Coronavirus Research Tracking - 4 September
Excess deaths, aerosol transmission, corticosteroids, types of immunity, vaccine trials, and tracing infections.
In this week’s Research Tracker we look at papers that can be loosely linked through the theme of variability.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
Calculating Covid-related deaths is difficult
In response to political questioning about the number of Covid-related deaths in the US, the CDC produced an update of its methods and results for counting “excess deaths.” This is the number of direct and indirect deaths that may be attributed to the pandemic. The CDC rejected claims that there is an over-counting of deaths caused by Covid-19.
A news article in Nature discusses the difficulties in accurately estimating the impact the pandemic has had on mortality. There is wide variation between countries on reported excess deaths. This in part reflects inconsistencies in reporting on deaths directly attributable to Covid-19 and those due to delayed diagnosis or treatment of other health conditions.
Incomplete data makes it difficult to compare the effectiveness of different public health measures between countries. Better information from more affluent countries is expected to emerge eventually.
Genetic variability in three genes may influence infection susceptibility
An article in Trends in Genetics describes how variations in the expression levels of three genes may affect the risk of infection by SARS-CoV-2. One of the genes is for the ACE2 receptor. The other two can influence whether the receptor is taken into the cell when the virus binds, or whether the receptor is shed from the cell surface before the virus can bind to it.
A variety of single nucleotide polymorphisms in or near these genes have been found and some may influence gene expression. They authors suggest that a risk score based on the variation patterns could be developed that might be able to distinguish people who are more or less susceptible to infection. Further research on this is required.
The virus is not always found in the breath of infected people
Research published in Clinical infectious Diseases examined the concentrations of SARS-CoV-2 produced in the breaths of 49 Covid-19 patients, as well as in the air and on a range of surfaces in their hospital rooms. Quantitative PCR was used to detect and measure viral presence and abundance. The virus was found in only about one quarter of the breath samples, and in less that 5% of the air and surface samples.
Viral concentrations in breaths varied considerably, but sampling sizes were too small to see if this variation related to severity of symptoms. There was a tendency for viral concentrations to be highest in the earlier stages of disease, though that needs further study.
Viral RNA was rarely found on door handles, which may suggest a low probability of infection from surfaces, at least in this study. The infectivity of viral exhalations was not tested.
Possible aerosol transmission via drains in an apartment complex
A study by Chinese scientists concluded that the spread of an infection in a high-rise apartment complex was probably due to faecal aerosols traveling through drains. An initial infection in a 15th floor apartment spread to two other apartments on the 25th and 27th floors. Air and surface sampling, along with CCTV footage, did not identify potential contacts between the apartment residents.
However, a tracer gas released in the bathroom of the original infected apartment indicated that aerosols could reach the higher apartments if the floor drains did not have water in them. A similar pattern of transmission was seen during the SARS outbreak.
The risk of this mode of transmission appears low, given the absence of transmission to other apartments in the building, as well as the absence (at this stage) of reports for similar transmission patterns in the large number of high-rise apartment buildings in that city or elsewhere. The paper was published in Annals of Internal Medicine.
Transmission on a bus
Aerosol transmission, by a different route, was also inferred in a study published in JAMA Internal Medicine. Researchers were able to trace infections related to a trip to an outdoor religious event. The index patient on one of the buses infected 29 other people who attended. Four of these were people she had close contact with at the event. Twenty five were other passengers on her bus (which had 67 passengers). No one on a second bus that went to the same event became infected, providing a quasi-control.
Tracing identified where everyone sat on the infected bus, and showed that those infected did not all have close contact on or off the bus with the infected woman. Those sitting next to windows or doors were less likely to become infected, so the researchers concluded that the air conditioning system helped spread the virus within the bus.
Corticosteroid treatments reduce deaths
A meta-analysis of seven randomised clinical trials (including a trial run in Australia and New Zealand) assessed the overall effect that corticosteroid treatments had on the death of hospitalised patients 28 days after Covid-19 symptoms appeared. It found that corticosteroid treatments (dexamethasone, methylprednisolone, and hydrocortisone) resulted in fewer deaths, longer survival times and fewer adverse events, compared with a placebo or usual care.
The analysis wasn’t able to determine the most effective doses of the steroids, nor assess whether the treatments subsequently resulted in adverse effects.
The study was published in the Journal of the American Medical Association, alongside three of the studies that it included.
Scimex has Expert Reactions to this paper.
Disease severity influences strength of neutralising antibody response
Research published in Signal Transduction and Targeted Therapy found that a stronger neutralising antibody response is associated with more severe Covid-19 disease in patients who recovered. There was also variation between patients on the types of neutralising antibodies that they produced. Patients without symptoms did not produce neutralising antibodies, which could mean that they are more susceptible to re-infection. A caveat is that only small numbers of patients were tested.
Four types of immunity
An article in Stat summarises the views of scientists on the four different types of immunity that may from infection by, or vaccination against, SARS-CoV-2:
Sterilizing immunity - prevents further infections
Functional immunity - subsequent infections asymptomatic or mild
Waning immunity - immunity declines over time
Lost immunity - immunity disappears after a certain time
Functional immunity was seen by many of those interviewed as the most likely. However, the article notes that there is currently insufficient information to be certain what types of immunity will develop. It is possible that different people may develop different types of immunity to the virus.
International multi-vaccine trials needed
A paper published in The Lancet describes the WHO Solidarity Vaccine trial. This aims to undertake randomised control trials that evaluate the efficacy and safety of multiple Covid-19 vaccines. The authors, who are part of the initiative, point out that this approach is more efficient and equitable than running many smaller independent trials. It also notes that the approach may help reduce the risk of political and economic pressures leading to the approval of vaccines that are only weakly effective, or which have undergone less robust evaluation.
The limits of persuasion
A perspective in the New England Journal of Medicine looks at the history of contact tracing in the 19th and early 20th Centuries. It notes that to have a meaningful impact contact tracers need to establish rapport with the contact. This requires tact, patience, and empathy, skills that are hard to teach.
It suggests that, in the US at least, Covid-19 contact tracers are being asked to do more, with less training and regulatory powers, than their earlier counterparts. This can make tracking, tracing and isolating much less effective.