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