Even with promising news on vaccine development and mass vaccination globally, tracking, tracing and mass testing of the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) continues to be very essential to public health policy responses towards Coronavirus 2019 (COVID‑19) pandemic. Diagnostic testing remains vital in detection of the virus, understanding its emergence and occurrence, case management and suppression of its transmission. This study aimed at comparing diagnostic sensitivity and specificity between antigen rapid diagnostic test (Ag-RDT) and reverse transcriptase polymerase chain reaction (rt-PCR), determining the presence of SARS-CoV-2 in nasopharyngeal swab (NPs) and stool samples as well as determining the presence of immunoglobulin M (IgM) and immunoglobulin G (IgG) among symptomatic and asymptomatic individuals for COVID-19 disease in Siaya and Kisumu counties. This study recruited 92 participants each providing three clinical samples including NPs, stool and blood. The NP swab samples were tested using both Ag-RDT and rt-PCR, stool samples were run through rt-PCR and the blood samples were tested by enzyme-linked immunosorbent assay at a level 3 safety laboratory at Kenya Medical Research Institute, Kisian. The overall pooled sensitivity and specificity of Ag-RDT were 76.3% (95% CI, 59.8-88.6%) and 96.3% (95% CI, 87.3- 99.5%) respectively with a negative and positive predictive value of 85% (95% CI, 73.8%- 93.0%) and 93% (95% CI, 78.6%-99.2%) respectively. A Cohen’s kappa value of 0.75 at (95% CI, 0.74-0.77) was obtained, showing a substantial agreement between rt-PCR and Ag-RDT. The area under the receiver operating characteristic (ROC) curve was 0.87 at (95% CI, 0.80-0.94) indicating excellent performance of the Ag-RDT. The average cycle threshold (Ct) value of targeted genes; nucleocapsid (N) and open reading frames1ab (ORF 1ab) gene were 30.00 and 32.90 for NP samples and 32.74 and 33.86 for stool samples. The lowest Ct values of (19.28 and 23.11) for N gene and 23.35 and 22.48) for ORF1ab were obtained in NP swab and stool samples respectively. The mean IgM and IgG antibody response to SARS-CoV-2 was 1.11 (95% CI, 0.78-1.44) and 0.88 (95% CI, 0.65-1.11), 4.30 (95% CI, 3.30-5.31) and 4.16 (95% CI, 3.32-5.00) in asymptomatic and symptomatic individuals respectively. In conclusion, the sensitivity of Ag-RDT 76.3% was lower compared to that of rt-PCR assay, however its high specificity of 96.3%, positive and negative predictive values of 93% and 85% respectively and its fast test output implies that individuals infected with SARS-CoV-2 can be traced faster. This corroborates that Ag- RDT is important for screening COVID-19 in areas that lack suitable laboratories with rt- PCR diagnostics. The high cycle threshold in stool samples indicates low viral load which may cause transmission of the virus. IgM and IgG antibody response to SARS-CoV-2 revealed that asymptomatic individuals had higher mean antibody ratios and were considered to be the most exposed. This study is of a great significance as it addresses a pressing public health issue, and recommends the most suitable diagnostic test (rt-PCR) and clinical samples (nasopharyngeal swab) for the detection of SARS-CoV-2.