Antibody dependent enhancement (ADE), a phenomenon where antibodies enhance viral entry and access to host immune cells is a characteristic of SARS-CoV-2. This clinical study consisting of 100 RT-PCR confirmed COVID-19 patients (both ICU and non-ICU patients) shows a possible correlation between IgG targeting the N-protein of SARS-CoV-2 and ADE. There are various SARS-CoV-2 structural proteins (N, S, E and M protein) with different functions and the S protein has been shown to be responsible for disrupting interactions between the viral protein and host receptor. Therefore, the authors carried out serum IgG analysis to accurately and specifically measure IgG targeting the N protein (anti-N protein IgG). Statistical analyses were also carried out to make comparisons between age, gender, comorbidities and how these factors relate to COVID-19 and anti-N protein IgG. Observations of these analyses showed that patients with high risk of admission to the ICU and poorer COVID-19 outcomes had higher levels of anti-N protein IgG. Although little is known about the mechanism of ADE in SARS-CoV-2, the findings of this study suggest that high concentrations of IgG targeting the N-protein of SARS-CoV-2 is related to poor clinical outcomes and can therefore be measured as one of the initial diagnostic factors and used as a factor to study COVID-19 progression.