quote:

SARS-CoV-2, voorheen bekend als 2019-nCoV, is een virus dat de besmettelijke luchtwegaandoening COVID-19 bij mensen veroorzaakt.SARS-CoV-2 is een virus-stam uit het geslacht betacoronavirussen uit de onderfamilie van coronavirussen.

SPOILER

SPOILER

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Op dinsdag 17 maart 2020 17:03 schreef Kyran het volgende:
Goed idee. Alleen denk ik dat er te weinig peer reviewed artikelen zullen zijn de komende tijd. Misschien uitbreiden naar ook niet peer reviewed artikelen?

Gewoon een idee

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Fosun Pharma and BioNTech form COVID-19 vaccine strategic alliance in China

(15 March 2020, Shanghai, Hong Kong) – Today, Fosun Pharma industrial, a subsidiary company of Shanghai Fosun Pharmaceutical (Group) Co., Ltd (“Fosun Pharma” or “the Group”; Stock Code: 600196.SH, 02196.HK) and BioNTech SE (NASDAQ: BNTX, “BioNTech” or “the Company”) announced a strategic development and commercialization collaboration to advance BioNTech’s mRNA vaccine in China for the prevention of COVID-19 infections.

Under the terms of the agreement, the two Companies will work jointly on the development of COVID-19 vaccines based on BioNTech’s mRNA technology platform in China. The Companies will collaborate to conduct clinical trials in China leveraging Fosun Pharma’s extensive clinical development, regulatory, and commercial capabilities in the country. BioNTech will supply the mRNA vaccine for clinical trials from GMP manufacturing facilities in Europe.

mRNA is a nucleic acid molecule that carries genetic information. The mRNA vaccine introduces the genetic information into the body, so that the cells in the body produce the corresponding antigen, which induces the body to produce neutralizing antibodies and stimulates the response of T cells, and fights against the virus through the dual mechanisms of humoral immunity and cellular immunity. In the face of a sudden epidemic, compared with traditional vaccines, synthesis and production process of mRNA vaccine is more convenient, and has strong immunogenicity, which does not need additional adjuvant as needed by the traditional vaccine, and with good safety.

BioNTech is a leading mRNA technology company that has diversified mRNA platform technologies, integrated R&D system and strong manufacturing capability. “The mRNA technology introduces genetic information into human body, then the body's own cells produce the corresponding proteins that cure or prevent disease. Fosun Pharma R&D has been tracking the development of this technology. The two companies expect further cooperation in this field,” says Dr. Aimin Hui, President of Fosun Pharma Global R&D.

“We see this collaboration as an important step in our global effort to expedite the development of mRNA vaccines to prevent COVID-19 infection. Fosun Pharma shares our commitment to move rapidly to address the COVID-19 outbreak and brings deep development experience and an extensive network in the pharmaceutical market in China,” says Founder and CEO of BioNTech, Ugur Sahin, M.D.

Wu Yifang, President and CEO of Fosun Pharma states, “A potential pandemic requires a collective effort and both companies are passionate about contributing to the fight against the current coronavirus outbreak. We are excited to collaborate with BioNTech, one of the leading companies worldwide in the mRNA field. Our shared objective is to develop a vaccine against the coronavirus and to be able to rapidly manufacture a vaccine to turn the tide of COVID-19 infection.”

Under the terms of the agreement, Fosun Pharma will pay BioNTech up to $85 million in licensing fees (including a down payment, clinical development registration and sales milestone payments) as agreed, and a sales commission equal to 35% of the product's annual gross profit during the agreed sales commission period. Meanwhile, Fosun Pharma has agreed to make an equity investment of USD 50 million (EUR 44 million) for 1,580,777 ordinary shares in BioNTech.

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Op dinsdag 17 maart 2020 19:42 schreef merdobach het volgende:
Is al bekend welke onderzoeken het rivm gebruikt?

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Op dinsdag 17 maart 2020 19:34 schreef Momo het volgende:
Ook even hier een linkje naar het topic van @:_I over de verschillende mutaties van Corona virus die nu in de wereld rond gaan. Zo kun je bijvoorbeeld zien dat het Corona virus dat nu vooral actief in de VS vooral uit Azië komt en niet uit Europa. De varianten die je vooral in Nederland vind zijn afkomstig uit Noord-Italië.

Nextstrain

En de website waar dat op staat:
https://nextstrain.org/ncov?c=country&f_country=Japan,USA,China&l=radial

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Op dinsdag 17 maart 2020 20:33 schreef Breekfast het volgende:

[..]

Ik heb geen verstand van het verloop van mutaties bij virussen. Maar is er ook al iets te zeggen of de verschillende aftakkingen zich anders (bijvoorbeeld agressiever of milder) gedragen? Of is het daar nog te vroeg voor? Of zijn de mutaties die in zo'n korte periode optreden überhaupt niet significant genoeg?

Als je naar de sterftecijfers in Italië kijkt dan zou je bijna denken dat daar een meer agressieve variant heerst. Maar dat kan ook hele andere oorzaken hebben (gemiddelde leeftijd van de geïnfecteerden, worden alle besmettingen vastgesteld/geregistreerd, enzovoort).

SPOILER

It is improbable that SARS-CoV-2 emerged through laboratory manipulation of a related SARS-CoV-like coronavirus. As noted above, the RBD of SARS-CoV-2 is optimized for binding to human ACE2 with an efficient solution different from those previously predicted7,11. Furthermore, if genetic manipulation had been performed, one of the several reverse-genetic systems available for betacoronaviruses would probably have been used19. However, the genetic data irrefutably show that SARS-CoV-2 is not derived from any previously used virus backbone20. Instead, we propose two scenarios that can plausibly explain the origin of SARS-CoV-2: natural selection in an animal host before zoonotic transfer; and (ii) natural selection in humans following zoonotic transfer. We also discuss whether selection during passage could have given rise to SARS-CoV-2.

1. Natural selection in an animal host before zoonotic transfer
As many early cases of COVID-19 were linked to the Huanan market in Wuhan1,2, it is possible that an animal source was present at this location. Given the similarity of SARS-CoV-2 to bat SARS-CoV-like coronaviruses2, it is likely that bats serve as reservoir hosts for its progenitor. Although RaTG13, sampled from a Rhinolophus affinis bat1, is ~96% identical overall to SARS-CoV-2, its spike diverges in the RBD, which suggests that it may not bind efficiently to human ACE27 (Fig. 1a).

Malayan pangolins (Manis javanica) illegally imported into Guangdong province contain coronaviruses similar to SARS-CoV-221. Although the RaTG13 bat virus remains the closest to SARS-CoV-2 across the genome1, some pangolin coronaviruses exhibit strong similarity to SARS-CoV-2 in the RBD, including all six key RBD residues21 (Fig. 1). This clearly shows that the SARS-CoV-2 spike protein optimized for binding to human-like ACE2 is the result of natural selection.

Neither the bat betacoronaviruses nor the pangolin betacoronaviruses sampled thus far have polybasic cleavage sites. Although no animal coronavirus has been identified that is sufficiently similar to have served as the direct progenitor of SARS-CoV-2, the diversity of coronaviruses in bats and other species is massively undersampled. Mutations, insertions and deletions can occur near the S1–S2 junction of coronaviruses22, which shows that the polybasic cleavage site can arise by a natural evolutionary process. For a precursor virus to acquire both the polybasic cleavage site and mutations in the spike protein suitable for binding to human ACE2, an animal host would probably have to have a high population density (to allow natural selection to proceed efficiently) and an ACE2-encoding gene that is similar to the human ortholog.

2. Natural selection in humans following zoonotic transfer
It is possible that a progenitor of SARS-CoV-2 jumped into humans, acquiring the genomic features described above through adaptation during undetected human-to-human transmission. Once acquired, these adaptations would enable the pandemic to take off and produce a sufficiently large cluster of cases to trigger the surveillance system that detected it1,2.

All SARS-CoV-2 genomes sequenced so far have the genomic features described above and are thus derived from a common ancestor that had them too. The presence in pangolins of an RBD very similar to that of SARS-CoV-2 means that we can infer this was also probably in the virus that jumped to humans. This leaves the insertion of polybasic cleavage site to occur during human-to-human transmission.

Estimates of the timing of the most recent common ancestor of SARS-CoV-2 made with current sequence data point to emergence of the virus in late November 2019 to early December 201923, compatible with the earliest retrospectively confirmed cases24. Hence, this scenario presumes a period of unrecognized transmission in humans between the initial zoonotic event and the acquisition of the polybasic cleavage site. Sufficient opportunity could have arisen if there had been many prior zoonotic events that produced short chains of human-to-human transmission over an extended period. This is essentially the situation for MERS-CoV, for which all human cases are the result of repeated jumps of the virus from dromedary camels, producing single infections or short transmission chains that eventually resolve, with no adaptation to sustained transmission25.

Studies of banked human samples could provide information on whether such cryptic spread has occurred. Retrospective serological studies could also be informative, and a few such studies have been conducted showing low-level exposures to SARS-CoV-like coronaviruses in certain areas of China26. Critically, however, these studies could not have distinguished whether exposures were due to prior infections with SARS-CoV, SARS-CoV-2 or other SARS-CoV-like coronaviruses. Further serological studies should be conducted to determine the extent of prior human exposure to SARS-CoV-2.

3. Selection during passage
Basic research involving passage of bat SARS-CoV-like coronaviruses in cell culture and/or animal models has been ongoing for many years in biosafety level 2 laboratories across the world27, and there are documented instances of laboratory escapes of SARS-CoV28. We must therefore examine the possibility of an inadvertent laboratory release of SARS-CoV-2.

In theory, it is possible that SARS-CoV-2 acquired RBD mutations (Fig. 1a) during adaptation to passage in cell culture, as has been observed in studies of SARS-CoV11. The finding of SARS-CoV-like coronaviruses from pangolins with nearly identical RBDs, however, provides a much stronger and more parsimonious explanation of how SARS-CoV-2 acquired these via recombination or mutation19.

The acquisition of both the polybasic cleavage site and predicted O-linked glycans also argues against culture-based scenarios. New polybasic cleavage sites have been observed only after prolonged passage of low-pathogenicity avian influenza virus in vitro or in vivo17. Furthermore, a hypothetical generation of SARS-CoV-2 by cell culture or animal passage would have required prior isolation of a progenitor virus with very high genetic similarity, which has not been described. Subsequent generation of a polybasic cleavage site would have then required repeated passage in cell culture or animals with ACE2 receptors similar to those of humans, but such work has also not previously been described. Finally, the generation of the predicted O-linked glycans is also unlikely to have occurred due to cell-culture passage, as such features suggest the involvement of an immune system18.

Conclusions
In the midst of the global COVID-19 public-health emergency, it is reasonable to wonder why the origins of the pandemic matter. Detailed understanding of how an animal virus jumped species boundaries to infect humans so productively will help in the prevention of future zoonotic events. For example, if SARS-CoV-2 pre-adapted in another animal species, then there is the risk of future re-emergence events. In contrast, if the adaptive process occurred in humans, then even if repeated zoonotic transfers occur, they are unlikely to take off without the same series of mutations. In addition, identifying the closest viral relatives of SARS-CoV-2 circulating in animals will greatly assist studies of viral function. Indeed, the availability of the RaTG13 bat sequence helped reveal key RBD mutations and the polybasic cleavage site.

The genomic features described here may explain in part the infectiousness and transmissibility of SARS-CoV-2 in humans. Although the evidence shows that SARS-CoV-2 is not a purposefully manipulated virus, it is currently impossible to prove or disprove the other theories of its origin described here. However, since we observed all notable SARS-CoV-2 features, including the optimized RBD and polybasic cleavage site, in related coronaviruses in nature, we do not believe that any type of laboratory-based scenario is plausible.

More scientific data could swing the balance of evidence to favor one hypothesis over another. Obtaining related viral sequences from animal sources would be the most definitive way of revealing viral origins. For example, a future observation of an intermediate or fully formed polybasic cleavage site in a SARS-CoV-2-like virus from animals would lend even further support to the natural-selection hypotheses. It would also be helpful to obtain more genetic and functional data about SARS-CoV-2, including animal studies. The identification of a potential intermediate host of SARS-CoV-2, as well as sequencing of the virus from very early cases, would similarly be highly informative. Irrespective of the exact mechanisms by which SARS-CoV-2 originated via natural selection, the ongoing surveillance of pneumonia in humans and other animals is clearly of utmost importance.

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Op woensdag 18 maart 2020 10:43 schreef Momo het volgende:
Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1

A novel human coronavirus that is now named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (formerly called HCoV-19) emerged in Wuhan, China, in late 2019 and is now causing a pandemic.1 We analyzed the aerosol and surface stability of SARS-CoV-2 and compared it with SARS-CoV-1, the most closely related human coronavirus.2

We evaluated the stability of SARS-CoV-2 and SARS-CoV-1 in aerosols and on various surfaces and estimated their decay rates using a Bayesian regression model (see the Methods section in the Supplementary Appendix, available with the full text of this letter at NEJM.org). SARS-CoV-2 nCoV-WA1-2020 (MN985325.1) and SARS-CoV-1 Tor2 (AY274119.3) were the strains used. Aerosols (<5 μm) containing SARS-CoV-2 (105.25 50% tissue-culture infectious dose [TCID50] per milliliter) or SARS-CoV-1 (106.75-7.00 TCID50 per milliliter) were generated with the use of a three-jet Collison nebulizer and fed into a Goldberg drum to create an aerosolized environment. The inoculum resulted in cycle-threshold values between 20 and 22, similar to those observed in samples obtained from the upper and lower respiratory tract in humans.

Our data consisted of 10 experimental conditions involving two viruses (SARS-CoV-2 and SARS-CoV-1) in five environmental conditions (aerosols, plastic, stainless steel, copper, and cardboard). All experimental measurements are reported as means across three replicates.

SARS-CoV-2 remained viable in aerosols throughout the duration of our experiment (3 hours), with a reduction in infectious titer from 103.5 to 102.7 TCID50 per liter of air. This reduction was similar to that observed with SARS-CoV-1, from 104.3 to 103.5 TCID50 per milliliter (Figure 1A).

SARS-CoV-2 was more stable on plastic and stainless steel than on copper and cardboard, and viable virus was detected up to 72 hours after application to these surfaces (Figure 1A), although the virus titer was greatly reduced (from 103.7 to 100.6 TCID50 per milliliter of medium after 72 hours on plastic and from 103.7 to 100.6 TCID50 per milliliter after 48 hours on stainless steel). The stability kinetics of SARS-CoV-1 were similar (from 103.4 to 100.7 TCID50 per milliliter after 72 hours on plastic and from 103.6 to 100.6 TCID50 per milliliter after 48 hours on stainless steel). On copper, no viable SARS-CoV-2 was measured after 4 hours and no viable SARS-CoV-1 was measured after 8 hours. On cardboard, no viable SARS-CoV-2 was measured after 24 hours and no viable SARS-CoV-1 was measured after 8 hours (Figure 1A).

Both viruses had an exponential decay in virus titer across all experimental conditions, as indicated by a linear decrease in the log10TCID50 per liter of air or milliliter of medium over time (Figure 1B). The half-lives of SARS-CoV-2 and SARS-CoV-1 were similar in aerosols, with median estimates of approximately 1.1 to 1.2 hours and 95% credible intervals of 0.64 to 2.64 for SARS-CoV-2 and 0.78 to 2.43 for SARS-CoV-1 (Figure 1C, and Table S1 in the Supplementary Appendix). The half-lives of the two viruses were also similar on copper. On cardboard, the half-life of SARS-CoV-2 was longer than that of SARS-CoV-1. The longest viability of both viruses was on stainless steel and plastic; the estimated median half-life of SARS-CoV-2 was approximately 5.6 hours on stainless steel and 6.8 hours on plastic (Figure 1C). Estimated differences in the half-lives of the two viruses were small except for those on cardboard (Figure 1C). Individual replicate data were noticeably “noisier” (i.e., there was more variation in the experiment, resulting in a larger standard error) for cardboard than for other surfaces (Fig. S1 through S5), so we advise caution in interpreting this result.

We found that the stability of SARS-CoV-2 was similar to that of SARS-CoV-1 under the experimental circumstances tested. This indicates that differences in the epidemiologic characteristics of these viruses probably arise from other factors, including high viral loads in the upper respiratory tract and the potential for persons infected with SARS-CoV-2 to shed and transmit the virus while asymptomatic.3,4 Our results indicate that aerosol and fomite transmission of SARS-CoV-2 is plausible, since the virus can remain viable and infectious in aerosols for hours and on surfaces up to days (depending on the inoculum shed). These findings echo those with SARS-CoV-1, in which these forms of transmission were associated with nosocomial spread and super-spreading events,5 and they provide information for pandemic mitigation efforts.

[ afbeelding ]

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Op dinsdag 17 maart 2020 20:36 schreef Momo het volgende:

[..]

https://www.globaltimes.cn/content/1181612.shtml

Dat vermoeden is er wel. Waarschijnlijk wordt daar nu meer onderzoek naar gedaan.

quote:

Op donderdag 19 maart 2020 21:55 schreef Cesare-Borgia het volgende:
Ik probeer het nog één keer zo nadat mijn topic gesloten werd.
Chinees ziekenhuis heeft hun bevindingen omtrent corona virus op papier gezet. vooral gericht op medisch personeel maar heel interessant om te lezen. Zou eigenlijk onder al het personeel in ziekenhuis verspreid moeten worden.

Via onderstaande link te downloaden.

https://covid-19.alibabacloud.com

quote:

Longartsen met handen in haar: ‘Aanbevolen medicijnen hebben niet veel effect, maar wel bijwerkingen’

Longartsen zitten met hun handen in het haar omdat er geen effectieve behandeling is voor het coronavirus. In een nieuwe Nederlandse richtlijn die specialisten gisteren met elkaar bespraken, staat dat er nog onvoldoende bewijs is voor de werking van de in de richtlijn genoemde medicijnen. Sommigen richten wellicht zelfs meer schade aan dan dat ze goed doen. ,,In de praktijk zien we in Brabant tot nu toe niet veel effect van die medicijnen, maar hebben patiënten wel last van bijwerkingen.’’

De eerste behandelresultaten stemmen de voorzitter van de Nederlandse Vereniging van Artsen voor Longziekten en Tuberculose (NVALT) Leon van den Toorn treurig. ,,Wat we tot nu toe in de praktijk zien in de regio Brabant is dat de aanbevolen medicijnen niet veel effect lijken te hebben’’, verklaart Van den Toorn. ,,Maar patiënten hebben in ieder geval wel last van bijwerkingen, zoals depressieve klachten, misselijkheid en braken.’’

Hartritmestoornissen

In de databank voor bijwerkingen Lareb staat dat chloroquine naast maagdarmklachten en hoofdpijn bijvoorbeeld ook ernstige hartklachten en hartritmestoornissen kan veroorzaken. ,,Gebruik dit medicijn NIET als u deze hartritmestoornis heeft’’, klinkt het dringende advies.

Volgens de longarts, die zelf werkzaam is in het Rotterdamse Erasmus MC is het middel dat ‘in Nederland verreweg het meest geprobeerd wordt ‘chloroquine’, een medicijn dat ook gebruikt wordt om malaria te voorkomen. ,,Niet alle ziekenhuizen zijn er enthousiast over, maar de in meeste ziekenhuizen wordt het wel gegeven bij de ziekere patiënten.’’ Of er in Nederland mensen gered zijn met dat middel? ,,Zo kun je dat niet zeggen, heel veel weten we er nog niet over’’, erkent de voorman. Bovendien benadrukt hij: ,,Je weet natuurlijk ook niet wat er met die mensen was gebeurd als je het middel níet had toegepast.’’

Reageerbuisjes

Longartsen staan mede door het gebrek aan bewijs voor grote dilemma’s bij de behandeling van coronapatiënten. ,,In lekentaal komt het er simpel gezegd op neer dat de medicijnen in reageerbuisjes zijn onderzocht’’, legt Van den Toorn uit. ,,In het laboratorium zijn er aanwijzingen dat die medicijnen mogelijk iets tegen het virus doen, maar we weten nog niet of dat daadwerkelijk het geval is als je er mensen mee behandelt.’’

De voorzitter van de longartsen pleit voor gedegen onderzoek naar de medicijnen die tot nu toe geprobeerd zijn tegen het nieuwe coronavirus. Hij krijgt bijval van arts-microbioloog Marc Bonten uit het UMC Utrecht: ,,De middelen die er nu zijn moeten getest worden op twee dingen: één, of ze mensen beter maken, en twee, of ze veilig gebruikt kunnen worden. Die middelen moeten op grote schaal bij mensen gebruikt gaan worden, om te zien of ze effect hebben.’’

Testen op mensen

De Rotterdamse longarts Hans in ‘t Veen uit het Franciscus Gasthuis en Vlietland herkent de moeilijkheden. ,,Er zijn drie problemen: De medicatie is niet beschikbaar, de medicatie is vaak toxisch en we weten zelfs niet eens of het helpt.’’ Volgens hem gaat er over die richtlijn ‘zeker veel discussie’ komen. ,,Als het niet bewezen is en heel schadelijk is: moet je de vraag stellen of je de behandelingsadviezen zo nadrukkelijk kan opschrijven?’’ zo nuanceert hij de aanbeveling hardop.

Om te achterhalen of de middelen werken moeten mensen min of meer gaan functioneren als proefkonijn. Bonten: ,,Het zijn helaas echte mensen die je daarvoor nodig hebt, maar je moet die medicijnen onderzoeken. Anders weten we over een half jaar nog steeds niet wat de beste behandeling is.’’
In levensgevaar

De richtlijn beveelt specialisten aan om de omstreden middelen alleen te gebruiken bij patiënten met ‘ernstige klachten’ en als mensen in levensgevaar zijn. Gisteren spraken artsen via een videoconferentie over de richtlijn: ,,De bewijslast voor de middelen die in de richtlijn genoemd worden is helaas flinterdun’’, erkent Van den Toorn. ,,Daarom is er continue overleg, wordt van vele patiënten bijgehouden wat de behandeling is geweest en proberen we daar uiteindelijk wijzer van te worden. Ondertussen wachten we ook op de uitkomsten van studies die nog lopen. Alleen het duurt nog wel even voordat daar de resultaten van binnenkomen: dat gaat niet in een week.’’

Naast chloroquine, is er ook nog een een ander malariamedicijn ‘hydroxychloroquine’, ,,Dat lijkt op chloroquine en wordt in sommige ziekenhuizen ook toegepast’’, weet Van den Toorn. En verder is er de virusremmer ‘remdesivir’. Dit middel werd oorspronkelijk gebruikt tegen de extreem dodelijke ziekte ebola, maar viel af omdat andere middelen beter bleken te werken. In Nederland wordt het volgens Van den Toorn nog bijna niet voorgeschreven, omdat dat middel heel slecht beschikbaar is’.

Strijd zonder wapens

Zo lijken de doktoren een oneerlijke strijd te voeren tegen het nieuwe coronavirus dat in steeds meer landen om zich heen slaat. Of je dat een strijd zonder wapens kunt noemen? Van den Toorn geeft toe: ,,Tot nu toe voeren we oorlog zonder goede wapens, maar we gaan er desondanks vanuit dat we de strijd uiteindelijk gaan winnen. Bovendien knapt het overgrote deel van de patiënten op, óók zonder die medicijnen, dus dat geeft hoop.’’

quote:

• Iceland has tested 9 768 individuals for COVID-19, which translates to 26 762 per million, compared with 6 343 in South Korea and 13 999 in Bahrein
• Iceland has tested a higher proportion of inhabitants than any other country after deCode genetics started offering free screening among the general, non-symptomatic, non-quarantined population
• deCode has published the results of a total of 5 571 tests. Those have yielded 48 positive results (0.86%) indicating that the prevelance of the virus is modest among the general population.
• A total of 473 cases have been identified in Iceland since the first case on February 28th. One person with COVID-19 has died. Twelve individuals with COVID-19 are hospitalized.

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Infervision: Our AI Detects Deadly Coronavirus via CT Lung Screening

The lung cancer detection company has launched a deep learning-based coronavirus detection system in Wuhan.

Infervision (推想科技) described its coronavirus detection model as working through CT lung screening. This means that the new model detects ground-glass opacities (GGO) in the lung that may later be confirmed as one of the complications of the virus.

The firm's model has already been used by Wuhan Tongji Hospital, one of the frontline hospitals that has been fighting with the epidemic in Wuhan. It is set to be deployed in multiple other hospitals in the near future, Infervision said.

“It serves as a surrogate to PCR diagnostic as the lab capacities aren't enough to keep up with the rising number of suspected cases in the afflicted regions," added the company.

Another diagnostics solution support for the rising crisis was launched by Shenzhen-based genomics giant BGI Genomics (300676: SH) on January 28. The company's stocks opened around 10% up as the mainland's stock markets open on January 3, 2020.

“The new coronavirus may cause infections with no symptoms and sicken otherwise healthy people,” postulated the Lancet, showing how hard it is presently for hospitals in Wuhan, which are racing against time to diagnose large numbers of patients.

The new diagnostic solutions possess tremendous importance for the afflicted region, considering the symptoms of the new virus are similar to other fast-spreading diseases like flu, complicating the process and creating excess demand thanks to a large number of concerned patients who need to be assessed. "Symptomatic patients are piling up in the hospital – AI can help triage the patients quickly," said the firm. "Patients have been seen without any noticeable symptoms like fever or cough, but showing large GGOs in the lung,"

The Beijing-based private firm had long been drawing the attention of wealthy venture capitalists, including Qiming Venture Partners and Sequoia China; it has secured around USD 100 million since its inception in January 2016. The team has been adopting deep learning technology broadly in the medical imaging field.

The firm was involved in an early victory in this complex battle: for the first time since the emergence of the new virus in late 2019, the number of new suspected coronavirus cases in China started to drop, over two consecutive days, on December 31 and January 1, 2020 - mostly driven by faster diagnostic solutions. PCR diagnostics had shown that it could play a crucial role.

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Op donderdag 26 maart 2020 11:35 schreef Momo het volgende:
[ afbeelding ]
Datagraver

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Op donderdag 26 maart 2020 15:31 schreef Momo het volgende:
[ afbeelding ]

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Op dinsdag 31 maart 2020 09:48 schreef Momo het volgende:
Estimating the number of infections and the impact of non-pharmaceutical interventions on COVID-19 in 11 European countries

[ afbeelding ]

Deze is wel interessant qua geschatte deel van de bevolking dat besmet is.

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Op woensdag 8 april 2020 12:50 schreef Mondkapje het volgende:
Hoe kan Oudewater in de provincie Utrecht zo hoog scoren? Veel grote veeteeltbedrijven in de buurt soms?

OUDEWATER
Bij de tien Nederlandse gemeenten met de meeste coronapatiënten in het ziekenhuis per 100.000 inwoners staat Oudewater op plaats 6. Het is de enige Utrechtse gemeente in dit lijstje. Ook in gemeenten rond Oudewater, zoals Lopik, Montfoort, Woerden en IJsselstein, zijn relatief meer inwoners in het ziekenhuis opgenomen met corona.
https://www.rtvutrecht.nl(...)ekenhuisopnames.html

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Op woensdag 8 april 2020 12:51 schreef Momo het volgende:

[..]

Kun je dit even in een ander topic posten?

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Op woensdag 8 april 2020 13:37 schreef Mondkapje het volgende:

[..]

Dit gaat over statistieken toch?

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Op woensdag 8 april 2020 10:39 schreef Momo het volgende:
Waarom Europeanen misschien harder getroffen worden door het virus, nog niet peer reviewed maar wel geschikt voor hier.

ACE2 variants underlie interindividual variability and susceptibility to COVID-19 in Italian population

quote:

The temporal association of introducing and lifting non-pharmaceutical interventions with the time-varying reproduction number (R) of SARS-CoV-2: a modelling study across 131 countries

Research in context
Evidence before this study
The time-varying reproduction number (R; also known as Rt), defined by the expected number of secondary cases arising from a primary case infected at time t, is a metric that describes viral transmission at the population level. An R value above 1 indicates a growing outbreak, and an R value below 1 indicates a shrinking outbreak. We searched PubMed, medRxiv, and bioRxiv for studies that reported the effects of introducing and lifting non-pharmaceutical interventions (NPIs) on R of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) published between Jan 1 and Aug 5, 2020, using the keywords “COVID-19”, “SARS-CoV-2”, “intervention”, and “transmission”. No language restriction was applied. Studies in China, Hong Kong, South Korea, Singapore, and many European countries showed that several NPIs, including school closure, physical distancing, and lockdown, could reduce R substantially to near or below 1. However, little is known about the effects on R following the relaxation of these NPIs.
Added value of this study
To the best of our knowledge, this study is the first to explicitly quantify the effects of both introducing and lifting individual NPIs on R over time. By linking a global dataset of country-level daily R values with a global dataset of country-level policies on NPIs, we modelled the change in R values (as R ratio) from day 1 to day 28 following the introduction and relaxation of eight individual NPIs among 131 countries. We found that reopening schools, lifting bans on public events, lifting bans on public gatherings of more than ten people, lifting requirements to stay at home, and lifting internal movement limits were associated with an increase in R of 11–25% on day 28 following the relaxation. However, the effects of introducing and lifting NPIs were not immediate; it took a median of 8 days (IQR 6–9) following the introduction of NPIs to observe 60% of their maximum reduction in R and even longer (17 days [14–20]) following the relaxation to observe 60% of the maximum increase in R. A similar delay in response to the introduction and relaxation of NPIs was also identified using Google mobility data. We compared four different candidates of composite NPIs that countries might consider in response to a possible resurgence of COVID-19.
Implications of all the available evidence
We quantified the change in transmission of SARS-CoV-2, as measured by R, following the introduction and relaxation of individual NPIs, and found a delay of 1–3 weeks in observing the effects of introducing and lifting these NPIs. These findings provide additional evidence that can inform policy-maker decisions on which NPIs to introduce or lift and when to expect a notable effect following the introduction or the relaxation.

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Genomic evidence for reinfection with SARS-CoV-2: a case study
Summary
Background
The degree of protective immunity conferred by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently unknown. As such, the possibility of reinfection with SARS-CoV-2 is not well understood. We describe an investigation of two instances of SARS-CoV-2 infection in the same individual.
Methods
A 25-year-old man who was a resident of Washoe County in the US state of Nevada presented to health authorities on two occasions with symptoms of viral infection, once at a community testing event in April, 2020, and a second time to primary care then hospital at the end of May and beginning of June, 2020. Nasopharyngeal swabs were obtained from the patient at each presentation and twice during follow-up. Nucleic acid amplification testing was done to confirm SARS-CoV-2 infection. We did next-generation sequencing of SARS-CoV-2 extracted from nasopharyngeal swabs. Sequence data were assessed by two different bioinformatic methodologies. A short tandem repeat marker was used for fragment analysis to confirm that samples from both infections came from the same individual.
Findings
The patient had two positive tests for SARS-CoV-2, the first on April 18, 2020, and the second on June 5, 2020, separated by two negative tests done during follow-up in May, 2020. Genomic analysis of SARS-CoV-2 showed genetically significant differences between each variant associated with each instance of infection. The second infection was symptomatically more severe than the first.
Interpretation
Genetic discordance of the two SARS-CoV-2 specimens was greater than could be accounted for by short-term in vivo evolution. These findings suggest that the patient was infected by SARS-CoV-2 on two separate occasions by a genetically distinct virus. Thus, previous exposure to SARS-CoV-2 might not guarantee total immunity in all cases. All individuals, whether previously diagnosed with COVID-19 or not, should take identical precautions to avoid infection with SARS-CoV-2. The implications of reinfections could be relevant for vaccine development and application.

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Op maandag 2 november 2020 12:03 schreef Momo het volgende:
Ik schop dit topic toch weer omhoog, er zijn recent ook weer veel publicaties uitgekomen die ook meer zorgvuldig zijn

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The major genetic risk factor for severe COVID-19 is inherited from Neanderthals

Abstract

A recent genetic association study1 identified a gene cluster on chromosome 3 as a risk locus for respiratory failure after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A separate study (COVID-19 Host Genetics Initiative)2 comprising 3,199 hospitalized patients with coronavirus disease 2019 (COVID-19) and control individuals showed that this cluster is the major genetic risk factor for severe symptoms after SARS-CoV-2 infection and hospitalization. Here we show that the risk is conferred by a genomic segment of around 50 kilobases in size that is inherited from Neanderthals and is carried by around 50% of people in south Asia and around 16% of people in Europe.

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Dexamethasone in hospitalised patients with COVID-19: addressing uncertainties

The impressive results of the RECOVERY trial established that a moderate dose of dexamethasone (6 mg daily for 10 days) reduced mortality in hospitalised patients with COVID-19 and respiratory failure who required therapy with supplemental oxygen or mechanical ventilation.
The data also indicated that dexamethasone might increase mortality in hospitalised patients who were not receiving oxygen. This landmark trial and the subsequent practice guidelines from several academic and health organisations recommending dexamethasone use in patients with severe COVID-19 have changed clinical practice for hospitalised patients on supplemental oxygen or mechanical ventilation
These favourable findings are supported by three other trialsof glucocorticoids for COVID-19, which stopped enrolment in early June, 2020, when the RECOVERY trial results were released. Each of these trials showed some evidence of benefit, although none had completed enrolment. A prospective meta-analysis of these and other trials, totalling 1703 participants (1007 [59%] from the RECOVERY trial), confirmed a reduction in 28-day mortality (summary odds ratio [OR] 0·66, 95% CI 0·53–0·82; p<0·001), with minimal heterogeneity across studies.6
While confirming beneficial effects of corticosteroids for critically ill hospitalised patients with COVID-19, some unanswered questions and issues remain that deserve discussion and should be addressed in future research.

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Early Hydroxychloroquine but not Chloroquine use reduces ICU admission in COVID-19 patients

Highlights

•

After the global push for the use of Hydroxychloroquine and Chloroquine there is ongoing discussion about the effectivity of these drugs.
•

Findings of this observational study provide crucial data on a potential protective effect of Hydroxychloroquine in non-ICU, hospitalized COVID-19 patients.
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Early treatment with HCQ on the first day of admission is associated with a reduced risk of 53% in transfer to the ICU for mechanical ventilation.
•

This protective effect was not observed for Chloroquine, therefore these drugs cannot be regarded as interchangeable.

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Op maandag 2 november 2020 18:04 schreef Momo het volgende:

[..]

Effecten van Hydroxychloroquine op covid-19 patienten

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Op maandag 2 november 2020 20:05 schreef Discombobulate het volgende:

[..]

Nou, dat werd tijd na die hele media hetze tegen hydroxychloroquine. Het ging velen die voor HCQ waren namelijk om het zo vroeg mogelijk toedienen ervan, maar daar was tot voor kort weinig onderzoek naar gedaan.

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Op maandag 2 november 2020 20:12 schreef Momo het volgende:
Heb je het artikel gelezen? Dat hele zwart-wit verhaal van het werkt wel of niet. Het werkt alleen voor reductie ICU opnames, niet voor de sterftekans.

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Our data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection.

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Race, Ethnicity, and Age Trends in Persons Who Died from COVID-19 — United States, May–August 2020

Summary

What is already known about this topic?

Persons aged ≥65 years and members of minority racial and ethnic groups are disproportionately represented among COVID-19–associated deaths.

What is added by this report?

Analysis of 114,411 COVID-19–associated deaths reported to National Vital Statistics System during May–August 2020, found that 51.3% of decedents were non-Hispanic White, 24.2% were Hispanic or Latino (Hispanic), and 18.7% were non-Hispanic Black. The percentage of Hispanic decedents increased from 16.3% in May to 26.4% in August.

What are the implications for public health practice?

These results can inform public health messaging and mitigation efforts focused on prevention and early detection of infection among disproportionately affected groups so as to minimize subsequent mortality.

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Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: a systematic review and meta-analysis

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 and is spread person-to-person through close contact. We aimed to investigate the effects of physical distance, face masks, and eye protection on virus transmission in health-care and non-health-care (eg, community) settings.
Methods

We did a systematic review and meta-analysis to investigate the optimum distance for avoiding person-to-person virus transmission and to assess the use of face masks and eye protection to prevent transmission of viruses. We obtained data for SARS-CoV-2 and the betacoronaviruses that cause severe acute respiratory syndrome, and Middle East respiratory syndrome from 21 standard WHO-specific and COVID-19-specific sources. We searched these data sources from database inception to May 3, 2020, with no restriction by language, for comparative studies and for contextual factors of acceptability, feasibility, resource use, and equity. We screened records, extracted data, and assessed risk of bias in duplicate. We did frequentist and Bayesian meta-analyses and random-effects meta-regressions. We rated the certainty of evidence according to Cochrane methods and the GRADE approach. This study is registered with PROSPERO, CRD42020177047.

Findings

Our search identified 172 observational studies across 16 countries and six continents, with no randomised controlled trials and 44 relevant comparative studies in health-care and non-health-care settings (n=25 697 patients). Transmission of viruses was lower with physical distancing of 1 m or more, compared with a distance of less than 1 m (n=10 736, pooled adjusted odds ratio [aOR] 0·18, 95% CI 0·09 to 0·38; risk difference [RD] −10·2%, 95% CI −11·5 to −7·5; moderate certainty); protection was increased as distance was lengthened (change in relative risk [RR] 2·02 per m; pinteraction=0·041; moderate certainty). Face mask use could result in a large reduction in risk of infection (n=2647; aOR 0·15, 95% CI 0·07 to 0·34, RD −14·3%, −15·9 to −10·7; low certainty), with stronger associations with N95 or similar respirators compared with disposable surgical masks or similar (eg, reusable 12–16-layer cotton masks; pinteraction=0·090; posterior probability >95%, low certainty). Eye protection also was associated with less infection (n=3713; aOR 0·22, 95% CI 0·12 to 0·39, RD −10·6%, 95% CI −12·5 to −7·7; low certainty). Unadjusted studies and subgroup and sensitivity analyses showed similar findings.

Interpretation

The findings of this systematic review and meta-analysis support physical distancing of 1 m or more and provide quantitative estimates for models and contact tracing to inform policy. Optimum use of face masks, respirators, and eye protection in public and health-care settings should be informed by these findings and contextual factors. Robust randomised trials are needed to better inform the evidence for these interventions, but this systematic appraisal of currently best available evidence might inform interim guidance.

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COVID-19 outpatients: early risk-stratified treatment with zinc plus low-dose hydroxychloroquine and azithromycin: a retrospective case series study

Highlights

• First COVID-19 outpatient study based on risk stratification and early antiviral treatment at the beginning of the disease.
• Low-dose hydroxychloroquine combined with zinc and azithromycin was an effective therapeutic approach against COVID-19.
• Significantly reduced hospitalisation rates in the treatment group.
• Reduced mortality rates in the treatment group.

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Bidirectional associations between COVID-19 and psychiatric disorder: retrospective cohort studies of 62 354 COVID-19 cases in the USA

Background
Adverse mental health consequences of COVID-19, including anxiety and depression, have been widely predicted but not yet accurately measured. There are a range of physical health risk factors for COVID-19, but it is not known if there are also psychiatric risk factors. In this electronic health record network cohort study using data from 69 million individuals, 62 354 of whom had a diagnosis of COVID-19, we assessed whether a diagnosis of COVID-19 (compared with other health events) was associated with increased rates of subsequent psychiatric diagnoses, and whether patients with a history of psychiatric illness are at a higher risk of being diagnosed with COVID-19.

Methods
We used the TriNetX Analytics Network, a global federated network that captures anonymised data from electronic health records in 54 health-care organisations in the USA, totalling 69·8 million patients. TriNetX included 62 354 patients diagnosed with COVID-19 between Jan 20, and Aug 1, 2020. We created cohorts of patients who had been diagnosed with COVID-19 or a range of other health events. We used propensity score matching to control for confounding by risk factors for COVID-19 and for severity of illness. We measured the incidence of and hazard ratios (HRs) for psychiatric disorders, dementia, and insomnia, during the first 14 to 90 days after a diagnosis of COVID-19.

Findings
In patients with no previous psychiatric history, a diagnosis of COVID-19 was associated with increased incidence of a first psychiatric diagnosis in the following 14 to 90 days compared with six other health events (HR 2·1, 95% CI 1·8–2·5 vs influenza; 1·7, 1·5–1·9 vs other respiratory tract infections; 1·6, 1·4–1·9 vs skin infection; 1·6, 1·3–1·9 vs cholelithiasis; 2·2, 1·9–2·6 vs urolithiasis, and 2·1, 1·9–2·5 vs fracture of a large bone; all p<0·0001). The HR was greatest for anxiety disorders, insomnia, and dementia. We observed similar findings, although with smaller HRs, when relapses and new diagnoses were measured. The incidence of any psychiatric diagnosis in the 14 to 90 days after COVID-19 diagnosis was 18·1% (95% CI 17·6–18·6), including 5·8% (5·2–6·4) that were a first diagnosis. The incidence of a first diagnosis of dementia in the 14 to 90 days after COVID-19 diagnosis was 1·6% (95% CI 1·2–2·1) in people older than 65 years. A psychiatric diagnosis in the previous year was associated with a higher incidence of COVID-19 diagnosis (relative risk 1·65, 95% CI 1·59–1·71; p<0·0001). This risk was independent of known physical health risk factors for COVID-19, but we cannot exclude possible residual confounding by socioeconomic factors.
Interpretation
Survivors of COVID-19 appear to be at increased risk of psychiatric sequelae, and a psychiatric diagnosis might be an independent risk factor for COVID-19. Although preliminary, our findings have implications for clinical services, and prospective cohort studies are warranted.

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Age-specific mortality and immunity patterns of SARS-CoV-2

Estimating the size and infection severity of the SARS-CoV-2 epidemic is made challenging by inconsistencies in available data. The number of COVID-19 deaths is often used as a key indicator for the epidemic size, but observed deaths represent only a minority of all infections1,2. Additionally, the heterogeneous burden in nursing homes and variable reporting of deaths in elderly individuals can hamper direct comparisons across countries of the underlying level of transmission and mortality rates3. Here we use age-specific COVID-19 death data from 45 countries and the results of 22 seroprevalence studies to investigate the consistency of infection and fatality patterns across multiple countries. We find that the age distribution of deaths in younger age groups (<65 years) is very consistent across different settings and demonstrate how this data can provide robust estimates of the share of the population that has been infected. We estimate that the infection-to-fatality ratio (IFR) is lowest among 5-9 years old, with a log-linear increase by age among individuals older than 30 years. Population age-structures and heterogeneous burdens in nursing homes explain some but not all of the heterogeneity between countries in infection-fatality ratios. Among the 45 countries included in our analysis, we estimate approximately 5% of these populations had been infected by the 1st of September 2020, with much higher transmission likely to have occurred in a number of Latin American countries. This simple modelling framework can help countries assess the progression of the pandemic and can be applied wherever reliable age-specific death data exists.

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Mobility network models of COVID-19 explain inequities and inform reopening

The COVID-19 pandemic dramatically changed human mobility patterns, necessitating epidemiological models which capture the effects of changes in mobility on virus spread1. We introduce a metapopulation SEIR model that integrates fine-grained, dynamic mobility networks to simulate the spread of SARS-CoV-2 in 10 of the largest US metropolitan statistical areas. Derived from cell phone data, our mobility networks map the hourly movements of 98 million people from neighborhoods (census block groups, or CBGs) to points of interest (POIs) such as restaurants and religious establishments, connecting 57k CBGs to 553k POIs with 5.4 billion hourly edges. We show that by integrating these networks, a relatively simple SEIR model can accurately fit the real case trajectory, despite substantial changes in population behavior over time. Our model predicts that a small minority of “superspreader” POIs account for a large majority of infections and that restricting maximum occupancy at each POI is more effective than uniformly reducing mobility. Our model also correctly predicts higher infection rates among disadvantaged racial and socioeconomic groups2–8 solely from differences in mobility: we find that disadvantaged groups have not been able to reduce mobility as sharply, and that the POIs they visit are more crowded and therefore higher-risk. By capturing who is infected at which locations, our model supports detailed analyses that can inform more effective and equitable policy responses to COVID-19.

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The 40 health systems, COVID-19 (40HS, C-19) study

Background

The health, social and economic consequences of the severe acute respiratory syndrome coronavirus (SARS-CoV-2, henceforth COVID-19) pandemic have loomed large as every national government made decisions about how to respond. The 40 Health Systems, COVID-19 (40HS, C-19) study aimed to investigate relationships between governments’ capacity to respond (CTR), their response stringency, scope of COVID-19 testing and COVID-19 outcomes.

Methods

Data over March and April 2020 were extracted for 40 national health systems on prepandemic government CTR (Global Competitiveness Index), stringency measures (Oxford COVID-19 Government Response Tracker Stringency Index), approach to COVID-19 testing and COVID-19 cases and deaths (Our-World-in-Data). Multidimensional scaling (MDS) and cluster analysis were applied to examine latent dimensions and visualize country similarities and dissimilarities. Outcomes were tested using multivariate and one-way analyses of variances and Kruskal–Wallis H tests.

Results

The MDS model found three dimensions explaining 91% of the variance and cluster analysis identified five national groupings. There was no association between national governments’ prepandemic CTR and the adoption of early stringent public health measures or approach to COVID-19 testing. Two national clusters applied early stringency measures and reported significantly lower cumulative deaths. The best performing national cluster (comprising Australia, South Korea, Iceland and Taiwan) adopted relatively early stringency measures but broader testing earlier than others, which was associated with a change in disease trajectory and the lowest COVID-19 death rates. Two clusters (one with high CTR and one low) both adopted late stringency measures and narrow testing and performed least well in COVID-19 outcomes.

Conclusion

Early stringency measures and intrinsic national capacities to deal with a pandemic are insufficient. Extended stringency measures, important in the short term, are not economically sustainable. Broad-based testing is key to managing COVID-19.

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Transmission of SARS-CoV-2 on mink farms between humans and mink and back to humans

Abstract

Animal experiments have shown that non-human primates, cats, ferrets, hamsters, rabbits and bats can be infected by SARS-CoV-2. In addition, SARS-CoV-2 RNA has been detected in felids, mink and dogs in the field. Here, we describe an in-depth investigation using whole genome sequencing of outbreaks on 16 mink farms and the humans living or working on these farms. We conclude that the virus was initially introduced from humans and has since evolved, most likely reflecting widespread circulation among mink in the beginning of the infection period several weeks prior to detection. Despite enhanced biosecurity, early warning surveillance and immediate culling of infected farms, transmission occurred between mink farms in three big transmission clusters with unknown modes of transmission. Sixty-eight percent (68%) of the tested mink farm residents, employees and/or contacts had evidence of SARS-CoV-2 infection. Where whole genomes were available, these persons were infected with strains with an animal sequence signature, providing evidence of animal to human transmission of SARS-CoV-2 within mink farms.

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Persistence and Evolution of SARS-CoV-2 in an Immunocompromised Host

The coronavirus can mutate swiftly in one person’s body

The new coronavirus resurged again and again in the body of an infected man, eventually killing him while showing evidence of fast-paced evolution.

Manuela Cernadas and Jonathan Li at Brigham and Women’s Hospital in Boston, Massachusetts, and their colleagues followed the course of COVID-19 in a 45-year-old man with a long-standing autoimmune disorder, who was on a medication regimen that included powerful immunosuppressants (B. Choi et al. N. Engl. J. Med. https://doi.org/fhv8; 2020). Roughly 40 days after the man first tested positive for SARS-CoV-2, follow-up tests indicated that the virus was dwindling — but it surged back, despite antiviral treatment.

The man’s infection subsided and then returned twice more before he died, five months after his first COVID-19 diagnosis. Genomic analysis showed that the man had not been infected multiple times. Instead, the virus had lingered and quickly mutated in his body.

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Op zondag 15 november 2020 15:22 schreef Momo het volgende:

[..]

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Ranking the effectiveness of worldwide COVID-19 government interventions

Assessing the effectiveness of non-pharmaceutical interventions (NPIs) to mitigate the spread of SARS-CoV-2 is critical to inform future preparedness response plans. Here we quantify the impact of 6,068 hierarchically coded NPIs implemented in 79 territories on the effective reproduction number, Rt, of COVID-19. We propose a modelling approach that combines four computational techniques merging statistical, inference and artificial intelligence tools. We validate our findings with two external datasets recording 42,151 additional NPIs from 226 countries. Our results indicate that a suitable combination of NPIs is necessary to curb the spread of the virus. Less disruptive and costly NPIs can be as effective as more intrusive, drastic, ones (for example, a national lockdown). Using country-specific ‘what-if’ scenarios, we assess how the effectiveness of NPIs depends on the local context such as timing of their adoption, opening the way for forecasting the effectiveness of future interventions

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Immunological memory to SARS-CoV-2 assessed for greater than six months after infection

Abstract

Understanding immune memory to SARS-CoV-2 is critical for improving diagnostics and vaccines, and for assessing the likely future course of the pandemic. We analyzed multiple compartments of circulating immune memory to SARS-CoV-2 in 185 COVID-19 cases, including 41 cases at > 6 months post-infection. Spike IgG was relatively stable over 6+ months. Spike-specific memory B cells were more abundant at 6 months than at 1 month. SARS-CoV-2-specific CD4+ T cells and CD8+ T cells declined with a half-life of 3-5 months. By studying antibody, memory B cell, CD4+ T cell, and CD8+ T cell memory to SARS-CoV-2 in an integrated manner, we observed that each component of SARS-CoV-2 immune memory exhibited distinct kinetics.
Competing Interest Statement

A.S. is a consultant for Gritstone, Flow Pharma, Merck, Epitogenesis, Gilead and Avalia. S.C. is a consultant for Avalia. LJI has filed for patent protection for various aspects of T cell epitope and vaccine design work. Mount Sinai has licensed serological assays to commercial entities and has filed for patent protection for serological assays. D.S., F.A., V.S. and F.K. are listed as inventors on the pending patent application (F.K., V.S.), and Newcastle disease virus (NDV)-based SARS-CoV-2 vaccines that name F.K. as inventor. All other authors declare no conflict of interest.

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Interpretation
ChAdOx1 nCoV-19 appears to be better tolerated in older adults than in younger adults and has similar immunogenicity across all age groups after a boost dose. Further assessment of the efficacy of this vaccine is warranted in all age groups and individuals with comorbidities.

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Op donderdag 19 november 2020 10:53 schreef George_of_the_Jungle het volgende:
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32466-1/fulltext
[..]

En een press release over dezelfde studie: https://covid19vaccinetrial.co.uk/phase-ii-trial-publication

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Antibodies to SARS-CoV-2 are associated with protection against reinfection

Background It is critical to understand whether infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) protects from subsequent reinfection. Methods We investigated the incidence of SARS-CoV-2 PCR-positive results in seropositive and seronegative healthcare workers (HCWs) attending asymptomatic and symptomatic staff testing at Oxford University Hospitals, UK. Baseline antibody status was determined using anti-spike and/or anti-nucleocapsid IgG assays and staff followed for up to 30 weeks. We used Poisson regression to estimate the relative incidence of PCR-positive results and new symptomatic infection by antibody status, accounting for age, gender and changes in incidence over time. Results A total of 12219 HCWs participated and had anti-spike IgG measured, 11052 were followed up after negative and 1246 after positive antibody results including 79 who seroconverted during follow up. 89 PCR-confirmed symptomatic infections occurred in seronegative individuals (0.46 cases per 10,000 days at risk) and no symptomatic infections in those with anti-spike antibodies. Additionally, 76 (0.40/10,000 days at risk) anti-spike IgG seronegative individuals had PCR-positive tests in asymptomatic screening, compared to 3 (0.21/10,000 days at risk) seropositive individuals. Overall, positive baseline anti-spike antibodies were associated with lower rates of PCR-positivity (with or without symptoms) (adjusted rate ratio 0.24 [95%CI 0.08-0.76, p=0.015]). Rate ratios were similar using anti-nucleocapsid IgG alone or combined with anti-spike IgG to determine baseline status. Conclusions Prior SARS-CoV-2 infection that generated antibody responses offered protection from reinfection for most people in the six months following infection. Further work is required to determine the long-term duration and correlates of post-infection immunity.

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The effect of temperature and humidity on the stability of SARS-CoV-2 and other enveloped viruses

Abstract

Understanding the impact of environmental conditions on virus viability and transmission potential is crucial to anticipating epidemic dynamics and designing mitigation strategies. Ambient temperature and humidity are known to have strong effects on the environmental stability of viruses, but a general quantitative understanding of how temperature and humidity affect virus stability has remained elusive. We characterize the stability of SARS-CoV-2 on an inert surface at a variety of temperature and humidity conditions, and introduce a mechanistic model that enables accurate prediction of virus stability in unobserved conditions. We find that SARS-CoV-2 survives better at low temperatures and extreme relative humidities; median estimated virus half-life was more than 24 hours at 10 °C and 40 % RH, but approximately an hour and a half at 27 °C and 65 % RH. Moreover, our model predicts observations from other human coronaviruses and other studies of SARS-CoV-2, suggesting the existence of shared mechanisms that determine environmental stability across a number of enveloped viruses. Our results highlight scenarios of particular transmission risk and point to broad strategies for pandemic mitigation, while opening new frontiers for the mechanistic study of viral transmission.

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All close contacts of the asymptomatic positive cases tested negative, indicating that the asymptomatic positive cases detected in this study were unlikely to be infectious.

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In summary, the detection rate of asymptomatic positive cases in the post-lockdown Wuhan was very low (0.303/10,000), and there was no evidence that the identified asymptomatic positive cases were infectious.

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No evidence for increased transmissibility from recurrent mutations in SARS-CoV-2

COVID-19 is caused by the coronavirus SARS-CoV-2, which jumped into the human population in late 2019 from a currently uncharacterised animal reservoir. Due to this recent association with humans, SARS-CoV-2 may not yet be fully adapted to its human host. This has led to speculations that SARS-CoV-2 may be evolving towards higher transmissibility. The most plausible mutations under putative natural selection are those which have emerged repeatedly and independently (homoplasies). Here, we formally test whether any homoplasies observed in SARS-CoV-2 to date are significantly associated with increased viral transmission. To do so, we develop a phylogenetic index to quantify the relative number of descendants in sister clades with and without a specific allele. We apply this index to a curated set of recurrent mutations identified within a dataset of 46,723 SARS-CoV-2 genomes isolated from patients worldwide. We do not identify a single recurrent mutation in this set convincingly associated with increased viral transmission. Instead, recurrent mutations currently in circulation appear to be evolutionary neutral and primarily induced by the human immune system via RNA editing, rather than being signatures of adaptation. At this stage we find no evidence for significantly more transmissible lineages of SARS-CoV-2 due to recurrent mutations.

quote:

No study detected live virus beyond day 9 of illness, despite persistently high viral loads, which were inferred from cycle threshold values.

quote:

Findings
79 studies (5340 individuals) on SARS-CoV-2, eight studies (1858 individuals) on SARS-CoV, and 11 studies (799 individuals) on MERS-CoV were included. Mean duration of SARS-CoV-2 RNA shedding was 17·0 days (95% CI 15·5–18·6; 43 studies, 3229 individuals) in upper respiratory tract, 14·6 days (9·3–20·0; seven studies, 260 individuals) in lower respiratory tract, 17·2 days (14·4–20·1; 13 studies, 586 individuals) in stool, and 16·6 days (3·6–29·7; two studies, 108 individuals) in serum samples. Maximum shedding duration was 83 days in the upper respiratory tract, 59 days in the lower respiratory tract, 126 days in stools, and 60 days in serum. Pooled mean SARS-CoV-2 shedding duration was positively associated with age (slope 0·304 [95% CI 0·115–0·493]; p=0·0016). No study detected live virus beyond day 9 of illness, despite persistently high viral loads, which were inferred from cycle threshold values. SARS-CoV-2 viral load in the upper respiratory tract appeared to peak in the first week of illness, whereas that of SARS-CoV peaked at days 10–14 and that of MERS-CoV peaked at days 7–10.

quote:

Guidelines from the CDC and the WHO recommend the wearing of face masks to prevent the spread of coronavirus (CoV) disease 2019 (COVID-19); however, the protective efficiency of such masks against airborne transmission of infectious severe acute respiratory syndrome CoV-2 (SARS-CoV-2) droplets/aerosols is unknown. Here, we developed an airborne transmission simulator of infectious SARS-CoV-2-containing droplets/aerosols produced by human respiration and coughs and assessed the transmissibility of the infectious droplets/aerosols and the ability of various types of face masks to block the transmission. We found that cotton masks, surgical masks, and N95 masks all have a protective effect with respect to the transmission of infective droplets/aerosols of SARS-CoV-2 and that the protective efficiency was higher when masks were worn by a virus spreader. Importantly, medical masks (surgical masks and even N95 masks) were not able to completely block the transmission of virus droplets/aerosols even when completely sealed. Our data will help medical workers understand the proper use and performance of masks and determine whether they need additional equipment to protect themselves from infected patients.

IMPORTANCE
Airborne simulation experiments showed that cotton masks, surgical masks, and N95 masks provide some protection from the transmission of infective SARS-CoV-2 droplets/aerosols; however, medical masks (surgical masks and even N95 masks) could not completely block the transmission of virus droplets/aerosols even when sealed.

quote:

The researchers found that the chances of a person with coronavirus, regardless of their age, passing it on to a close contact ranged from 2.6% in the community to 9% in the household. The researchers found that children and young adults — who made up one-third of COVID cases — were especially key to transmitting the virus in the studied populations.

“Kids are very efficient transmitters in this setting, which is something that hasn’t been firmly established in previous studies,” Laxminarayan said. “We found that reported cases and deaths have been more concentrated in younger cohorts than we expected based on observations in higher-income countries.”

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Effectiveness of face masks for the population

Background: Health authorities and organizations consider non-medical face masks as an additional passive means to prevent virus diffusion. Communication strategies disseminate information among the population that such masks are essential for mitigating virus diffusion. However, scientific studies are not conclusive in showing the undisputed filtration efficiency of fabric/cloth facial masks (both commercial and homemade).

Objectives: This study examines scientific data about the effectiveness of face masks before and during the COVID-19 emergency. Present trends in the making of commercial and homemade fabric/cloth face masks are also examined.

Methods: Statistical data of published studies are analyzed and compared. Main considerations and suggestions are also extracted and discussed. Current approaches are examined for assessing the characteristics and effectiveness of fabric/cloth commercial and homemade face masks intended for the population.

Result: Conflicting data exist as to whether non-medical masks have a protective effect from the spread of respiratory viruses. Both medical masks (MDs) and respiratory personal protection equipment (PPE) show a given effectiveness value.

Conclusion: Concerning commercial and homemade fabric/cloth masks, giving general indications on the choice of materials and their assemblage is difficult as it is not possible to assess the effectiveness of the filter media with respect to the kind of multiphase fluid that may be emitted upon breathing, sneezing, or coughing under different environmental conditions. This is particularly important because airflow rate, temperature, humidity, and duration of use will affect the performance of filter media. Moreover, while a mask may have excellent filter media, droplets may leak into the face-piece unless there is an adequate facial seal. In the presence of leaks, any type of mask may actually offer less protection independently of its nominal filtering effìciency.

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Model-based evaluation of school- and non-school-related measures to control the COVID-19 pandemic


Background In autumn 2020, many countries, including the Netherlands, are experiencing a second wave of the COVID-19 pandemic. Health policymakers are struggling with choosing the right mix of measures to keep the COVID-19 case numbers under control, but still allow a minimum of social and economic activity. The priority to keep schools open is high, but the role of school-based contacts in the epidemiology of SARS-CoV-2 is incompletely understood. We used a transmission model to estimate the impact of school contacts on transmission of SARS-CoV-2 and to assess the effects of school-based measures, including school closure, on controlling the pandemic at different time points during the pandemic.

Methods and Findings The age-structured model was fitted to age-specific seroprevalence and hospital admission data from the Netherlands during spring 2020. Compared to adults older than 60 years, the estimated susceptibility was 23% (95%CrI 20—28%) for children aged 0 to 20 years and 61% (95%CrI 50%—72%) for the age group of 20 to 60 years. The time points considered in the analyses were August 2020 when the effective reproduction number (Re) was estimated to be 1.31 (95%CrI 1.15—2.07), schools just opened after the summer holidays and measures were reinforced with the aim to reduce Re to a value below 1, and (ii) November 2020 when measures had reduced Re to 1.00 (95%CrI 0.94—1.33). In this period schools remained open. Our model predicts that keeping schools closed after the summer holidays, in the absence of other measures, would have reduced Re by 10% (from 1.31 to 1.18 (95%CrI 1.04—1.83)) and thus would not have prevented the second wave in autumn 2020. Reducing non-school-based contacts in August 2020 to the level observed during the first wave of the pandemic would have reduced Re to 0.83 (95%CrI 0.75—1.10). Yet, this reduction was not achieved and the observed Re in November was 1.00. Our model predicts that closing schools in November 2020 could reduce Re from the observed value of 1.00 to 0.84 (95%CrI 0.81—0.90), with unchanged non-school based contacts. Reductions in Re due to closing schools in November 2020 were 8% for 10 to 20 years old children, 5% for 5 to 10 years old children and negligible for 0 to 5 years old children.

Conclusions The impact of measures reducing school-based contacts, including school closure, depends on the remaining opportunities to reduce non-school-based contacts. If opportunities to reduce Re with non-school-based measures are exhausted or undesired and Re is still close to 1, the additional benefit of school-based measures may be considerable, particularly among the older school children

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Exclusive: Kids catch and spread coronavirus half as much as adults, Iceland study confirms

Big decisions around COVID-19 and children have been heavy on politics and short on science. New large-scale studies are changing that.

“They can and do get infected and transmit to others, but they do both less frequently than adults,” says Kári Stefánsson, the chief executive of deCODE.

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Evidence of Long-Distance Droplet Transmission of SARS-CoV-2 by Direct Air Flow in a Restaurant in Korea

Abstract

Background

The transmission mode of severe acute respiratory syndrome coronavirus 2 is primarily known as droplet transmission. However, a recent argument has emerged about the possibility of airborne transmission. On June 17, there was a coronavirus disease 2019 (COVID-19) outbreak in Korea associated with long distance droplet transmission.

Methods

The epidemiological investigation was implemented based on personal interviews and data collection on closed-circuit television images, and cell phone location data. The epidemic investigation support system developed by the Korea Disease Control and Prevention Agency was used for contact tracing. At the restaurant considered the site of exposure, air flow direction and velocity, distances between cases, and movement of visitors were investigated.

Results

A total of 3 cases were identified in this outbreak, and maximum air flow velocity of 1.2 m/s was measured between the infector and infectee in a restaurant equipped with ceiling-type air conditioners. The index case was infected at a 6.5 m away from the infector and 5 minutes exposure without any direct or indirect contact.

Conclusion

Droplet transmission can occur at a distance greater than 2 m if there is direct air flow from an infected person. Therefore, updated guidelines involving prevention, contact tracing, and quarantine for COVID-19 are required for control of this highly contagious disease.

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Inferring the effectiveness of government interventions against COVID-19

Abstract

Governments are attempting to control the COVID-19 pandemic with nonpharmaceutical interventions (NPIs). However, the effectiveness of different NPIs at reducing transmission is poorly understood. We gathered chronological data on the implementation of NPIs for several European, and other, countries between January and the end of May 2020. We estimate the effectiveness of NPIs, ranging from limiting gathering sizes, business closures, and closure of educational institutions to stay-at-home orders. To do so, we used a Bayesian hierarchical model that links NPI implementation dates to national case and death counts and supported the results with extensive empirical validation. Closing all educational institutions, limiting gatherings to 10 people or less, and closing face-to-face businesses each reduced transmission considerably. The additional effect of stay-at-home orders was comparatively small.

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Dynamic Change of COVID-19 Seroprevalence among Asymptomatic Population in Tokyo during the Second Wave

Conclusions and Relevance: COVID-19 infection may have spread widely across the general population of Tokyo despite the very low fatality rate. Given the temporal correlation between the rise in seropositivity and the decrease in reported COVID-19 cases that occurred without a shut-down, herd immunity may be implicated.

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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19), has caused a global pandemic, and safe, effective vaccines are urgently needed. Strong, Th1-skewed T cell responses can drive protective humoral and cell-mediated immune responses and might reduce the potential for disease enhancement. Cytotoxic T cells clear virus-infected host cells and contribute to control of infection. Studies of patients infected with SARS-CoV-2 have suggested a protective role for both humoral and cell-mediated immune responses in recovery from COVID-19. ChAdOx1 nCoV-19 (AZD1222) is a candidate SARS-CoV-2 vaccine comprising a replication-deficient simian adenovirus expressing full-length SARS-CoV-2 spike protein. We recently reported preliminary safety and immunogenicity data from a phase 1/2 trial of the ChAdOx1 nCoV-19 vaccine (NCT04400838)7 given as either a one- or two-dose regimen. The vaccine was tolerated, with induction of neutralizing antibodies and antigen-specific T cells against the SARS-CoV-2 spike protein. Here we describe, in detail, exploratory analyses of the immune responses in adults, aged 18–55 years, up to 8 weeks after vaccination with a single dose of ChAdOx1 nCoV-19 in this trial, demonstrating an induction of a Th1-biased response characterized by interferon-γ and tumor necrosis factor-α cytokine secretion by CD4+ T cells and antibody production predominantly of IgG1 and IgG3 subclasses. CD8+ T cells, of monofunctional, polyfunctional and cytotoxic phenotypes, were also induced. Taken together, these results suggest a favorable immune profile induced by ChAdOx1 nCoV-19 vaccine, supporting the progression of this vaccine candidate to ongoing phase 2/3 trials to assess vaccine efficacy.

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Abstract

More than 190 vaccines are currently in development to prevent infection by the novel severe acute respiratory syndrome coronavirus 2. Animal studies suggest that while neutralizing antibodies against the viral spike protein may correlate with protection, additional antibody functions may also be important in preventing infection. Previously, we reported early immunogenicity and safety outcomes of a viral vector coronavirus vaccine, ChAdOx1 nCoV-19 (AZD1222), in a single-blinded phase 1/2 randomized controlled trial of healthy adults aged 18–55 years (NCT04324606). Now we describe safety and exploratory humoral and cellular immunogenicity of the vaccine, from subgroups of volunteers in that trial, who were subsequently allocated to receive a homologous full-dose (SD/SD D56; n = 20) or half-dose (SD/LD D56; n = 32) ChAdOx1 booster vaccine 56 d following prime vaccination. Previously reported immunogenicity data from the open-label 28-d interval prime-boost group (SD/SD D28; n = 10) are also presented to facilitate comparison. Additionally, we describe volunteers boosted with the comparator vaccine (MenACWY; n = 10). In this interim report, we demonstrate that a booster dose of ChAdOx1 nCoV-19 is safe and better tolerated than priming doses. Using a systems serology approach we also demonstrate that anti-spike neutralizing antibody titers, as well as Fc-mediated functional antibody responses, including antibody-dependent neutrophil/monocyte phagocytosis, complement activation and natural killer cell activation, are substantially enhanced by a booster dose of vaccine. A booster dose of vaccine induced stronger antibody responses than a dose-sparing half-dose boost, although the magnitude of T cell responses did not increase with either boost dose. These data support the two-dose vaccine regime that is now being evaluated in phase 3 clinical trials.

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Infectivity of asymptomatic versus symptomatic COVID-19

Negative binomial regression revealed that when adjusted for age, gender, and serology of index case, the incidence of COVID-19 among close contacts of a symptomatic index case was 3·85 times higher than for close contacts of an asymptomatic index case (95% CI2·06–7·19; p<0·0001; appendix).

Our findings suggest that people with asymptomatic COVID-19 are infectious but might be less infectious than symptomatic cases. We also identified that the proportion of close contacts who became infected did not depend on the serology status of the index case. One reason for this observation could be that close contacts tend to live or work with the index case and are exposed because of their regular contact with a person who was infectious before turning seropositive.

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High rate of persistent symptoms up to 4 months after community and hospital-managed SARS-CoV-2 infection

Recovery after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains uncertain. A considerable proportion of patients experience persistent symptoms after SARS-CoV-2 infection which impacts health-related quality of life and physical function. Multi-disciplinary follow-up is recommended for patients with post-COVID illness and to assess health-related quality of life and physical function.

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Antibody Status and Incidence of SARS-CoV-2 Infection in Health Care Workers

Background

The relationship between the presence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the risk of subsequent reinfection remains unclear.

Methods

We investigated the incidence of SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) in seropositive and seronegative health care workers attending testing of asymptomatic and symptomatic staff at Oxford University Hospitals in the United Kingdom. Baseline antibody status was determined by anti-spike (primary analysis) and anti-nucleocapsid IgG assays, and staff members were followed for up to 31 weeks. We estimated the relative incidence of PCR-positive test results and new symptomatic infection according to antibody status, adjusting for age, participant-reported gender, and changes in incidence over time.

Results

A total of 12,541 health care workers participated and had anti-spike IgG measured; 11,364 were followed up after negative antibody results and 1265 after positive results, including 88 in whom seroconversion occurred during follow-up. A total of 223 anti-spike–seronegative health care workers had a positive PCR test (1.09 per 10,000 days at risk), 100 during screening while they were asymptomatic and 123 while symptomatic, whereas 2 anti-spike–seropositive health care workers had a positive PCR test (0.13 per 10,000 days at risk), and both workers were asymptomatic when tested (adjusted incidence rate ratio, 0.11; 95% confidence interval, 0.03 to 0.44; P=0.002). There were no symptomatic infections in workers with anti-spike antibodies. Rate ratios were similar when the anti-nucleocapsid IgG assay was used alone or in combination with the anti-spike IgG assay to determine baseline status.

Conclusions

The presence of anti-spike or anti-nucleocapsid IgG antibodies was associated with a substantially reduced risk of SARS-CoV-2 reinfection in the ensuing 6 months. (Funded by the U.K. Government Department of Health and Social Care and others.)

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Transmission of SARS-CoV-2 LineageB.1.1.7 in England: Insights from linkingepidemiological and genetic data

The SARS-CoV-2 lineage B.1.1.7, now designated Variant of Concern 202012/01 (VOC) byPublic Health England, originated in the UK in late Summer to early Autumn 2020. We examineepidemiological evidence for this VOC having a transmission advantage from severalperspectives. First, whole genome sequence data collected from community-based diagnostictesting provides an indication of changing prevalence of different genetic variants through time.Phylodynamic modelling additionally indicates that genetic diversity of this lineage has changedin a manner consistent with exponential growth. Second, we find that changes in VOCfrequency inferred from genetic data correspond closely to changes inferred by S-gene targetfailures (SGTF) in community-based diagnostic PCR testing. Third, we examine growth trends inSGTF and non-SGTF case numbers at local area level across England, and show that the VOC
has higher transmissibility than non-VOC lineages, even if the VOC has a different latent periodor generation time. Available SGTF data indicate a shift in the age composition of reportedcases, with a larger share of under 20 year olds among reported VOC than non-VOC cases.Fourth, we assess the association of VOC frequency with independent estimates of the overallSARS-CoV-2 reproduction number through time. Finally, we fit a semi-mechanistic modeldirectly to local VOC and non-VOC case incidence to estimate the reproduction numbers overtime for each. There is a consensus among all analyses that the VOC has a substantialtransmission advantage, with the estimated difference in reproduction numbers between VOCand non-VOC ranging between 0.4 and 0.7, and the ratio of reproduction numbers varyingbetween 1.4 and 1.8. We note that these estimates of transmission advantage apply to a periodwhere high levels of social distancing were in place in England; extrapolation to othertransmission contexts therefore requires caution

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Association between upper respiratory tract viral load, comorbidities, disease severity and outcome of patients with SARS-CoV-2 infection

Abstract
Background

There is limited information on the association between upper respiratory tract (URT) viral loads, host factors, and disease severity in SARS-CoV-2 infected patients.
Methods

We studied 1,122 patients (mean age: 46 years) diagnosed by PCR. URT viral load, measured by PCR cycle threshold, was categorized as high, moderate or low.
Results

There were 336 (29.9%) patients with comorbidities; 309 patients (27.5%) had high, 316 (28.2%) moderate, and 497 (44.3%) low viral load. In univariate analyses, compared to patients with moderate or low viral load, patients with high viral load were older, had more often comorbidities, developed symptomatic disease, were intubated and died; in addition, patients with high viral load had longer stay in intensive care unit and longer intubation compared to patients with low viral load (p-values <0.05 for all). Patients with chronic cardiovascular disease, hypertension, chronic pulmonary disease, immunosuppression, obesity and chronic neurological disease had more often high viral load (p-value<0.05 for all). Multivariate analysis found that a high viral load was associated with COVID-19. The level of viral load was not associated with any other outcome.
Conclusions

URT viral load could be used to identify patients at higher risk for morbidity or severe outcome.

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6-month consequences of COVID-19 in patients discharged from hospital: a cohort study

Background
The long-term health consequences of COVID-19 remain largely unclear. The aim of this study was to describe the long-term health consequences of patients with COVID-19 who have been discharged from hospital and investigate the associated risk factors, in particular disease severity.

Methods
We did an ambidirectional cohort study of patients with confirmed COVID-19 who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7, 2020, and May 29, 2020. Patients who died before follow-up, patients for whom follow-up would be difficult because of psychotic disorders, dementia, or re-admission to hospital, those who were unable to move freely due to concomitant osteoarthropathy or immobile before or after discharge due to diseases such as stroke or pulmonary embolism, those who declined to participate, those who could not be contacted, and those living outside of Wuhan or in nursing or welfare homes were all excluded. All patients were interviewed with a series of questionnaires for evaluation of symptoms and health-related quality of life, underwent physical examinations and a 6-min walking test, and received blood tests. A stratified sampling procedure was used to sample patients according to their highest seven-category scale during their hospital stay as 3, 4, and 5–6, to receive pulmonary function test, high resolution CT of the chest, and ultrasonography. Enrolled patients who had participated in the Lopinavir Trial for Suppression of SARS-CoV-2 in China received severe acute respiratory syndrome coronavirus 2 antibody tests. Multivariable adjusted linear or logistic regression models were used to evaluate the association between disease severity and long-term health consequences.

Findings
In total, 1733 of 2469 discharged patients with COVID-19 were enrolled after 736 were excluded. Patients had a median age of 57·0 (IQR 47·0–65·0) years and 897 (52%) were men. The follow-up study was done from June 16, to Sept 3, 2020, and the median follow-up time after symptom onset was 186·0 (175·0–199·0) days. Fatigue or muscle weakness (63%, 1038 of 1655) and sleep difficulties (26%, 437 of 1655) were the most common symptoms. Anxiety or depression was reported among 23% (367 of 1617) of patients. The proportions of median 6-min walking distance less than the lower limit of the normal range were 24% for those at severity scale 3, 22% for severity scale 4, and 29% for severity scale 5–6. The corresponding proportions of patients with diffusion impairment were 22% for severity scale 3, 29% for scale 4, and 56% for scale 5–6, and median CT scores were 3·0 (IQR 2·0–5·0) for severity scale 3, 4·0 (3·0–5·0) for scale 4, and 5·0 (4·0–6·0) for scale 5–6. After multivariable adjustment, patients showed an odds ratio (OR) 1·61 (95% CI 0·80–3·25) for scale 4 versus scale 3 and 4·60 (1·85–11·48) for scale 5–6 versus scale 3 for diffusion impairment; OR 0·88 (0·66–1·17) for scale 4 versus scale 3 and OR 1·77 (1·05–2·97) for scale 5–6 versus scale 3 for anxiety or depression, and OR 0·74 (0·58–0·96) for scale 4 versus scale 3 and 2·69 (1·46–4·96) for scale 5–6 versus scale 3 for fatigue or muscle weakness. Of 94 patients with blood antibodies tested at follow-up, the seropositivity (96·2% vs 58·5%) and median titres (19·0 vs 10·0) of the neutralising antibodies were significantly lower compared with at the acute phase. 107 of 822 participants without acute kidney injury and with estimated glomerular filtration rate (eGFR) 90 mL/min per 1·73 m2 or more at acute phase had eGFR less than 90 mL/min per 1·73 m2 at follow-up.

Interpretation
At 6 months after acute infection, COVID-19 survivors were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations, and are the main target population for intervention of long-term recovery.

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Assessing Mandatory Stay‐at‐Home and Business Closure Effects on the Spread of COVID‐19

Background and Aims

The most restrictive non‐pharmaceutical interventions (NPIs) for controlling the spread of COVID‐19 are mandatory stay‐at‐home and business closures. Given the consequences of these policies, it is important to assess their effects. We evaluate the effects on epidemic case growth of more restrictive NPIs (mrNPIs), above and beyond those of less restrictive NPIs (lrNPIs).

Methods

We first estimate COVID‐19 case growth in relation to any NPI implementation in subnational regions of 10 countries: England, France, Germany, Iran, Italy, Netherlands, Spain, South Korea, Sweden, and the US. Using first‐difference models with fixed effects, we isolate the effects of mrNPIs by subtracting the combined effects of lrNPIs and epidemic dynamics from all NPIs. We use case growth in Sweden and South Korea, two countries that did not implement mandatory stay‐at‐home and business closures, as comparison countries for the other 8 countries (16 total comparisons).

Results

Implementing any NPIs was associated with significant reductions in case growth in 9 out of 10 study countries, including South Korea and Sweden that implemented only lrNPIs (Spain had a non‐significant effect). After subtracting the epidemic and lrNPI effects, we find no clear, significant beneficial effect of mrNPIs on case growth in any country. In France, e.g., the effect of mrNPIs was +7% (95CI ‐5%‐19%) when compared with Sweden, and +13% (‐12%‐38%) when compared with South Korea (positive means pro‐contagion). The 95% confidence intervals excluded 30% declines in all 16 comparisons and 15% declines in 11/16 comparisons.

Conclusions

While small benefits cannot be excluded, we do not find significant benefits on case growth of more restrictive NPIs. Similar reductions in case growth may be achievable with less restrictive interventions.

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Op zondag 17 januari 2021 02:20 schreef Wegenbouwer het volgende:

[..]

Over het effect van verplichte maatregelen in 10 landen waaronder Nederland.

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Increased infections, but not viral burden, with a new SARS-CoV-2 variant

Background A new variant of SARS-CoV-2, B.1.1.7/VOC202012/01, was identified in the UK in December-2020. Direct estimates of its potential to enhance transmission are limited.

Methods Nose and throat swabs from 28-September-2020 to 2-January-2021 in the UK’s nationally representative surveillance study were tested by RT-PCR for three genes (N, S and ORF1ab). Those positive only on ORF1ab+N, S-gene target failures (SGTF), are compatible with B.1.1.7/VOC202012/01. We investigated cycle threshold (Ct) values (a proxy for viral load), percentage of positives, population positivity and growth rates in SGTF vs non-SGTF positives.

Results 15,166(0.98%) of 1,553,687 swabs were PCR-positive, 8,545(56%) with three genes detected and 3,531(23%) SGTF. SGTF comprised an increasing, and triple-gene positives a decreasing, percentage of infections from late-November in most UK regions/countries, e.g. from 15% to 38% to 81% over 1.5 months in London. SGTF Ct values correspondingly declined substantially to similar levels to triple-gene positives. Population-level SGTF positivity remained low (<0.25%) in all regions/countries until late-November, when marked increases with and without self-reported symptoms occurred in southern England (to 1.5-3%), despite stable rates of non-SGTF cases. SGTF positivity rates increased on average 6% more rapidly than rates of non-SGTF positives (95% CI 4-9%) supporting addition rather than replacement with B.1.1.7/VOC202012/01. Excess growth rates for SGTF vs non-SGTF positives were similar in those up to high school age (5% (1-8%)) and older individuals (6% (4-9%)).

Conclusions Direct population-representative estimates show that the B.1.1.7/VOC202012/01 SARS-CoV-2 variant leads to higher infection rates, but does not seem particularly adapted to any age group.

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Individuals discharged from hospital following COVID-19 face elevated rates of multi-organdysfunction compared with background levels, and the increase in risk is neitherconfined to the elderly nor uniform across ethnicities.The diagnosis, treatment and preventionof PCSrequire integrated rather than organ-or disease-specific approaches. Urgent research is required to establish risk factors for PCS

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An Early Assessment of Curfew and SecondCOVID-19 Lock-down on Virus Propagationin France∗

This note provides an early assessment of the reinforced measures to curb the COVID-19pandemic in France, which include a curfew of selected areas and culminate in a second COVID-19-relatedlock-down that started on October 30, 2020 and is still ongoing. We analyse the change in virus propagationacross age groups and across départements using an acceleration index introduced in Baunez et al. (2020).We find that while the pandemic is still in the acceleration regime, acceleration decreased notably withcurfew measures and this more rapidly so for the more vulnerable population group, that is, for peopleolder than 60. Acceleration continued to decline under lock-down, but more so for the active populationunder 60 than for those above 60. For the youngest population aged 0 to 19, curfew measures did not reduce acceleration but lock-down does. This suggests that if health policies aim at protecting the elderly population generally more at risk to suffer severe consequences from COVID-19, curfew measures may be effective enough. However, looking at the departmental map of France, we find that curfews have notnecessarily been imposed in départements where acceleration was the largest.

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The Effect of Curfew Enforcement on Health Care Provision in COVID-19 Pandemic

The COVID-19 disease occurred in the final weeks of 2019. As part of the fight against COVID-19, countries have taken actions such as travel restrictions, suspension of border crossings and international flights, voluntary home isolation, public activities restriction, and curfews. The objective of this study is to identify the effect of curfew enforcement during the COVID-19 pandemic to determine and identify whether curfew has a positive effect on the health care workload. The number of patients admitted to Sakarya University Training and Research Hospital, their means of arrival, hospitalization-discharge, demographic characteristics were examined retrospectively for the period of curfew in April and May 2020 and the corresponding days in 2019. The significant statistical differences between the two periods were analyzed. The results of this research reveal that 24.488 patients were admitted to our emergency department. Of these patients, 12813 (52.3%) were male, 11675 (47.7%) were female. The number of emergency department admissions of the pediatric age group decreased from 1822 (8.9%) to 33 patients (0.8%). Moreover, the number of patients admitted to the emergency service in the related period of 2019 was 20548 (83.9%), while this figure decreased to 3940 individuals (16.1%) during the curfew period. It was implied that curfew could reduce the unnecessary admissions to hospitals, the number of ambulance usage, and provide a positive contribution to the reduction in traumas, car accidents, work accidents, and forensic cases during pandemic.

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Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected 78 million individuals and is responsible for over 1.7 million deaths to date. Infection is associated with development of variable levels of antibodies with neutralizing activity that can protect against infection in animal models1,2. Antibody levels decrease with time, but the nature and quality of the memory B cells that would be called upon to produce antibodies upon re-infection has not been examined. Here we report on the humoral memory response in a cohort of 87 individuals assessed at 1.3 and 6.2 months after infection. We find that IgM, and IgG anti-SARS-CoV-2 spike protein receptor binding domain (RBD) antibody titres decrease significantly with IgA being less affected. Concurrently, neutralizing activity in plasma decreases by fivefold in pseudotype virus assays. In contrast, the number of RBD-specific memory B cells is unchanged. Memory B cells display clonal turnover after 6.2 months, and the antibodies they express have greater somatic hypermutation, increased potency and resistance to RBD mutations, indicative of continued evolution of the humoral response. Analysis of intestinal biopsies obtained from asymptomatic individuals 4 months after the onset of coronavirus disease-2019 (COVID-19), using immunofluorescence, or polymerase chain reaction, revealed persistence of SARS-CoV-2 nucleic acids and immunoreactivity in the small bowel of 7 out of 14 volunteers. We conclude that the memory B cell response to SARS-CoV-2 evolves between 1.3 and 6.2 months after infection in a manner that is consistent with antigen persistence.

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Op woensdag 24 februari 2021 12:54 schreef George_of_the_Jungle het volgende:
Op basis daarvan zou je kunnen zeggen dat de kans op besmetting eigenlijk alleen in restaurants echt hoger is, en mogelijk ook in cafes. OR = odds ratio
Winkelen, salons, thuisbezoek, public transport heeft allemaal niet of nauwelijks invloed. Mogelijk is er een verhoogde kans in gyms en kerken, maar dat is niet overtuigend.

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Op woensdag 24 februari 2021 15:14 schreef RM-rf het volgende:

[..]

volgens mij kun je dat nog lang niet uit dat onderzoek halen...
het betreft een specifiek naar beweegpatronen, waarbij men het beweegpatroon en activiteiten van personen die covid-positief waren vastgelegd heeft (359 personen uit 10 verschillende staten, telefonisch ondervraagt, daarnaast ook een controlegroep van 160 personen, die niet covid-positief waren )
de eerste groep van 154 personen had aangegeven een directe contactpersoon te hebben die al eerder als covid-positief gemeld was (en dus een mogelijke bron van de besmetting was)
en een andere groep van 205 personen kon niet aangeven of ze een andere contactpersoon hadden die als mogelijke bron kon gelden.

Ze vergelijken nu het beweegpatroon van de besmette mensen met de controlegroep van niet besmette, waarbij er onderscheid gemaakt wordt tussen mensn die een direkte contactpersoon hadden die ook besmet was of die dat niet konden aangeven.

Het enige wat mij heel duidelijk opvalt is de ontzettend hoge score van mensen die geen bekend covid-positieve contactpersoon hebben, maar wel zelfs positief getest zijn, en die kennelijk zeer regelmatig nog een bar bezocht hebben.
(de band loopt overigens verder naar rechts en valt buiten de grafiek tot een maximale breedte van boven de 10, de afbeelding was niet breed genoeg om dat weer te geven).

verder lijken overall besmette personen vaker cafe's, restaurants, fitness studios en/of kerken te bezoeken dan de controlegroep, maar dat bewijst an sich nog niet dat dat de plek is waar ze besmet zijn...
hooguit wijst hun beweegpatroon wel op dat ze sociaal actiever zijn dan anderen.

Dat bv zaken als winkelen of gebruik van OV, en het hebben van thuisbezoek niet opvallend er uitsteekt, kan goed komen doordat het ook geen substantiele verschillen zijn tussen mensn die wél bemet raken en die die dat niet doen... wat echter ok niet veel bewijst over het risico, hooguit dat weinig mensen er geheel mee kunnen of willen ophouden, het vavak gewoon essentiele activiteiten zijn die iedereen moet doen

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Op vrijdag 19 maart 2021 09:20 schreef DrParsifal het volgende:
via twitter om gelijk een samevatting te hebben:
https://twitter.com/Roxytonin/status/1372801396039249923