Coronavirus Research Tracking - 17 July

Progress on vaccines, lessons from other coronaviruses, Covid-19 symptoms.

In this week’s Research Tracker we cover a variety of topics - progress on vaccines, Covid-19 symptoms, large scale antibody testing, and debates about transmission pathways.

The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre. As this is a new service, please don’t hesitate to provide feedback.

Moderna’s mRNA vaccine stimulates antibodies in Phase I clinical trial

So far progress on Covid-19 vaccine development has been reported through press releases. This week Moderna published the results of its Phase I clinical trial (to determine safety) on 45 healthy adults in the New England Journal of Medicine. All subjects developed antibodies, with those receiving stronger doses tending to produce more antibodies. Some of the volunteers experienced adverse effects, but not significant enough to prevent further trials.

Results on the University of Oxford’s vaccine’s Phase I trial are expected to be published next week in The Lancet.

The Guardian provides an update on progress of selected vaccine trials. The Biorender Covid-19 Vaccine Tracker shows progress on all vaccine trials.

A good editorial alongside the Moderna paper in the New England Journal of Medicine outlines the challenges in developing vaccines. Any or all of the vaccines that pass Phase I and II clinical trials can still fail.

Old vaccines for new pathogens

Three existing vaccines - one for tuberculosis (BCG), the Measles, Mumps & Rubella (MMR) vaccine, and a polio vaccine - have been suggested as useful for helping combat Covid-19.

Research published in the Proceedings of the National Academy of Sciences found that in Europe higher levels of BCG vaccination correlated with lower levels of Covid-19 mortality. Further research is necessary to determine if the BCG vaccine could be an effective treatment. Clinical trials of the BCG vaccine are already underway for Covid-19.

Live attenuated vaccines, like BCG, are known to be able to provide some nonspecific protection against infections. Other researchers have suggested, in a paper published online in mBio, that another attenuated vaccine, MMR, may also be useful. They suggest clinical trials with it should also be undertaken.

For similar reasons a perspective in Science advocates testing the oral Polio vaccine against Covid-19. The Biorender Covid-19 Vaccine Tracker site indicates that clinical trials on both MMR and the oral polio vaccine are underway in Egypt and Guinea-Bissau, respectively.

Learning about immunity from other coronaviruses

A helpful review, shortly to be published in Immunity, provides good context for understanding potential immunity to SARS-CoV-2.  It summarises the immune responses to other coronaviruses. Both humoral and cellular immune responses are important for protection. It notes that antibody responses to other coronaviruses can decline quickly, resulting in short term or partial immunity. 

The paper also describes the dysregulation that can occur in T cell responses to these viruses, which is also seen in some cases of Covid-19. This suggests that immune responses to infection by, and vaccination against, SARS-CoV-2 may be similar to other coronaviruses. 

The authors conclude with several critical research questions that still need to be examined. For example, there is still limited information about the effectiveness of neutralizing antibodies and SARS-CoV-2-specific T cell responses in reducing disease severity or virus transmission. More longitudinal studies of immunity to the virus are also required.

A recent pre-print addresses that last issue. It tested for antibodies in 65 infected patients for up to 94 days. Antibody levels tended to peak on average 23 days after symptom onset and then decreased 2- to 23-fold. A few of the patients with initial high levels of neutralising antibodies maintained relatively high levels, while others dropped quickly to low levels. Their ability to resist re-infection was not tested.

Covid-19 symptoms can persist

An Italian study of 143 people recovering from Covid-19 found that 60 days after symptoms appeared 87% still had some symptoms, such as fatigue, shortness of breath, and joint or chest pains.

Anecdotal reports of long-lasting symptoms are also appearing, but more studies of larger groups of patients are necessary to understand the longer term health impacts of Covid-19.

Surprising medical conditions that may be linked to infections

Diabetes is known to be a pre-existing condition that may lead to more severe Covid-19 symptoms. A letter in the New England Journal of Medicine reports the possibility that the virus may also cause diabetes. This needs further research.

A range of neurological conditions can occur in some Covid-19 patients. In a small study of 43 patients, published in the journal Brain, conditions affecting the brain or nervous system included brain swelling and inflammation, strokes, Guillain-Barré syndrome, and other central nervous system disorders. The causes and effects between Covid-19 and these conditions needs further study.

The most common symptoms and conditions

A review of research and clinical reports, published in the Journal of the American Medical Association, summarised the type and frequency of medical conditions associated with people hospitalised with Covid-19. The most common conditions are fever (70%-90%), dry cough (60%-86%), shortness of breath (53%-80%), fatigue (38%), muscle pains (15%-44%), nausea or diarrhea (15%-39%), and general weakness (25%).

Approximately 5% of patients experienced severe symptoms requiring intensive care, and more than 75% of hospitalised patients needed supplemental oxygen. 

Factors that increase the risk of dying

Nature published a review of the medical records of nearly 11,000 people in the UK who died from Covid-19 along with the records of 17 million other patients. The study found that the key factors that increase the risk of dying from Covid-19 include being male, older, being socially deprived, and from a non-white ethnic group. Diabetes, severe asthma, and various other medical conditions were also important risk factors. Patients older than 80 were at least 20 times more likely to die from Covid-19 than those in their 50s.

New York Times’ Treatment Tracker

The NY Times has created a useful tracker of 20 coronavirus treatments (drugs and physical treatments). It identifies which have the strongest evidence of effectiveness (such as Remdesivir and ventilators) down to those they label as pseudoscience (injecting bleach).

Their tracker lists hydroxychloroquine and chloroquine as “not promising”. A just released pre-print paper on a randomised controlled trial of hydroxychloroquine (as part of the UK’s excellent RECOVERY trials) found that the drug did not reduce mortality of hospitalised patients. It did, however, increase the length of hospital stay and the risk of needing mechanical ventilation or dying.

Nationwide antibody testing in Spain finds low levels of exposure

Spain has had nearly 250,000 reported infections of SARS-CoV-2. A nationwide randomised sampling of 61,000 households tested for IgG antibodies to the virus. Two methods were used; a simpler point-of-care test and a more complex immunoassay. Both gave similar results, with 5.0% and 4.6% testing positive, respectively. One in three infections appeared to be asymptomatic.

The testing confirmed that close contact with infected people, particularly those in the same household, increases viral transmission. The results were published in The Lancet.

Debate about airborne transmission

There is evidence that the virus may be able to be spread in small droplets produced by talking or breathing, though this is contested as this news feature in Nature summarises. The WHO acknowledges the research but its most recent scientific brief notes that further research is necessary.

A useful paper that looks at the issue was published in the Journal of the American Medical Association. It notes that other respiratory diseases, such as colds and flu, are not typically transmitted through aerosols. Data on the reproductive rate (R0) of SARS-CoV-2 also suggests that its transmissibility is lower than expected if infection via aerosols was significant.

N95 masks would also be expected to be much more effective at blocking transmission than simple cloth masks, but this too doesn’t appear to be the case. Finally, epidemiological studies reinforce that close contact is the most common pathway for infections. This suggests that transmission is probably mostly by larger droplets (caused by coughing, sneezing, singing or shouting) and from contaminated surfaces.

Other SMC resources