Managing COVID-19: Vaccines and Long COVID

Our understanding of SARS-CoV-2 and its evolutionary processes has been much improved over the last wave of infection. In the future, one may look back and define the appearance of the Omicron variant as a watershed moment for our efforts in tackling the pandemic – one that made us realize we truly are in for the long haul. New understandings from throughout the industry and academia shed light on the function of vaccines across variants, the development of novel treatments and vaccinations. Crucially, a steady stream of research has been forthcoming regarding the causative methods and physiological consequences of long COVID – which will be critical as our outlooks regarding the coronavirus transition to a more long-term view.

A Cross-Specific Immune Response

As the developed world raced to slow down the Omicron wave and lessen the impact of severe disease, we relied (perhaps too heavily) on rapid rollouts of booster vaccinations. While we were aware of Omicron’s capacity for vaccine evasion, we were not quite sure why booster jabs provided additional protection. Initial speculations posited that the T-cell response of the immune system was not variant-specific and was responsible for the efficacy of vaccination against the variant. A preprint article to be published in Cell confirms these findings, showing that T-cell memory can provide a breadth of protection against early variants regardless of the initial vaccination platform. Booster vaccines also showed some increases in memory B cells that could be induced to produce antibodies that recognize Omicron, although the response was not as strong as for the variant the vaccine was designed for. 

Vaccines and Variants

These understandings will be crucial as we turn our attention to other variants – such as Omicron BA.2, which has shown a much higher capability for transmission than its ancestral BA.1 lineage. It is expected that BA.2 will not be able to easily evade immune responses elicited by Omicron infections or vaccinations. On a brighter note, Pfizer/BioNTech and Moderna have provided updates on the clinical development of their Omicron-specific vaccines, with the former already having commenced their first clinical study. The industry remains somewhat sceptical about the utility of these vaccines by the time they are approved; Omicron is already showing signs of having peaked and plateauing. However, a variant that evolves from Omicron may retain enough genetic similarity for these product candidates to remain effective.

Still, the rate of decline in new infections in countries such as the United Kingdom is not as fast as some may have anticipated – with the R number estimated to be 0.95. This is in line with the high reinfection risk associated with Omicron – something that is now reflected in official British government statistics, which have just started including reinfections. WHO officials have gone to great lengths to urge that current vaccinations are better than no vaccinations. However, they also recognize that living with COVID will likely involve a similar process to living with the flu – where a global committee comes together to decide which variants of the virus will be included in annual multivalent vaccines. 

Equitable Vaccines

On the other hand, the problem of improving vaccine access outside developed countries remains significant. Numerous initiatives have yielded fruitful results; most recently, Afrigen announced positive progress in its efforts to copy the Moderna mRNA vaccine. This was a joint effort between Afrigen and the WHO tech-transfer hub in South Africa. The transfer hub was founded with the aim of assisting researchers in producing mRNA vaccines. After Moderna, Pfizer and BioNTech all ignored the requests of the hub for assistance, the WHO determined the Moderna vaccine to be the easiest copy – in part because Moderna has vowed not to enforce its own patents. mRNA vaccines raise other needs, such as ultracold storage and transport, which African infrastructure may not currently be able to meet. Regardless, the wider availability of expertise is expected to aid in tackling vaccine inequity – which will be crucial in suppressing COVID.

Approaching a Better Understanding of Long COVID

The results from a controversial human challenge trial, where volunteers were deliberately infected with live virus for observational study, have recently been published. While the study has yielded some insights – such as the possibility of the incubation period of the virus being shorter, it has also raised significant controversy. Many in the scientific community do not consider the results of the study valuable enough considering the risk and long-lasting effects of infection. Over a dozen participants reported loss of smell and taste, with three reporting it for over 90 days after infection, a tell-tale sign of long COVID.

Long COVID and Alzheimer’s 

Worryingly, a new study comparing the brains of long COVID patients with those from Alzheimer’s sufferers found striking similarities. Both groups exhibited increased levels of tau proteins in neurofibrillary tangles and amyloid plaques, which are the key physiological markers for Alzheimer’s disease. This may suggest an increased risk of dementia for COVID survivors, exhibiting our need for further investigation into long COVID and its long-term consequences. The observations were also concordant with the finding of leaky ryanodine receptors in COVID-19 survivors that regulate calcium levels. The study began with the pursuit of understanding the “brain fog” symptom of long COVID, which may be related to this physiology. 

Predicting and Detecting Long COVID

Another preprint article set to be published in Cell has also identified four risk factors for the development of long COVID, which include high viral load early in the onset of the disease – as would be expected. Other factors are the presence of specific autoantibodies, the reactivation of Epstein-Barr Virus infection and Type II diabetes – a long known comorbidity for COVID. Establishing a set of predictive biomarkers for long COVID will be crucial in triaging treatments as we move to the future, where chronic long COVID will likely be a higher public health burden.

However, even finding the physiological presence of long COVID can prove challenging when using diagnostics we would traditionally be inclined to. It is known to cause microclots in the blood, which are not typically picked up in routine blood tests. New research also shows that while routine CT scans may not show symptoms of lung dysfunction, a novel MRI test using xenon can demonstrate deficiencies in gas exchange that are symptomatic from long COVID. These findings are indicative of our need to improve our methods for recognizing the condition. 

We see a stark improvement in our understanding of COVID variants, and the implications that arise from them for our established vaccinology. Our familiarity with long COVID and its causative functions is also of crucial importance. These are the two key concerns we will need to address if we hope to live in a society where SARS-CoV-2 is managed effectively on a long-term basis.

Nick Zoukas, Former Editor, PharmaFEATURES