Long-Term Effects of COVID-19 and Animal Challenge of Vaccines: COVID Science News Wk 27/9

4 min readAug 2, 2020

Vaccine Tests

Derek Lowe over at the In The Pipeline blog has collected the animal challenge data for the leading vaccine candidates. Here I will try to provide a somewhat complementary summary to what is provided there. [1]

It is important to note that there are many possible caveats in using animal models for assessing the effectiveness of vaccines. This can be especially relevant for viruses, which can be very host specific. For example, HIV is very hard to study in primates, as they have their own variant adapted to their immune system, called simian immunodeficiency virus (SIV). [2,3]

The rhesus macaque animal model does appear to be a valuable one when it comes to SARS-CoV-2, however it has not been characterised to the fullest extent when it comes to infectiousness. [4–6]

Data for animal models have been released for the vaccine efforts from Inovio, J&J, Moderna and Oxford/AstraZeneca. [7–10]

Neutralising antibody titres for the various vaccine candidates for inoculated rhesus macaques. Top left: J&J; top right: Inovio; bottom left: Moderna; bottom right: Oxford/AstraZeneca. Credit: [7–10]

An interesting point is that the J&J team found that T-cell response does not correlate with protection of the animals against infection with SARS-CoV-2. This serves to complicate the picture of immunity even more, as it was definitely an unexpected result. Perhaps this reflects an important difference between the animal models and human patients?

The amount of virus used in each study varies quite widely and it is not well understood which dose is most representative of viral loads that a patient might encounter. For a more in-depth look at these studies, see source 1, very highly recommended.

Pfizer has announced that they are dropping 3 of the 4 candidates for the coronavirus, including BNT162b1 which is the vaccine for which all the data has been released so far. They will be proceeding with BNT162b2 instead. [11]

Transmission and Disease Physiology

A case study from a hair salon in Missouri provides some more support for the use of face coverings. Two stylists contracted SARS-CoV-2 and remained at work for 8 and 5 days since symptom onset, where both stylists and clients were mandated to use face coverings. No clients contracted the virus. [12]

A new preprint from the US shows that aerosol transmission (see previous blog [13]) is possible by demonstrating cultivation of virus from air samples passed through filters for various particle sizes. However, some objections have been raised as to the infectiousness of the virus cultured. Overall, the work seems to support the notion that aerosol transmission can happen, albeit not with very high efficiency. [14–16]

Case-fatality ratio (CFR) describes the fraction of deaths compared to the number of diagnosed cases. This number is highly dependent on the number of cases detected. Infection-fatality ratio (IFR) describes the fraction of deaths compared to the number of total infected patients, including those undiagnosed and asymptomatic, thus presenting a more objective measure of the mortality of the virus.

A meta-analysis of 24 studies which estimated IFR concludes that IFR is likely to be around 0.7 % with a high degree of heterogeneity, this time updated with risk-of-bias stratification for the included studies. [17]

Analysis of viral load for patients shows that children above the age of 5 carry a comparably amount of virus as adults, whereas children below 5 years old carry a bit less. The infectiousness of the virus has not been characterised. However, this indicates that school-age children are probably also capable of spreading the virus similar to adults. [18]

Follow-up of patients in Italy who suffered from COVID-19 and recovered indicates that upon recovery only 13 % of patients (n = 143) were completely symptom free 60 days after the first onset of symptoms. Notably, the patients were typically in their 50s and overweight (BMI ~26). [19]

In addition to complications potentially causing diabetes (see previous blog [20]) the acute cardiac injury in COVID-19 patients has raised concerns over long-term cardiac problems such as arrhythmia. Neurological damage has also been observed and also likely has long term effects. Overall, these observations show that COVID-19 almost definitely has long term detrimental effects that may severely compound future illness. [21–23]

Therapeutics

Tocilizumab, an anti-IL-6 antibody which had previously shown positive results for treating patients with severe COVID-19 has failed phase III clinical trials (no data yet). [24,25]

References

Long-Term Effects of COVID-19 and Animal Challenge of Vaccines: COVID Science News Wk 27/9

Written by Michael Bogdos