Can hydroxychloroquin in combination with azithromycin (antibiotics) help treat COVID-19 patients? 

Daily thoughts & numbers on the COVID-19 pandemic from a M.D. working in the front lines at the Emergency Department in a hospital in Stockholm, Sweden. 

In the absence of a vaccine, several already known and tested drugs have been speculated to help mitigate the effects of SARS-CoV-2.

Two of the most promising is the combination of the anti-malaria drug hydroxychloroquine (Plaquenil) with the antibiotic Azithromycin.

In a (very) small study, twenty COVID-19 confirmed patients were treated with hydroxychloroquine, six were treated with the combination of hydroxychloroquine, and sixteen were used as control. *

The results were quite promising (however such as small sample size & NON-randomized study makes the study flawed in power and design, and more data is still needed):

Figure 2. Percentage of patients with PCR-positive nasopharyngeal samples from inclusion to day6 post-inclusion in COVID-19 patients treated with hydroxychloroquine only, in COVID-19 patients treated with hydroxychloroquine and azithomycin combination, and in COVID-19 control patients. *

In the choice between chloroquine and hydroxychloroquine, the latter seems to be more effective and with less side-effects. As one in vitro study comparing the two concluded: *

Chloroquine has been sporadically used in treating SARS-CoV-2 infection. Hydroxychloroquine shares the same mechanism of action as chloroquine, but its more tolerable safety profile makes it the preferred drug to treat malaria and autoimmune conditions. We propose that the immunomodulatory effect of hydroxychloroquine also may be useful in controlling the cytokine storm that occurs late-phase in critically ill SARS-CoV-2 infected patients.  (…) The pharmacological activity of chloroquine and hydroxychloroquine was tested using SARS-CoV-2 infected Vero cells. Physiologically-based pharmacokinetic models (PBPK) were implemented for both drugs separately by integrating their in vitro data. (…) Hydroxychloroquine was found to be more potent than chloroquine to inhibit SARS-CoV-2 in vitro. *

One small study is, of course, not enough and more rigorous studies with a larger number of patients are being conducted.

Another alternative being explored, and that seems promising, is Remdesivir, an antiviral drug that was developed against the Ebola-virus.

In Stockholm, right now, the drug that sometimes is used/tested on COVID-19 patients with more severe symptoms is chloroquine and not hydroxychloroquine. The rationale behind that seems to be that our infection doctors have more clinical experience with chloroquine than Plaquenil.

COVID-19 Numbers Sweden 2020-03-27 *

• 92 deaths nationally
  • 62 of them in Stockholm
• 3 046 confirmed cases nationally
  
  (Number of COVID-19 cases over time in Sweden, updates during mornings so todays numbers are not yet complete until the next day).
• Intensive care Sweden: *
  • 214 COVID-19 confirmed patients treated in total so far
  • 9,4 days from symptoms to ICU
  • 25,7 % women
    
    Total number of recorded of COVID-19 patients needing ICU care each week. From Week 10 it seems to more than double each week, 5 →  24  → 127 → (284 this week up until now, however since it’s only friday this weeks numbers are yet incomplete)

COVID-19 Numbers Globally (updated today 2020-03-27 at 10:00 CET) *

• 23 335 confirmed deaths
• 509 164 confirmed cases
• 201 countries , areas or territories with cases

Financial Times Cumulative Number of Deaths Selected Countries (updated yesterday 2020-03-26 at 19:00 GMT) *

New Resources Added to ※ CTSOP 

• STUDY 1 – Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an openlabel non-randomized clinical trial
• STUDY 2 – In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
• Radiopaedia on COVID-19 radiology

Image: CT thorax of a patient with COVID-19 pneumonia *

CT image above from Radiopaedia: *

The primary findings on CT in adults have been reported ^{13,17,27,28,36}:

• ground-glass opacities (GGO): bilateral, subpleural, peripheral
• crazy paving appearance (GGOs and inter-/intra-lobular septal thickening)
• air space consolidation
• bronchovascular thickening in the lesion
• traction bronchiectasis

The ground-glass and/or consolidative opacities are usually bilateral, peripheral, and basal in distribution ^2,32.

A retrospective study of 112 patients found 54% of asymptomatic patients had pneumonic changes on CT ⁶⁷.

Some papers suggest that CT has a sensitivity that could justify its use in the early imaging in the acute setting in select cases. Yet its use as a primary screening tool is currently discouraged, not least because these studies tended to suffer from selection bias ^52,57,87,88. In a recent investigation, these chest CT findings had the highest discriminatory value (p<0.001) ⁵¹:

• peripheral distribution
• ground-glass opacity
• bronchovascular thickening (in lesions) *

That’s it until tomorrow, keep calm and stay safe!