loads and disease severity among infected people who were either hospitalized with serious illness or had mild disease and recovered at home .
Compared with people who had mild disease , those with illness serious enough to require hospitalization not only had greater viral loads but also increased markers of inflammation , worse respiratory illness and a dip in infection-fighting white blood cells . People with higher viral loads tended to have more severe disease and greater risk of dying .
The findings suggest that viral load profiles could be helpful predictors in who might get severely sick , but beyond risk stratification , the observations hint at a possible mechanism underlying the different disease trajectories .
It suggests that people exposed to a higher initial dose of the virus are more prone to severe disease and that these people ’ s immune systems may not be able to control and minimize viral replication . As a result , the virus may escape the lungs , invade the blood and seed infection in other organs , fueling widespread inflammation and illness .
Antibodies : Quality over quantity
Antibodies , proteins made by the immune system in response to pathogens , are a well-established hallmark of immune function . Traditionally , higher levels of antibodies , or titers , have been thought to portend a more robust immune response .
But emerging evidence suggests that when it comes to antibodies in COVID-19 , antibody accuracy and precision may be more important than levels of antibodies produced . Research by Alter and colleagues found that COVID-19 patients who recovered and those who succumbed to the disease exhibited differences in the types of antibodies they made . The key difference , the study showed , was the part of the virus that antibodies glommed onto .
For example , people who developed antibodies mostly targeting the spike protein — the structure that SARS-CoV-2 uses to enter human cells — were more likely to survive than people who developed antibodies primarily targeting another part of the virus , known as the nucleocapsid .
In other words , Alter says , producing antibodies may not be enough . What matters is whether these antibodies home in on the right target . The research also showed that antibodies able to “ recruit ” the immune system to fight the infection evolved rapidly in individuals who survived , but their evolution was blunted among those who ultimately died .
Yet another newly published study led by Alter also reinforced the notion that the type of antibodies rather than merely their levels may be important in creating immune memory against SARS-CoV-2 following initial infection .
The work demonstrates that when it comes to rendering people immune to subsequent encounters with SARS-CoV-2 what may be more important is whether an individual has developed robust levels of antibodies against specific parts of the virus .
Another small study of 113 patients led by MassCPR researcher Alejandro Balazs offers a similarly intriguing observation : that the quality of antibodies may matter more than their quantity . Patients who went on to develop severe illness or died of COVID-19 did not necessarily have fewer antibodies . Their antibodies , however , appeared to be less fit and less capable of blocking the virus .
Memories from encounters past One important question about the host-pathogen interaction has been whether some people may have partial immunity to SARS-CoV-2 from previous exposure to viruses from the same family .
Understanding such cross-immunity offers one possible explanation behind the observation that people with similar risk profiles , such as age or underlying conditions , may experience SARS-CoV-2 infection differently : Their preexisting immunity dampens disease severity .
A study led by Manish Sagar and Joseph Mizgerd , MassCPR members at Boston University , suggests that people whose immune systems bore markers of recent infections with other coronaviruses — less virulent cousins of SARS-CoV-2 — were not protected from SARS-CoV-2 but when infected with it , they tended to have milder disease .
Understanding variations in immune response to different coronaviruses , could help scientists identify dents in the pathogen ’ s armor and build therapies that target those areas of vulnerability .
A study led by MassCPR member and HMS geneticist Stephen Elledge mapped the footprints of human antibody responses made against seven coronaviruses , including common cold viruses and SARS-CoV-2 .
The analysis revealed differences in the antibody responses of patients who had different outcomes , ranging from mild infection to critical illness . The insights identify vulnerable spots on the virus that could serve as targets of immune defense and inform the design of antibody-based therapies and vaccines .
“ Data suggest that cross-reactive immune responses somehow confer natural immunity against the new virus , and if we could understand how this happens , we could get a better handle on designing vaccines against this specific virus , but also against any coronavirus that pops up in the future ,” Alter says .
Cellular defenses Thus far , the role of cellular immunity in SARS-CoV-2 infection remains poorly understood .
Rapidly growing evidence over the past several months has pointed to the critical role of T cells in COVID-19 . But there remain key unknowns : How soon after infection do T cells get activated to halt the spread of the virus ? Does the strength of the response vary from individual to individual and , if so , what factors underlie such variations ? Are T cell and antibody responses related to one another and , if so , how do they modulate each other ? How long do T cells retain memory of SARS-CoV-2 ?
The answers to these questions have therapeutic implications . Designing treatments and vaccines that stimulate antibody and cellular responses would be an important goal , not only for reining in SARS-CoV-2 but also for dealing with novel coronaviruses that are likely to emerge in the future .
Knipe and Alter says that traditionally vaccine developers have focused on designing vaccines that marshal neutralizing antibodies . But as our understanding of the interplay between the immune system and SARS-CoV-2 grows , the two researchers added , it will be important to go beyond neutralizing antibodies and to design vaccines that stimulate other forms of defense .
These include T cell immunity or opsonization and phagocytosis , the process of coating microbes with sticky proteins , encapsulating them and devouring them .
“ Developers design vaccines with antibody-based protection as an end goal in mind , but what we have learned over the years from many clinically approved vaccines is that they can work through mechanisms other than neutralizing antibodies ,” Alter says .