Coronaviruses are important human and animal pathogens. By the end of 2019, a novel coronavirus was identified as the cause of a cluster of pneumonia cases in Wuhan, a city in the Hubei Province of China. It rapidly spread, resulting in an epidemic throughout China, followed by an increasing number of cases in other countries throughout the world. In February 2020, the World Health Organization designated the disease COVID-19, which stands for coronavirus disease 2019. The disease was subsequently declared as a global pandemic. The virus that causes COVID-19 is designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Being a disease known to medical science for less than a year, it has to be admitted that understanding on COVID-19 is still evolving.

Magnitude of the problem
Since the first reports of cases from Wuhan, cases have been reported in all continents, except for Antarctica. At the time of preparing this manuscript, global case tally has crossed 30 million with reported deaths nearing 10 lakhs. The reported case counts underestimate the overall burden of COVID-19, as only a fraction of acute infections are diagnosed and reported. Seroprevalence surveys in the United States and Europe have suggested that actual values exceed the incidence of reported cases by approximately 10-fold or more. India has more than 50 lakh reported cases with above 80000 deaths.

Source of The Virus
The closest similarity of SARS-CoV-2 is to bat coronaviruses, and it appears likely that bats are the primary source; whether COVID-19 virus is transmitted directly from bats or through some other mechanism (eg, through an intermediate host) is unknown. Understanding on the mode of transmission is incomplete. In Wuhan, at the beginning of the outbreak, association with a seafood market that sold live animals was noted, where most patients had worked or visited. However, as the outbreak progressed, person-to-person spread became the main mode of transmission.
Person-to-person spread is thought to occur through close-range contact, mainly via respiratory droplets. Virus is released in the respiratory secretions when a person with infection coughs, sneezes, or talks and can infect another person if it makes direct contact with the mucous membranes (nose, eyes, mouth, respiratory tract etc). Infection might also occur if a person's hands are contaminated by droplets or by touching contaminated surfaces and then they touch their eyes, nose, or mouth. Droplets typically do not travel more than six feet (about two meters). SARS-CoV-2 can also be transmitted through the airborne route (through inhalation of particles smaller than droplets that remain in the air over time and distance), but the extent to which this mode of transmission has contributed to the pandemic is controversial. Scattered reports of SARS-CoV-2 outbreaks (eg, in a restaurant, on a bus) have highlighted the potential for airborne transmission in enclosed, poorly ventilated spaces.

Period of infectivity
The precise interval during which an individual with SARS-CoV-2 infection can transmit infection to others is uncertain. The potential to transmit SARS-CoV-2 begins prior to the development of symptoms and is highest early in the course of illness; the risk of transmission decreases thereafter. Transmission after 7 to 10 days of illness is unlikely, particularly for otherwise immunocompetent patients with non-severe infection. Infected individuals are more likely to be contagious in the earlier stages of illness. One modeling study suggested that infectiousness started 2-3 days prior to symptom onset, peaked 1 day before symptom onset, and declined within seven days of symptoms. Infectivity of asymptomatic persons is less known.
The risk of transmission varies by the type and duration of exposure, use of preventive measures, and the amount of virus in respiratory secretions. The risk of transmission after contact with an individual with COVID-19 increases with the closeness and duration of contact and appears highest with prolonged contact in indoor settings.

Personal protective measures
Considering the global pandemic scenario and community transmission, personal protection advices have been issued by the World Health Organisation.

1. Practice social distancing by avoiding crowds, gatherings and maintaining a distance of six feet (two meters) from others when in public

2. Wear masks when out in public. Most individuals in the community can wear a non-medical mask (eg, a cloth or fabric mask). Individuals who are >60 years old or have underlying medical comorbidities should wear a medical mask, as should those who have symptoms consistent with COVID-19

3. Diligent hand washing, particularly after touching surfaces in public. Use of hand sanitizer that contains at least 60 percent alcohol is a reasonable alternative if the hands are not visibly dirty

4. Respiratory hygiene (eg, covering the cough or sneeze)

5. Avoiding touching the face (in particular eyes, nose, and mouth)

6. Cleaning and disinfecting objects and surfaces that are frequently touched.

7. Ensure adequate ventilation of indoor spaces.

A substantial proportion of patients infected with SARS-CoV-2 do not exhibit any symptoms or very subtle symptoms indistinguishable from a common viral flu. There are no symptoms that are diagnostic of COVID-19. The incubation period for COVID-19 may be as long as 14 days, with most cases occurring four to five days after exposure. Fever, cough, cold, muscle pain, body pain, headache, diarrhea, and loss of senses of smell or taste, are some of the common reported symptoms. Pneumonia is the most frequent serious manifestation of infection, with approximately 15 percent of patients developing severe infection with shortness of breath and low oxygen levels. Many other complications have been reported, blood clots resulting in heart attack, stroke, kidney failure etc. Mortality rate has varied between 1-5% in general.

The Lung and Covid-19

Pneumonia appears to be the most frequent serious manifestation of infection, characterized primarily by fever, cough, dyspnea, and bilateral infiltrates on chest Xray or CT scan of the chest. However, other features, including upper respiratory tract symptoms, myalgias, diarrhea, and smell or taste disorders, are also common. Although some clinical features (in particular smell or taste disorders) are more common with COVID-19 than with other viral respiratory infections, there are no specific symptoms or signs that can reliably distinguish COVID-19. However, development of shortness of breath approximately one week after the onset of initial symptoms may be suggestive of COVID-19.

Respiratory failure and acute respiratory distress syndrome (ARDS) are the most dreaded complication in patients with severe disease and can manifest shortly after the onset of breathlessness. In a study of 138 patients with extensive pneumonia, ARDS developed in 20 percent after a median of eight days after the onset of symptoms; mechanical ventilation was implemented in 12.3 percent. Although not noted in the majority of patients, gastrointestinal symptoms (eg, nausea and diarrhea) may be the presenting complaint in some patients.

Diagnostic tests
Diagnostic testing is advised in persons with consistent symptoms who reside in or have traveled to areas with community transmission or who have had recent close contact with a confirmed or suspected case of COVID-19. If possible, all symptomatic patients with suspected COVID-19 should undergo testing. However, limitations in testing capacity may preclude testing all patients with suspected infection; suggested priorities include hospitalized patients and symptomatic individuals who are health care workers, work or reside in congregate living settings, or have risk factors for severe disease. Nucleic acid amplification testing (NAAT), most commonly with a reverse-transcription polymerase chain reaction (RT-PCR) assay, to detect SARS-CoV-2 RNA from the upper respiratory tract is the preferred initial diagnostic test. A positive NAAT for SARS-CoV-2 confirms the diagnosis of COVID-19. However, in many symptomatic individuals, a single negative NAAT result is sufficient to exclude the diagnosis of COVID-19. However, if initial testing is negative but the suspicion for COVID-19 remains high and confirming the presence of infection is important for management or infection control, we suggest repeating the test. Estimated false-negative rates have ranged from less than 5 to 30 percent.  Rapid antigen testing can provide faster results although the detection rate is much lower than RT-PCR. Serologic tests detect antibodies to SARS-CoV-2 in the blood and can help identify patients who previously had COVID-19. Detectable antibodies generally take several days to weeks to develop and hence serologic tests have less utility for diagnosis in the acute setting.

Treatment of COVID-19
The optimal approach to treatment of COVID-19 is uncertain. The suggestions made here are based on limited data and might evolve rapidly as clinical data emerges. Many patients with known or suspected COVID-19 have mild disease that does not warrant hospital-level care. Having such patients recover at home is preferred, as it prevents additional potential exposures in the health care setting and reduces burden on the health care system. The evaluation of hospitalized patients with documented or suspected COVID-19 should assess for features associated with severe illness (severe shortness of breath, low oxygen, extensive pneumonia) and identify organ dysfunction or other comorbidities that could complicate potential therapy.

Patients hospitalized with COVID-19 should receive pharmacologic prophylaxis for venous thromboembolism (blood clotting). COVID-19 has been associated with thromboembolic complications. Fever should be treated with temperature lowering medicines like paracetamol. Supplemental oxygen should be given for subjects with low oxygen levels. Low dose steroids benefit patients with hypoxia (low oxygen). Oxygen delivery via a high flow nasal cannula device has proved to be beneficial in COVID-19. Lying on the front aspect of the chest (prone position) improves oxygenation in severely hypoxic patients. Non invasive or ventilatory support may be needed in non-responding hypoxia. Nutrition and general nursing care is of paramount importance.

There is a healthy degree of uncertainty on drugs that are effective for COVID-19. Agents that have been tried include hydroxychloroquine and chloroquine, azithromycin, ivermectin, Favipiravir, remdesivir, tocilizumab, convalescent plasma etc. Institutional protocols are developed by many hospitals taking into account the local prevailing scenario. Growing experience might help us to form evidence based guidelines and universal protocols.

The global crisis created by Covid-19 pandemic has resulted in an unprecedented research effort and global coordination has resulted in a rapid development of vaccine candidates and initiation of trials. There have been difficulties in the development of coronavirus vaccines historically. Coronavirus vaccines in animal models that mimic human disease have been immunogenic but generally not shown to effectively prevent acquisition of disease. Further, there is a concern that vaccination, as with natural coronaviral infection, may not induce long lived immunity and re-infection may be possible. In some ways more concerning has been vaccine associated disease enhancement. Development of new vaccines is a time consuming process and 3-5 years is considered a short time for a new vaccine to be commercially available after initiation of research. In keeping with the primary medical doctrine of “cause no harm”, a candidate vaccine has to go through stringent tests in various phases before it gets approval nod from regulatory bodies. Even with accelerated approval pathways awaiting Covid 19 vaccines, the author is pessimistic with regard to launch of a vaccine in the next year.

Dr. Rajesh V
Chief Consultant in Pulmonary Medicine
Rajagiri Hospital, Aluva

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