COVID-19 Science update: Week starting 15/06/2020

4 min readJun 20, 2020

Breaking News

A press release from the RECOVERY trial reports that dexamethasone (an anti-inflammatory corticosteroid) showed positive effects on patients who suffered from COVID-19. The full data have not been disclosed and we should be conservative until they are! [1,2]

So far, all we know is that apparently dexamethasone reduced mortality by 35% in ventilated patients, 20 % in patients receiving oxygen and not at all for patients who did not need respiratory support. [2,3]

Preliminary data on dexamethasone from RECOVERY. Credit: @FranziscoMarty_ on twitter, see [4].

In comparison to remdesivir, dexamethasone seems to offer complementary effects. Remdesivir helps less severe patients and dexamethasone (and other immune-modulating therapies) help with patients in critical condition. This strongly supports the hypothesis that COVID-19 is comprised of a viral response phase and a host inflammatory response phase. [2,4]

Graph of COVID-19 disease progression. Credit: @AndyBiotech on twitter, see [3].

This is not the first drug to show a reduction in deaths for COVID-19 patients, despite what various headlines claim. Remdesivir, IF-β1b/lopinavir-ritonavir/ribavirin and tocilizumab have all shown such data. [5–7]

Infections & Physiology

Researchers in the UK used reported death data in 11 European countries to estimate the effect of non-pharmaceutical interventions. They find that lockdown and social distancing were by far the most effective measures, reducing reproduction number by ~80 % and preventing ~3 million deaths in these countries. [8]

The study of fully asymptomatic patients is extremely challenging for a number of reasons. [9]

A team from China has identified asymptomatic patients and followed their progress and biomarkers. In this study, this constitutes 20 % of the studied patients. Comparisons were made to mildly ill patients.

Radiological anomalies were observed for 67 % of asymptomatic patients in at least one lung. Asymptomatic patients shed virus significantly longer than symptomatic patients with mild COVID-19. They also lost their developed (IgG) antibodies after a time, much more often than symptomatic patients (40 % vs. 13 %). T-cell immunity was not tested, so it is unclear if these seronegative patients displayed immunity. Asymptomatic patients showed no inflammatory biomarkers. [10]

In short, the above study suggests that 20 % of the infected remain asymptomatic, while being potentially more infectious, potentially having long term lung complications and a portion may not develop immunity.

Data for viral shedding and IgG levels in asymptomatic vs. symptomatic patients. Credit: Long et al. Nature Medicine 2020, see [10].

Analysis of the data in various US states shows that state which mandated the use of masks fared better at curbing infections. In my opinion, the quantifications offered in the study are not meaningful given that other measures were not adequately accounted for. [11]

A variant of SARS-CoV-2 (S protein D614G) which has been identified in some regions has been studied. The authors find that this variant is probably more infectious but does not seem to increase disease severity. [12,13]

Vaccine News

A team from Israel reports animal study results for their vaccine (vesicular stomatitis virus with SARS-CoV-2 spike protein). It raises neutralising antibodies and protects hamsters from infection. [14]

Vaccines against other viruses are known to have beneficial non-specific effects. For example, the oral poliovirus vaccine was used in Bulgaria in 1975 to control an enterovirus 71 outbreak. It has been suggested that such effects could be useful against SARS-CoV-2. [15]

A colossal effort of studying 3,819 important (artificial) mutants of SARS-CoV-2 (specifically on the RBD of Spike) was undertaken by scientists in the US. In short, they identified mutants that are more efficient at infecting cells. However, they did not identify any of these mutants in the real world. In addition, this work implies that the currently developed vaccines and antibodies have very likely picked a good target. [16,17]

Immune Cells & Antibodies

Differences in immune cells (B cells and T cells) are observed between mild and severe cases of COVID-19. Cross-reactive T-cells, which decrease with age, seem to play an important role, suggesting a reason for the higher susceptibility of the elderly to COVID-19. [18]

Analysis of plasma from recovered patients showed that though the individual characteristics vary widely, all patients showed some rare, potent RBD-specific antibodies. These are the types of antibodies that most vaccines aim to raise, which again validates current approaches to vaccine development. [19]

Meanwhile, similar monoclonal antibodies, intended for industrial production and use as therapeutics, are being reported by the hundreds. There is now a comprehensive library of sequences. [20–22]

Therapeutics

A pre-print has appeared detailing the use of low-dose lung radiation therapy as a treatment method. The results are extremely preliminary and also uncontrolled so interpretation is impossible. A clinical trial is under way and hopefully will shed light on the matter. [23]

The US FDA has withdrawn both chloroquine (CQ) and hydroxychloroquine (HCQ) from their list of medicines with Emergency Use Authorisation for COVID-19. The FDA states “[…] CQ and HCQ are unlikely to be effective in treating COVID-19 [..]”. [24]

References

COVID-19 Science update: Week starting 15/06/2020

Written by Michael Bogdos