Clinical management of COVID-19

Today, the world stands in the combat against the coronavirus disease 2019 (COVID-19), an unfolding viral pandemic exacting a significant toll on the human race. With its beginnings in Wuhan city, China, as a cluster of cases of pneumonia with unidentified aetiology, it was soon identified to be caused by a novel strain of coronavirus (CoV), now named severe acute respiratory syndrome CoV-2 (SARS-CoV-2), which spread primarily through droplets, respiratory secretions and direct contact12. As of mid-April 2020, the infection has spread to over 185 countries, infected more than two million people and resulted in over 127,000 deaths globally3.

COVID-19 in majority of the population (80%) presents as an asymptomatic or mild infection4. However, the disease is known to cause severe pneumonia and multiple complications, especially in certain high-risk groups. These remaining 20 per cent of infected patients will need admission and hospital care, including five per cent of them who require intensive care and ventilator support4. Multiple protocols and management strategies are currently being developed worldwide to overcome this issue. However, in resource-limited settings like India which deal with a huge population base, it is critical for the doctors to be well equipped to speedily identify and treat patients who require admission and critical care. This will ensure proficient utilization of resources and facilities available without overburdening the existing healthcare system. Thus, an attempt was made to summarize the clinical management of COVID-19 for Indian physicians.

High-risk groups

COVID-19 is peculiar in its disproportionate case fatality rates among patients >60 yr as opposed to young adults or paediatric population. The highest mortality rates were seen among individuals above 80 yr of age at 14.8 per cent. These results were brought out in one of the largest data analyses conducted in China involving 72,314 patient records5. While patients with no prior comorbid conditions had a case fatality rate of 0.9 per cent, it was notably higher among those with specific underlying comorbidities, making these population groups high-risk and more vulnerable to severe COVID-195. These high-risk groups and age-wise case fatality rates are depicted in Table I. While further research is going on, the data suggests that tobacco smoking is also a risk factor for COVID-19. Smokers (both former and current) are more likely to have severe symptoms, are admitted to intensive care unit (ICU), need mechanical ventilation or die compared to non-smokers67.

It is imperative to recognize these susceptible groups, educate them regarding the infection and precautionary measures as well as be aware of their tendency for worse outcomes (Table I). When treating such patients, a multidisciplinary approach is preferred with a keen eye to avoid unwarranted polypharmacy and adverse drug reactions8.

Symptoms and warning signs

The incubation period of COVID-19 is 1-14 days (mean duration of 5-7 days), with peak viraemia occurring before the onset of symptoms. This underlines the transmission potential of asymptomatic or minimally symptomatic patients2910. The most common presenting features of COVID-19 infection are fever (80-90%), cough (60-80%) and dyspnoea (18-46%). Other symptoms at presentation include myalgia or fatigue, sore throat, nasal congestion, headache, nausea, vomiting and diarrhoea611. On examination, findings of pneumonia may be present in a minority8. Warning signs or red flag signs that can assist in triage, indicating the need for urgent care, are summarized in Table II.

Laboratory findings

Alteration in laboratory parameters may provide insight into the pre-test probability of an underlying COVID-19 infection. While total counts are normal in majority of the patients, leucopenia may be seen in one-third but leucocytosis is rare (<10%)6. Lymphocytopenia is commonly recognized in these patients6. The common laboratory abnormalities seen with COVID-19 infection are summarized in Table III. Procalcitonin levels are typically not elevated, and the presence of elevated levels should raise the suspicion of a superadded bacterial infection12. Chest X-rays/imaging are often abnormal even in early disease and reveal bilateral, peripheral and ill-defined interstitial infiltrates with ground-glass opacification or lobular and subsegmental consolidation111314.

Complications

COVID-19 can take a rapidly progressive and fulminant course, giving rise to various complications that could result in a fatal illness. The common complications seen with COVID-19 are summarized in Table III61114. Some of the rare complications that have been reported include rhabdomyolysis and disseminated intravascular coagulation6. Early suspicion and intensive monitoring for these complications as well as prompt, appropriate supportive measures may help reduce untoward outcomes.

Categorization of disease severity, testing and admission strategy

During the pandemic period, when a patient presents to the emergency department with fever, cough or breathlessness, a high level of suspicion for COVID-19 infection must be entertained. The physician must keep a watch for the warning signs and initiate early resuscitative and supportive measures if these are detected. Table IV elaborates the categorization of suspected COVID-19 patients into mild, moderate and severe disease based on their presenting symptoms and signs. Most patients with COVID-19 have self-resolving mild disease mimicking other upper respiratory infections. Hence, they are low priority for testing and can be safely managed with home isolation16. The suggested testing strategy and the level of care based on the disease severity and risk category are summarized in Table IV.

Careful triaging of patients with COVID-19, at the time of first contact with the healthcare system, will help prioritize patients based on the risk group, critical nature and severity of illness as well as resources available. These measures will help decrease the load on the hospitals by reducing unnecessary admissions to the inpatient wards and ICUs, allowing for the allocation of hospital beds, ventilators and supportive devices to patients with more severe disease. In addition, this might prevent burnout among treating healthcare workers and reduce transmission in the hospital.

Sample collection and laboratory confirmation

Sample collection for the detection of SARS-CoV-2 infection should be carried out as early as possible in patients with suspected COVID-19 falling into the moderate and severe groups. The high upper respiratory viral load in COVID-19 makes nasopharyngeal swab the recommended sample for confirmatory testing. Sputum collection and testing should be considered only for patients with productive cough, while the induction of sputum is not advised as aerosols produced by the procedure can facilitate disease transmission. For intubated patients, a lower respiratory tract aspirate or bronchoalveolar lavage sample is preferred. Swabs are to be placed in a viral transport medium and transported on ice to the laboratory. Hospital staff responsible for collecting, transporting, testing and analysis of the respiratory samples must ensure the usage of appropriate personal protective measures.

The recommended diagnostic test is the reverse transcription-polymerase chain reaction (RT-PCR) on respiratory samples. Though initial studies revealed low sensitivities of 30-60 per cent, newer assays show improved results17. Based on the CoV grouping criterion, RdRp (RNA-dependent RNA polymerase) gene assay with a lower level of detection of 3.8 copies per reaction at 95 per cent detection probability is considered the reference standard PCR18.

The U.S. Food & Drug Administration (FDA) has recently approved a rapid diagnostic test capable of providing the results within 45 minutes19. Cepheid's COVID-19 test, a molecular PCR-based assay, has succeeded in demonstrating high accuracy using the company's GeneXpert machine19. Antibody detection may reveal positivity about a week after the onset of illness and hence has no role in the diagnosis in the first week of illness. However, it will be a cost-effective test for diagnosis in the second week of illness. In addition, it is expected to be useful in epidemiological studies in the estimation of community prevalence of the disease. Antigen tests, while still in the conceptual and design stage, once developed will provide rapid results and may be carried out as the point-of-care test.

General treatment measures

Patients are categorized based on the severity of disease (Table IV) for further decisions on hospitalization and treatment options. The treatment includes antiviral drugs or specific therapy and supportive management of complications, including advanced organ support, if required. The theoretical concern that non-steroidal anti-inflammatory drugs (NSAIDs) worsen outcomes in COVID-19 infections as these upregulate angiotensin-converting enzyme 2 (ACE-2) levels in the lung, the entry receptor for the virus, remains yet to be proven20. Small studies have also revealed that NSAID exposure is independently associated with the occurrence of pleuro-pulmonary complications in patients with community-acquired pneumonias21. For the above reasons, paracetamol may be preferred over NSAIDs in COVID-19 management.

The mechanism of lung injury produced by COVID-19 also appears to be through its effect on ACE-2, though this has not yet been confirmed. This has in turn led to the hypothesis that patients with cardiac diseases, hypertension or diabetes being treated with ACE inhibitors or angiotensin receptor blockers are at higher risk for severe COVID-19 infection as they upregulate increased ACE-2 receptor expression20. There is no clear clinical evidence for the same and hence, cessation or a change in medication for the general population on regular treatment with ACE inhibitors or angiotensin II receptor blockers (ARBs) for the underlying comorbid disease is not recommended22. However, change to an alternate regimen may be considered for patients who are admitted and positive for COVID-19 for the period of their illness. These decisions need to be made by the treating team on a case-by-case basis after taking into consideration the patient's underlying comorbidity and weighing the potential risks and benefits.

Specific treatments and treatment strategy

With the evolving challenges brought about by this public health emergency, there is a pressing need for the timely identification and development of drugs that can be used in the treatment of COVID-19 infections. A wide range of drugs that have earlier been approved for other indications as well as several investigational drugs are being studied through clinical trials for benefit in COVID-1923. As the COVID-19 pandemic evolves, more and more scientific data supporting various management and treatment options have been brought to light. However, it is of utmost importance for the treating physician to exercise caution and critically appraise the available data prior to incorporating various pharmaceutical agents into clinical practice.

At present, the role of specific antiviral medication is at best adjunctive in nature. The following drugs have shown some promise for the management of COVID-19:

Management of Critically Ill Covid-19 Patient

Severe SARS-CoV-2 pneumonia may require supportive intensive care. Lung protective ventilation strategies, careful fluid monitoring, prone ventilation and when clinically indicated extracorporeal membranous oxygenation have been recommended in the management of the critically ill. However, certain aspects of intensive care are unique in view of the pathology and risk to healthcare workers, and these unique features are summarized below:

Infection control in SARS-CoV-2

The predominant mode of person-to-person transmission in SARS-CoV-2 infection is by close contact with infected individuals generating respiratory droplets. The virus is capable of staying active on inanimate surfaces for several hours, making fomite transmission likely62. Airborne transmission though possible, does not appear to be a major mechanism62. This has particular implications due to shortage of personal protective equipment in various settings. Aerosol-generating procedures may generate smaller particles which may stay in the air for a longer time. Distant spread of such particles to produce secondary infection seems unlikely63. Table VI presents the safety measures for infection control to be followed among healthcare professionals.

Conclusion

Tackling the evolving COVID-19 pandemic requires a multifaceted approach. The government, health sector, community as well as each individual have a key role to play in the prevention of transmission of infection. Healthcare professionals should be trained in the clinical management of this rapidly spreading viral illness to enable them to swiftly and confidently detect and treat all infected individuals. It is of paramount importance that healthcare professionals are actively involved in infection control and provided adequate personal protective equipment to safeguard not only themselves but those surrounding them as well.

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Conflicts of Interest: None.