Study Finds Unvaccinated Primary Healthcare Workers Sustained Seropositivity Up To 20 Months After COVID-19 And Long-Lasting SARS-CoV-2 Humoral Immunity!

COVID-19 Research: A new longitudinal cohort study led by researchers from the Universitat de Barcelona - Spain and The Barcelona Institute of Science and Technology - Spain has found that unvaccinated primary healthcare workers sustained seropositivity up to 20.5 months after COVID-19 and long-lasting SARS-CoV-2 humoral immunity!


 
The COVID-19 Research team that also included researchers from other hospitals and research entities in Spain evaluated the persistence of IgM, IgA, and IgG to SARS-CoV-2 spike and nucleocapsid antigens up to 616 days since the onset of symptoms in a longitudinal cohort of 247 primary health care workers from Barcelona, Spain, followed up since the start of the pandemic.
 
The researchers also assessed factors affecting antibody levels, including comorbidities and the responses to variants of concern as well as the frequency of reinfections.
 
Shockingly, even with a gradual and significant decline in antibody levels with time, seropositivity to five SARS-CoV-2 antigens combined was always higher than 90% over the whole study period.
 
Interestingly, in a subset of 23 participants who had not yet been vaccinated by November 2021, seropositivity remained at 95.65% (47.83% IgM, 95.65% IgA, 95.65% IgG).
 
Also, IgG seropositivity against Alpha and Delta predominant variants was comparable to that against the Wuhan variant, while it was lower for Gamma and Beta (minority) variants and for IgA and IgM.
 
The study findings also showed that antibody levels at the time point closest to infection were associated with age, smoking, obesity, hospitalization, fever, anosmia/hypogeusia, chest pain, and hypertension in multivariable regression models. Up to 1 year later, just before the massive roll out of vaccination, antibody levels were associated with age, occupation, hospitalization, duration of symptoms, anosmia/hypogeusia, fever, and headache. In addition, tachycardia and cutaneous symptoms associated with slower antibody decay, and oxygen supply with faster antibody decay.
 
Only eight reinfections (3.23%) were detected in low responders, which is consistent with a sustained protective role for anti-spike naturally acquired antibodies.
 
Importantly, stable persistence of IgG and IgA responses and cross-recognition of the predominant variants circulating in the 2020–2021 period indicate long-lasting and largely variant-transcending humoral immunity in the initial 20.5 months of the pandemic, in the absence of vaccination.
 
The study findings were published in the peer reviewed journal: BMC Medicine. (Springer) https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-022-02570-3
 
This is the first longitudinal cohort study to assess the levels of immunoglobulins M (IgM), G (IgG), and A (IgA) against the spike and nucleocapsid proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 247 primary health care workers in Barcelona, Spain across 616 days from the onset of the COVID-19 dis ease.
 
To date, even with the impetus to develop vaccines and vaccinate the global population against SARS-CoV-2, a significant portion of the world’s population are still unvaccinated and protected largely by antibody responses to an initial SARS-CoV-2 infection.
 
Some past studies have shown that the antibody responses to SARS-CoV-2 infections are active for up to one year in the body after recovery.
https://pubmed.ncbi.nlm.nih.gov/34183003/
 
https://www.sciencedirect.com/science/article/pii/S2352396421005995
 
Typically, the human humoral immune responses to COVID-19 largely comprise immunoglobulins specific to the viral antigens, such as spike and nucleocapsid proteins. In the initial stages of the infection, IgM and IgA dominate the immune response, while IgM and IgG are responsible for most of the neutralizing activity.
 
However, waning humoral immunity and the emergence of immune-evading SARS-CoV-2 variants can increase the susceptibility to reinfections.
 
Importantly, many studies have found strong correlations between comorbidities and the severity of COVID-19, but the effect of comorbidities on the antibody levels from previous infections has not been investigated.
 
Properly comprehending the persistence of SARS-CoV-2 infection-induced immunity and the variation in antibody levels due to comorbidities is essential for developing treatment and prevention strategies against emerging SARS-CoV-2 variants.
 
This longitudinal cohort study included 247 COVID-19-positive healthcare workers in Barcelona, Spain; samples were collected at different time points between March 2020 and November 2021.
 
Rapid COVID-19 diagnostic tests and quantitative reverse transcription polymerase chain reaction (qRT-PCR) tests were used to detect SARS-CoV-2 infections in symptomatic participants or healthcare workers who had been in contact with COVID-19 patients.
 
The study team also analyzed the effect of a wide range of comorbidities such as diabetes mellitus, chronic obstructive pulmonary disease, cardiovascular diseases, autoimmune diseases, cancer, and many more on the antibody responses to SARS-CoV-2 infections.
 
The antibody responses were quantified based on the IgG, IgA, and IgM levels against SARS-CoV-2 spike protein, subunit S2, nucleocapsid protein, receptor binding domain (RBD), and the C-terminal region. Linear mixed models were used to model the change in antibody levels over time.
 
Inclusive of all baseline tests, nine samples were collected from each individual throughout the study.
 
The first and last three samples were measured for antibodies against the RBD of the Alpha, Beta, Gamma, and Omicron SARS-CoV-2 variants. The frequency of reinfections was also determined.
 
The study findings showed that while a significant but gradual decline was noted in antibody levels over time, the seropositivity against the five SARS-CoV-2 proteins cumulatively remained above 90% during the study period. The seropositivity in the unvaccinated subset was 95.65%.
 
The highest seropositivity was for IgA and IgG (95.65% for both), with mainly anti-spike protein and anti-RBD responses for IgG and anti-spike responses for IgA and lower for IgM (47.83%), which were primarily anti-RBD responses.
 
Both the Alpha and Delta variant RBDs elicited similar IgG seropositivity as the original Wuhan-Hu-1 strain, but the seropositivity values were lower for the Beta and Gamma variants.
 
Interestingly, the reinfection rate in the unvaccinated frontline healthcare workers was only 3.23%, while in recovered COVID-19 patients, it was between 0 and 20%.
 
The cumulative reinfection rate was as low as 0.65%.
 
Importantly, on average, the reinfected individuals were 43.9 ± 9.5 years old, and 62.5% had at least one comorbidity.
 
Also, among the reinfected cases, 85.7% experienced similar symptoms as the first infection, while the rest had milder symptoms. None of the reinfections were more severe than the original infection.
 
Detailed correlation analyses between antibody levels and comorbidities, clinical manifestations, and baseline characteristics closest to the time of infection and just before vaccination revealed that fever, anosmia, and dysgeusia were associated with higher antibody levels, as was hypertension.
 
Disease severity and hospitalization was associated with sustained high levels of IgG, indicating that the severity of COVID-19 did not decrease the memory B cell or plasma cell stability.
 
The study findings indicated that anti-SARS-CoV-2 antibodies persist in the body for close to 1.7 years after infection. Unvaccinated individuals exhibited greater than 90% seropositivity for more than 20 months after COVID-19.
 
Importantly, high IgG levels appeared to protect individuals against reinfections with the wildtype strain and Alpha variant in the absence of vaccinations.
 
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