Coronavirus Research Tracking - 18 September
Acute and chronic impacts on the heart and brain, effects of obesity, adaptive immunity, strength of evidence for public health measures, and funding biases
This week’s Research Tracker has long-term and balance related themes.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
Cardiac problems associated with infection
A commentary in Science provides a good overview of heart conditions seen in some Covid-19 patients. It is still uncertain whether the virus directly or indirectly is the cause, and whether there are long lasting effects from the cardiac disruptions. Further research is needed.
The nervous system can also be affected
Research, not yet peer reviewed, has demonstrated that the virus can infect clumps of brain tissue in the lab, causing neuronal damage. It can also enter brain cells in mice who express the human ACE2 receptor. Evidence of the virus was also found, to varying extents, in the brains of three people who died from Covid-19-related conditions, though brain damage wasn’t the cause of death.
A review of cases reporting the virus in neurological tissue has just been published in Cell. Brain damage due to Covid-19 appears relatively rare but there is evidence that some infections may affect the brain in several ways. The authors conclude that it is possible that some recovered Covid-19 patients may have long-term neurological or psychiatric complications.
Studies of long-term effects are just beginning
A news feature in Nature provides a good summary of the different types of longer-term health conditions that are starting to emerge following recovery from Covid-19, even for those with mild disease. It notes that several projects are starting to monitor the longer term effects post-infection. One, in the UK, plans to monitor 10,000 people for 12 months.
Understanding how obesity affects Covid-19
A news item in Science provides an informative overview of how obesity may exacerbate Covid-19. It describes how both physical and physiological factors in overweight people create additional medical complications. The article points out that obese people are rarely included in clinical trials, so developing effective treatments for them lags.
Serious cases of Covid-19 don’t always involve a “cytokine storm”
A paper in the Journal of the American Medical Association compared the levels of three cytokines in a small group of ICU patients with Covid-19, to other ICU patients. The cytokine levels in the Covid-19 patients were usually lower than those in the other patients, so uncontrolled production of cytokines, leading to excessive inflammation, is not always a factor in more severe Covid-19 cases.
Uncoordinated adaptive immune responses in more severe Covid-19
Previous issues of the Weekly Highlights have featured papers that point to a dysfunctional immune response in patients with severe Covid-19 outcomes. A recent paper in Cell demonstrates this clearly.
It compared virus-specific CD4+ (T-helper) and CD8+ (T-killer) T cell populations and neutralising antibody activity in both Covid-19 patients (still ill or recovering) and uninfected people. Surprisingly, levels of neutralising antibodies were not correlated with disease severity. But strong responses from both the T-helper and T-killer cells were found in those with milder Covid-19, indicating the key roles both these types of T cells play in controlling infections. Older aged patients (over 65) tended to have disrupted T cell coordination and worse outcomes.
An article in Science discusses the significance of this study.
Potent small molecules that may reduce infections
A study of human antibody components found that one molecule - called Ab8 - was very effective in blocking the receptor-binding domain of the spike protein, preventing binding with the ACE2 cell receptor. Tests in mice and hamsters found that Ab8 blocked or reduced infection or symptoms at low doses. It has not yet been tested on people. The research was published in Cell.
In similar research, a paper in Nature identified several neutralising single domain antibodies (fragments of complete antibodies) that also show strong binding to the receptor-binding domain. These block or inhibit binding between the virus and ACE2 receptor in cell assays. Such “mini-antibodies” may be easier to produce than full sized ones.
Immunity to human coronaviruses doesn’t last long
A Dutch study of HIV/AIDS in men has been collecting serum samples about every 6 months since 1989. A recent paper in Nature Medicine reports that samples from 10 of the participants were tested for antibodies against four common human coronaviruses. Re-infections with the same coronavirus occurred between six and 105 months later, with re-infection often occurring after 12 months. It is uncertain whether immune responses to SARS-CoV-2 will be the same.
Strength of evidence for public health control measures
The UK’s Cochrane Library, which examines the strength and quality of evidence related to improving health, published three rapid reviews this week:
One looks at the effectiveness of travel-related control measures. It concludes that the quality of evidence is low and variable, and often based on models rather than well designed studies. The review emphasises that entry and exit symptom screening measures on their own are not likely to be effective at detecting all incoming, or outgoing, cases so other measures are also needed.
A second review looks at universal screening for the virus, based on 22 published studies. It concludes that screening, using a variety of methods, of people without symptoms is likely to miss many who are infected. Other public health measures, such as masks, physical distancing, and isolation also need to be in place during outbreaks.
The third review looks at quarantining, with and without other measures. Fifty one studies were assessed. These were mainly modelling studies and were difficult to compare due to different assumptions in each model. All the studies indicate that quarantine is important in reducing infections and mortality during the pandemic, but there is more uncertainty over the magnitude of the effect.
More research into novel treatments is required
An editorial in Science Signalling is critical of “… a nearly monomaniacal focus on diagnostic testing … [that] … reflects the current thinking of limiting transmission as the main mechanism for disease control.” It advocates for more research funding into better ways to treat the lung, heart and blood conditions that Covid-19 causes, and to better understand why some existing treatments are more effective than others. It is also critical of US hospital and healthcare financial practices that can limit clinical inquiries into the causes and consequences of new diseases like Covid-19.