Navigating the unknowns in COVID-19 the ACP way

In the face of the COVID-19 pandemic which has taken the world by storm, the lack of approved treatments targeted towards coronavirus has left physicians worldwide grappling with the situation. To help them navigate the black box of COVID-19 management, the ACP* has released a behemoth 28-chapter guide to arm physicians in the virus-infested battle field.

The ACP physician’s guide culls authoritative clinical information from international and institutional resources — including the WHO, US CDC, NIH, FDA, ATS, ACR, and IDSA**, among others — and is constantly updated as new data become available. [https://assets.acponline.org/coronavirus/scormcontent/?&_ga=2.87204191.65677456.1590033057-1972446618.1589780091#/, accessed 21 May 2020]  

Seeing that robust clinical data from randomized controlled trials are thin on the ground, experts pointed out that current available guidance, especially for treatment, relies mostly on experts’ opinions.

“There are [currently] no FDA-approved drugs for the treatment of COVID-19,” wrote panel experts for the NIH guidelines, which is also included in the pharmacotherapy treatment chapter of the ACP guide for physicians. “Recommended clinical management of patients with COVID-19 includes infection prevention and control measures and supportive care, including supplemental oxygen and mechanical ventilatory support when indicated.”

The guidelines should serve as a guide, rather than prescriptions, to supporting clinical responses to COVID-19, the experts advised.

“As in the management of any disease, treatment decisions ultimately reside with the patient and their healthcare provider,” they stated.

Diverse findings: From head to toe

“[COVID-19 patients] can experience a range of clinical manifestations, from no symptoms to critical illness,” the experts’ panel observed. While presentation as acute respiratory disease may be mild, it can culminate in severe viral pneumonia.

“Full characterization of the spectrum of COVID-19 is ongoing, but the primary presentation is an influenza-like illness with lower respiratory tract symptoms,” said the experts.

Fever, cough, and shortness of breath are some of the most frequently reported symptoms of COVID-19. Additional symptoms may include sore throat, fatigue, muscle pain, and headache.

But these are not the only symptoms associated with the disease. Less typical symptoms involving other organ systems such as diarrhoea, nausea, delirium, rashes, and chickenpox-like lesions have been reported in some COVID-19 cases.

Even more bizarre is the surfacing of the “COVID toes” from recent case reports. A potential skin manifestation of COVID-19 infection, this condition is characterized by pernio-like lesions, or chilblains — typically a reaction to cold temperatures.

COVID toes can manifest as purple or red tender bumps on the toes or hands, often with pain, or even a burning sensation. It can be painful and, worse, can lead to tissue death, if left untreated. Nonetheless, it tends to heal without long-term sequelae. Thus far, it is most commonly, though not exclusively, seen in younger people who showed few other symptoms or none. [Pediatr Dermatol 2020;doi:10.1111/pde.14227; Zhonghua Xue Ye Xue Za Zhi 2020;doi:10.3760/cma.j.issn.0253-2727.2020.0006; Int J Dermatol 2020;59:739-743]

Of note, patients with atypical symptoms may also develop classic symptoms, or not at all.  

Anosmia as symptom

The nose may hold a clue when it comes to identifying COVID-19. Initially taken as anecdotes, several studies have now provided empirical evidence that loss of smell, or anosmia, was highly prevalent among infected patients. Distortion of sense of taste (dysgeusia) was also common.

“Anosmia, in particular, has been seen in patients ultimately testing positive for the coronavirus with no other symptoms. We propose that these symptoms be added to the list of screening tools for possible COVID-19 infection,” recommended the AAO-HNS***.

Following these discoveries, anosmia is now officially added to the US CDC’s list of COVID-19 symptoms.  

“COVID-19 is not associated with the symptoms that are typically associated with a viral cold such as nasal blockage or mucus production,” said Dr Ahmad Sedaghat from the University of Cincinnati Medical Center, Cincinnati, Ohio, US, who is the principal investigator of one of the anosmia studies. “This distinction is also why it is fairly easy to distinguish COVID-19 from seasonal allergies.” [Otolaryngol Head Neck Surg 2020;doi:10.1177/0194599820929185]

“The occurrence of sudden onset anosmia without nasal obstruction is highly predictive of COVID-19 and should trigger the individual to immediately self-quarantine with presumptive COVID-19 [and further testing],” he highlighted.

Though the anosmia and dysgeusia reported were mostly profound and not mild, the rate of sensory recovery was encouragingly high and rapid, typically occurring within 2–4 weeks of infection, noted the researchers led by Dr Carol Yan from UC San Diego Health, San Diego, California, US. [Int Forum Allergy Rhinol 2020;doi:10.1002/alr.22579]

Tell-tale signs from the ground and lab

Amidst the diverse clinical findings, vital signs to look out for on physical examination include fever, increased respiratory rate, and reduced oxygen saturation. In addition, auscultation of the lungs typically reveals relatively benign or quiet sound relative to dyspnoea and hypoxia, according to the ACP guide.

While routine laboratory testing is nonspecific, commonly reported findings include lymphocytopenia, thrombocytopenia, decreased albumin, and elevations in C-reactive protein, liver transaminase, LDH^#, ferritin, and D-dimers.

Based on chest imaging guidance statements from ACR, “A normal chest CT does not mean a person does not have COVID-19 infection — and an abnormal CT is not specific for COVID-19 diagnosis.”

Nonetheless, experts noted that imaging may be useful when worsening respiratory status calls for radiologic assessment, or alternatively, when viral testing is not readily accessible.

“A normal CT should not dissuade a patient from being quarantined or provided other clinically indicated treatment ... Clearly, locally constrained resources may be a factor in such decision making,” according to the ACR guidance. 

In addition, characteristics of patients may foretell the likely course of disease. As per statement from the US CDC, “Older adults and people who have severe underlying medical conditions like heart or lung disease or diabetes seem to be at higher risk for developing more serious complications from COVID-19 illness.”

Confirmation of diagnosis is via viral RT-PCR testing of respiratory specimens. Also in the pipeline is fluorescent immunoassay for viral antigen, which provides a more rapid point-of care test compared with the current RT-PCR method. 

No licensed therapy yet

Being in the limelight lately are two classes of therapies: antivirals (such as remdesivir, lopinavir, and ritonavir) and immunomodulators (for instance, interleukin inhibitors, interferons, and immune globulins).

Despite claims about successful treatment of COVID-19 with several agents, no drug has currently been proven to be effective and safe, both of which require definitive evidence from clinical trials.

“[Overall,] there are insufficient data to recommend either for or against the use of any antiviral or immunomodulatory therapy in patients with COVID-19 who have mild, moderate, severe, or critical illness,” according to recommendation from the NIH guidelines. [https://covid19treatmentguidelines.nih.gov/overview/, accessed 21 May 2020]

Specifically, the ACP also advises against the use of chloroquine or hydroxychloroquine, either alone or in combination with azithromycin, both as prophylaxis or treatment of COVID-19 in view of known harms and uncertain evidence of benefit. However, clinicians may choose to use the therapy in hospitalized COVID-19 patients in the context of a clinical trial, keeping in mind the principle of shared and informed decision making. [Ann Intern Med 2020;doi:10.7326/M20-1998]

Ventilators: 1 vs all

When it comes to ventilator support for hospitalized COVID-19 patients who are critically ill, experts generally discourage against sharing one mechanical ventilator among multiple patients because it is not safe to do so with the current equipment.

The position was further explained in a national consensus statement jointly issued by multiple societies^##, which explains that “The physiology of patients with COVID-19-onset acute respiratory distress syndrome (ARDS) is complex. Even in ideal circumstances, ventilating a single patient with ARDS and nonhomogenous lung disease is difficult and is associated with a 40–60 percent mortality rate. Attempting to ventilate multiple patients with COVID-19 ... could lead to poor outcomes and high mortality rates for all patients cohorted.”

“In accordance with the exceedingly difficult, but not uncommon, triage decisions often made in medical crises, it is better to purpose the ventilator to the patient most likely to benefit than fail to prevent, or even cause, the demise of multiple patients,” they added.

How about concomitant meds?

For COVID-19 patients who are taking inhaled or oral corticosteroids, NSAIDs, ACEis, ARBs^###, or statins for a pre-existing condition, they should continue with their medications, urged the experts.

However, initiation of statins or ACEis/ARBs for the purpose of treating COVID-19 is not recommended, unless in the setting of a clinical trial.