Evidence that cross-reactive immunity from common human coronaviruses may influence response to SARS-CoV-2

In a recent study published in the journal Vaccinesresearchers in Saudi Arabia and the United States examined immune responses and immunoglobulin G (IgG) cross-reactivity in people infected with Middle East respiratory syndrome coronavirus (MERS-CoV) and Middle East respiratory syndrome coronavirus 2 severe acute respiratory (SARS-CoV-2).

Image credit: NIAID

Human CoVs (HCoVs) are enveloped ribonucleic acid (RNA) viruses of the Coronaviridae family that cause flu-like illnesses, pneumonia, bronchiolitis and an exacerbation of underlying lung disease. SARS-CoV-2, a new beta-CoV that causes coronavirus disease 2019 (COVID-19), was first detected in Wuhan, China, and has so far caused over 757 million cases and 6.85 million deaths worldwide.

Another infectious respiratory disease, MERS, was first reported in 2012 in the Middle East. Globally, approximately 2,600 cases of MERS-CoV have been recorded to date. MERS-CoV is endemic in the region and causes recurrent community outbreaks. Several variants of SARS-CoV-2 have emerged throughout the COVID-19 pandemic. The impact of these variants on immunity against the virus may be influenced by previous exposure to related CoVs, such as MERS-CoV, SARS-CoV and seasonal CoVs.

SARS-CoV, SARS-CoV-2 and MERS-CoV share significant sequence homology and potential epitopes that can trigger adaptive immune responses. Additionally, a high level of cross-reactivity was observed between B and T cell epitopes and antibodies against structural proteins of SARS-like viruses and SARS-CoV-2. Nevertheless, there is limited evidence on cross-reactive immunity between MERS-CoV and SARS-CoV-2.

The study and the conclusions

The present study assessed humoral immune responses against SARS-CoV-2 and MERS-CoV in Saudi individuals. Eligible participants were 18 years of age or older and recruited into four groups: naïve controls of MERS-CoV/SARS-CoV-2 (C-Gp) infection, individuals infected with SARS-CoV-2 (SV- Gp), MERS-CoV-infected subjects (MV-Gp) and persons infected with MERS-CoV and SARS-CoV-2 (SV-MV-Gp).

Participants without polymerase chain reaction (PCR) testing and those with known immunological disease, malignancy, or on immunosuppressive therapy were excluded. Serum samples were collected and tested for antibodies against MERS-CoV and SARS-CoV-2 by enzyme immunoassay (ELISA). Specifically, IgG antibodies against MERS-CoV S1 antigen and SARS-CoV-1 spike receptor binding domain (RBD) were measured in serum.

Thirty-four participants, including 12 women, with an average age of 40.3 years, were recruited. Thirteen participants were controls; eight had SARS-CoV-2 infection, five had a history of infection with both viruses, and eight had MERS-CoV infection. Most participants (97%) received at least two doses of the COVID-19 vaccine.

All SV-MV-Gp and SV-Gp participants were double vaccinated and three received a booster. Controls and individuals infected with SARS-CoV-2 alone showed no reactivity against the MERS-CoV S1 antigen, while three MV-Gp participants and two SV-MV-Gp participants showed reactivity. Among SV-MV-Gp participants, 40% had positive borderline IgG reactivity against MERS-CoV, compared to 37.5% of MV-Gp subjects. IgG levels between MV-Gp and SV-MV-Gp subjects were statistically correlated.


In summary, the study showed that individuals with a history of both SARS-CoV-2 and MERS-CoV infections have significantly higher IgG levels against MERS-CoV than those infected with MERS-CoV. CoV. The findings suggest that cross-reactive immune responses from common HCoVs may shape immunity to SARS-CoV-2. Notably, the sample size was small, warranting large-scale multicenter studies in the future.

Written by

Tarun Sai Lomte

Tarun is a writer based in Hyderabad, India. He holds an MSc in Biotechnology from Hyderabad University and is passionate about scientific research. He enjoys reading research articles and literature reviews and is passionate about writing.


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