DHM COVID-19 Clinical Dispatch
Bite-sized, weekly clinical updates
Issue #8: Post-infectious Immunity
In this issue we dive into the question of whether COVID infection provides lasting immunity to both individuals and the population as a whole.
Several studies have demonstrated that the vast majority of patients develop neutralizing antibodies in response to SARS-CoV-2 infection. We begin by highlighting one of the first studies to explore a COVID-specific T-cell response, a process that might confer more durable immunity.
We then explore the role of antibody testing in COVID-19 and provide patient-level FAQ for convalescent individuals. We end with the concept of herd immunity and ask how this might be achieved in COVID-19.
As always, be sure to check our "What We're Reading," our weekly literature round-up at the end. Happy Thursday!
Our take-home message this week:
An early humoral response to SARS-CoV-2 infection has been well-established in humans. While antibody testing is useful to identify prior infection, it is still unknown whether the presence of these antibodies reflects true immunity to subsequent re-inoculation.
Herd immunity through natural infection with COVID-19 would require an unfathomable proportion of the population to become infected, thus vaccination is currently the only reasonable path toward herd immunity.
- COVID Clinical Working Group
Spaced Learning Corner: Quiz Yourself!
In the JAMA study (Elharrar et al.) of 24 non-ventilated patients with hypoxemic respiratory failure, which significant outcome was noted in those tolerating >3 hours of proning?
a) Reduced mortality
b) Reduced length of stay
c) Non-sustained improvement in PaO2 during proning
d) Sustained improvement in SpO2 for 7 days
e) Sustained improvement in SpO2 for 3 days
Find the answer here!
Quick Lit - Article of the Week
While a humoral response to SARS-CoV-2 infection has been well-established, there remains a paucity of data regarding a potential T-cell mediated immune response. This process is explored in the study above, and if present may lead to more durable immunity than a humoral response alone.
Antibody Testing and “Immunity Passports”
"If I get COVID-19, I'm good... right?"
As noted above, multiple studies have described the development of neutralizing antibodies (NAbs) in response to natural infection with SARS-CoV-2 (see the graphic below from Sethuraman et al, JAMA).
While there have been promising studies in convalescent macaques suggesting immunity to re-inoculation of SARS-CoV-2 (1, 2), no such study could be ethically performed in humans.
It is tempting to suggest that the presence of NAbs might infer immunity, though this remains unknown. Additionally, even if NAbs do develop, they may likely wane over time - this is the case for pertussis, rotavirus, and even SARS-COV-1. A study on re-infection with endemic coronaviruses suggests that reinfection does occur with the same strain of Coronavirus within 1 year.
For now, positive antibody testing should be only used as an indicator for exposure. While these tests have limited clinical utility for individuals at this point, they remain an important metric on a population level. As suggested by Randolph et al, mass serological testing may be useful in determining the number of individuals infected with SARS-CoV-2 and whether we are close to achieving the threshold required for herd immunity.
For our Patients: Post-infectious FAQ
I've tested positive for COVID-19. Do I have to worry about getting infected again?
This is still unknown. Some research suggests recovered patients might not become re-infected in the short-term.
I've tested positive for COVID-19 and am now feeling better. Do I have to worry about infecting others?
So far it seems that people with COVID-19 are most likely to infect others from 1-3 days before to 7-10 days after symptom onset. This is not well-studied and further research is needed in this area.
I tested positive for COVID antibodies. Does this mean I am immune?
We don't yet know whether having antibodies means you are immune to COVID-19. You should continue to take the same precautions as before. These include wearing a mask, washing your hands and staying 6 feet apart from others.
Information at an 8th grade readability level
Herd Immunity in COVID: Power in numbers?
Information and graphics from Randolph et al, in JAMA.
What is herd immunity?
Herd immunity (H.I.) occurs when a large enough proportion of individuals are immune, thereby conferring indirect protection to susceptible individuals. This might be achieved either from natural infection or vaccination.
In the simplest model of transmission, the threshold of immunity within a population required to achieve herd immunity can be calculated from the R0 (the average number of secondary infections caused by a single infectious individual within a susceptible population).
Will we achieve herd immunity from COVID?
The herd immunity threshold for SARS-CoV2 is debated. This depends on the R0 for SARS-CoV-2, which varies in studies from 2.0 to 6.0.
Graphic A visually depicts the relationship between H.I. and R0 (H.I. = 1-1/R0)
Graphic B compares the H.I. thresholds of various infectious diseases, based on their R0.
While this model provides a useful estimate threshold required for herd immunity, it is likely too simplistic for real-world application. Complexities such as variable disease severity and transmission dynamics between individuals, non-homogeneous population mixing and globally limited healthcare resources are significant limitations to this basic model.
Additionally, effectiveness of herd immunity depends on the strength and duration of immunity, factors still not fully characterized for SARS-COV2. If immunity wanes over time, communities would remain vulnerable to periodic outbreaks.
Can herd immunity be achieved through natural infection (without a
vaccine)?
Until a viable vaccine is developed, herd immunity could only be reached via natural infection. This would require an untenable number of infected individuals and an estimated 30 million deaths before herd immunity might be achieved. At this point, herd immunity through natural infections likely isn’t the answer.
Herd Immunity in COVID: Power in numbers?
Short summaries of articles our team finds interesting this week.
“Herd Immunity: Understanding COVID-19” (Randolph et al, Immunity, May 2020): This article discusses the concept of herd immunity and R0 and applies this to what is currently known about COVID-19. The authors delve into epidemiological variations in different regions and populations and immunologic considerations (such as weaning of immunity over time) in the context of attaining herd immunity.
“Interpreting Diagnostic Tests for SARS-CoV-2” (Sethuraman, JAMA, May 2020): This viewpoint piece discusses nuances of diagnostic testing for COVID-19. The authors provide data on the sensitivity, specificity, and time course of positivity of the RT-PCR, IgM ELISA, and IgG ELISA assays and illustrate the utility of various tests over the course of COVID-19 infection.
“SARS-CoV-2 infection protects against rechallenge in rhesus macaques” (Chandrashekar et al, Science, May 2020): This study of 9 macaques infected with SARS-CoV-2 found that all subjects developed rapid humoral and cellular immune responses when re-inoculated with the virus 35 days later.
“Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals” (Grifoni et al, Cell, June 2020): This translational study utilized convalescent plasma to ask questions about the nature of the immune response in patients with previous SARS-CoV-2 infection as a step towards informing vaccine development efforts. They found that CD4+ and CD8+ T cells against SARS-CoV-2 were found in 100% and 70% of patients, respectively, and that the majority of these T cells were directed against crucial viral protein antigens..
“Antibody responses to SARS-CoV-2 in patients with COVID-19” (Long et al, Nature Medicine, April 2020): This study examines the dynamics of the antibody response following SARS-CoV-2 infection and found that of 70 patients with COVID-19, 100% sero-converted within 19 days of the onset of symptoms, with higher titers detected in patients who experienced a more severe form the disease.
Links
Questions, thoughts, insights? Share them on our Clinical Knowledge Portal!
Prior Dispatches:
Issue 1: GI symptoms in COVID
Issue 2: Predictors of Severe COVID Disease
Issue 3: Hypercoagulability in COVID-19
Issue 4: SARS-CoV-2 and the Inflammatory Response
Issue 5: Remdesivir for COVID-19
Issue 6: Convalescent Plasma
Issue 7: ARDS
