Curating COVID-19 – January 2023

Fantastic Four

Persistent symptoms after SARS-CoV-2 infection have been a key point of interest for researchers, and now four subphenotypes of post-acute symptoms have been established across a range of organs and symptoms: cardiac and renal systems; respiratory system, sleep, and anxiety problems; musculoskeletal and nervous systems; and digestive and respiratory systems (1).

In a Molecular State

A transcriptome-wide analysis of acute COVID-19 patients has identified blood gene expression changes associated with long-term sequelae (2). Distinct signatures were already present during the acute stages of infection, including a relationship between lower total immunoglobulins and sequelae. The work demonstrates the need to consider the acute phase of SARS-CoV-2 infection to improve our understanding of long-term symptoms.

Reaching Far and Wide

Conducting autopsies on patients who died with COVID-19, researchers have demonstrated that SARS-CoV-2 is widely distributed throughout the body and that replication is evident in multiple respiratory and non-respiratory tissues (3). In one case, viral RNA was detected in multiple sites, including the brain, as late as 230 days post-symptom onset – suggesting that SARS-CoV-2 can persist in the body for months in some patients.

Equal Footing?

Over half a billion people have been infected with SARS-CoV-2 at least once and the majority of the population have been vaccinated, meaning many of us now carry antibodies against it. But are all these immune responses equal? New research suggests that individuals who receive monoclonal antibodies before a two-dose mRNA vaccination have a unique immune response, with biased germinal center and memory B cell selection (4).

Antibody Answers

Researchers have tracked longitudinal antibody responses in individuals after repeated mRNA vaccination and found an increase in IgG4 antibodies (5). They also detected spike-specific IgG4 antibodies in half of the serum samples collected between five to seven months after the second immunization, which showed no IgG4 at previous time points. IgG4 levels rose sharply after the third immunization. Now, more research is needed to clarify the mechanisms behind this response and whether it affects future infections or booster vaccinations.

Infant Insights

Infant macaques who were immunized against SARS-CoV-2 with lower vaccine doses sustain protection from a heterologous SARS-CoV-2 variant one year later (6). At the one-year mark, the macaques showed a similar immune response in quality and durability to that of similar adult macaque vaccines. The findings add to growing support for optimized vaccination in infancy.