March 3rd, 2020

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Ингибиторы широкого спектра для коронавирусов

В прошлом году опубликовали  эту статью, и, в принципе, сейчас самое время продолжать исследования, тк Ковид-19  будет персистировать еще долго. Конечно, это исследования "ин витро" и на животных.
Coronaviruses (CoVs) act as cross-species viruses and have the potential to spread rapidly into new host species and cause epidemic diseases. Despite the severe public health threat of severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome CoV (MERS-CoV), there are currently no drugs available for their treatment; therefore, broad-spectrum inhibitors of emerging and endemic CoVs are urgently needed. To search for effective inhibitory agents, we performed high-throughput screening (HTS) of a 2,000-compound library of approved drugs and pharmacologically active compounds using the established genetically engineered human CoV OC43 (HCoV-OC43) strain expressing Renilla luciferase (rOC43-ns2Del-Rluc) and validated the inhibitors using multiple genetically distinct CoVs in vitro. We screened 56 hits from the HTS data and validated 36 compounds in vitro using wild-type HCoV-OC43. Furthermore, we identified seven compounds (lycorine, emetine, monensin sodium, mycophenolate mofetil, mycophenolic acid, phenazopyridine, and pyrvinium pamoate) as broad-spectrum inhibitors according to their strong inhibition of replication by four CoVs in vitro at low-micromolar concentrations. Additionally, we found that emetine blocked MERS-CoV entry according to pseudovirus entry assays and that lycorine protected BALB/c mice against HCoV-OC43-induced lethality by decreasing viral load in the central nervous system. This represents the first demonstration of in vivo real-time bioluminescence imaging to monitor the effect of lycorine on the spread and distribution of HCoV-OC43 in a mouse model. These results offer critical information supporting the development of an effective therapeutic strategy against CoV infection..

Кстати- интересная деталь- коронавирусы поражают не только респираторную систему, но и желудочно-кишечную, и ЦНС. У родственника Ковид-19, САРС, такая способность обнаружена была.

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Врачам на заметку

Staff safety during emergency airway management for COVID-19 in Hong Kong:

Medical professionals caring for patients with coronavirus disease 2019 (COVID-19) are at high risk of contracting the infection
Aerosol-generating procedures, such as non-invasive ventilation (NIV), high-flow nasal cannula (HFNC), bag-mask ventilation, and intubation are of particularly high risk. ...All medical personnel involved in the management of patients with suspected COVID-19 must adhere to airborne precautions, hand hygiene, and donning of personal protective equipment. All aerosol-generating procedures should be done in an airborne infection isolation room. Double-gloving, as a standard practice at our unit, might provide extra protection and minimise spreading via fomite contamination to the surrounding equipment after intubation.
...to avoid confusion and potential harm, we do not recommend using NIV or HFNC until the patient is cleared of COVID-19. Airway devices providing 6 L/min or more of oxygen are considered high-flow and we discourage their use if an airborne infection isolation room is unavailable.

 (Пациентам на заметку:  врачи не рекомендуют  использование масок и канюлей  исходя  не из нужд пациентов, а из того, что при их использовании возрастает риск для инфицирования медперсонала, ввиду аэросолизации  выделяемого возбудителя)

We recommend that endotracheal intubation is done by an expert specialised in the procedure, and early intubation should be considered in a patient with deteriorating respiratory condition. For all cases, backup airway plans should be ready.
We recommend avoiding bag mask ventilation for as long as possible; and optimising preoxygenation with non-aerosol-generating means. Methods include the bed-up-head-elevated position, airway manoeuvres, use of a positive end expiratory pressure valve, and airway adjuncts. If manual bagging is required, we suggest gentle ventilation via a supraglottic device instead of bag mask ventilation.
Although no robust evidence is available to show that the use of supraglottic devices are less aerosol-generating than BMV, the devices are easy to insert and can achieve sufficient seal pressure. They also help to spare manpower and thus reduce staff exposure.


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Индекс риска летального исхода

Для коронавирусных пациентов предложен врачами из Уханьского госпиталя Ханкоу. Этот индекс поможет прогнозировать течение заболевания и принимать решение "тройкам" (в условиях перегруженности госпиталей). Основан он на показателе воспаления- уровне в крови С-реактивного белка. Закономерно,  что чем больше его уровень (особенно у тех, кому за 60) -тем тяжелее протекает (и будет протекать) заболевание. Авторы предлагают "рубежными" уровень 34 мг  на литр, и возраст в 60 лет.
The study was done by creating 3 subgroups of the people infected using age and CRP ( the severity of the virus based on inflammation in the liver). Mortality of the disease is measured along a 12 day period.

Tier 1:

Age > 60

CRP > 34 mg/L (severe symptoms)

Mortality: 33.2%

Tier 2:

Age < 60

CRP > 34 mg/L (severe symptoms)

Or

Age > 60

CRP < 34 mg/L (less severe symptoms)

Mortality: 5.6%

Tier 3:

Age < 60

CRP < 34 mg/L (Less Severe Symptoms)

Mortality: 0.0%

The 577 patients that were used in the study were admitted to Wuhan Hankou hospital between timeframe of January 21st to February 5th. Median age was 55 with 22.8% of patients having severe pneumonia and 37.7% tested positive for SARS-CoV-2.

It must be noted that "less severe" is the not the same as "mild cases" which seem to be about 80% of all cases. Cumulative mortality was 8.7%.