Enlarge / A phlebotomist draws blood meant for antibody testing. (credit: Frederic J. Brown / Getty Images )

We've tended to treat the RNA-based vaccines from Moderna and Pfizer/BioNTech as functionally equivalent. They take an identical approach to producing immunity and have a very similar set of ingredients. Clinical trial data suggested they had very similar efficacy—both in the area of 95 percent.

So it was a bit of a surprise to have a paper released yesterday indicating that the two produce an antibody response that's easy to distinguish, with Moderna inducing antibody levels that were more than double that seen among people who received the Pfizer/BioNTech shot. While it's important not to infer too much from a single study, this one was large enough that the results are likely to be reliable. If so, the results serve as a caution that we might not want to base too many of our expectations on relatively crude measures of antibody levels.

The new study

The work itself was remarkably simple. A Belgian medical center was vaccinating its staff and asked for volunteers willing to give blood samples. Samples were taken both prior to vaccination and six to 10 weeks after, with the levels of antibody specific to the SARS-CoV-2 spike protein tested at both points. About 700 participants received the Moderna vaccine, while roughly 950 took the one from Pfizer/BioNTech.

Enlarge / The structure of the SARS-CoV-2 spike protein. (credit: University of Arkansas )

Over the summer, you could almost hear a sigh of relief rising from the portion of the research community that was tracking the evolution of the SARS-CoV-2 virus. Viruses, especially those new to their hosts, often pick up mutations that help them adapt to their new habitat, or they evade drugs or immune attacks. But SARS-CoV-2 seemed to be picking up mutations at a relatively sedate pace, in part because its virus-copying enzymes had a feature that lets them correct some errors.

But suddenly, new variants appear to be everywhere , and a number of them appear to increase the threat posed by the virus. A new study helps explain the apparent difference: while new base changes in the virus' genetic material remain rare, some deletions of several bases appear to have evolved multiple times, indicating that evolution was selecting for them. The research team behind this new work found evidence that these changes alter how the immune system can respond to the virus.

This looks familiar

The researchers' interest in deletions started with their involvement with an immunocompromised cancer patient, who held off the infection for over two months without being able to clear the virus. Samples obtained from late in the infection revealed two different virus strains that each had a deletion in the gene encoding the spike protein that SARS-CoV-2 uses to attach to and enter cells.

Enlarge / SOUTH TANGERANG, INDONESIA - JANUARY 7, 2021: A patient recovered from COVID-19 donate plasma at Indonesia Red Cross Transfusion Center in South Tangerang. (credit: Barcroft Media / Getty Images )

It's clear that the immune system can mount a robust response to SARS-CoV-2, as the vaccine trials have made clear. Beyond that, though, there are a lot of question marks. People exposed to the virus don't always produce much in the way of antibodies to it, and there have been a number of cases of reinfection. We're not sure how long immunity lasts or whether it correlates with antibody levels or something else–there hasn't even been great evidence that antibodies are helpful.

To give some sense of the challenge of sorting all of this out, we're going to look at three recently published papers that get at the interplay between the immune system and COVID-19. One finally provides some evidence that antibodies might be protective, another indicates that tamping down the inflammatory response might help, while the third suggests that immunosuppressives don't affect disease outcomes at all.

Antibodies good

Antibodies are a relatively easy way to track an immune response, and they've been used for that throughout the pandemic. But early studies found the number of antibodies produced in response to an infection varied dramatically between patients. There have also been clinical trials testing whether using antibodies obtained from those formerly infected could help treat those suffering from COVID-19 symptoms, with the FDA eventually granting this a controversial Emergency Use Authorization. President Trump also received an experimental treatment of mass produced SARS-CoV-2-specific antibodies.

Enlarge / T-cells attacking a cell recognized as foreign. (credit: NIH )

We're still struggling to understand whether infection with SARS-CoV-2, with our without COVID-19 symptoms, provides protection from further infections. Antibodies are an indicator of immunity and are the easiest aspect of the immune response to track. But data indicates that the generation of antibodies is highly variable , and their production may start fading within months. But there are many other aspects to the immune response, many of them centered on T cells. And here again, the response seems to be extremely complex .

Now, additional studies are coming out looking at other specialized aspects of the immune response. While these results provide some cause for optimism in terms of long-lasting immunity, there remain large numbers of unknowns.

Go with the flow

The two studies we'll look at were enabled by a technique called "flow cytometry" that's proven very useful for studying the immune response. It basically helps researchers get past the biggest issue with these studies: there's an abundance of very similar-looking cells involved in an immune response. While a trained eye can tell a T cell from a macrophage using a microscope, knowing there are T cells doesn't tell us much. Not only would we like to know how many of them there are, we'd need to know what types of T cells are present. T cells may help the production of antibodies, they may kill infected cells, they might be used to remember exposure to pathogens, etc.

Enlarge / Medical staff wearing personal protective equipment (PPE) as a precautionary measure against the COVID-19 coronavirus approach Lei Muk Shue care home in Hong Kong on August 23, 2020. (credit: Getty | May James )

A healthy, 33-year-old man in Hong Kong is now the first person in the world confirmed to have been reinfected by the pandemic coronavirus, SARS-CoV-2—which has currently infected more than 23 million people worldwide.

The man’s first infection was in late March. He reported having a cough with sputum, fever, sore throat, and a headache for three days before testing positive for the virus on March 26. Though his symptoms subsided days later, he was hospitalized on March 29 and remained in the hospital until April 14, when he tested negative for SARS-CoV-2 in two tests taken 24-hours apart.

About 4.5 months later, the man tested positive for the virus again. This time, his infection was caught during entry screening at a Hong Kong airport, as he returned from a trip to Spain, via the United Kingdom, on August 15. Though he had no symptoms, he was again hospitalized. Clinical data showed he had signs of an acute infection, but he remained asymptomatic throughout his time in the hospital.