Hyperglycaemia Does Not Impair Antibody Response Against SARS-CoV-2
By Denise Baez
Diabetes does not affect the ability to mount an appropriate humoral response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), according to a study published in Diabetologia.
“Since people with diabetes are at high risk for the severe forms of COVID-19 [coronavirus disease 2019] pneumonia, they are likely to be among the first to benefit from a future vaccination against SARS-CoV-2,” wrote Lorenzo Piemonti, MD, San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy, and colleagues. “Therefore, knowing whether the humoral response against SARS-CoV-2 in individuals with diabetes is present and superimposable to that of those without diabetes is of fundamental importance.”
The researchers used a highly specific and sensitive measurement of antibodies by fluid-phase luciferase immunoprecipitation assays to characterise the Immunoglobulin (Ig) G, IgM, and IgA response against multiple antigens of SARS-CoV-2 in a cohort of 509 patients with laboratory-confirmed COVID-19 at their institution between February 25, 2020, and April 19, 2020. Antibody titres were analysed according to the presence of hyperglycaemia at the time of, or during, hospitalisation.
Of the 509 patients, 452 were hospitalised and 79 were admitted to the intensive care unit. A total of 139 (27.3%) patients had diabetes, of which 90 (17.7%) had diabetes diagnosed prior to the hospital admission.
In patients with COVID-19 pneumonia, the anti-receptor-binding domain (RBD) IgG, the anti-S1+S2 IgG, and the anti-nucleoclapsid protein (NP) IgG titres increased from week 1 to week 3, followed by stabilisation or marginal decline at week 4 and beyond. Similarly, the IgM titre of anti-RBD and anti-S1+S2 antibodies increased from week 1 to week 2 or 3, followed by a decline thereafter. There was an increase in all antibody prevalence with the duration of symptoms.
“A higher quantitative response of anti-RBD IgG at weeks 2 and 3 after the onset of symptoms and an earlier decline of IgM titre at week 3 was present in individuals with diabetes compared with those without,” the authors noted. “These marginal differences might be a random effect or could represent a specific characteristic of the humoral response of people with diabetes.”
Of the measured antibody responses, positivity for IgG against the SARS-CoV-2 spike RBD was predictive of survival rate (]hazard ratio [HR for time to death of 0.4; 95% confidence interval [CI], 0.23-0.71; P = .002), even when the analysis was performed separately in patients with (HR = 0.37; 95% CI, 0.17-0.81; P = .013) or without (HR = 0.43; 95% CI, 0.19-0.95; P = .038) diabetes.
Diabetes was independently associated with risk of death (HR = 2.32; 95% CI, 1.44-3.75; P = .001), even after adjustment for age, sex, and other relevant comorbidities. There was also a strong association between higher glucose levels and risk of death, regardless of diabetes diagnosis (HR = 1.14 × 1.1 mmol/l; 95% CI 1.08-1.21; P
“The observed increased severity and mortality risk of COVID-19 pneumonia in patients with hyperglycaemia was not the result of an impaired humoral response against SARS-CoV-2,” the authors wrote. “Receptor-binding domain IgG positivity was associated with a remarkable protective effect, allowing for a cautious optimism about the efficacy of future vaccines against SARs-COV-2 in people with diabetes. On the other hand, blood glucose levels were strongly associated with an increased mortality risk for COVID-19 pneumonia. It is not possible to prove causality on the basis of the available observational studies, and further longitudinal studies are needed to draw definitive conclusions.”