Coronavirus : A Detailed Discussion

Coronaviruses are a group of related viruses that cause diseases in mammals and birds. Largely enveloped RNA viruses which mostly cause common colds, lower respiratory tract infections.

• The novel corona viruses are MERS SARS and SARS-CoV-2 the causative of COVID-19, In humans, coronaviruses cause respiratory tract infections that can be mild, such as some cases of the common cold (among other possible causes, predominantly rhinoviruses), and others that can be lethal, such as SARS, MERS, and COVID-19. Human Corona viruses are difficult to cultivate and therefore poorly characterised
• Animal corona viruses cause diseases of economic importance in domestic animals, Symptoms in other species vary: in chickens, they cause an upper respiratory tract disease, while in cows and pigs they cause diarrhea.

PROPERTIES :

The viral envelope consists of a lipid bilayer where the membrane (M), envelope (E) and spike (S)structural proteins are anchored. A subset of coronaviruses (specifically the members of betacoronavirus subgroup A) also have a shorter spike-like surface protein called hem-agglutinin esterase (HE).

• Enveloped 120-160nm unsegmented genome SSRNA(27-32kb) largest genome among RNA viruses
• Polyadynylated at 3′ end and the isolated genome is infectious 
• 20nm long club shaped projections on outer surface suggesting the solar corona 
• Viral structures include 50-6-kDa phosphorylated nucleocapsid(N), 20-35 kDa membrane glycoprotein(M) which interact with the nucleocapsid(N) and spike.
• All corona viruses encode genes in the following order : POL-S-E-M-N-3′

The club-shaped viral spike peplomers (colored red), create the look of a corona surrounding the virion seen under an electron microscope.

There are totally 6 human corona viruses :

• 229E, NL63, OC43, HKU1, SARS-CoV, MERS-CoV, SARS-CoV-2
• Six species of human coronaviruses are known, with one species subdivided into two different strains, making seven strains of human coronaviruses altogether. Four of these strains produce the generally mild symptoms of the common cold:
  • Human coronavirus OC43 (HCoV-OC43), of the genus β-CoV
  • Human coronavirus HKU1 (HCoV-HKU1), β-CoV, its genome has 75% similarity to OC43
  • Human coronavirus 229E (HCoV-229E), α-CoV
  • Human coronavirus NL63 (HCoV-NL63, New Haven coronavirus), α-CoV
  • Three strains (two species) produce symptoms that are potentially severe; all three of these are β-CoV strains:
  • Middle East respiratory syndrome-related coronavirus (MERS-CoV), previously known as novel coronavirus 2012 and HCoV-EMC
  • Severe acute respiratory syndrome coronavirus (SARS-CoV or “SARS-classic”)
  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), previously known as 2019-nCoV or “novel coronavirus 2019”

  The coronaviruses HCoV-229E, -NL63, -OC43, and -HKU1 continually circulate in the human population and cause respiratory infections in adults and children world-wide.

• In domestic animals

  • Infectious bronchitis virus (IBV) causes avian infectious bronchitis.
  • Porcine coronavirus (transmissible gastroenteritis coronavirus of pigs, TGEV).
  • Bovine coronavirus (BCV), responsible for severe profuse enteritis in of young calves.
  • Feline coronavirus (FCoV) causes mild enteritis in cats as well as severe Feline infectious peritonitis (other variants of the same virus).
  • the two types of canine coronavirus (CCoV) (one causing enteritis, the other found in respiratory diseases).
  • Turkey coronavirus (TCV) causes enteritis in turkeys.
  • Ferret enteric coronavirus causes epizootic catarrhal enteritis in ferrets.
  • Ferret systemic coronavirus causes FIP-like systemic syndrome in ferrets.
  • Pantropic canine coronavirus.
  • Rabbit enteric coronavirus causes acute gastrointestinal disease and diarrhea in young European rabbits. Mortality rates are high.
  • Porcine epidemic diarrhea virus (PED or PEDV), has emerged around the world.

REPLICATION :

The life cycle of a coronavirus

A number of the nonstructural proteins coalesce to form a multi-protein replicase-transcriptase complex (RTC). The main replicase-transcriptase protein is the RNA-dependent RNA polymerase (RdRp). It is directly involved in the replication and transcription of RNA from an RNA strand. The other nonstructural proteins in the complex assist in the replication and transcription process. The exoribonuclease non-structural protein, for instance, provides extra fidelity to replication by providing a proofreading function which the RNA-dependent RNA polymerase lacks.

One of the main functions of the complex is to replicate the viral genome. RdRp directly mediates the synthesis of negative-sense genomic RNA from the positive-sense genomic RNA. This is followed by the replication of positive-sense genomic RNA from the negative-sense genomic RNA.

The Coronaviruses do not grow well in cell culture and replicate in the cytoplasm.

They attach to receptors of target cells by glycoprotein on viral envelop( S&HE).

The receptors for attachment are:

• Aminopeptidase N for 229E
• Angiotensin Converting Enzyme 2 for SARS-CoV
• Dipeptidyl Peptidase 4 for MERS-CoV

INFECTION:

These viruses are highly species specific and show tropism for epithelial cells of the respiratory and gastrointestinal tract.

They have the potency to disseminate in Vivo and are usually but not always restricted to the the Upper respiratory tract.

SARS-CoV:

• Causes serious respiratory infection, Pneumonia like illness and progressive respiratory failure.
• The Viruses cn be detected in kidney, liver,small intestines and in stools
• This virus is believed too have originated in bats and amplified in palm civets and transmitted to humans through live animal markets.
• Some have caused gastroenteritis like the porcine transmissible gastroenteritis coronavirus.

CLINICAL FINDINGS :

• Common Cold which is afebrile in adult patients and is similar to those produced by Rhinoviruses typified by nasal discharge.
• Incubation period- 2 to 7 days averaging at 6 days. The symptoms last 1 week and the lower tract is mostly involved although pneumonia may occur.
• Asthmatic children may have wheezing attacks and respiratory symptoms are exacerbated in adults with COPD.
• Common early symptoms include, fever, malaise,chills,headache,dizzinessand cough, sore throat followed by a few days later by shortness of breath.

  

  Typical CT imaging findings

• Abnormal chest X-ray findings, progression to Acute respiratory distress, requirement of ventilatory support and death from progressive respiratory failure.
• The SARS involves a cytokine storm in about 2 weeks.
• MERS cause mild to severe respiratory syndrome and the incubation period is 2-13 days.
• Lab findings; Leukopenia, lymphopenia, thrombocytopenia and elevated lactate dehydrogenase.

IMMUNITY :

• Immunity against surface projection antibodies is probable for protection.

95% people with SARS and MERS developed antibody response to viral antigen detectable by Fluorescent Antibody test or ELISA.

LAB DIAGNOSIS:

CDC rRT-PCR test kit for COVID-19

The standard method of testing is real-time reverse transcription polymerase chain reaction (rRT-PCR). The test is typically done on respiratory samples obtained by a nasopharyngeal swab, however a nasal swab or sputum sample may also be used.Results are generally available within a few hours to two days.Blood tests can be used, but these require two blood samples taken two weeks apart and the results have little immediate value.

TREATMENT:

• Some medical professionals recommend paracetamol (acetaminophen) over ibuprofen for first-line use. The WHO does not oppose the use of non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen for symptoms, and the FDA says currently there is no evidence that NSAIDs worsen COVID-19 symptoms.
• While theoretical concerns have been raised about ACE inhibitors and angiotensin receptor blockers, as of 19 March 2020.
• Other Schedule H Drugs: 

1. Hydroxychloroquine
2. Choloroquine
3. Tocilizumab- Investigational for Patient with Shock
4. Lopinavir/Ritonavir- Negative RCT
5. Convalescent Serum- Emergency IND
6. Corticosteroids