immune profiles of patients across the spectrum of infections . The study will track immune-marker changes over time to glean telltale differences between persistent shedders , chronically infected individuals , and those who clear the virus quickly . The work could also help identify immune markers associated with risk for re-infection .
One important aspect of chronic infection is that it increases the risk for introducing new mutations . Chronically infected people thus are reservoirs of ongoing viral replication and may contribute to the development of new , fitter viral variants .
Twists to the plot
One of the greatest surprises about the host-pathogen interaction , Alter said , was the realization that when it comes to immune response , location matters . In SARS-CoV-2 , the body appears to deploy different immune mechanisms that limit viral replication and infection in the upper airways versus the lungs .
“ We really don ’ t have a good handle on this even though we ’ ve been studying flu and tuberculosis and so many other respiratory pathogens for a long time ,” Alter said . “ It really kind of opened our eyes to the importance of understanding the lung-specific immune response .”
This difference was borne out in the vaccine data , which showed different markers of immunity that suggest the virus is controlled differently in the upper airway ( nose and pharynx ) than in the lower airway ( trachea , bronchi and lungs ).
“ This really draws our attention to the idea that maybe people with asymptomatic or mild infections are able to resist through completely different mechanisms than people in whom the virus gets into the lungs , that they have this entirely different immune repertoire that they can leverage to fight the disease ,” Alter says .
Not just small adults
How the pathogen affects people of various ages has yielded some of the most tantalizing observations and greatest surprises in the pandemic . How children respond to the virus has been on such surprise that may offer valuable clues beyond the pediatric population .
Typically , respiratory pathogens — such as those causing flu , whooping cough , TB , RSV — lead to worse disease in children . The opposite is true with SARS-CoV-2 — children have been largely spared serious illness .
One explanation could be that children tend to do better because they may have been more recently exposed to other corona viruses and have some cross-over immunity against this class of viruses . Yet another possibility arises from age-related cellular differences .
SARS-CoV-2 invades human cells through the ACE-2 receptor on the surface of cells , the gateway for viral invasion . Children have fewer such receptors on their cells , an observation that provides a plausible explanation for lack of severe disease in the vast majority of children . In any case , Alter said , the story is likely more complicated than the presence or absence of ACE2 receptors , begging the question of which immune-protective mechanisms may be at play .
The difference may arise from a more “ naïve ” immune response that may shield children from the aberrant immune-fueled inflammation seen in adult severe disease .
“ It could be that children ’ s immune systems do not respond so powerfully to the spike protein , which adults have seen in the past and which can trigger a more aberrant immune response , leading to severe inflammation and worse disease ,” Knipe says .
Nonetheless , a small subset of previously healthy children infected with SARS-CoV-2 can mount a powerful immune response and develop a serious , at times life-threatening , condition known as multi-system inflammatory syndrome in children ( MIS-C ).
The condition , which resembles Kawasaki disease and toxic shock syndrome and could affect several organs including the heart , typically emerges about a month after infection with SARS-CoV-2 .
MassCPR member Adrienne Randolph , a critical-care specialist and immuno-biologist at Boston Children ’ s Hospital and a principal investigator of a multicenter national trial of COVID-19 in children and young adults , described the development of this illness in previously healthy children and adolescents infected with SARS-CoV-2 .
A newly published study led by Randolph sheds light on the different ways in which the virus can affect children and adolescents , drawing a clear immunologic distinction between youngsters who develop serious COVID-19 and those who develop MIS-C .
This pediatric condition is reminiscent of certain inflammatory syndromes seen in adults , a similarity that may point to a common immune profile or immune phenotype , Alter said , with the two conditions being merely the pediatric and adult versions of the same physiologic phenomenon .
“ I think the jury ’ s still out on why kids are somehow protected against this respiratory pathogen and not others ,” Alter says . “ That to me is like a big black box . If we could understand that , maybe that would allow us to think through how we can make better vaccines against other respiratory pathogens too .”
The heart of COVID-19
Much has been said and written about the spectrum of severity of COVID-19 and its ability to affect people with varying degrees of virulence . But another just as confounding aspect of the illness is the variability in the type of organ damage it can inflict .
For one person it could be the heart , for another the kidneys , for yet another the brain or the lungs . One of the greatest uncertainties is whether there exists an underlying mechanism that unifies these disparate manifestations .
Case in point — the heart . That COVID-19 can affect the heart is indisputable . How it does so remains an evolving mystery . Scientists have hypothesized that there may be several mechanisms , yet much is unclear . One question looms large : Is SARS-CoV-2 a mere amplifier of preexisting heart problems , direct cause of cardiac muscle demise or an indirect driver of myocardial injury ?
It is this question that has dominated the efforts and focus of pathogenesis working group member Christopher Newton-Cheh , a transplant cardiologist and cardiovascular geneticist at Mass General and assistant professor of medicine at HMS .
COVID-19 could be damaging the heart in several ways , both direct and indirect . For example , it could be the proverbial straw that breaks the camel ’ s back and causes cardiac damage in those with underlying , even if unrecognized , heart disease . Or it could be causing heart injury by damaging the blood vessels and causing blood clots , a known complication of COVID-19 . It may also be causing the heart to work harder leading the muscle ’ s demand for oxygen to outstrip supply . And the widespread inflammation of COVID-19 could also cause collateral damage to the heart , as well as other tissues .
Yet another possibility is that the virus may infiltrate the cells of the heart muscle and damage them directly , thus injuring the heart . However , Newton-Cheh notes , emerging pathology reports from biopsies and autopsies suggest this is not a common route of heart damage . Complicating matters further could be that the