COVID-19: Assessing Antibody Responses and Clinical Outcomes in Severe Disease

Individuals on PrEP who become infected with HIV, such as those with poor adherence to treatment, may have delayed seroconversion on blood-based and oral-fluid-based rapid antibody tests.2 In one study, oral antibody reactivity was first observed a median of 125 days (range, 14-547 days) after HIV RNA or antibodies were observed in the blood.13 In another study, individuals who received PrEP were 3.49 times more likely than those on placebo to experience a delay of >100 days in detecting the infection.14 Based on these and other findings in the literature, it has been suggested that laboratory-based serum or plasma HIV tests should be used whenever possible to monitor individuals on PrEP.2 Additionally, in the setting of known or suspected poor PrEP adherence, the threshold for augmenting p24/IgM/IgG assays with NAT should be lowered.2

Individuals on PrEP who become infected with HIV, such as those with poor adherence to treatment, may have delayed seroconversion on blood-based and oral-fluid-based rapid antibody tests.2 In one study, oral antibody reactivity was first observed a median of 125 days (range, 14-547 days) after HIV RNA or antibodies were observed in the blood.13


In another study, individuals who received PrEP were 3.49 times more likely than those on placebo to experience a delay of >100 days in detecting the infection.14 Based on these and other findings in the literature, it has been suggested that laboratory-based serum or plasma HIV tests should be used whenever possible to monitor individuals on PrEP.2 Additionally, in the setting of known or suspected poor PrEP adherence, the threshold for augmenting p24/IgM/IgG assays with NAT should be lowered.2

Levels of immunoglobulin G antibodies against nucleocapsid, the spike protein, and the receptor binding domain were related to viral clearance.

Data published in Clinical Infectious Diseases revealed that most patients with severe coronavirus disease 2019 (COVID-19) developed antibodies targeting the nucleocapsid (N), the spike protein (S), the receptor binding domain (RBD), and the developing neutralizing antibodies (NAbs) ─ but these do not clearly correlate with clinical outcomes. The levels of immunoglobulin G (IgG) antibodies against N, S, and RBD were, however, related to viral clearance.

Investigators measured antibodies in longitudinal plasma samples from the LOTUS China trial via microneutralization assay and ELISA, while viral load was determined using real-time reverse transcription polymerase chain reaction (RT-PCR). The relationship between antibody titers, adverse outcome, and clinical improvement was then investigated.  

A total of 576 plasma samples and 576 throat swabs were collected from 191 people with COVID-19. The rate of antibody positivity at day 28 post-symptom onset was 100% for RBD-immunoglobulin M (IgM), 97.8% for S-IgM, 100% for N-IgG, 100% for RBD-IgG, 91.1% for N-IgM, and 91.1% for NAbs. In both survivors and non-survivors, NAbs titers increased over time and also correlated to IgG antibodies for N, S, and RBD, but their presence showed no statistical correlation with death.

After adjusting for age, gender, and days from symptoms onset to sampling, results of  a multivariable regression model demonstrated that increasing titers for N-IgG (slope, -2.11; 95% CI, -3.04 to -1.18), S-IgG (slope -2.44; 95% CI, -3.35 to -1.54), and RBD-IgG (slope -1.43; 95% CI, -1.98 to -0.88; P < 0001 for all) were negatively correlated with viral load. Finally, investigators reported that S-IgG titers were lower in patients that didn’t survive compared to those that did (P =.020) at week 4 after symptoms onset.

The study was limited due to the lack of mild and asymptomatic cases. Further studies would be needed to clarify antibody dynamics in varying COVID-19 stages involving less severe infection and a longer follow-up period after discharge. The overall small sample size of 191 patients is also a limitation. Investigators also acknowledge that whether antibodies to other coronaviruses induce cross-reaction to SARS-CoV-2 or contribute to disease severity also requires further investigation.

Investigators believe that the lower S-IgG titers in the convalescent stage in non-survivors indicate it as a predictor of intensive care. “Our findings provide useful information for understanding disease pathogenesis, evaluation of novel therapeutics, and development of vaccines,” they concluded.

Reference

Ren L, Fan G, Wu W, et al. Antibody responses and clinical outcomes in adults hospitalized with severe COVID-19: a post hoc analysis of LOTUS China trial [published online August 25, 2020]. Clin Infect Dis. doi: 10.1093/cid/ciaa1247