The following is a brief overview of the clinical course of coronavirus disease along with current and emerging therapies.
Clinical course of infection:
- Ranges from asymptomatic infection, mild upper respiratory tract illness and severe viral pneumonia with respiratory failure (ARS = acute respiratory failure).
- Typical symptoms include fever (>37.3⁰C), cough, sputum production and fatigue.
- Duration of viral shedding is 8-37 days (mean 20 days in survivors, continued until death in fatal cases).
Duration of symptoms:
- Fever duration median 12 days (range 8-13 days)
- Cough 19 days (12-23)
- Dyspnoea started average seven days after disease onset
- Throat swab specimens for polymerase chain reaction (PCR) test
Risk factors for poor prognosis, severe disease or ICU admission:
- Higher SOFA score (Sequential Organ Failure Assessment)
- D-dimer levels >1mcg/mL on admission
Risk factors associated with mortality:
- Advanced age – mean 69 years non-survivors (range 63-76) vs survivors mean 52 years (range 45-58)
- Higher frequency of complications
- Signs of sepsis
- Coronary heart disease
- Lymphopenia, leucocytosis (baseline lymphocyte count significantly higher in survivors)
- Elevated alanine aminotransferase (ALT), lactate dehydrogenase, troponin (high sensitivity), creatine kinase (CK), D-dimer, ferritin, interleukin-6 (IL-6), prothrombin time, creatinine, procalcitonin.
- Respiratory failure
- Heart failure
- Septic shock
- Ventilator-associated pneumonia
- Acute kidney injury (AKI)
- Acute respiratory distress syndrome (ARDS)
- Acute cardiac injury
- Pneumonia or bacteraemia (secondary bacterial infection)
- Coagulopathy (3-second extension of prothrombin time or 5-second extension of activated partial thromboplastin time (APTT))
- Hypoproteinaemia (albumin < 25g/L)
The following excerpt of drug treatments and emerging therapies is published in BMJ Best Practice – COVID-19, 2020:
Symptom relief: give an antipyretic/analgesic for the relief of fever and pain. There have been media reports stating that non-steroidal anti-inflammatory drugs such as ibuprofen could worsen COVID-19. However, there is currently no strong evidence to support this, and the situation is being monitored closely.
Antimicrobials: start empirical antimicrobials to cover other potential bacterial pathogens that may cause respiratory infection according to local protocols. Give within 1 hour of initial patient assessment for patients with suspected sepsis. Choice of empirical antimicrobials should be based on the clinical diagnosis, and local epidemiology and susceptibility data. Consider treatment with a neuraminidase inhibitor until influenza is ruled out. De-escalate empirical therapy based on microbiology results and clinical judgement. Some patients with severe illness may require continued antimicrobial therapy once COVID-19 has been confirmed depending on the clinical circumstances.
Corticosteroids: corticosteroids are being used in some patients with COVID-19; however, they have been found to be ineffective and are not recommended. The WHO (as well as other international pneumonia guidelines) do not routinely recommend systemic corticosteroids for the treatment of viral pneumonia or acute respiratory distress syndrome unless they are indicated for another reason. A randomised controlled trial investigating the use of corticosteroids in patients with COVID-19 is in progress.
Various antivirals (monotherapy and combination therapy) are being trialled in patients with COVID-19 (e.g., oseltamivir, lopinavir/ritonavir, ganciclovir, favipiravir, baloxavir marboxil, umifenovir, ribavirin, interferon alfa); however, there are no data to support their use. Results from one small case series found that evidence of clinical benefit with lopinavir/ritonavir was equivocal. A randomised controlled trial of approximately 200 patients in China found that treatment with lopinavir/ritonavir was not beneficial compared with standard care alone (primary outcome was time to improvement) in hospitalised patients with severe COVID-19. Remdesivir shows in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has been used to treat patients in China, as well as the first patient in the US. Clinical trials with remdesivir have started in the US and in China.
Intravenous immunoglobulin is being trialled in some patients with COVID-19; however, there are no data to support this.
Chloroquine and hydroxychloroquine
Chloroquine and hydroxychloroquine are being trialled in some patients with COVID-19. Chloroquine shows in vitro activity against SARS-CoV-2. An expert consensus guideline in China recommends chloroquine in mild to severe cases of COVID-19 as it may improve the success rate of treatment, shorten hospital stay, and improve patient outcome.
Angiotensin-II receptor antagonists
Angiotensin-II receptor antagonists such as losartan are being investigated as a potential treatment because it is thought that the angiotensin-converting enzyme-2 (ACE2) receptor is the main binding site for the virus.
Convalescent plasma from patients who have recovered from viral infections has been used as a treatment in previous virus outbreaks including SARS, avian influenza, and Ebola virus infection. A clinical trial to determine the safety and efficacy of convalescent plasma in patients with COVID-19 has started in China; however, there is no data on its use as yet.
Other drugs that may show promise for the treatment of COVID-19 include teicoplanin and camostat mesylate.
- Beeching NJ, Fletcher TE, Fowler R. BMJ Best Practice: COVID-19. London: BMJ Publishing Group; 2020.
- Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020; pii: S0140-6736(20)30566-3.