Researchers at Boston University found that owing to genetic similarities with the SARS-CoV-2, prior exposure to other coronaviruses primes the immune system to mount a better response to the virus responsible for COVID-19. Although this doesn't prevent people from contracting COVID-19, it does lessen the severity of the disease.
In their report, which was published Sept. 30 in The Journal of Clinical Investigation, the researchers drew attention to two things: the extensive sequence homology shared by other coronaviruses and SARS-CoV-2, and how the human immune system works. Specifically, they focused on a critical component of adaptive immunity called immunological memory that allows the body to respond faster and more reliably to a previously encountered pathogen.
Adaptive immunity and genetic similarities between coronaviruses
Severe acute respiratory syndrome coronavirus-2, or SARS-CoV-2, may be a new strain, but a large portion of its genomic sequence remains homologous with those of other coronaviruses endemic in the human population. The seasonal common cold, for instance, is caused by four different endemic coronaviruses (eCoVs), namely, HCoV-OC43, HCoVHKU1, HCoV-NL63 and HCoV-229E. Research suggests that these four are to blame for the majority of the upper and lower respiratory tract infections developed by both children and adults each year.
For months since the coronavirus pandemic began, researchers have been baffled by the large discrepancies between infected individuals, particularly the severity of the symptoms they manifested. While some experienced only mild symptoms, others suffered from severe illnesses that often aggravated pre-existing conditions. But there are some individuals who seem to have better immune responses to the virus. Despite contracting COVID-19 from positively identified symptomatic carriers, these people, amazingly, do not show any symptoms at all.
But recent findings may have uncovered a possible answer to this puzzle. According to European researchers, memory T cells and B cells, which are at the core of adaptive immunity, are generated in response to coronavirus infection, and these virus-specific immune cells may be able to confer long-lasting immunity against the same pathogen. With the genetic similarities between endemic coronaviruses and SARS-CoV-2, it is possible that asymptomatic individuals may not be showing any symptoms because the long-lived memory T cells they've accumulated recognized SARS-CoV-2 and produced a robust response against it.
The possibility of already-established immune responses cross-reacting against SARS-CoV-2 is what the Boston researchers explored in their study. By looking at whether previous infections can elicit immunological memory in COVID-19 patients and whether this has any effect on infection risk and disease severity, the researchers hoped to understand how certain types of immune responses could be used to limit the damage caused by COVID-19.
Immunity built up from previous eCOV infections matters
For their study, the researchers examined SARS-CoV-2 infections and COVID-19 outcomes in a total of 15,928 different patients. These patients had previously been assessed with a comprehensive respiratory panel polymerase chain-reaction (CRP-PCR) test, which is used to detect nucleic acids belonging to the four eCoVs plus 16 other pathogens.
The researchers looked at the patients' CRP-PCR results from May 2015 to March 2020 to find out how many had tested positive for an eCoV at some point. Of the more than 15,000 patients, 875 turned out to be eCoV+, while the remaining 15,053 never had a documented eCoV infection. In terms of demographic characteristics, no significant differences between the eCoV+ and eCOV- groups were found.
The researchers also looked at the COVID-19 test results of the patients but restricted their analysis to those who were still alive prior to March 11, 2020, were above 18 years of age and were first tested for COVID-19 at least seven days after their latest CRP-PCR test. All the selected participants had relatively similar levels of pre-existing morbidity.
Th researchers reported that a significantly higher proportion of eCoV+ patients (15.2 percent) were tested for COVID-19 than eCoV- patients (11.2 percent). This remained true even after adjusting for race, ethnicity, COPD, HIV, number of comorbidities and level of clinical care received. Among those tested for COVID-19, 470 (25.9 percent) had positive results and 252 (53.6 percent) were hospitalized during the study period.
Although the frequency of documented SARS-CoV-2 infection did not differ between the eCoV+ and eCoV- groups, the researchers found that the former had significantly lower odds for intensive care unit (ICU) admission or requiring mechanical ventilation than the latter. The risk of needing ICU care remained considerably lower for eCoV+ patients even after adjusting for age, gender and body mass index.
In addition, the number of hospitalized patients who died over follow-up was lower for the eCoV+ group than the eCoV- group. When the researchers looked at blood inflammatory markers, they found that eCoV+ patients had lower levels of the markers C-reactive protein (CRP) and lactate dehydrogenase (LDH) than eCoV- patients, suggesting decreased cytokine storm and inflammatory injuries.
According to the researchers, these findings not only meant less severe outcomes from similar viral loads for those who were eCoV+ at some point, but that the eCoV+ patients had more subdued inflammatory responses soon after SARS-CoV-2 infection.
"Our results show that people with evidence of a previous infection from a "common cold" coronavirus have less severe COVID-19 symptoms," said Manish Sagar, the study's lead author. (Related: Infected patients develop long-term immunity to coronavirus.)
Despite this, however, Manish and his colleagues also pointed out that pre-existing immunity does not always equate to disease prevention.
"Here, we show that individuals with[,] as compared to without[,] a relatively recent documented eCoV were tested at greater frequency for respiratory infections but had similar [rates] of SARS-CoV-2 acquisition. Importantly, the patients with a previously detected eCoV had less severe coronavirus disease-2019 (COVID-19) illness. Our observations suggest that pre-existing immune responses against endemic human coronaviruses can mitigate disease manifestations from SARS-CoV-2 infection," the researchers concluded in their report.
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