cross-sectional study from the Lombardy region in Italy, IgG serological testing was conducted on health workers from April 1 to May 26, 2020. The results showed that some professionals accustomed to managing infectious diseases had a higher risk of SARS-CoV-2 infection. This is related to the repeated exposure of health workers to COVID-19 patients. One should be reminded that attention must be paid to the personal protection of key populations to reduce the risk of infection in the occupational environment, including current immigration management and related staff. People who have been exposed to fever or respiratory symptoms since December 2019 are more susceptible to SARS-CoV-2 infection because these people were more likely to be exposed to SARS-CoV-2.
Similar to SARS-CoV and the Middle East Respiratory Syndrome Coronavirus (MERS-COV), SARS-CoV-2 infection can stimulate the humoral immune response.[10–12] Understanding the positive rate of antibodies on a population-level and the dynamic characteristics of humoral immunity is critical to formulating vaccination strategies, especially for middle-aged and elderly people with common underlying diseases. The key to controlling COVID-19 is the development of effective vaccines. Although a variety of effective vaccines are currently available in China, such as inactivated vaccines, adenovirus vector vaccines, subunit recombinant protein vaccines, etc., for a large number of middle-aged and elderly people with underlying diseases, the task of vaccination is still arduous, in which the scientific formulation of vaccination strategies and procedures is especially important. Therefore, it is essential to further detect IgG antibodies and neutralizing antibodies of SARS-CoV-2 to assess the dynamic changes in the attenuation of the immune function in patients with underlying disease over a long period of time.
In our study, the positive conversion rate of neutralizing antibodies of people with underlying diseases was higher than that of those without underlying diseases at each stage of the test. In people with and without underlying diseases, we have observed that the positive conversion rate of neutralizing antibodies in symptomatic patients at all stages was higher than that of asymptomatic patients. This result may be related to patients with underlying diseases being more likely to be infected with SARS-CoV-2 and become symptomatic infections.[14, 15]
The neutralizing antibody response helps to prevent reinfection with the virus.[16, 17] A study in Iceland showed that the total antibody titer did not decrease significantly within 4 months after the infection was confirmed. A study by Cesheng Li et al. included 869 patients who recovered from natural infections in Wuhan, from whom 1782 plasma samples were collected and analyzed. The results showed that more than 70% of plasma donors could continue to produce detectable receptor-binding domain (RBD)-IgG for more than 1 year after diagnosis. Our research found that the IgG titer decreased significantly regardless of the underlying disease, while the neutralizing antibody titer remained stable within the 9 months. Regardless of whether the antibody-positive patients had symptoms, the neutralizing antibody titer did not decrease significantly during the study period in either group (underlying disease and non-underlying disease), suggesting that it may be unnecessary to differentiate between these two groups of people in the future vaccination process.
Some studies have also performed a linear fit of antibody titers. However, there is currently no study comparing the decline rate of IgG titers in positive patients with different underlying diseases. Therefore, we compared the decline rate of IgG in people with and without underlying diseases. The IgG titer of people with underlying disease declined slightly, but there was no difference between the regression coefficients of the two groups. Therefore, the immune protection after receiving vaccination may not have a significant impact, and there is no need to formulate a special immunization program for people with underlying diseases.
We conducted a study on symptomatic and asymptomatic patients. Regardless of whether the two groups had underlying diseases, the proportion of people positive for IgA, IgM, and IgG gradually decreased over time, while the ratio of neutralizing antibodies was relatively stable. Combined with the results of our previous studies, it indicates that asymptomatic infections in the real world will likely be an important part of the immune population. Therefore, a scientific and objective understanding of their antibody levels and changes is critical for formulating future vaccination strategies and procedures for such populations. It is also the key to preventing the continuous spread of the COVID-19 pandemic and the continuous mutation of the virus as soon as possible.
The constant mutation of the virus has caused concern worldwide because it may spread more quickly, and the effectiveness of vaccines against these mutated viruses may also be reduced, especially for middle-aged and elderly people with underlying diseases. A Danish study showed that previous infections could only provide 47% protection in people 65 years of age and older, indicating that the elderly are more likely to be infected with COVID-19 again. An Israeli study showed that, including the elderly, two doses of Pfizer’s BioNTech COVID-19 vaccine have a 95% protection rate against infection, hospitalization, severe illness, and death. However, as elderly are the main population of basic diseases, studies on whether different vaccination strategies should be formulated to improve the effectiveness of protection have been lacking. Our research suggests that as long as the vaccination conditions are met, the presence or absence of underlying diseases will not significantly affect post-vaccination immunity and effectiveness. In any case, taking personal protective measures, maintaining a safe social distance, and vaccinating as soon as possible are still the most reliable prevention and control measures in the context of the continuing COVID-19 pandemic.
This study also has certain limitations. Firstly, some symptomatic patients reported that they had symptoms, in which case recall bias may have occurred. Secondly, after the Wuhan lockdown, we followed up with the patients, but there were quite a few asymptomatic people with infection, and we could not determine the time of their initial infection. Finally, since more than half of the infected people in mainland China are concentrated in Wuhan, the extrapolation of the results may be limited, although this limitation is likely small.