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

[Wits_End]

Something positive-sounding for once: some apparent progress in vaccine development:

http://www.msn.com/en-gb/news/world...sed-for-final-testing/ar-BB16JEn9?ocid=ASUDHP

The first COVID-19 vaccine tested in the U.S. revved up people’s immune systems just the way scientists had hoped, researchers reported Tuesday -- as the shots are poised to begin key final testing.

“No matter how you slice this, this is good news,” Dr. Anthony Fauci, the U.S. government’s top infectious disease expert, told The Associated Press.

 

[Snow Leopard]

https://www.nejm.org/doi/full/10.1056/NEJMoa2022483

Notable aspects: the highest dose (250 μg) caused headache in 100% of recipients, fever in over 50%, along with severe fatigue in some recipients of this dosage. One recipient in the lowest dosage (25 μg) group had a significant immunological reaction (urticaria).

Notably even the lowest dosage resulted in seroconversion and the mean level of antibodies exceeded that of the convalescent plasma of COVID-19 patients.

Thus I am surprised at the choice of 50μg dose, a 100μg dose for the phase II trials.

Seroconversion was rapid for binding antibodies, occurring within 2 weeks after the first vaccination, but pseudovirus neutralizing activity was low before the second vaccination, which supports the need for a two-dose vaccination schedule.

This is only suggestive evidence, in fact it is impossible to say whether one or two doses is necessary without participants being directly exposed to the virus. I suspect this point will be ignored however and subsequent trials (and ultimately clinical dosage) will recommend two doses.

In this interim report of follow-up of participants through day 57, we were not able to assess the durability of the immune responses; however, participants will be followed for 1 year after the second vaccination with scheduled blood collections throughout that period to characterize the humoral and cellular immunologic responses. This longitudinal assessment is relevant given that natural history studies suggest that SARS-CoV and MERS-CoV (Middle East respiratory syndrome coronavirus) infections, particularly mild illnesses, may not generate long-lived antibody responses.20-22

While this is a cause for concern, there is no concerning evidence so far to suggest that the immune responses won't be durable. Some researchers and journalists mistakenly confuse antibody kinetics 6-12 months post-infection with memory T-cell and B-cell responses. This decline in antibody kinetics observed post-COVID19 is normal and expected. The same kinetics occur after most infections where the virus is effectively neutralised and indeed similar kinetics are observed after measles vaccinations for example, yet no one is claiming that measles vaccinations only work for 6-12 months.

 

[Peter]

Merged thread

Randomized Re-Opening of Training Facilities during the COVID-19 pandemic

The train-study. Pre-print and not peer reviewed. The Norwegian institute of public health and Atle Fretheim involved. That is the guy who sent some quite interesting mails to Cochrane last year when discussing the get-saga. This seems to be a great example of questionable design and how not to do it. Hurried covid-19 research and damaging side-effects. The last thing you probably should do, is go very public and state that training in gyms are safe?

I thought today’s comment in the newspaper Aftenposten by prof. Joar Vittersø was quite good and to the point. Google translate.

Misleading about the spread of Corona and traning in gyms

Joar Vittersø
Professor, University of Tromsø

A Norwegian study found that people who trained at gyms in Oslo in May and June did not contract covid-19 infection. The discovery has received a great deal of attention and has been featured in the New York Times, Science and the Norwegian media.

The researchers behind the study are quoted as saying that it is safe to use gyms. This is a misleading message from a bad research project.

Joar Vittersø is Professor of Social Psychology at the University of Tromsø.
None of those who trained were infected with corona. The study therefore shows nothing other than what we know from before: No infection is transmitted if there is no infection to be transmitted. One does not need to do research to reach that conclusion. No matter what non-infected people are allowed to do in an experiment, they will not infect each other.

When the researchers saw that none of the participants had covid-19, they should put the study in the drawer. Instead, they wrote an article as if they had made an interesting discovery. The consequence is that they have spread an undocumented message about security.

The study shows another unfortunate consequence of urgency research. The results have been published as a so-called pre-print, which means that no experts have assessed the quality of the study. We do not know what the peers will say in this case, but the criticism in the article's online comment field is predominantly negative. And that is more than fair given the lack of quality.

Researchers, like everyone else, should be careful about spreading uncertain knowledge where the consequences of making mistakes can endanger life and health.

We can also ask if it is ethically justifiable to start a study where the intention is to let people who are infected with a potentially deadly virus train with someone who is not infected, to see if new cases of infection occur!

We know that people in gyms can infect each other with covid-19. If the study contributes to such facts being ignored, the consequence may be more spread of infection. Then we have a deplorable example of how meaningless research and hasty conclusions can increase the risk of disease.

Maybe the health authorities should warn against misinterpretations of this study?


https://www.medrxiv.org/content/10.1101/2020.06.24.20138768v2

Protocol can be downloaded here
https://www.trainstudy.no/about/

 

[anciendaze]

Moved from the Worldwide spread and control thread.

As if we didn't have enough to worry about, there are now multiple reports that COVID-19 inflammatory syndrome sometimes occurs in adults.

 

[mango]

Result from a local Swedish study. Gothenburg is Sweden's second largest city.

Three percent of Gothenburgers had covid-19

Just over 3 percent of all Gothenburgers who received a sampling kit sent home during week 27 [29 June - 5 July] tested positive for covid-19, reports GP.

Of the 17,000 tests that were randomly sent home in the mailbox, about 6,000 were returned for analysis. The test was sent home to people in different districts and at different ages.

Magnus Lindh, section manager for clinical microbiology at Sahlgrenska University Hospital and responsible for the project, says that they hoped to get around 10,000 answers from the survey, which is the largest to date in Gothenburg.

The test only shows those who had an ongoing covid-19 infection and not if those tested have antibodies.

https://omni.se/tre-procent-av-goteborgarna-hade-covid-19/a/kJAaqA

The original source is paywalled:
Göteborgs-Posten: Resultaten har kommit – så många var smittade i Göteborg

 

[JaneL]

Dr Fauci on This Week in Virology with Vincent Racaniello! Discussing SARS-Cov-2 transmission, testing, immunity, pathogenesis, vaccines and preparedness.

 

[Wits_End]

Information on which treatments appear to work - and which don't:

http://www.msn.com/en-gb/news/uknew...elp-hurt-for-covid-19/ar-BB16Siwt?ocid=ASUDHP

Fresh studies give more information about what treatments do or don’t work for COVID-19, with high-quality methods that give reliable results.

British researchers on Friday published their research on the only drug shown to improve survival -- a cheap steroid called dexamethasone. Two other studies found that the malaria drug hydroxychloroquine does not help people with only mild symptoms.

See also http://www.msn.com/en-gb/news/world...mune-cells/ar-BB16SzLZ?li=AAnZ9Ug&ocid=ASUDHP

 

[Amw66]

The COVID19 symptom tracker app developed by KCL is distinguishing different groups via symptoms.

Would this not be an idea for ME?

 

[rvallee]

The COVID19 symptom tracker app developed by KCL is distinguishing different groups via symptoms.

Would this not be an idea for ME?

Those groups don't appear to mean much besides making arbitrary distinctions, to the patient community anyway. When you don't ask the right questions, you will rarely get relevant answers. Too much anchoring on typical symptoms and arbitrary lines in the sand.

This is one such comment but there are a few more of the same issue:





To his credit, Spector appears to be willing to adapt:

 

[Amw66]

Those groups don't appear to mean much besides making arbitrary distinctions, to the patient community anyway. When you don't ask the right questions, you will rarely get relevant answers. Too much anchoring on typical symptoms and arbitrary lines in the sand.

This is one such comment but there are a few more of the same issue:





To his credit, Spector appears to be willing to adapt:

Thanks @rvallee . I didn't dig deep enough, but liked the potential for something along lines of decent collaboration between researchers and patients to use machine learning to dig deeper into potential subgròups.

Be interesting to see where this goes

 

[Caroline Struthers]

Merged thread

Randomized Re-Opening of Training Facilities during the COVID-19 pandemic

The train-study. Pre-print and not peer reviewed. The Norwegian institute of public health and Atle Fretheim involved. That is the guy who sent some quite interesting mails to Cochrane last year when discussing the get-saga. This seems to be a great example of questionable design and how not to do it. Hurried covid-19 research and damaging side-effects. The last thing you probably should do, is go very public and state that training in gyms are safe?


https://www.medrxiv.org/content/10.1101/2020.06.24.20138768v2

Protocol can be downloaded here
https://www.trainstudy.no/about/

Yes, Fretheim is the one who refused to allow Cochrane to withdraw the Exercise review. He led on a Norwegian schools study which was rejected (in my view quite sensibly) http://www.isrctn.com/ISRCTN44152751. Hilda Bastian who is leading the Independent Advisory Group for the update of the Cochrane exercise review commented on the gym study pre-print that she thought it was great they had done it, but they were too positive in the pre-print. She didn't criticise it as much as others. In May she Tweeted to Fretheim that she was disappointed the schools study wasn't going ahead. In my view neither the gym or the proposed schools studies are ethical.

 

[Hoopoe]

A Norwegian study found that people who worked out at gyms in Oslo in late May and early June did not contract COVID-19 infections. The discovery has received a great deal of attention and has been featured in the New York Times, Science and the Norwegian media.

The researchers behind the study are quoted as saying that it is safe to use gyms.

This is a misleading message from a flawed research project.

The experiment is flawed because none of those who trained at the gyms were infected with corona. The study therefore shows nothing else than what we already know: No infection can be transmitted if there is no infection to transmit. No research is needed to reach that conclusion. No matter what non-infected people are subjected to in an experiment, they will not infect each other.

When the researchers realized that none of their participants had COVID-19, they should have simply filed the study in the drawer. Instead, a manuscript was written up as if a randomized controlled trial experiment with an important discovery had been completed.

https://sciencenorway.no/epidemic-o...s-can-infect-each-other-with-covid-19/1713638

 

[Arnie Pye]

Title : Thyroid Function Analysis in 50 Patients with COVID-19:A Retrospective Study

Authors : Min Chen, Weibin Zhou, and Weiwei Xu

Link to full paper PDF : https://www.liebertpub.com/doi/pdfplus/10.1089/thy.2020.0363

Abstract
Background: Since the outbreak of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, it has affected >200 countries, areas, or territories in 6 continents. At present, whether COVID-19 has an effect on thyroid function is unclear. The aim of this study was to evaluate thyroid function in patients with COVID-19.

Methods: Clinical manifestations, laboratory results, and chest computed tomography scans were retrospectively reviewed for 50 patients with laboratory-confirmed COVID-19 without a history of thyroid disease who underwent thyroid function testing during their course of COVID-19 infection and after recovery. They were admitted to the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China, between January and March 2020. Healthy participants who underwent routine physical checkups and non-COVID-19 pneumonia patients with a similar degree of severity during the same period were included in the study as the control group. Thyroid hormone and thyrotropin (TSH) levels were analyzed and compared between the COVID-19 and control groups.

Results: TSH lower than the normal range was present in 56% (28/50) of the patients with COVID-19. The levels of TSH and serum total triiodothyronine (TT3) of the patients with COVID-19 were significantly lower than those of the healthy control group and non-COVID-19 pneumonia patients. The more severe the COVID-19, the lower the TSH and TT3 levels were, with statistical significance (p < 0.001). The degree of the decreases in TSH and TT3 levels was positively correlated with the severity of the disease. The total thyroxine (TT4) level of the patients with COVID-19 was not significantly different from the control group. All the patients did not receive thyroid hormone replacement therapy. After recovery, no significant differences in TSH, TT3, TT4, free triiodothyronine (fT3), and free thyroxine (fT4) levels were found between the COVID-19 and control groups.

Conclusions: The changes in serum TSH and TT3 levels may be important manifestations of the courses of COVID-19.

 

[Anna H]

Emerging need of therapeutic strategies to mitigate the complex long-term symptoms after mild to moderate COVID-19

Abstract
The widespread SARS-CoV-2 infections in many countries, including Sweden, has spurred a rise of complex and non-classical symptoms in young and middle-aged persons, without prior medical conditions. Many report long-lasting symptoms, also after the initial infection phase. Herein, we report a case of a previously healthy woman who contracted COVID-19 in March. After an initial mild infection phase, a surge of elevated and persistent symptoms occurred that also included a sudden drop in saturation and coincided with development of SARS-CoV-2-specific antibodies. The lack of guidance for symptomatic treatment for the case subject herein, along with others experiencing the same symptoms, is a problem and clinical studies are warranted for mild/moderate outpatient cared COVID-19 cases, to aid long-term symptom relief. During the post viral phase of the disease course, the patient reported treatment by both hospital and primary care physicians with over-the-counter as well as prescription medications such as N-acetylcysteine, loratadine, acetylsalicylic acid and amitriptyline along with non-pharmacological treatment.

https://www.researchgate.net/public...term_symptoms_after_mild_to_moderate_COVID-19

I personally found this very interesting because it resembles the progression of the disease for my mum. After approximately 8-9 weeks with mild symptoms she got worse and developed extreme fatigue, covid skin rashes and severe indigestion. She's also got covid toes. She's never had respiratory issues or even a fever.
This was very helpful for me to read.

I found it through this paywalled article :
https://www.dn.se/debatt/flodvag-av-langtidssjuka-covid-19-patienter-vantar/

"Covid-19 has only been known for six months and we do not yet understand all the mechanisms that control the development of the disease. There is therefore a very high risk that we will have more unpleasant surprises than the ones we have already received.

There just came rom disturbing news from Italy that many infected people who are not in the risk groups can be at great risk of never recovering from covid-19. In the Netherlands, a study was recently conducted on 1,622 covid-19 patients with long-term symptoms. The average age of these patients was 53 years and 91 percent of them had not needed hospital care during the course of the disease and thus fall into the category of "mild symptoms". Before they fell ill, 85 percent of these people were classified as healthy. One to several months after falling ill with covid-19, only 6 percent considered themselves healthy.

[...] Many are also met withddisbelief and are diagnosed with "anxiety", a diagnosis that was also mentioned in an article in DN, as a possible explanation for the patients' symptoms. We find it very difficult to attribute these types of ailments to anxiety disorders.

In anxiety disorders, hyperventilation can be a symptom that can lead to a lack of oxygen in the brain. Covid-19 patients do not hyperventilate, on the contrary, they often have difficulty breathing. However, it is completely logical and expected that some of the symptoms in patients with long-term covid-19 correspond to anxiety symptoms. Many research reports show an increased risk of blood clots, so-called venous and arterial thromboses, in covid-19 patients. Blood clots can lead to a lack of oxygen in a variety of tissues and thus cause similar symptoms as in an anxiety attack."

ETA: article
Link to full-text pdf:

 

[JaneL]

It looks like the hypothesis that SARS-CoV-2 accidentally escaped from a lab in Wuhan is still on the cards...

A Proposed Origin for SARS-CoV-2 and the Covid-19 Pandemic
by Jonathan Latham, PhD and Allison Wilson, PhD

In all the discussions of the origin of the COVID-19 pandemic, enormous scientific attention has been paid to the molecular character of the SARS-CoV-2 virus, including its novel genome sequence in comparison with its near relatives. In stark contrast, virtually no attention has been paid to the physical provenance of those nearest genetic relatives, its presumptive ancestors, which are two viral sequences named BtCoV/4991 and RaTG13.

This neglect is surprising because their provenance is more than interesting. BtCoV/4991 and RaTG13 were collected from a mineshaft in Yunnan province, China, in 2012/2013 by researchers from the lab of Zheng-li Shi at the Wuhan Institute of Virology (WIV). Very shortly before, in the spring of 2012, six miners working in the mine had contracted a mysterious illness and three of them had died (Wu et al., 2014). The specifics of this mystery disease have been virtually forgotten; however, they are described in a Chinese Master’s thesis written in 2013 by a doctor who supervised their treatment.

We arranged to have this Master’s thesis translated into English. The evidence it contains has led us to reconsider everything we thought we knew about the origins of the COVID-19 pandemic. It has also led us to theorise a plausible route by which an apparently isolated disease outbreak in a mine in 2012 led to a global pandemic in 2019.

The origin of SARS-CoV-2 that we propose below is based on the case histories of these miners and their hospital treatment. This simple theory accounts for all the key features of the novel SARS-CoV-2 virus, including ones that have puzzled virologists since the outbreak began.

The theory can account for the origin of the polybasic furin cleavage site, which is a region of the viral spike protein that makes it susceptible to cleavage by the host enzyme furin and which greatly enhances viral spread in the body. This furin site is novel to SARS-CoV-2 compared to its near relatives (Coutard, et al., 2020). The theory also explains the exceptional affinity of the virus spike protein for human receptors, which has also surprised virologists (Letko et al., 2020; Piplani et al, 2020; Wrapp et al., 2020; Walls et al., 2020). The theory further explains why the virus has barely evolved since the pandemic began, which is also a deeply puzzling aspect of a virus supposedly new to humans (Zhan et al., 2020; van Dorp et al., 2020; Chaw et al., 2020). Lastly, the theory neatly explains why SARS-CoV-2 targets the lungs, which is unusual for a coronavirus (Huang et al., 2020).

We do not propose a specifically genetically engineered or biowarfare origin for the virus but the theory does propose an essential causative role in the pandemic for scientific research carried out by the laboratory of Zheng-li Shi at the WIV; thus also explaining Wuhan as the location of the epicentre.

The media, normally so enamoured of controversy, has largely declined even to debate the possibility of a laboratory escape. Many news sites have simply labelled it a conspiracy theory.

The principal reason for media dismissals of the lab origin possibility is a review paper in Nature Medicine (Andersen et al., 2020). Although by Jun 29 2020 this review had almost 700 citations it also has major scientific shortcomings. These flaws are worth understanding in their own right but they are also useful background for understanding the implications of the Master’s thesis.

In the article the authors explain the flaws of the Andersen paper (which was posted earlier in this thread) as well as give a detailed description of their own hypothesis.

https://jonathanlatham.net/a-proposed-origin-for-sars-cov-2-and-the-covid-19-pandemic/

(Edit: typo)

 

[Leila]

About post Covid, no mentioning of "ME" or "CFS" though so I post it here

Over half of coronavirus patients in Spain have developed neurological problems, studies show
New research indicates that Covid-19 is causing a wide range of disorders in the nervous system and may be directly attacking the brain

"For Segura, finding the endothelial cells (the thin layer of cells that line the interior surface of blood vessels) in the samples of analyzed brain tissue could indicate that the coronavirus has overcome the blood-brain barrier, and that the neurological problems have not been caused by weakness from the immune system’s response to Covid-19. According to Segura, the world is facing “a respiratory virus that is also neurotoxic.”"

 

[Wits_End]

There was an interesting report on the BBC 10 o'clock news tonight to the effect that scientists are rather clearer now about the risk factors caused by Covid-19, such as gender, ethnicity, job, pre-existing conditions and so on, and that they've created a "Covid score" system, whereby you use your age as a starting point and then add and subtract points according to which risk factors apply to you. I suspect that it's not quite as straightforward at the report made it sound, but it did sound as though it might be a useful starting point.

 

[rvallee]

 

[Trish]

BBC News:
Coronavirus vaccine: UK government signs deals for 90 million doses
https://www.bbc.co.uk/news/health-53469269

The UK government has signed deals for 90 million doses of promising coronavirus vaccines that are being developed.

The vaccines are being researched by an alliance between the pharmaceutical companies BioNtech and Pfizer as well as the firm Valneva.

The new deal is on top of 100 million doses of the Oxford University vaccine being developed by AstraZeneca.

However, it is still uncertain which of the experimental vaccines may work.

A vaccine is widely seen as the best chance of getting our lives back to normal. [...]

Meanwhile, the government is hoping to get half a million people to sign up to trials of vaccines in the UK through the NHS Covid-19 vaccine research registry website.

At least eight large scale coronavirus vaccine trials are expected to take place in the UK.

I have just heard an item on the 1pm BBC Radio 4 news suggesting a vaccine could be available as early as October - if the trial starting in August shows it is effective.

 

[MEMarge]

https://www.bbc.co.uk/news/health-53467022

Stephen Holgate is a co-founder of Synairgen. They originally developed this for asthma and COPD etc

"The treatment from Southampton-based biotech Synairgen uses a protein called interferon beta which the body produces when it gets a viral infection."

"The initial findings suggest the treatment cut the odds of a Covid-19 patient in hospital developing severe disease - such as requiring ventilation - by 79%"