COVID19 Treatment

By Dr Deepu Changappa Cheriamane

Treatment

No specific treatment or vaccine exists for COVID-19 (July 2020). Therefore resources have been concentrated on public health measures to prevent further interhuman transmission of the virus. This has required a multipronged approach and for individuals includes meticulous personal hygiene, social distancing, the avoidance of large crowds/crowded environments and where necessary, self-isolation.

In healthcare facilities, concerted efforts are required to effect rapid diagnosis, quarantine infected cases and provide effective supportive therapies. This will encompass empirical treatments with antibiotics, antivirals, and supportive measures.

Mechanical ventilation, both invasive and non-invasive, and extracorporeal membrane oxygenation (ECMO) have also been used where clinically necessary.

Proning

Historical studies have demonstrated a net benefit for patients with moderate to severe ARDS being turned prone. Many health care facilities have adopted the practice of turning the sicker COVID-19 patients into a prone position, so-called "proning" to improve their lung oxygenation.

Antiviral therapy

Whilst specific antiviral therapies for SARS-2-CoV do not currently exist, the combination of the protease inhibitors, ritonavir, and lopinavir, or a triple combination of these antiviral agents with the addition of ribavirin, showed some success in the treatment of SARS, and early reports suggested similar efficacy in the treatment of COVID-19. However, a more recent randomized, controlled open-label trial failed to demonstrate any added benefit of lopinavir-ritonavir combination therapy.

Remdesivir, a drug originally developed to treat Ebola virus and shown to be effective against MERS-CoV and SARS-CoV, showed promising in vitro results against SARS-CoV-2. A preliminary trial in May 2020 showed a significant decrease in time to recovery, from 15 to 11 days, in those treated with remdesivir. Other antivirals in phase III trials include oseltamivir, ASC09F (HIV protease inhibitor), lopinavir, ritonavir, darunavir, and cobicistat.

Dexamethasone, was demonstrated in the large RECOVERY (Randomized Evaluation of COVid-19 thERapY) randomized controlled trial, in June 2020 to decrease deaths by a third in those on mechanical ventilation (p=0.0003), and by a fifth those non-ventilated patients requiring oxygen (p=0.0021). No benefit was seen in those not needing respiratory support.

In early 2020, published reports showed that two antimalarial drugs, chloroquine, and its close chemical derivative, hydroxychloroquine, had strong anti-SARS-2-CoV activity in vitro. An initial open-label, randomized clinical trial, demonstrated a significant reduction of viral carriage, and a lower average carrying duration in patients treated with hydroxychloroquine. Furthermore, a combination with the antibiotic azithromycin resulted in a synergistic effect. However this trial was later strongly criticized for methodological flaws and questionable conclusions. Later studies have failed to replicate beneficial effects of these agents and also highlight potential side-effects.

Passive immunity

Treatment with convalescent plasma (plasma from patients who have recovered from COVID-19 which therefore contains anti-SARS-CoV-2 antibodies) or hyperimmune immunoglobulin (purified antibodies prepared from convalescent plasma) has shown some success in some critically ill patients. Reports are still preliminary and about a small number of patients. A Cochrane review in May 2020 failed to find convincing evidence that convalescent plasma was an effective treatment, but this will be kept under active review.

Vaccines

The primary target in developing coronavirus vaccines has been the spike protein (S protein) which is on the surface of the virion particle, and in vivo is the most important antigen for triggering an immune response. Human vaccines for coronaviruses have been under development since the SARS outbreak, but none are yet available. Over 125 vaccine candidates are now in preclinical trials.

NSAIDs

Emerging expert opinion is that non-steroidal anti-inflammatory drugs (NSAIDs) are relatively contraindicated in those with COVID-19. This is based upon several strands of "evidence":

since 2019 the French government National Agency for the Safety of Medicines and Health Products has advised against the routine use of NSAIDs as antipyretic

previous research has shown that NSAIDs may suppress the immune system 

anecdotal reports from France suggest that young patients on NSAIDs, otherwise previously fit and well, developed more severe COVID-19 symptoms

However, it is important to note that there is currently (March 2020) no published scientific evidence showing that NSAIDs increase the risk of developing COVID-19 or worsen established disease. Also, at least one report shows antiviral activity by indomethacin (an NSAID) against SARS-CoV (cause of SARS).

Prognosis

Progressive deterioration of imaging changes despite medical treatment is thought to be associated with poor prognosis. There is an increased risk of death in men over the age of 60 years old. The mortality rate is estimated to be 3.6%.

Early reports show that in some well patients, the RT-PCR test remains falsely positive despite an apparent clinical recovery. This raises the concern that asymptomatic carriage may occur.

Risk factors for severe illness or poor outcome

general

1. old age

2. people in a long-term care facility or nursing home

3. male gender

comorbidities

4. cardiovascular disease

5. diabetes mellitus

6. hypertension

7. chronic respiratory disease, e.g. COPD

8. cancer

9. chronic liver disease

10. chronic renal disease

11. immunosuppression

patient condition and laboratory values at hospital admission 

12. high sequential organ failure assessment (SOFA) score on admission

13. D-dimer levels greater than 1µg/mL on hospital admission

14. elevated levels of IL-6, troponin I, lactate dehydrogenase

15. lymphopenia

Pregnancy

In general, pregnant women do not have worse outcomes than non-pregnant women with COVID-19.. In a cohort of 427 women in the UK, 10% required a admission to critical care for respiratory support and 1% succumbed to the disease .