Several coronaviruses are known to infect a wide range of hosts that includes many animals and humans. The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This coronavirus is an extremely infectious, positive-sense, and single-stranded RNA virus that has claimed more than 4.3 million lives worldwide. SARS-CoV-2 belongs to the genus betacoronavirus of the family coronaviridae.
Scientists believe that SARS-CoV-2 infected humans via zoonotic transmission. Owing to the current pandemic, there has been a renewed interest in the scientific community to study the seasonal circulating strains of human coronaviruses (HCoVs), such as HCoV-NL63, HCoV-OC43, HCoV-229E, and HCoV-HKU1. These viruses mostly cause respiratory tract infections in children. Some of them are asymptomatically infected, while others show symptoms of common bronchiolitis and pneumonia. Mostly, HCoVs cause mild symptoms affecting the upper respiratory tract of the infected individual.
Previous research on HCoV-NL63
Among the members of the Coronaviridae family, HCoV-NL63 has been classified as an alphacoronavirus. Similar to the SARS-CoV-2, HCoV-NL63 also binds to angiotensin-converting enzyme 2 (ACE2) on the cell surface to enter the host cell. In 2003, this virus was first isolated, in the Netherlands, from a 7-month-old child (using a nasopharyngeal sample) who was suffering from bronchiolitis, fever, and conjunctivitis. HCoV-NL63 infects the lower respiratory tract and is often asymptomatic, making it difficult for researchers to detect its prevalence.
Another study had been conducted in Germany, for the period between 1999 to October 2001, to study the prevalence of HCoV-NL63 in children. In this study, researchers had collected 1,756 respiratory samples to detect HCoV-NL63 using RT-PCR. The samples were collected from children who were around 3 years of age and were either hospitalized or visited outpatient clinics with pneumonia-like symptoms.
In this study, researchers estimated the annual prevalence of HCoV-NL63 infections to be seven per thousand children, and the rate of hospitalization was reported to be twenty-two per hundred thousand children. Previous studies have also revealed the prevalence of winter to spring seasonal HCoV-NL63 infection in Western Europe and the United Kingdom. In these studies, the virus was not detected in the summer.
Typically, immune protection generated post seasonal coronavirus infection is short-lived. A longitudinal cohort study had been conducted in Amsterdam that performed serological assays in 10 healthy adult males, periodically every 3–6 months for 35 years. This study found reinfection with seasonal coronaviruses occurred within 6 to 105 months after initial infection. However, in most cases, reinfection occurred after 12 months from the initial infection. Interestingly, this study had shown reinfection with HCoV-NL63 infections as a rare event. This is because only 2.5 infections per individual were detected over an average monitoring time of 20 years.
Importance of HCoV-NL63 in therapeutics
As stated above, researchers have renewed their interest in HCoVs, particularly because of cross-reactive immune responses between SARS-CoV-2 and seasonal coronaviruses. Recently, scientists used HCoVs as a low virulence viral model to evaluate the efficacy of antiviral treatments for COVID-19. Among HCoVs, researchers stated that HCoV-NL63 could be the most appropriate for these studies because other HCoVs have some limitations, e.g., propagation of HCoV-HKU1 in cell lines is extremely difficult.
To validate the use of HCoV-NL63 to determine the efficacy of therapeutics for COVID-19 disease, the assessment of neutralizing antibodies to HCoV-NL63 is important. In this context, a new study has been published in the MPDI journal Viruses, which focuses on determining the seroprevalence of neutralizing antibodies against HCoV-NL63, in healthy adults, in a cross-sectional study.
In this study, researchers randomly selected one hundred plasma samples from healthy blood donors. The SARS-CoV-2-negative blood samples were collected by the Australian Red Cross Lifeblood in August 2020. The mean age of donors was 48.3 years, and the majority of the donors (56%) were male. The blood donors were from five states in Australia – namely, Queensland, New South Wales, Northern Territory, South Australia, and Tasmania.
Researchers of this study performed a microneutralization assay with plasma diluted from 1:10 to 1:160, which were tested using the HCoV-NL63 Amsterdam-1 strain. They determined the presence of neutralizing antibodies against HCoV-NL63 in 71% of the plasma samples with a median geometric mean titer of 14. This result is in line with previous research that reported sera of the recovered COVID-19 patients contained neutralizing antibodies, 3–7 months following asymptomatic SARS-CoV-2 infection, and 2–3 years post-symptomatic SARS-CoV-1 infection. The present research also reported a reduction in HCoV-NL63 neutralizing antibody titers with increasing age. However, sex did not have any impact on the development of neutralizing antibody titers.
This study revealed the presence of detectable neutralizing antibodies in 71% of the donors residing in Australia. Therefore, the authors of this study highlighted the possibility of using HCoV-NL63 as a human challenge model for more pathogenic coronaviruses.