A search for "COVID" in PubMed returns more than 1200 articles. Most of these are commentaries, brief reviews, opinions, or news pieces. Understandably, a global outbreak has unearthed a global range of views. But some of these articles, like nuggets of gold in a river bed thick with sand, describe important new research on this newly discovered virus, SARS-CoV-2, and the disease it causes, COVID-19.

There are several online lists of articles about SARS-CoV-2 and COVID-19, including by the WHO, but it can be hard to separate the gold from the sand. So this weekly blog will update the research community on the latest research, only including studies that add to our understanding of the virus. This is mainly intended to help virologists, and those researching the disease, who are busy in their labs day and night. But it may be of interest to the wider community too.

For the moment, this will just focus on research that has been peer reviewed and published in a journal, and not include pre-prints. This is more for ease of curation than anything else - pre-prints continue to be an invaluable way of sharing information quickly. 

If I have missed any important studies, and I probably have, please add them in the comments!

Mental health

Survey of Chinese healthcare workers

I highly recommend this survey of 1257 healthcare workers in China, to monitor their mental health. The findings make for a challenging, if perhaps unsurprising, read. Many reported symptoms of depression (50%), anxiety (45%), insomnia (34%) and distress (72%). Those working in Wuhan reported higher levels of mental health symptoms than those elsewhere in China, and frontline health care workers who directly dealt with patients also reported higher levels. This is a timely reminder that there is a huge psychological burden on our healthcare workers and that they need appropriate mental health support, to be able to care for the rest of society.

Epidemiology

18% of cases on the Diamond Princess were asymptomatic

This important study from the Diamond Princess outbreak tracked the disease in patients, monitored symptoms, and carried out modelling to determine that 17.9% of those infected with SARS-CoV-2 had no symptoms. Viral loads were similar in those with and without symptoms, so it seems clear that those with no cough or fever are able to pass on the infection. It is worth noting that many of the residents on the cruise ship were over 60; if that age group are more likely to show symptoms (which seems possible), then the proportion of asymptomatic individuals may be even higher.

Why are case fatality rates so high in Italy?

A thorough analysis of the Italian outbreak estimates that the case fatality ratio, as of 16th March, is 7.2% (1625 deaths out of 22,512 cases). This varies considerably by age, with less than 1% fatal cases in those aged 0-59, 3.5% in those 60-69, 12.8% in those 70-79, and rising to 20% in those over 80 years. When compared to China, where the overall case fatality rate is a much lower 2.3%, the rates are strikingly similar in those less than 69, but higher in Italians over 70. The authors suggest three possible reasons for this discrepancy: Italy has an elderly population with 23% over age 65; those with comorbidies that may have contributed to death, such as diabetes, cancer, and ischaemic heart disease, were included as deaths due to COVID-19, whereas they may not be coded as such in all countries; and thirdly, on 25th February Italy decided to only test those with severe clinical disease, and so many patients with mild symptoms or who were asymptomatic were not included. In South Korea, where many more people are tested, the case fatality rate is even lower than China, at 1%. Given the growing research on asymptomatic infections, the proportion of those infected that have a fatal outcome is likely to be considerably lower.

Patients are infectious early in disease

This study measured viral load in the nose and throat of 17 symptomatic patients from Zhuhai, Guangdong, China, and 1 asymptomatic patient who was positive for SARS-CoV-2. Viral loads were highest soon after symptoms appeared, and higher in the nose than the throat. This is markedly different from SARS, where the peak infectiousness was after several days of illness, and more similar to influenza, where patients are also infectious early in the disease (even before symptoms). The asymptomatic patient shed as much virus as those with symptoms, again suggesting that asymptomatic carriers may be important in the spread of the disease.

Family infected from a patient without symptoms

A case study from Zhejiang, China where 8 members of a family was infected by family members before they had any symptoms. This continues the theme that individuals with no symptoms can be infectious.

Scotland's index case had mild disease

The first case of COVID-19 in Scotland is described, in a patient who returned from a rugby match in Italy. As with most, this patient had a mild disease with a cough and fever, and continued to exercise during his illness.

Immune response

Reduction of CD4+ T cells in COVID-19 patients...

Peripheral blood leukocytes from 16 patients in Kunming, China, were analysed. Those who had severe disease showed some differences in immune cell composition, including a reduction in granulocytes and a reduction of multi-functional CD4+ T cells, compared to the mild group. There is a detailed analysis of various cytokines between healthy, mild, and severe cases, which is worth a look if you want more details of the immune response to the virus.

...and exhaustion of cytotoxic T lymphocytes

In another study of the immune response to infection, this time from 68 COVID-19 patients in Hefei and Fuyang, China, the authors showed exhaustion of T and NK cells. They correlate this with SARS-CoV-2 induced NKG2A expression, a marker of functional exhaustion of cytotoxic T lymphocytes.

Receptor binding 

A single vaccine for SARS and COVID-19

A rare study on the biology of the virus shows that SARS-CoV-2 spike protein binds to both human and bat ACE2 receptors. Interestingly, there was cross-reactivity between SARS-CoV and SARS-CoV-2 antibodies, suggesting that a single vaccine could be developed for both SARS and COVID-19. This cross-reactivity should also be considered with any antibody-based diagnostic test.

Diagnostics 

Virus neutralisation assay using pseudotypes

A VSV-based SARS-CoV-2 pseudotype was created, as well as a neutralisation assay that can detect whether a patient has been previously infected with the virus. Unlike a standard neutralisation assay, the pseudotype can be used in BSL-2 facilities, rather than BSL-3. Sera from COVID-19 patients showed strong neutralising potency.

Clinical findings

Tracking lung disease over time

A series of CT scans at different stages of infection with COVID-19 allowed clinicians to track the course of lung disease in 81 patients from China. Interestingly, chest CT abnormalities could be observed in patients before the onset of symptoms, suggesting that this could aid with diagnostics.

CT scans of COVID-19 patients

There are several additional case studies of clinical findings, all from China, which are listed below, starting with the CT scans or lung X-rays of 573 COVID-19 patients from Zhejiang province in China.

CT scans of 27 COVID-19 patients in Wuhan, China.

CT scans of 53 patients in China with confirmed COVID-19 infection.

CT scan of a 59 year old woman from Wuhan with COVID-19 pneumonia.

Mild disease in children

Symptoms and CT scans of 25 paediatric cases of COVID-19, again showing mostly mild disease.

Image by Nino Carè from Pixabay