Ahmed Negida, MBBCh

School of Pharmacy and Biomedical Sciences, University of Portsmouth, UK

School of Medicine, Zagazig University, Egypt

Email: ahmed.said.negida@gmail.com 

Before You Read

– This information is intended for the use of healthcare professionals only but should not be followed by the public.

– The information enclosed does not constitute or reflect the opinions of my institutions nor the professional organizations to which I belong. 

– The present information was selected precisely from the most recent research findings to reflect up-to-date guidance for the management of COVID-19.

– I have no conflict of interest related to the context of this work.

1. Prevention and Prophylaxis

1.1. Pharmaceutical Prevention

There are no currently approved evidence-based pharmaceutical interventions that can protect against SARS-CoV-2 infection.

There are currently several vaccines under development but none has proven effective. Of them 4 vaccines are in the clinical trial phases.

Two of them have shown initial safety (US Moderna vaccine & the Chinese vaccine) while one of them failed to protect against infection in monkeys and is considered futile until otherwise proven (Oxford Uni vaccine).

The expert opinion suggested the use of low dose hydroxychloroquine or chloroquine particularly for 15 days by healthcare workers for prophylaxis against the infection. However, this opinion has been criticized and has to be revised in light of the more frequent side effects reported by hydroxychloroquine or chloroquine use in COVID-19 patients.

Currently, there is NO EVIDENCE to support the use of any drug for the prevention of SARS-CoV-2 infection.

1.2. Non-pharmaceutical Measures

– Diligent hand washing

– Respiratory hygiene (eg, covering the cough or sneeze).

– Avoiding touching the face

– Do not wear contact lenses

– Cleaning and disinfecting objects and surfaces that are frequently touched.

– Surgical or clothes masks

– Social/physical distancing

– Stay-at-home

– School, venue, and nonessential business closure

– No public gatherings

– Travel restriction

2. Classification of COVID-19 patients

Currently, there are several clinical and radiologic classifications for COVID-19 severity. Herein, we classify the patients into non-severe and severe/critical cases, as follows:

Non-severe COVID-19 patients

– Mild to high fever

– Pneumonia symptoms

– Detectable CT/CXR findings of viral pneumonia

– Normal oxygen saturation

– Respiratory rate < 30/minute

Severe & critical COVID-19 patients

– Stressful respiration

– Respiratory rate > 30/minute

– In the resting state, Oxygen saturation <93%

3. General considerations for the treatment of all COVID-19 patients

– Antibiotic therapy of pneumonia is provided in case of evident bacterial infection.

– D-dimer levels are measured and monitored; initiate Low molecular weight heparin therapy if the D-dimer is > 2 mg/L (in the absence of any contraindications for anticoagulation therapy).

– Recently, the dual treatment strategy has been suggested. The suggestion implied that COVID-19 patients are initially treated with antiviral therapies (if available), then start a course of immune therapy after 7 days [Expert opinion].

4. Treatment of Non-severe COVID-19 patients

Antiviral drugs that showed initial efficacy

1- Remdesivir

This drug gained FDA emergency approval. For doses, follow the FDA recommendations here: https://www.fda.gov/media/137566/download. Current evidence on its efficacy can be classified as “class 2B”. Data from a well-designed RCT of +1000 patients showed that Remdesivir accelerates the recovery (shortens the hospital stay), however, it has no impact on decreasing the mortality risk. 

2- The triple antiviral therapy

If Remdesivir is not available, the triple antiviral therapy might be used as “off-label”. The regimen includes a 14-day combination of lopinavir 400 mg and ritonavir 100 mg every 12 h, ribavirin 400 mg every 12 h, and three doses of 8 million international units of interferon beta-1b on alternate days. Current evidence on its efficacy can be classified as “class 2B”. In a randomized-controlled study, between Feb 10 and March 20, 2020, 127 patients were recruited; 86 were randomly assigned to the combination group and 41 were assigned to the control group. The median number of days from symptom onset to start of study treatment was 5 days (IQR 3–7). The combination group had a significantly shorter median time from the start of study treatment to negative nasopharyngeal swab (7 days [IQR 5–11]) than the control group (12 days [8–15]; hazard ratio 4·37 [95% CI 1·86–10·24], p=0·0010). Adverse events included self-limited nausea and diarrhea with no difference between the two groups. One patient in the control group discontinued lopinavir-ritonavir because of biochemical hepatitis. No patients died during the study. In conclusion, this triple therapy might accelerate the recovery but does not decrease the risk of death.

Antiviral drugs that are currently under evaluation (no sufficient evidence to confirm their efficacy)

1- Ivermectin

600 µg/kg (maximum dose of 60 mg) by mouth daily for three days with the possibility of extension to six (6) days if still hospitalized

2- Favipiravir

3- EIDD 2108

4- Arbidol 

No Antiviral Treatment

In the absence of the previously mentioned drugs, no antiviral treatment should be given to non-severe COVID-19 patients. [Expert opinion of the US NIH Expert Panel]

Antiviral drugs that are not effective for treating COVID-19 patients

1- Hydroxychloroquine or Chloroquine with or without Azithromycin

2- Lopinavir/Ritonavir combination therapy alone

3- Oseltamivir (Tamiflu)

5. Treatment of Severe & critical COVID-19 patients

The treatment plan is the same as non-severe patients plus the following consideration:

– Those patient need hospitalization

– ICU admission (when needed)

– Respiratory support (oxygen therapy and MV when needed)

– Convalescent plasma therapy was used successfully in many case series of severe COVID-19 patients but no evidence from well-designed RCTs.

– Besides the D-dimer and coagulation profile, inflammatory cytokines’ levels, in particular, IL-6 should be also monitored.

– Tocilizumab, an IL-6 inhibitor, showed promising results in observational retrospective studies while there is no evidence from well-designed randomized-controlled trials on its efficacy in COVID-19 patients. For patients with elevated IL-6 or evident cytokine storms, Tocilizumab may be used. 

– If Tocilizumab is not available, Methylprednisolone may be used as an alternative. 

– Alternative biological agents for Tocilizumab are Sarilumab and Siltuximab. However, there is no data on their efficacy in this population. Few observational reports were published but they do not establish a benefit from Sarilumab or Siltuximab. Clinical trials in Belgium and Spain are currently ongoing to test their efficacy.