COVID 19: Treatment and Prevention (Part I)

hemagglutinin-esterase, sialic acid

2 of the non-SARS human species of the betacoronavirus genus, HCoV-OC43 and HCoV-HKU1, have __-__ activity and probably utilize __ __ residues as receptors

polyadenylated

3'-end of COVID-19 is ___

capped

5'-end of COVID-19 is ___

1. 229E 2. NL63 3. OC43 4. HKU1

7 Coronavirus serotypes have been associated with disease in humans: 1. HCoV-___ (alpha coronavirus) 2. HCoV-___ (alpha coronavirus) 3. HCoV-___ (beta coronavirus) 4. HCoV-___ (beta coronavirus) 5. MERS-CoV (the beta coronavirus that causes MERS) 6. SARS-CoV (the beta coronavirus that causes SARS) 7. SARS-CoV-2 (COVID-19)

11.5 days

97.5% of people infected with SARS-CoV-2 will exhibit symptoms by __ __

Rhinolophus affins bat

A coronavirus closely related to SARS-CoV-2 sampled from a __ __ __ in Yunnan in 2013 has now been identifed

COVID-19

A disease caused by SARS-CoV-2 that can trigger a respiratory tract infection It can affect your -Upper Resp. Tract (sinuses, nose, throat) -Lower resp. tract (windpipe and lungs)

Reversed halo sign (atoll sign)

A focal rounded GGO surrounded by a more or less complete rign like consolidation

Subpleural curvilinear line

A thin curvilinear opacity with 1-3mm thickness, lying less than 1cm from and parallel to the pleural surface

Human coronavirus 229E and Human coronavirus NL63

Alpha-coronavirus only contains 2 coronaviruses:

enveloped

Alphacoronavirus is enveloped/naked

Consolidation

Alveolar air being replaced by pathological fluids, cells, or tissues, manifested by an increase in pulmonary paraenchymal density that abscures the margins of underlying vessels and airway walls.

4

Animal and human coronaviruses fall into __ distinct genera

mild, children

Anyone can get COVID-19 and most infections are usually __, especially in __ and young adults

2015

As of __ there were no further reports of cases of SARS

Nucleocapsid proetein (N)

Associates with the RNA genome to form the nucleocapsid May be involved in the regulation of viral RNA synthesis and may interact with M protein during virus budding

third (SARS, then MERS, now COVID-19)

Covid-19 is the __ documented spillover of an animal coronavirus to humans

baciliform

Bafinivirus is in the shape of ___ (170-200 x 75-88nm)

MERS-CoV, SARS-CoV, and SARS-CoV-2

Betacoronavirus genus also contains several bat viruses: (3) Although they are genetically somewhat distant from HCoV-OC43 and HCoV-HKU1

CoV-OC43 and HKU1

Betacoronaviruses (2)

Betacoronavirus 1

Bovine coronavirus is so similar to HCoV-OC43 that the 2 viruses have been merged into a single species termed ___ __

severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

COVID-19

1. Spike glycoprotein 2. N 4. Hemagglutinin-esterase dimer

COVID-19 Virus Particles 1. __ __ (S) 2. RNA and __ protein 3. Envelope 4. ___-__ ___ (HE)

24 hours

COVID-19 cardboard surfaces last for __ __

4 hours

COVID-19 copper surfaces last for __ __

seventh

COVID-19 is the __ member of the Coronaviridae known to infect humans

2, 3 days

COVID-19 plastic or stainless steel surfaces last for __ __

person-to-person contact

COVID-19 spreads the same way other coronaviruses do, mainly through __-__-__ __ -Spreads when a sick person coughs or sneezes

pneumonia, septic shock

COVID-19 virus can lead to __ , respiratory failure, __ __, and death

infants, children

Certain common cold coronaviruses cause diarrhea in __ and __

Cold

Cold vs. Flu Cough is mild to moderate

Flu

Cold vs. Flu Coughing is common, and can become severe

Cold

Cold vs. Flu Diarrhea never occurs

Flu

Cold vs. Flu Diarrhea occurs sometimes in children

Flu

Cold vs. Flu Extreme exhaustion is usual and starts early

Cold

Cold vs. Flu Extreme exhaustion never occurs

Flu

Cold vs. Flu Fatigue and weakness is intence and can last up to 2-3 weeks

Cold

Cold vs. Flu Fatigue and weakness is mild

Cold

Cold vs. Flu Fever is rare

Flu

Cold vs. Flu General aches or pains are usual and often severe

Flu

Cold vs. Flu Headache is intense

Cold

Cold vs. Flu Headache is rare

Flu

Cold vs. Flu High fever that can last 3-4 days

Both

Cold vs. Flu Loss of smell and taste occurs sometimes

both

Cold vs. Flu Shortness of breath is rare

Cold

Cold vs. Flu Slight general aches and pains

Cold

Cold vs. Flu Sneezing is usul

Flu

Cold vs. Flu Sneezing only occurs sometimes

Both

Cold vs. Flu Sore throat is common

Cold

Cold vs. Flu Stuffy nose is common

Flu

Cold vs. Flu Stuffy nose occurs sometimes

Coronavirinae, Torovirinae

Coronaviridae there are 2 sub-families: __ and __

mammals, birds

Coronavirinae infects __ and __

spherical

Coronavirinae is ___ (120-160nm)

Coronaviridae, Nidovirales

Coronavirus belongs to ___ Family and above that Order ___

largest

Coronavirus has the __ known viral RNA genomes, with a length of 26-32kb

central nervous system

Coronavirus role in the __ __ __ diseases, except for a single case report of encephalitis in a severly immunocompormised infant, has been suggested but no proven

1. Fever 2. Cough 3. trouble breathing

Coronavirus symptoms are a 1. __ of 100F or higher 2. ___ 3. ___ __

1960's

Coronavirus was identified in the __

1. +ssRNA, is 2. Largest 3. IV

Coronavirus: 1. ___, it (is/is not) enveloped, and it's genome size is 26-32kb. 2. (Smallest/Largest) +ssRNA virus 3. Coronavirus is a Class ___ virus

Nidovirales

Coronaviruses are classified as a family within the ___ order, viruses that replicate using a nested set of mRNAs

human, animal

Coronaviruses are important __ and __ pathogens

enveloped, +

Coronaviruses are medium sized __ (+/-)-stranded RNA viruses whose name derives from their characteristic crown-like appearance in electron micrographs

bats

Coronaviruses are widespread among birds and mammals with __ being host to the largest variety of genotypes

severe acute respiratory syndrome (SARS) and Middle East Respiratory syndrome (MERS)

Coronaviruses have led to 2 serious outbreaks before December 2019

nose, sinuses, upper throat, are not

Coronaviruses infect __, __, or __ __ Most coronaviruses are/are not dangerous

N protein

Cytotoxic T lymphocytes recognize portions of the __ __ have been identified

Serology, CT scans, and RT-PCR

Diagnosis of COVID-19 is:

HCoV-OC43, HCoV-229E

Discovered in the 60's and were shown in volunteer experiments to produce common colds in adults Studies in the 70's and 80's linked them to as much as 1/3 of upper Resp. tract infections during winter outbreaks 5-10% of overall colds in adults, and som proportion of lower respiratory illness in children

1/3

During epidemics, common cold coronaviruses are the cause of up to __ of community acquired upper resp. tract infections in adults Probaly also play a role in severe resp. infections in both children and adults

Symptoms of COVID-19

Fever or chills Cough Shortness of breath or difficulty breathing Fatigue Muscle or body aches Headache New loss of taste or smell Sore throat Congestion or runny nose Nausea or vomiting Diarrhea Trouble breathing Persistent pain or pressure in the chest New confusion Inability to wake or stay awake Pale, gray, or blue-colored skin, lips, or nail beds, depending on skin tone

Pangolins

Found throughout Southeast Asia They're used as both a food source and their scales are utilized in traditional Chinese medicine SARS-CoV-like CoV was detected from lung samples of 2 dead Malayan ____

+ssRNA

Genome of COVID-19

1. positive, polyprotein, non-structural 2. 4 a) Spike (S), membrane (M), envelope (E), and nucleocapsid (N)

Genome of Coronaviruses 1. The first two-thirds of the 26-32 Kb, ___ sense RNA genome encodes a large __ (ORF1a/b) that's proteolytically cleaved to generate 15 or 16 __-___ proteins (nsps; nsps for severe acute respiratory syndrome coronavirus) 2. The 3'-end third of the genome encodes four structural set of accessory proteins: a) Spike (S), membrane (M), envelope (E), and nucleocapsid (N) b) Along with a set of accessory proteins that are unique to each virus species 3. Some SARS-CoV viruses express an additional structural protein

Alpha coronavirus

HCoV-229E and HCoV-NL63

aminopeptidase N (APN)

HCoV-229E like several animal alphacoronaviruses utilizes ___ as its major receptor

S, M, N, E, HE

HCoV-229E, HCoV-NL63, and the SARS coronavirus possess four genes that encode the __,__,__, and ___ proteins respectively Whereas HCoV-OC43 and HCoV-HKU1 also contain a 5th gene that encodes the ___ protein

angiotensin-converting enzyme 2 (ACE-2)

HCoV-NL63 like SARS-CoV and SARS-CoV-2 (betacoronaviruses), uses ___-__ __ __

Membrane (M) protein

Has a short N-terminal domain that projects on the external surface of the envelope and spans the envelope 3x leaving a long C terminus inside the envelope

Ground glass opacity (GGO)

Hazy areas with slightly increased density in lungs without obscuration of bronchial and vascular margins which may be caused by partial displacement of air due to partial filling of airspaces or intterstitial thickening

Mouse

Important animal Betacoronaviruses: __ hepatitis virus, a lab model for both viral hepatitis and demyelinating CNS disease and Bovine coronavirus, a diarrhea-causing virus of cattle

transmissable gastroenteritis virus, feline infectious peritonitis virus

Important animal alphacoronaviruses are transmissable gastroenteritis virus of pigs and feline infectious peritonitis virus. There are also several related bat coronaviruses among the alphacoronaviruses.

14 days

Monitoring people exposed to SARS-CoV-2 for __ __ for development of symptoms should be sufficient to identify 99% of cases or more

Fever, fatigue, and lack of appetite

Most common symptoms among people who had COVID-19: -___ (99%) -___ (70%) -___ __ ___ (40%)

several hours

Most viruses can live for __ __ on a surface that they land on

outbreak, coronavirus

In early 2020, after a December 2019 __ in China, the WHO identified SARS-CoV-2 as a new type of ___ The outbreak quickly spread around the world

E, M, N

In the SARS-CoV the __ protein along with __ and __ are required for propery assembly and release of the virus.

Fall, winter

In the U.S. regular coronaviruses are more common in the __ and __ but anyone can come down with a coronavirus infection at any time.

5-6 days (14 days)

Incubation period of COVID-19 is:

Himalayan palm civets or raccoon dogs

Intermediate host of SARS-CoV are possibly

SARS

Little further info. developed after this until the emergence of ___ in 2002 and the development of molecular diagnostic methods -Then HCoV-NL63 and HCoV-HKU1 were quickly discovered and found to have worldwide distribution

Middle East Respiratory Syndrome

MERS

Saudi Arabia

MERS first appeared in __ __ and then in other countries in the Middle East, Africa, Asia, and Europe

September 2012, present

MERS has appeared since __ __ to the __

cytokine release syndrome, cytokine storm

Many COVID-19 complications may be caused by a condition known as __ __ __ or a __ __ This is when an infection triggers your immun esystem to flood your bloodstream with inflammatory proteins called cytokines; they can kill tissue and damage your organs

FIbrosis lesions

May form during the healing of pulmonary chronic inflammation or proliferative diseases with gradual replacement of cellular components by scar tissues

tissue culture

None of the common cold human coronaviruses replicate easily in __ __, and until recently have impedded progress in their study

Vascular enlargement

Often described as the dilatation of pulmonary vessels around and within the lesions on CT images

65

People over __ are the most likely to get a serious illness

Spike protein (S)

Projects through the viral envelope and forms the characteristic spikes in the coronavirus "crown" Heavily glycosylated, probably forms a homotrimer, and mediates receptor binding and fusion with the host cell membrane.

Deltacoronavirus

Recently discovered avian coronaviruses found in several species of songbirds

Nodules

Refers to a rounded or irregular opacity with well or poorly defined edges, measuring less than 3cm in diameter

Air bubble sign

Refers to a small air-containing space in the lung, which might be the pathological dilation of a physiological space or a cross section of the bronchiolectasis or associated with the process of consolidation resorption

Community spread

Refers to someone who gets the virus even though they haven't been out of the country or haven't been exposed to someone who's traveled abroad or who has COVID-19

1. RNA polymerase 2. mRNA, 3'

Replication of viral RNA occurs in the host cytoplasm by a unique mechanism in which: 1. ___ __ binds to a leading sequence and then detaches and reattaches at multiple locations 2. Allows for the production of a nested set of __ molecules with common __ ends

catherin, endocytosis

S-protein are __-dependent and independent __ mediated entry

Severe acute respiratory syndrome

SARS

November 2002-July 2003

SARS was rampant around:

new CoV

Sequence analysis against coronavirus reference genomes -Sequences were best matched to SARS-CoV-2s (Avg. 95.41%) The dead Malayan pangolins may carry a __ __ closely related to SARS-CoV-2

26-32kb

Size of COVID-19 genome

mild

Some people have no symptoms, most have __ illness It can be severe and sometimes fatal

bats

Subsequent studies found that SARS-CoV originated from __ and interspecies transmission to humans took place via an intermediate host

14 days

Symptoms start about 1 day after exposure, but can be as long as __ __

True

T/F Some people who don't have the virus don't have symptoms, but they can still spread the virus

False (You won't know)

T/F In most cases you will know whether you have a coronavirus or a different cold-causing virus such as a rhinovirus

True (most likley as a young child)

T/F: Almost everyone gets a coronavirus infection at least once in their life

viral assembly

The M protein plays an important role in __ __

HE genes

The __ __ of coronaviruses have sequence homology with influenza C, H glycoprotein and may reflect an early recombination between the 2 viruses.

PCR

The ____ may be used for the diagnosis of each of the 4 coronaviruses, and has allowed substantial investigation into their epidemiology and pathogenicity

HCoV-229E and HCoV-NL63

The alphacoronavirus genus includes 2 human virus species

pleural changes

including pleural thickening and pleural effusion were reported in COVID-19, among which, the former sign is more prevalent

Alpha, Beta, Delta, Gamma

The coronavirus subfamily is further classified into 4 genera:

88, 50

The genetic sequence of the COVID-19 showed more than ___ identity to SARS-CoV and __ to the MERS-CoV, and both originate in bats

S, M, N, HE, and E

The genome encodes 4/5 structural proteins:

neuraminic acid

The hemagglutinin moiety binds to __ __ on the host cell surface, possibly permitting initial adsorption of the virus to the membrane The esterase cleaves acetyl groups from ** ***

Betacoronavirus

The hemagglutinin-esterase glycoprotein (HE) is found ONLY in the ___, HCoV-OC43 and HKU1

glycoprotein spikes, helical, spherical

The host-derived membrane is studed with ___ ___ and surrounds the genome, which is encased in a nucleocapsid that is ___ in its relaxed form but assumes a roughly ___ shape in the virus particle

Alpha and beta coronaviruses

The human coronaviruses are in 2 of these 4 genera (A,B,G,D)

S protein

The major antigens that stimulate neutralizing antibody, as well as important targets of cytotoxic lymphocytes are on the __ __

5 days

The median incubation period from infection with SARS-CoV-2 to onset of symptoms is apx. __ __

9th century BC

The oldes common ancestor of coronavirus has been dated as far back as the __ __ __ Some studies published in 1990 specified the most recent common ancestors as follows: -Betacoronavirus (3300 BC) -Deltacoronavirus (3000 BC) -Gammacoronavirus (2800 BC) -Alphacoronavirus (2400 BC)

Envelope (E) protein

The small __ __ leaves its C terminus inside the envelope and then either spans the envelope or bends around and projects its N terminus internally. Function isn't known

runny nose, coughing, sore throat, and (sometimes) a fever

The symptoms of most coronaviruses are similiar to any other upper resp. infection including a:

L and S

There are 2 strains of COVID-19

Beta

There are at least 4 subgroups in the __-coronavirus (A, B, D, C)

crazy paving pattern

Thickened interlobular septa and intralobular lines with superimposition on a GGO background, resmbling irregular paving stones, which was not frequently observed as GGO and consolidation

Reticular pattern

Thickened pulmonary interstitial structures such as interlobular septa and intralobular lines, manifested as a collection of innumerable small linear opacities on CT images

nursing homes, weakened

Those who live in __ __ or long-term care facilities, who have ___ immune systems, or who have medical conditions including -High bpm -Heart disease -Lung disease -Asthma -Kidney disease -Obesity -Diabetes -Cancer treatment -Liver disease -Cigarette smoking

MERS

Traced to zoonotic transmission of a novel coronavirus (likely from bats via dromedary camels) in Saudi Arabia -27 countries -2494 cases -858 deaths

True

True or False: That's why it's important to disinfect surfaces to get rid of virus

False (cannot catch)

True or False: There is evidence that humans can catch coronavirus from an animal

True

True or False: Determining the source virus in the animal populaiton from teh market is challenging

1. spikes 3. plasma membrane 4. cytoplasm 5. budding

Virus Replication 1. Cell surface receptors via ___ 2. Endocytosis 3. Release genome via fusion of viral envelope with the __ __ 4. Replication in ___ 5. Exit-___

betacoronavirus, 2B

WHO has classifed COVID-19 as a ___ of group __

low

Your risk of infection of COVID-19 is __ if you: -Aren't in an area where COVID-19 is spreading -Haven't traveled from an area where it's spreading -Haven't been in contact with someome who has it

L strain, S

__ __ was more common in early stages of the outbreak; the __ type is older

April 2014

__ __: The first American was hospitalized for MERS in Indiana and another case was reported in Florida -Both had just returned from Saudi Arabia

May 2015

__ __: There was an outbreak of MERS in South Korea, which was the largest outbreak outside of the Arabian Peninsula

Pre-symptomatic

__-__ conditions may be contagious (2-3 days before symptoms) -Asymptomatic transmission

HCoV-OC43

__-__ is thought to have jumped from 1 animal host to the other as recently as 1890

S protein, ACE2, CD209L, L-SIGN, DPP4

___ ___= binds to cellular receptors ___=SARS-CoV and SARS-CoV-2 ___/___-__=SARS-CoV ___=MERS-CoV

Torovirus, Bafinivirus

___ infects mamamls, while __ infects fish

Air bronchogram

a pattern of air filled (lowattenuation) bronchi on a background of opaque (highattenuation) airless lung and was reported to be another CT manifestation of COVID-19

Avian Infectious Bronchitis Virus (AIBV)

an important veterinary pathogen causing respiratory and reproductive tract disease in chickens caused by gamma-coronoviruses

Beta coronavirus

causes SARS-CoV, MERS-CoV, and SARS-CoV2 (COVID-19)

HCoV-OC43, HCoV-NE63, HCoV-HKU1, and HCoV-229E

common cold human coronaviruses

Halo sign

nodules or masses surrounded by ground glass

Gammacoronavirus

primarily avian coronaviruses

swab test

the most common method looks for signs of the virus in your upper resp. tract

SARS

was initiated by zoonotic transmission of a novel coronavirus in China -26 countries -8,098 cases -774 deaths