Covid-19: Razvoj vakcine, imunitet i primena medikamenata

[Ayatollah]

U toku je 301 kliničko istraživanje vezano za Covid-19 (podaci od pre nedelju dana):

 

[mustang]

najs... samo da ne odustanu ako ovo uskroo prodje  kao sa prethodnim (sars, mers)

[kud u maglu Simoviću]

@pt 2.0 ovi elisa testovi što ćemo mi^tm da pravimo

jel to nešto tipa videla žaba da se konj potkiva ili nešto validno

 

gledam neku ignjtovićku na tv što objašnjava slučaj

Edited April 13, 2020 by kud u maglu Simoviću

[vememah]

Opinion

 

Who Is Immune to the Coronavirus?

 

About this question, too, decisions with great consequences are being made, as they must be, based on only glimmers of data.

 

By Marc Lipsitch
Marc Lipsitch (@mlipsitch) is Professor in the Departments of Epidemiology and Immunology and Infectious Diseases at Harvard T.H. Chan School of Public Health, where he also directs the Center for Communicable Disease Dynamics.

 

April 13, 2020

 

 

Among the many uncertainties that remain about Covid-19 is how the human immune system responds to infection and what that means for the spread of the disease. Immunity after any infection can range from lifelong and complete to nearly nonexistent. So far, however, only the first glimmers of data are available about immunity to SARS-CoV-2, the coronavirus that causes Covid-19.

What can scientists, and the decision makers who rely on science to inform policies, do in such a situation? The best approach is to construct a conceptual model — a set of assumptions about how immunity might work — based on current knowledge of the immune system and information about related viruses, and then identify how each aspect of that model might be wrong, how one would know and what the implications would be. Next, scientists should set out to work to improve this understanding with observation and experiment.

The ideal scenario — once infected, a person is completely immune for life — is correct for a number of infections. The Danish physician Peter Panum famously figured this out for measles when he visited the Faroe Islands (between Scotland and Iceland) during an outbreak in 1846 and found that residents over 65 who had been alive during a previous outbreak in 1781 were protected. This striking observation helped launch the fields of immunology and epidemiology — and ever since, as in many other disciplines, the scientific community has learned that often things are more complicated.

One example of “more complicated” is immunity to coronaviruses, a large group of viruses that sometimes jump from animal hosts to humans: SARS-CoV-2 is the third major coronavirus epidemic to affect humans in recent times, after the SARS outbreak of 2002-3 and the MERS outbreak that started in 2012.

Much of our understanding of coronavirus immunity comes not from SARS or MERS, which have infected comparatively small numbers of people, but from the coronaviruses that spread every year causing respiratory infections ranging from a common cold to pneumonia. In two separate studies, researchers infected human volunteers with a seasonal coronavirus and about a year later inoculated them with the same or a similar virus to observe whether they had acquired immunity.

In the first study, researchers selected 18 volunteers who developed colds after they were inoculated — or “challenged,” as the term goes — with one strain of coronavirus in 1977 or 1978. Six of the subjects were re-challenged a year later with the same strain, and none was infected, presumably thanks to protection acquired with their immune response to the first infection. The other 12 volunteers were exposed to a slightly different strain of coronavirus a year later, and their protection to that was only partial.

In another study published in 1990, 15 volunteers were inoculated with a coronavirus; 10 were infected. Fourteen returned for another inoculation with the same strain a year later: They displayed less severe symptoms and their bodies produced less of the virus than after the initial challenge, especially those who had shown a strong immune response the first time around.

No such human-challenge experiments have been conducted to study immunity to SARS and MERS. But measurements of antibodies in the blood of people who have survived those infections suggest that these defenses persist for some time: two years for SARS, according to one study, and almost three years for MERS, according to another one. However, the neutralizing ability of these antibodies — a measure of how well they inhibit virus replication — was already declining during the study periods.

These studies form the basis for an educated guess at what might happen with Covid-19 patients. After being infected with SARS-CoV-2, most individuals will have an immune response, some better than others. That response, it may be assumed, will offer some protection over the medium term — at least a year — and then its effectiveness might decline.

Other evidence supports this model. A recent peer-reviewed study led by a team from Erasmus University, in the Netherlands, published data from 12 patients showing that they had developed antibodies after infection with SARS-CoV-2. Several of my colleagues and students and I have statistically analyzed thousands of seasonal coronavirus cases in the United States and used a mathematical model to infer that immunity over a year or so is likely for the two seasonal coronaviruses most closely related to SARS-CoV-2 — an indication perhaps of how immunity to SARS-CoV-2 itself might also behave.

If it is true that infection creates immunity in most or all individuals and that the protection lasts a year or more, then the infection of increasing numbers of people in any given population will lead to the buildup of so-called herd immunity. As more and more people become immune to the virus, an infected individual has less and less chance of coming into contact with a person susceptible to infection. Eventually, herd immunity becomes pervasive enough that an infected person on average infects less than one other person; at that point, the number of cases starts to go down. If herd immunity is widespread enough, then even in the absence of measures designed to slow transmission, the virus will be contained — at least until immunity wanes or enough new people susceptible to infection are born.

 

At the moment, cases of Covid-19 have been undercounted because of limited testing — perhaps by a factor of 10 in some places, like Italy as of late last month. If the undercounting is around this level in other countries as well, then a majority of the population in much (if not all) of the world still is susceptible to infection, and herd immunity is a minor phenomenon right now. The long-term control of the virus depends on getting a majority of people to become immune, through infection and recovery or through vaccination — how large a majority depends on yet other parameters of the infection that remain unknown.

One concern has to do with the possibility of reinfection. South Korea’s Centers for Disease Control and Prevention recently reported that 91 patients who had been infected with SARS-CoV-2 and then tested negative for the virus later tested positive again. If some of these cases were indeed reinfections, they would cast doubt on the strength of the immunity the patients had developed.

An alternative possibility, which many scientists think is more likely, is that these patients had a false negative test in the middle of an ongoing infection, or that the infection had temporarily subsided and then re-emerged. South Korea’s C.D.C. is now working to assess the merit of all these explanations. As with other diseases for which it can be difficult to distinguish a new infection from a new flare-up of an old infection — like tuberculosis — the issue might be resolved by comparing the viral genome sequence from the first and the second periods of infection.

For now, it is reasonable to assume that only a minority of the world’s population is immune to SARS-CoV-19, even in hard-hit areas. How could this tentative picture evolve as better data come in? Early hints suggest that it could change in either direction.

It is possible that many more cases of Covid-19 have occurred than have been reported, even after accounting for limited testing. One recent study (not yet peer-reviewed) suggests that rather than, say, 10 times the number of detected cases, the United States may really have more like 100, or even 1,000, times the official number. This estimate is an indirect inference from statistical correlations. In emergencies, such indirect assessments can be early evidence of an important finding — or statistical flukes. But if this one is correct, then herd immunity to SARS-CoV-19 could be building faster than the commonly reported figures suggest.

Then again, another recent study (also not yet peer-reviewed) suggests that not every case of infection may be contributing to herd immunity. Of 175 Chinese patients with mild symptoms of Covid-19, 70 percent developed strong antibody responses, but about 25 percent developed a low response and about 5 percent developed no detectable response at all. Mild illness, in other words, might not always build up protection. Similarly, it will be important to study the immune responses of people with asymptomatic cases of SARS-CoV-2 infection to determine whether symptoms, and their severity, predict whether a person becomes immune.

The balance between these uncertainties will become clearer when more serologic surveys, or blood tests for antibodies, are conducted on large numbers of people. Such studies are beginning and should show results soon. Of course, much will depend on how sensitive and specific the various tests are: how well they spot SARS-CoV-2 antibodies when those are present and if they can avoid spurious signals from antibodies to related viruses.

Even more challenging will be understanding what an immune response means for an individual’s risk of getting reinfected and their contagiousness to others. Based on the volunteer experiments with seasonal coronaviruses and the antibody-persistence studies for SARS and MERS, one might expect a strong immune response to SARS-CoV-2 to protect completely against reinfection and a weaker one to protect against severe infection and so still slow the virus’s spread.

But designing valid epidemiologic studies to figure all of this out is not easy — many scientists, including several teams of which I’m a part — are working on the issue right now. One difficulty is that people with a prior infection might differ from people who haven’t yet been infected in many other ways that could alter their future risk of infection. Parsing the role of prior exposure from other risk factors is an example of the classic problem epidemiologists call “confounding” — and it is made maddeningly harder today by the fast-changing conditions of the still-spreading SARS-CoV-19 pandemic.

And yet getting a handle on this fast is extremely important: not only to estimate the extent of herd immunity, but also to figure out whether some people can re-enter society safely, without becoming infected again or serving as a vector, and spreading the virus to others. Central to this effort will be figuring out how long protection lasts.

With time, other aspects of immunity will become clearer as well. Experimental and statistical evidence suggests that infection with one coronavirus can offer some degree of immunity against distinct but related coronaviruses. Whether some people are at greater or lesser risk of infection with SARS-CoV-2 because of a prior history of exposure to coronaviruses is an open question.

And then there is the question of immune enhancement: Through a variety of mechanisms, immunity to a coronavirus can in some instances exacerbate an infection rather than prevent or mitigate it. This troublesome phenomenon is best known in another group of viruses, the flaviviruses, and may explain why administering a vaccine against dengue fever, a flavivirus infection, can sometimes make the disease worse.

Such mechanisms are still being studied for coronaviruses, but concern that they might be at play is one of the obstacles that have slowed the development of experimental vaccines against SARS and MERS. Guarding against enhancement will also be one of the biggest challenges facing scientists trying to develop vaccines for Covid-19. The good news is that research on SARS and MERS has begun to clarify how enhancement works, suggesting ways around it, and an extraordinary range of efforts is underway to find a vaccine for Covid-19, using multiple approaches.

More science on almost every aspect of this new virus is needed, but in this pandemic, as with previous ones, decisions with great consequences must be made before definitive data are in. Given this urgency, the traditional scientific method — formulating informed hypotheses and testing them by experiments and careful epidemiology — is hyper-accelerated. Given the public’s attention, that work is unusually on display. In these difficult circumstances, I can only hope that this article will seem out of date very shortly — as much more is soon discovered about the coronavirus than is known right now.

https://www.nytimes.com/2020/04/13/opinion/coronavirus-immunity.html

Edited April 13, 2020 by vememah

[pt 2.0]

1 hour ago, kud u maglu Simoviću said:

@pt 2.0 ovi elisa testovi što ćemo mi^tm da pravimo

jel to nešto tipa videla žaba da se konj potkiva ili nešto validno

 

gledam neku ignjtovićku na tv što objašnjava slučaj

Ne znam o tome ništa stvarno.

Niti sam stručna da procenim.

[kud u maglu Simoviću]

on. tnx

nešto sam permutovao da možda imaš neki info više

[pt 2.0]

1 hour ago, kud u maglu Simoviću said:

on. tnx

nešto sam permutovao da možda imaš neki info više

O tome nemam.

[vememah]

Quote

 

China begins phase-II clinical trial of Covid-19 vaccine in Wuhan

Updated : April 13, 2020 11:28 PM IST

 

Chinese scientists have started the second phase of a clinical trial of a vaccine for coronavirus at the country's epicentre Wuhan as the global race to develop a drug to curb the pandemic intensified.

The vaccine, developed by the Institute of Biotechnology, Academy of Military Medical Sciences of China for the novel coronavirus has entered Phase II of a human clinical trial on Sunday with 500 volunteer participants, state-run China Daily reported on Monday.

The eldest volunteer is 84-year-old Wuhan resident Xiong Zhengxing, who completed the vaccination on Monday morning, accompanied by his daughter.

The vaccine is developed by genetic engineering methods and is used to prevent diseases caused by novel coronavirus infections, the report said.

The first phase of the vaccine clinical trial focused on its safety, while the second phase weighs more on its efficacy. Unlike the first phase, the second phase recruited more participants and introduced a placebo control group.

Volunteer recruitment for the vaccine began on Thursday. It is China's first candidate for the virus that entered clinical human testing. The Phase I trial was conducted in March.

Following the outbreak of Covid-19, many other Chinese institutes are also stepping up efforts to develop vaccines for the disease.

China has stepped up the process to finalise vaccines to counter Covid-19 after Kaiser Permanente research facility in Seattle and Washington stole the march and began human trials.

There is a global race to develop the vaccine. India's Serum Institute of India and Bharat Biotech lab too are developing the vaccine besides Australia and the UK.

Currently, there are no effective drugs for the deadly disease, although several candidate drugs are in clinical trials.

Scientists say China may have a head start on the development of the vaccine as it was the first to map out the genome sequence of the novel coronavirus as the virus surfaced in Wuhan in December last year. China subsequently shared the sequence with the WHO, the US and other countries, setting off the race to develop the vaccine.

 

https://www.cnbctv18.com/healthcare/china-begins-phase-ii-clinical-trial-of-covid-19-vaccine-in-wuhan-5682301.htm?fbclid=IwAR3gAs7VhbTqgN4NRCy5-oEZdWVxyiVYuT1k7P9wmZf4DEufzeffuJezMl0

[borris_]

 

Quote

 

The fight against the COVID-19 epidemic has involved the exploration of numerous therapeutic pathways, which have given rise to research in vitro and in vivo. However, practitioners around the world did not wait for the results of this research to use what appeared to them to be the most adequate treatment (1). This implicates the need of being quick in carrying out research and then disseminating the results to doctors confronted with the epidemic in the field, to guide their therapeutic management of patients.

The use of potential treatments on patients makes it possible to produce data, which can then be used in research. In the scientific community, conducting randomized double-blind clinical trials has become the gold standard for validating the effectiveness of a treatment. However, when the urgency is to treat life-threatened patients, it is unethical to give them a placebo when the state of the art gives the doctor the intimate conviction that the risk-benefit balance is in favor of the administration of the treatment that he wishes to experience. We must therefore not forget that single-arm studies, without randomization, can be just as convincing as randomized studies.

Two elements appear crucial to us for a study carried out without randomization to be significant. First, it must study clearly identified endpoints. For COVID19, we identify three: mortality, transition to intensive care, and viral load. It must also be comparative. The study needs to compare the results following the use of a treatment to a series of historical results, or to a series of results in other health care centers.

Today, 5 therapeutic pathways are emerging to fight against the coronavirus epidemic and are the subject of clinical trials worldwide: chloroquine / hydroxychloroquine, hydroxychloroquine combined with azithromycin, lopinavir / ritonavir (kaletra), remdesivir and the use of plasma from patients with COVID-19 infection. We propose to review the results published on the subject of these 5 therapeutic pathways.

Concerning chloroquine/hydroxychloroquine alone, the results of three studies have been published: one in France involving 24 patients and concluding to the effectiveness of the treatment (2), and two in China, the first not concluding to be effective following the experiment on 15 patients with control group (3), the second having concluded that hydroxychloroquine is effective following an experiment on 31 patients with control group (4). Two limits in these studies limit knowledge today. First, these studies report neither the same duration of treatment, nor the same dosage. Then, the two Chinese studies do not give details concerning the other treatments used within the framework of the protocol. The in vitro results show an effectiveness of chloroquine and hydroxychloroquine (5).

Regarding the use of the hydroxychloroquine + azithromycin combination, our team published observational studies, the first relating to 80 patients (6), the second relating to 1061 patients (7). Both conclude that this treatment is effective for the three endpoints defined above. Our points of comparison are, concerning the duration of viral carriage, Chinese studies on the natural history of the disease (8), and concerning the clinical aspects, studies carried out in Marseille in services not using this prescription.

Regarding kaletra, a comparative study with two arms concluded that it was ineffective (9). Its effectiveness in vitro remains to be demonstrated.

Regarding remdesivir, an interesting study funded by Gilead was published in the New England Journal of Medicine (10). It only allows concluding that the remdesivir is extremely toxic to the patients to whom it was administered (60% of serious side effects). While it is encouraging to see that serious teams, like the one who wrote this article, understand that it is unethical to give a placebo to a life-threatening patient, it should not imply that to forget that a study that includes neither end-point nor comparison, cannot allow to conclude anything.

The use of plasma is a theoretically interesting idea. However, only two studies without end point or comparison have been published to date (11-12). Scientifically, this solution poses a problem because the use of plasma is difficult to envisage in non-serious forms of the disease. In severe forms, the problem is not virological but immune.

In view of these data from the literature, IHU doctors have made the decision to continue the treatment of patients with COVID19 with a hydroxychloroquine+azithromycin protocol.

 

Yanis Roussel, Didier Raoult

 

https://www.mediterranee-infection.com/actualite-du-traitement/

[goofs]

25 minutes ago, Host said:

U medjuvremenu je Raoult napravio siru studiju. Ovog puta je objavio samo abstrakt sa dosta snalazljivom interpretacijom rezultata. Tvrdi da je smrtnost u grupi tretiranoj chloroquinom 0.5%, medjutim zavrsio je studiju pre poznatog ishoda za jos 2% pacijenata koji su zaglavili na respiratoru duze od 10 dana (sto su pacijenti sa vrlo losom prognozom). 

 

Sto znaci da je smrtnost izmedju 0.5% i 2.5%, sto je otprilike jednako smrtnosti i grupacije koja nije tretirana chloroquinom. 

 

Tako sam mogao i ja da izadjem i da kazem - "Virus je opasan, mozda cete umreti, a mozda i necete" 

[TdEII]

 Tako nekako. I uslut je ozbiljno zajebao i neke kliničke studije: "Discovery, a randomized trial launched in at least seven European countries to study the efficacy of hydroxychloroquine and several other treatments, is struggling to recruit participants in France, says Jean-François Bergmann, a former head of infectious disease at the Saint Louis Hospital in Paris. (Macron has met with Discovery’s leaders as well.) “In some hospitals, four out of five patients are declining to take part and refuse any treatment but hydroxychloroquine,” Bergmann says, adding that France is witnessing a form of “medical populism” that is “slowing the emergence of the truth.”

 

Is France’s president fueling the hype over an unproven coronavirus treatment?

Edited April 15, 2020 by TdEII
Dodat link

[mackenzie]

Quote

We recorded 52 patients (AS-7, EU-21, AF-3, NA-14, SA-7) who received Ivermectin (150 mcg/Kg) once after mechanical ventilation was instituted.

Compared to 1,918 conventionally treated patients we observed a survival benefit for ivermectin (mortality rate 18.6% vs 7.7%; HR 0.18, 95% CI (0.07-0.48), log rank (Mantel-Cox) p<0.001). The hospital length of stay was 15.7 +/- 8.1 days vs 10.9 +/- 6.1 days, p<0.001 and intensive care unit length of stay 8.2 +/- 6.2 days vs 6.0 +/- 3.9 days, p<0.001 respectively.

https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3570270

[3opge]

https://www.msn.com/en-us/money/topstocks/gilead-stock-surges-15percent-after-report-says-coronavirus-drug-trial-shows-encouraging-early-results/ar-BB12KfxA

 

Gilead stock surges 15% after report says coronavirus drug trial shows encouraging early results

Gilead Sciences shares surged by more than 15% in after-hours trading Thursday after details leaked of a closely watched clinical trial of the company’s antiviral drug Remdesivir, showing what appears to be promising results in treating Covid-19.

The University of Chicago’s phase 3 drug trial found that most of its patients had “rapid recoveries in fever and respiratory symptoms” and were discharged in less than a week, health-care publication STAT News reported.

“The best news is that most of our patients have already been discharged, which is great. We’ve only had two patients perish,” University of Chicago infectious disease specialist Kathleen Mullane said, according to STAT News, which obtained a video of her remarks.

Gilead didn’t immediately respond to a request for comment.

The University of Chicago Medicine recruited 125 patients with the virus into Gilead’s two late-stage clinical trials, 113 of whom were severely ill. Gilead intends to enroll 4,000 people in its trials.

 

 

Edited April 17, 2020 by 3opge

[Kelt]

donacija plazme

 

nisam do sad zapazio da imamo nekog na forumu ko je imao virus (nadam se da će tako i da ostane)

[halloween]

1 hour ago, Kelt said:

donacija plazme

 

nisam do sad zapazio da imamo nekog na forumu ko je imao virus (nadam se da će tako i da ostane)

 

Čudno je da se ova vest pojavila po novinama, tabloidima, a nije na sajtu covid19.rs. Pozivamo sve da nam se jave, kaže premijerka, to je ta kampanja, a nigde procedure ko kome da se javi- kojim "nama", njoj, koje kategorije oni što misle da su preležali, oni koji su ležali pa ih otpustili? Ništa ovo nije ozbiljno.

Edited April 17, 2020 by halloween