The newly emerged coronavirus (SARS-CoV-2) continues to infect humans, and no completely efficient treatment has yet been found. Antibody therapy is one way to control infection caused by COVID-19, but the use of classical antibodies has many disadvantages. Heavy chain antibodies (HCAbs) are single-domain antibodies derived from the Camelidae family. The variable part of these antibodies (Nanobodies or VHH) has interesting properties such as small size, identify criptic epitopes, stability in harsh conditions, good tissue permeability and cost-effective production causing nanobodies have become a good candidate in the treatment and diagnosis of viral infections.

Totally 157 records (up to November 10, 2021), were recognized to be reviewed in this study. 62 studies were removed after first step screening due to their deviation from inclusion criteria. The remaining 95 studies were reviewed in details. After removing articles that were not in the study area, 45 remaining studies met the inclusion criteria and were qualified to be included in the systematic review.

In this systematic review, the application of nanobodies in the treatment and detection of COVID-19 infection was reviewed. The results of this study showed that extensive and sufficient studies have been performed in the field of production of nanobodies against SARS-CoV-2 virus and the obtained nanobodies have a great potential for use in patients infected with SARS-CoV-2 virus.

According to the obtained results, it was found that nanobodies can be used effectively in the treatment and diagnosis of SARS-CoV-2 virus.