Pulmonary function and comparative SARS-CoV-2 RBD-specific IgG antibody response among the COVID-19 recovered group

Abstract

Background: Coronavirus disease 2019 (COVID-19) is a highly contagious infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for millions of deaths and substantial morbidity worldwide. Several studies report that up to 50% of individuals who recover from acute SARS-CoV-2 infection experience a plethora of long-COVID symptoms that may persist for weeks, months, or even up to a year. Abnormal pulmonary function is one of the most critical manifestations of long-COVID, even after recovering from COVID-19. Understanding the long-term pulmonary consequences and immune response among individuals recovering from COVID-19, who experienced disease severity ranging from mild to severe, is crucial for comprehensive post-recovery care and vaccination strategies.

Methods: This prospective case-control study included 29 individuals who had recovered from COVID-19 with a history of mild to severe symptoms and 64 controls. Assessments of pulmonary functional measures, such as FVC, FEV1, FEV1/FVC ratio, FEF, MEF, and PEF were carried out following recovery from COVID-19. Additionally, IgG antibody responses were examined by ELISA for up to six months through multiple follow-ups following two doses of vaccination, with an additional follow-up 30 days after the booster dose (third dose).

Results: Pulmonary functional abnormalities were prevalent in the recovered group, which had previously exhibited varying symptom severity (53% mild, 66% moderate, and 50% severe) compared to the control group (23%). Higher IgG antibody titers were observed among the recovered group, with significantly elevated titers in severe and moderate cases following vaccination. After vaccination, the recovered group showed significantly higher titers at day 14, particularly in the severe (1418 IU/mL) and moderate (1390 IU/mL) groups, compared to the control group (968 IU/mL) (p < 0.005). Notably, antibody titers were negatively correlated with pulmonary function test (PFT) parameters such as Forced Vital Capacity (FVC) and Forced Expiratory Volume in 1 second (FEV1). All groups experienced a significant (p < 0.005) decrease in antibody titers within 90-120 days after receiving two doses of vaccination. After five to six months, antibody titers returned to baseline levels, highlighting the importance of vaccination and additional booster doses regardless of previous infection history. Overall, our study underscores the significance of pulmonary function assessment post-COVID-19 recovery for long-term respiratory health and emphasizes the importance of vaccination regardless of infection history.

Conclusion: To assess the impact of long-COVID on respiratory health, this study underscores the importance of evaluating pulmonary function in individuals, whether they had symptomatic or asymptomatic COVID-19. Furthermore, the findings from the immune response analysis highlight the critical role of vaccination, regardless of infection history, as a key strategy of pandemic preparedness.

Fig 1. Flowchart of the study participants’ enrollment, follow-up, and laboratory experiments conducted during the study period.

ELISA, Spirometry and Biochemistry tests were performed at several time points throughout the study period.

Fig 2. %predicted values for PFT parameters in the study groups were taken before and after vaccination.

These parameters include Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), FEV1/FVC ratio, Peak Expiratory Flow (PEF), Forced Expiratory Flow (FEF), and Maximal Expiratory Flow (MEF). Pre-V (Pre-Broncho) and Pre-V (Post-Broncho) represent PFT values obtained before and after the bronchodilation which was carried out before immunization. Post-V (Pre-Broncho) and Post-V (Post-Broncho) represent PFT values obtained before and after bronchodilation, which was performed after immunization.

Fig 3. Pattern of PFT parameters %predicted value changes among the participants who received bronchodilator.

Here, Pre-Broncho indicates the PFT %predicted values before the bronchodilator was given and Post-Broncho means PFT %predicted values after bronchodilator was administered. p-values were determined using the Wilcoxon signed-rank test.

Fig 4. Duration and breadth of SARS-CoV-2 RBD-specific IgG antibody (IU/mL) response.

Antibody titers were measured over six months follow- ups following several time points including day14, day30, day60, day90, day120, day150, day 180 and a further 30 days after booster dose among the study groups.

Fig 5. Correlation between pulmonary functional parameters (PFTs) and SARS-CoV-2 IgG antibody titers (IU/mL).

Antibody titers were measured after 14 days of two doses of vaccination among the study groups including the control, mild to moderate symptomatic group (MI to MO) and severe symptomatic group (SE) recovered from COVID-19. PFT parameters are presented in %predicted score value. The Pearson correlation method was used to calculate p-values.

Fig 6. PFT parameters vs antibody titers.

SARS-CoV-2 IgG antibody titer (IU/mL) among the study participants with PFT %predicted score with normal and abnormal values observed before and after vaccination, *** = p < 0.001.

Fig 7. Age-specific correlation patterns of SARS-CoV-2 IgG antibody titer among the study groups.

A) SARS-CoV-2 IgG antibody titer (IU/mL), 30 days after two doses of vaccination among the participants. B) SARS-CoV-2 IgG antibody titer (IU/mL), 30 days after booster dose (third dose) of vaccination among the study participants. The p-values were calculated using the Pearson correlation method.

Fig 8. Correlation pattern between pulmonary functional test (PFT) parameters and age across the study population.

Age in years and PFT parameters such as FVC, FEV1, FEV1/FVC, PEF L/s, FEF (25-75) L/s and MEF50 L/s are shown in %predicted score. P-values were determined using the Pearson correlation method.