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Nine Months, 28M Cases: How COVID-19’s Clinical Landscape Has Changed

Nine Months, 28M Cases: How COVID-19’s Clinical Landscape Has Changed

An artistic impression of coronaviruses. Image: PIRO4D/pixabay.

First described as a cluster of viral pneumonia cases of unknown cause in the Hubei province of China, COVID-19 has rapidly spread across the globe, causing widespread illness and death, with unparalleled global social and economic disruption.

As the disease spread like wildfire, clinical patterns, mortality rate, infectivity and complications seemed to vary considerably from place to place. In an attempt to better characterise this disease, there have been over 50,000 scientific articles published on COVID-19. Many of them became headlines for public consumption with little to no context.

As larger amounts of high-quality scientific data became available, our understanding of the disease and its impact has undergone significant refinement.

Disease process

SARS-CoV-2 is a coronavirus believed to be of animal origin. The virus primarily affects the upper respiratory tract (sinuses, nose and throat) and lower respiratory tract (windpipe and lungs), which serve as its route of entry. It is believed that this viral infection of the lung sometimes results in an excessive immune reaction in the patient. That is, in the process of attacking the virus, the patient’s own immune system damages the body. The degree of this immune response is what determines where on the spectrum of disease its patients lie.

As the receptor that the virus uses to infiltrate cells is present in other organs as well, a COVID-19 infection can involve the digestive system, kidneys, blood vessels, nasal passage, heart and nervous system too. In severe cases, there can be a cytokine storm – a widespread activation of the immune system resulting in damage to multiple organ-systems and possibly death. How or why COVID-19 affects different patients differently is still not fully understood.

In a broader sense, while COVID-19 can affect virtually any part of the body, the vast majority of cases are mild and present in a common and predictable manner, largely amenable to supportive treatments.

Clinical presentation

The mean incubation period following exposure to a patient with COVID-19 is approximately five days (and ranging from two to seven days), with the majority developing symptoms within 11.5 days of the infection. This is why a quarantine period of 14 days is accepted in most regions.

Mild symptoms – Most cases (around 80%) are mild and can be managed at home with supportive treatments like rest, fluids, anti-inflammatory agents and painkillers. The most common symptoms are fever, dry cough and fatigue. None of these symptoms are necessary to make a clinical diagnosis – meaning that patients of COVID19 may have all, none or some of these symptoms. Loss of smell (and taste) have also been described as characteristic symptoms of COVID19: around two-third of patients report this, while around 3% of patients have presented this as their only complaint.

Like other viral illnesses, COVID-19 can also present with muscle and joint pain, weakness and fatigue, and nausea, vomiting, diarrhoea or rashes. Older patients can have more atypical symptoms like confusion or delirium. These symptoms are very non-specific and can mimic a host of other illnesses, so establishing a diagnosis becomes difficult. However, in the context of rampant community transmission in most populations, any of them should warrant suspicion of COVID-19 and isolation, especially in a more vulnerable population.

The Indian Council of Medical Research (ICMR) recently amended recommendations to allow ‘testing on demand’, indicating that it acknowledges that there are definite advantages to testing even mildly asymptomatic patients: these patients can spread the disease (necessitating contact tracing) or become symptomatic later on, by which point valuable time may have been lost (24-36 hours are required for RT-PCR results in most places). Although any of these non-specific symptoms can be COVID19, the likelihood that any non-specific symptoms in isolation actually represent disease is significantly lower.

Symptoms requiring hospitalisation – The threshold for hospitalisation is highly variable. Patients with signs of moderate to severe disease may be comfortable and prefer treatment at home, while physicians may recommend hospitalising patients with mild disease but who are at risk of developing complications. Some of these predispositions are age (especially 60+ years), obesity, asthma or chronic obstructive pulmonary disease, diabetes and heart disease. For most people with moderate to severe disease, the predominant symptom is shortness of breath or breathing difficulties.

The screening test for lung function is pulse oximetry, which will determine if patients need oxygen supplementation. As lung inflammation worsens due to the disease, patients may need ventilatory support that delivers specific rates and volumes of oxygen to promote gas exchange. Severe lung involvement requires extracorporeal membrane oxygenation (ECMO) – the use of an external device that performs gaseous exchange temporarily until the patient’s lung function improves to the extent that it can resume this function itself.

Acutely ill patients requiring intensive care can also develop kidney injury, liver dysfunction and bleeding disorders. Patients with multi-system involvement have a limited chance of a complete recovery. Rarely, patients can develop other emergencies, such as abnormal abnormal heart rhythms (6%), heart attacks (7-28%) or stroke (6%). However it is difficult to know if it is correct to attribute all these to COVID-19; many of these patients had multiple underlying diseases and were critically ill.

Chronic health issuesLess than 5% of patients treated in hospital for COVID-19 require readmission, most commonly for breathing difficulties. This return occurred early – at a median of 4.5 days after discharge – and was more common in those with pre-existing illnesses. Another concern is that young, otherwise fit patients may go on to develop lung fibrosis, or damage and scarring of the lung. It is still unknown whether this is a predictable outcome or more of an idiosyncratic, ‘one-in-million’ occurrence.

Patients have also reported symptoms that fit the pattern of chronic fatigue syndrome, which is a debilitating chronic illness due to which patients complain of chest pain, gastrointestinal issues, cognitive disorders and profound fatigue. This syndrome has been reliably linked to recovery from other viral illnesses in the past. Patients who underwent prolonged intensive care have also reported post-intensive care syndrome, which ranges from post-traumatic stress disorder to neurological weakness or paralysis.

Some researchers have speculated, by extrapolating from other viral pneumonia, that COVID-19 survivors may be at increased risk of immune-related blood vessel dysfunction, predisposing them to heart attacks, stroke and other disorders. However it is too early to know for sure.

Reports of COVID-19 reinfection have also sparked significant interest in this prospect, but it is more likely to be the exception than the rule based on available information. It is additionally unclear if this small group of patients that has been reinfected is at risk of severe disease or spread of disease after recovery.

What has changed?

Today, we know that around 15% of patients are asymptomatic (i.e. have no symptoms whatsoever) and drive the spread of disease, and identifying them through screening and testing along with continued use of universal precautions is an important part of controlling the virus’s transmission. We also know that cytokine storms are more likely to be a rare occurrence rather than a dangerous reality for most patients, which is reassuring. We have also become more successful at treating critically ill COVID-19 patients, although the quality of care still varies from country to country.

For many people, neglecting hospital and emergency visits for other serious illnesses has proven costly. Although most patients recover well, there is no group that is truly invulnerable. In the absence of a reliable vaccine and herd immunity being patently unaffordable, prevention still reigns supreme: wear a mask, wash your hands and maintain physical distancing where possible. Continue to follow the science, and remember that this too shall pass.

Dr Narayana Subramaniam is a head and neck surgical oncologist at the Mazumdar Shaw Medical Centre, Bengaluru.

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