COVID-19 Pneumonia

INTRODUCTION

Coronavirus infection has drawn the attention of everyone all over the world. The infection which began in China has spread all over the globe and mankind is worried about the disease caused by the virus. Most of the human coronavirus infections have been recognised in the last two decades. The illness has ranged from common cold to more severe pandemics such as Severe acute respiratory syndrome (SARS), Middleeast respiratory syndrome (MERS) and a novel coronavirus disease (COVID-19) from a new strain of virus that had not been previously identified in humans. Coronaviruses are zoonotic and are transmitted between animals and humans. In the course of 5 months world has witnessed 6 million cases with a mortality of 3.6 lakhs. Among the worst affected countries, the US stands on the top with 13.6 million patients and death of 1.03 lakh. India has witnessed 1,68,173 cases with a mortality of 4,771 individuals on May 30, 2020.

Causative agent

Coronaviruses are enveloped, non-segmented, particles. They are spherical and the core beneath the greasy surface contains matrix protein enclosed within which is a single strand of positive-sense RNA¹ . The genetic material in the core can inject into vulnerable cells to infect them. There are spiky glycoprotein projections on the outer surfaces of the envelope, resembling the points of a crown or a halo. The viruses are named coronaviruses because of the crown-like (or ‘corona’ in Latin) appearance of their virus particles when seen under an electron microscope. The spikes bind and fuse with host-cell receptors and facilitate the entry of the virus into the host cell. On entry into the cell it gets uncoated and the genome gets transcribed and then translated to the new host and begins to replicate. The genetic material of the virus becomes host cell’s internal machinery. The cells are converted into a factory. New virions bud from host cell membrane.

Spread of infection

The role of environmental contamination in the transmission of COVID-19 is not yet clear. The infection spreads from person-to-person from close contact. The spread occurs via the respiratory tract through the droplets following cough or sneeze of the infected person. There is a suspicion that the infection can spread from fomites such as chair, door, utensils, door handle that have been touched by the infected persons. It must be noted that the spread can occur even when the person is asymptomatic.

People of all ages are susceptible to COVID-19. Older persons and persons with pre-existing medical conditions such as heart disease, asthma, diabetes appear to be more vulnerable to becoming severely ill with the virus.

Clinical features

The condition presents with fever, non-productive cough, dyspnoea, myalgia, and fatigue. The condition may progress to pneumonia and chest CT images showed bilateral ground=glass opacity. There is lymphopenia, prolonged prothrombin time, and elevated lactic dehydrogenase. The most common CT findings are bilateral, basal and peripheral predominant ground glass opacity, consolidation or both implying the presence of lung injury. The cases are confirmed by the study of throat swabs with real time reverse transcription polymerase chain reaction (RT-PCR). The patients exposed to the corona virus infection may remain asymptomatic or seriously ill requiring treatment is intensive care unit (ICU). After an incubation period varying from 2 to 14 days, the condition presents with symptoms similar to any other upper respiratory tract infection such as running nose, sneezing, sore throat, cough, shortness of breath and sometimes fever. Many of these symptoms simulate flu or a common cold. Due to similarities of the symptoms from different viruses, it becomes difficult to identify the disease based on symptoms alone. Complications include acute respiratory distress syndrome, shock, anaemia, acute cardiac injury and secondary infection. No antiviral treatment was found to be effective² . 2019-nCoV infection is clustered within groups of humans in close contact. It has affected older men with comorbidities³ .

Autopsy studies

Autopsy studies of the lungs from patients with Covid-19 has shown presence diffuse alveolar damage with perivascular T-cell infiltration. There are distinctive vascular features, consisting of severe endothelial injury. There is widespread thrombosis with microangiopathy. Alveolar capillary microthrombi were 9 times as prevalent in patients with Covid-19 as in patients with influenza (P<0.001)(4).

Diagnosis

The infection has to be suspected in persons who have visited areas with the outbreak of infection. Three specimens of serum, respiratory secretions (sputum, bronchoalveolar lavage fluid, tracheal aspirate) and upper respiratory tract secretions (nasal or throat swabs) should be sent to the laboratory identify the cause of the infection.

The samples are to obtained from the lower respiratory tract, including sputum, bronchoalveolar lavage (BAL) and tracheal aspirate. In situations where the sample can’t be obtained from the lower respiratory tract, samples from the upper respiratory tract (nasopharyngeal swab and oropharyngeal swab) can used. The swabs should be kept and transported in the tube with viral transport medium. Samples should be kept refrigerated at 4-8o C and sent to the laboratory with molecular diagnostic facility. Real-time reverse transcriptase–polymerase chain reaction (RT-PCR) tests for COVID-19 nucleic acid is used to determine positivity of the sample and those positive are to be notified immediately (5).

Prognosis

Old age, male sex, and presence of comorbidities and progressive radiographic deterioration on follow-up CT might be risk factors for poor prognosis in patients with COVID-19 pneumonia.

Many of the deaths seen during the current outbreak of COVID-19 is among elderly persons and those with pre-existing conditions that make them more susceptible to serious illness from the viral attack.

Treatment

There is no specific antiviral treatment available for any human coronavirus infection. The individuals who are affected by a coronavirus usually recover on their own. The suspected cases are to be kept isolated at designated medical institutions and treated. The treatment is essentially symptomatic and supportive. They are advised staying at home to rest. The approach to contain this disease is to control the source of infection, use of personal protection to reduce the risk of transmission, and early diagnosis, isolation and supportive treatment for affected patients. Paracetamol and acetaminophen are given for the treatment of pain and fever. The patients are advised to drink plenty of fluids. Though antiviral agents, antibacterial agents and methylprednisolone have been given to these patients, no effective outcomes have been noted³ .

Convalescent plasma has been used as a therapeutic method. People who have recovered from COVID-19 disease would demonstrate the presence of antibodies against the virus. Infusing the antibodies to critically ill patients is expected to improve the chance of survival. However, it appears to be not very effective.

1. Upper respiratory tract infection without lung infiltrates, positive PCR

Chloroquine phosphate 500 mg orally twice a day for 5 days

Oseltamivir 150 mg orally twice a day for 5 days

2. Treatment of COVID-19 pneumonia

Chloroquine phosphate 500 mg orally twice a day for 10 days

Darunavir 800 mg /Cobicistat 150 mg orally for 2 weeks or Atazanavir 400 mg once daily orally daily with food for 2 weeks, and Oseltamivir150 mg orally twice a day with or without Corticosteroids in the form of Methylprednisolone 40 mg intravenously every 12hours for 5 days

These medications disable viruses by interfering with their attempts to replicate in host cells. The ‘protease inhibitors’, have shown promise against coronaviruses as they help to alert the immune system to viral invaders. Potential broad-spectrum antiviral agents act by increasing activity of the endosomal pH required for virus/cell fusion as well as interfering with the glycosylation of cellular receptors of SARS-COV.

All elderly with COVID-19 positive persons should be treated as high risk category and admitted and observed for complications^6,7

Those who are showing features of ARDS should receive supplemental oxygen. Elective intubation and mechanical ventilatory support with low tidal volume in prone position has to be undertaken. Due to the aerosol generation, nebulization and non-invasive ventilation are to be avoided. Low dose methyl prednisolone may be administered in presence of cytokine storm syndrome.

Older adults exhibiting features of Cytokine Release syndrome should be monitored by Interleukin (IL)-6, C-reactive protein and Ferritin. High IL-6, elevated CRP. Raised ferritin, and low level of procalcitonin confirms presence of cytokine storm. Methyl prednisolone 0.5-1mg /kg per day in two divided doses intravenously for a maximum of 6 days are to be given. They may be given tocilizumab 8mg/Kg IV (maximum of 400 mg) over 60 minutes. If there is no response two more doses may be repeated at 8 hour intervals. Low dose steroids (methyl prednisolone) and antibiotics are necessary in presence of septic shock.

Fluid resuscitation should be carried out less aggressively.

The response has to be seen by administering Saline bolus. Low dose inotropes (Noradrenaline 0.5mcg/kg/minute) are to administered if dyspnoea worsens.

Careful evaluation of older persons is vital as there may be coexisting refractory hyperglycaemia, refractory hypertension, hypokalaemia, bacterial and fungal infections, glaucoma, delirium, severe lymphopenia, and macrophage activation syndrome.

Prevention of spread:

No vaccine is available for preventive use.

Steps to stop the virus from spreading

The countries embarked to contain the spread of the virus, must detect cases early and isolate people who test positive for the virus. On detection of a case, the focus should be to trace the contact and treat them, if already infected. Immediate medical care has to be given once the symptoms are manifested. Spread can be stopped by avoiding mass gathering in enclosed spaces. People should avoid all non-essential travel to countries where community spread of the virus is reported.

Discharge

The patients are discharged or quarantine discontinued if they fulfil the following criteria (8)

• normal temperature lasting longer than 3 days,

• resolved respiratory symptoms,

• substantially improved acute exudative lesions on chest computed tomography (CT) images, and

• 2 consecutively negative RT-PCR test results separated by at least 1 day

Reduction of risk

WHO has suggested that people can help to reduce their risk of getting respiratory illnesses by following simple measures.

• Wash your hands often with soap and water for at least 20 seconds, and help young children do the same. If soap and water are not available, use an alcohol-based hand sanitizer.

• Cover your nose and mouth with a tissue when you cough or sneeze, then throw the tissue in the trash.

• Avoid touching your eyes, nose, and mouth with unwashed hands.

• Avoid personal contact, such as kissing, or sharing cups or eating utensils, with sick people

• Clean and disinfect frequently touched surfaces and objects, such as doorknobs.