The biology of coronavirus COVID-19 - including research and treatments

It's curious that Swedish epidemiologists keep trying to find ways of claiming far more people have been infected than have tested positive.
Yes, what's up with that? I can't help wondering if and how it's connected to the stuff in the press in Sweden at the moment, to do with other countries' decisions to keep their borders closed to people from Sweden for now (Norway, among others), and earlier reports about the Swedish government trying to improve the country's image internationally in various ways (for example by asking international diplomats/ambassadors to portray Sweden's covid strategy in a more positive light).

Soon after it became clear that many countries wouldn't open their borders to Sweden for now, it was reported that testing would increase (thank you, finally!). That was about 3 weeks ago, I think?

For the last few weeks there have been plenty of articles in the press where "experts" are speculating about immunity, how many people in Sweden "actually" have been infected so far (as opposed to the numbers based on research and other official reports), and why the studies that show low numbers "might be wrong", etc... Articles here, here and here.

Here's an example of a recently published serological study done in May in Norrbotten (a relatively sparsely populated region in the North). "Region Norrbotten" is also the name of the local government responsible for healthcare etc.
Region Norrbotten said:
we invited 500 randomly selected men and women, 20 to 80 years of age (out of an adult population of 182 828) to blood sampling and a symptom survey. We performed sampling during week 22 and 23 (May 25-June 5).

We analysed antibodies with a validated assay (Abbott SARS-CoV-2 IgG kit) and positive samples were confirmed by asecond assay (Euroimmun Anti-SARS-CoV-2 ELISA (IgG).

425 participated (85 %). Non-participation was greatest among the youngest. 8 participants had positive serology (1.9 %) (95 % CI (0,8; 3,7) %). Positive serology was most common among the younger participants and lower among the elderly 65-80 years.

1.8 % of men and 2.0 % of women had antibodies against covid-19. None of those seropositive reported being unsymptomatic whereas 33 % of those seronegative had been unsymptomatic.

Conclusion
More than two months after the first case of covid-19 in Norrbotten, 1.9 % of the general population in theage span of 20-80 years old had antibodies. Expressed as aconfidence interval, this means that we estimate the number of persons in the county infected before week 18 to be between 1460 and 6760.

http://nll.se/sv/Halsa-och-sjukvard...id-19-antibodies-in-Norrbotten-County-Sweden/
This study didn't seem to get much attention in the press at all (the spotlight seems to be on the speculating "experts" instead), but here's an article in Aftonbladet. ("The alarm from Norrbotten - the herd immunity may never come")

Another recently published report on number of infected here, and another one here.

Also, the government has given the Public Health Authority the task of helping the local governments "restart" or increase their tracing efforts. However, in many regions the local healthcare system doesn't have the required capacity, they don't have time to make the phone calls, so they are now putting the responsibility on the patients, expecting the patients to do the actual tracing... The infected patients are told to contact the people they have been around, and in most cases it seems no one will check if the patients actually make those phone calls or not. Which obviously is a problem, it doesn't meet the requirements in WHO's guidelines. (Articles here, here and here).

Meanwhile, the Public Health Authority is pushing forward with the immunity approach. Here's a news article. And here are the new guidelines, published a couple of days ago. They are loosening some recommendations for people with confirmed antibodies:
Public Health Authority Google Translate said:
Based on the knowledge available today, it is likely that so-called IgG antibodies to covid-19 provide, in whole or in part, protection against a new infection with serious symptoms. In the updated guidance, the Public Health Authority assesses that a positive antibody test is likely to provide protection for up to six months from the person receiving his test result. [...]

- We currently believe that a positive antibody test increases the possibility of interacting with, in particular, close relatives, which can be especially important for people over 70 years and persons belonging to a risk group. They can also to a greater extent meet relatives who have antibodies even if they do not have them themselves. But you always have to make your own judgment based on the individual situation and take your own responsibility as an individual, says Karin Tegmark Wisell.

It can primarily be about spending time with close relatives such as family and friends - both indoors and outdoors. The restriction to refrain from larger social contexts remains.

There are plenty of news articles commenting on "the number of infected going down" despite a growing number of people not following the recommendations for social distancing etc, sending the message that "it might be because of the immunity",... (while the numbers are actually going up in several regions, and last week WHO registered the highest number of infected in Sweden so far.) Some are even making it sound as if this might the last bit of it, that things might be going back to something close to normal in the fall.

There is still a lot of focus on the number of deaths in care homes, for example this recent investigation by the newspaper Aftonbladet.

Data on the excess deaths in Sweden indicate that it's 200% higher for people who were born in another country (Irak, Somalia and Syria, in particular), suggesting that social structures is a huge factor.
 
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Almost two thirds of people who have died because of Covid-19 were disabled, statistics show, prompting calls for an inquiry into the deaths.

The figures come from an analysis by the Office for National Statistics, which compared death certificates from March 2 to May 15 with data from the 2011 census.

They found that 30.3 per cent of coronavirus deaths were among people who said their daily activities were “limited a lot” because of a health problem or disability, and 28.9 per cent among those whose activities were “limited a little”.

There were 22,447 deaths across the two categories, both considered disabled.
Paywall/sign-up wall, https://www.thetimes.co.uk/edition/news/two-in-three-victims-of-covid-19-had-a-disability-dcdx3gm20
 
I don't think this has been posted yet... NewScientist, 1st July 2020: Can we become immune to the coronavirus? What the evidence says so far

WHEN the novel pneumonia circulating in China was confirmed to be caused by a coronavirus, an already troubling situation suddenly got that bit worse. As a rule, coronaviruses don’t produce a very strong “immune memory”: the long-lasting response that allows our bodies to thwart a subsequent attack, and which makes vaccines possible. When reports emerged from Japan and China of people who had been given the all-clear catching the virus again, immunologists’ worst fears seemed to be confirmed.

But seven months later, hopes are …

Sorry for the cliffhanger, the rest is behind a paywall. If anyone has access I'd be interested to know more. Thanks...
 
The Swedish Research Council has announced which projects will be receiving grants for coronavirus and covid-19 research in their recent request for research grant applications. A total of 23 researchers will share SEK 33 million (approx GBP 2.84 million, EUR 3.1 million) in 2020. They approved 23 out of 255 applications.

Announcement in English here.

In Swedish here.

Here's a very informative and easy to read Twitter thread (in Swedish) about research funding, how the application process works, what the researchers can use the money for, and a short description of each of the 23 research projects:



There's one study on face masks, and another on long-term health consequences of covid. I had a quick look, but didn't see anything ME related (except that I recognised the name of one grantee because she is a well known ME denier...).
 
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Merged thread

Thailand Medical News

Could Study That Shows Proteins Nsp12 And 13 Of SARS-Cov-2 Causing Mitochondrial Dysfunction Explain For Prevalence Of Chronic Fatigue Syndrome In COVID-19 Patients?


Chronic Fatigue Syndrome: There has been so many clinical manifestation of Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) reported in COVID-19 patients experiencing mild to moderate symptoms and also in typically asymptomatic and also recovered COVID-19 patients. To date medical experts do not have a proper explanation for this.
However, browsing through various new COVID-19 preprint studies, Thailand Medical News came across a research from CSIR-Indian Institute of Chemical Biology and the Academy of Scientific and Innovative Research in which the researchers indicate that the proteins Nsp 12 and Nsp 13 from the SARS-CoV-2 coronavirus have the ability to scavenge for mitochondria (the cell’s powerhouses) and disrupt their functions. Hence we were wondering if this could be the reasons for the unexplained conditions of tiredness and lethargy associated with Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) seen in many COVID-10 patients.

The study is published on a preprint server and us yet to have been peer-reviewed. https://www.preprints.org/manuscript/202006.0352/v1

https://www.thailandmedical.news/ne...prevalence-of-chronic-fatigue-syndrome-in-cov
 
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My amateur opinion after Googling for 2 minutes and not reading the paper. Nope. Please tell me if I'm talking nonsense.

I think you would need a lot of these proteins in the body for there to be a significant ATP loss. Yet fatigue can also be a problem when there aren't many, if any, detectable viruses left in the host (doesnt't mean they are absent just that they aren't widespread). It's more likely that prolonged fatigue results from the body's response to the virus or damage the body.

The authors may be describing something that's interesting and possibly important but they don't show that this is relevant to ME/CFS.
 
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Merged thread

Thailand Medical News

Could Study That Shows Proteins Nsp12 And 13 Of SARS-Cov-2 Causing Mitochondrial Dysfunction Explain For Prevalence Of Chronic Fatigue Syndrome In COVID-19 Patients?


https://www.thailandmedical.news/ne...prevalence-of-chronic-fatigue-syndrome-in-cov

The idea that NSP12/13 could be a cause of CFS is the opinion of the journalist, CFS is not mentioned in the preprint at all.

The hypothesis doesn't really explain why symptoms persist for a long time even after the individual has recovered from the viral infection itself.
 
The Swedish Research Council has announced which projects will be receiving grants for coronavirus and covid-19 research in their recent request for research grant applications. A total of 23 researchers will share SEK 33 million (approx GBP 2.84 million, EUR 3.1 million) in 2020.
That's it? Wow. The sense of urgency is palpable... Is Sweden OK? Doesn't sound OK.
 
The Health and Social Care Secretary has announced the launch of a major £8.4 million research study into the long-term health effects of COVID-19 on hospitalised patients, which has been funded by the NIHR and UK Research and Innovation.

The researchers hope their findings will support the search for treatments for COVID-19 and the development of care pathways that will help patients recover as fully as possible after having experienced the disease.

Symptoms of COVID-19 have varied among those who have tested positive: some have displayed no symptoms, while others have developed severe pneumonia and, tragically, have even lost their lives.

For those who were hospitalised and have since been discharged, it is not yet clear what their medical, psychological and rehabilitation needs will be to enable them to make as full a recovery as possible.

The Post-Hospitalisation COVID-19 Study (PHOSP-COVID), led by the NIHR Leicester Biomedical Research Centre, will draw on expertise from a consortium of leading researchers and doctors from across the UK to assess the impact of COVID-19 on patient health and recovery.

This includes looking at possible ways to help improve the mental health of patients hospitalised with coronavirus, and how individual characteristics influence recovery, such as gender or ethnicity.
https://www.nihr.ac.uk/news/major-s...-effects-of-covid-19-launched-in-the-uk/25200
 
Effectiveness of isolation, testing, contact tracing, and physical distancing on reducing transmission of SARS-CoV-2 in different settings: a mathematical modelling study

https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30457-6/fulltext

INTERPRETATION: Consistent with previous modelling studies and country-specific COVID-19 responses to date, our analysis estimated that a high proportion of cases would need to self-isolate and a high proportion of their contacts to be successfully traced to ensure an effective reproduction number lower than 1 in the absence of other measures. If combined with moderate physical distancing measures, self-isolation and contact tracing would be more likely to achieve control of severe acute respiratory syndrome coronavirus 2 transmission.
 
LSHTM to play key role in new study into long-term health impacts of coronavirus

A major UK research study into the long-term health impacts of COVID-19 on hospitalised patients has been launched.

The PHOSP-COVID study has been awarded £8.4million jointly by UK Research and Innovation (UKRI) and the National Institute for Health Research (NIHR). This study is one of a number of COVID-19 studies that have been given urgent public health research status by the Department of Health and Social Care.

LSHTM will share expertise with a national consortium of leading researchers and clinicians from across the UK to assess the impact of COVID-19 on patients’ health and their recovery.
....
LSHTM is one of the partners working on this study – drawing on expertise from researchers from the Faculties of Public Health and Policy, Infectious and Tropical Diseases and the CureME research group.
https://www.lshtm.ac.uk/newsevents/...ew-study-long-term-health-impacts-coronavirus
 
Williamson et al. OpenSAFELY: factors associated with COVID-19 death in 17 million patients

Abstract
COVID-19 has rapidly afected mortality worldwide1 . There is unprecedented urgency to understand who is most at risk of severe outcomes, requiring new approaches for timely analysis of large datasets. Working on behalf of NHS England, here we created OpenSAFELY: a secure health analytics platform covering 40% of all patients in England, holding patient data within the existing data centre of a major primary care electronic health records vendor. Primary care records of 17,278,392 adults were pseudonymously linked to 10,926 COVID-19-related deaths. COVID-19-related death was associated with: being male (hazard ratio (HR) 1.59, 95% confdence interval (CI) 1.53–1.65); older age and deprivation (both with a strong gradient); diabetes; severe asthma; and various other medical conditions. Compared with people with white ethnicity, Black and South Asian people were at higher risk even after adjustment for other factors (HR 1.48, 1.30–1.69 and 1.44, 1.32–1.58, respectively). We have quantifed a range of clinical risk factors for COVID-19-related death in the largest cohort study conducted by any country to date. OpenSAFELY is rapidly adding further patients’ records; we will update and extend results regularly

Open Acces at: https://www.nature.com/articles/s41586-020-2521-4_reference.pdf
 
Made a Twitter thread about the OpenSafely study:



2) Data from china had previously indicated an increased risk of COVID-19-related death for persons with various chronic illnesses, from diabetes to heart disease. At the time, however, correction for correlation with age - also a significant risk factor - was not possible.

3) Now there is data from 17 million people in the UK, with more than 10.000 with COVID-19 related death. It shows what many expected: persons with various chronic illnesses are at increased risk of death, even when other risk factors such as age and sex are controlled for.

4) The authors write: “The UK has a policy of recommending shielding (staying at home at all times and avoiding any face to face contact) for groups identified as being extremely vulnerable to COVID-19 on the basis of pre-existing medical conditions.”

5) “We were able to evaluate the association between most of these conditions and death from COVID-19, and confirmed increased mortality risks, supporting the targeted use of additional protection measures for people in these groups.”

6) This may be relevant for ME/CFS patients.

Although ME/CFS wasn’t one of the conditions tested, there was an increased risk of COVID-19 related death for neurological conditions and autoimmune diseases such as rheumatoid arthritis or lupus.
 
The implications of silent transmission for the control of COVID-19 outbreaks

https://www.pnas.org/content/early/2020/07/02/2008373117

Abstract
Since the emergence of coronavirus disease 2019 (COVID-19), unprecedented movement restrictions and social distancing measures have been implemented worldwide. The socioeconomic repercussions have fueled calls to lift these measures. In the absence of population-wide restrictions, isolation of infected individuals is key to curtailing transmission.

However, the effectiveness of symptom-based isolation in preventing a resurgence depends on the extent of presymptomatic and asymptomatic transmission.

We evaluate the contribution of presymptomatic and asymptomatic transmission based on recent individual-level data regarding infectiousness prior to symptom onset and the asymptomatic proportion among all infections.

We found that the majority of incidences may be attributable to silent transmission from a combination of the presymptomatic stage and asymptomatic infections. Consequently, even if all symptomatic cases are isolated, a vast outbreak may nonetheless unfold.

We further quantified the effect of isolating silent infections in addition to symptomatic cases, finding that over one-third of silent infections must be isolated to suppress a future outbreak below 1% of the population.

Our results indicate that symptom-based isolation must be supplemented by rapid contact tracing and testing that identifies asymptomatic and presymptomatic cases, in order to safely lift current restrictions and minimize the risk of resurgence.
 
The implications of silent transmission for the control of COVID-19 outbreaks

https://www.pnas.org/content/early/2020/07/02/2008373117

The problem with all this discussion about "asymptomatic" transmission is they aren't actually asymptomatic. Such people often do have symptoms, but they don't report it. There also is an assumption by some that unless you have a fever, anosmia/hypogeusia or obvious shortness of breath, then you are "asymptomatic".

All of these claims from modelling that asymptomatic transmission is necessary (given known contact tracing) is speculative, given that contact tracing itself is always incomplete. It could simply be the contract tracing that is flawed, though I don't disagree with the conclusion that "symptom-based isolation must be supplemented by rapid contact tracing and testing". Given the recent putative opinion that COVID can spread via aerosols (and thus longer distances - 10m+, not 2m), the range of possible contacts increases significantly.
 
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