#Abstract:

Background:

A definitive treatment of SARS CoV-2 is yet to arrive and the human death toll rises exponentially globally. In this health emergency, it might be useful to look into the old therapies which could be effective against the virus. In vitro research showed Ivermectin could decrease the concentration of coronavirus 4000 to 5000 folds in living lung tissue.

Aim:

In this prospective study a combination of Ivermectin and Doxycycline will be evaluated therapeutically to treat COVID-19 patients.

Methods:

100 COVID-19 patients were enrolled in this study with a predefined inclusion and exclusion criteria. RT- PCR of the SERS-CoV-2 will be done at designated government hospitals. The clinical features and response to treatment were noted according to a dedicated protocol.

Results:

In this study male and female were 64 and 36 respectively, the age ranged between 8 to 84 years. Retesting was done between 4 and 18 days of starting medication. All patients tested negative and their symptoms improved within 72 hours. There were no noticeable side effects.

Conclusion:

Combination of Ivermectin and doxycycline was found to be very effective in viral clearance in mild and moderately sick COVID-19 patients. Medical societies and institutions should undertake larger multi center studies to validate and recommend this combination therapy to include in national guidelines

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Notes from the PDF.

The usual explanation of ivermectin's action, succinctly put: by blocking Importin α/β1, ivermectin prevents the virus from entering the nucleus and inhibiting the cell's immune response.

IMPα/β1 binds to the coronavirus cargo protein in the cytoplasm (top) and translocates it through the nuclear pore complex (NPC) into the nucleus where the complex falls apart and the viral cargo can reduce the host cellís antiviral response, leading to enhanced infection. Ivermectin binds to and destabilizes the IMPα/β1 heterodimer thereby preventing IMPα/β1 from binding to the viral protein (bottom) and preventing it from entering the nucleus. This, likely, results in reduced inhibition of the antiviral responses, leading to a normal, more efficient antiviral response1

Doxycycline is an anti-inflammatory.

In vitro studies showed Doxycycline to exert anti inflammatory effects at low (20 - 40mg/day) and high (100 or 200mg/day) doses with inhibitory action on metalloproteases and modulating effects of pro inflammatory cytokines IL 6, IL 8 and tumor necrosis factor alpha. The anti inflammatory properties of Doxycycline and other components of tetracycline has been demonstrated for several inflammatory airway diseases, including, acute respiratory distress syndrome. Thereby, low Doxycycline doses have been shown to be more effective than high doses to prevent induction of pro inflammatory cytokines (such as IL 6) in inflammatory diseases13. Doxycycline is rapidly and almost completely absorbed after oral administration and has half life of 16-18 hours.

The turn from doxycycline to this confused me:

Based on the available evidence, we believe Tetracyclines may be effective agents in the treatment of Covid-19 due to their ability to chelate Zinc compounds on matrix metalloprotienases (MMP) on which coronaviruses rely heavily for survival, cell infiltration, cell to cell adhesion and replication, many of which has Zinc as part of their MMP complex.14

Until Google showed me that doxycycline is a kind of tetracycline, sort of:

Doxycycline is a synthetic (man-made) antibiotic derived from tetracycline.

Google further informs me that doxycycline can chelate zinc.

From here, a long list of doxycycline's covid-19 related activities:

Doxycycline has been selected based on its ability to:

1) inhibit metalloproteinases (MMPs), implicated in initial viral entry into the cell as well as in acute respiratory distress syndrome (ARDS) associated with severe COVID-19 infection [13, 16];

2) potential to inhibit Papain-like proteinase (PLpro) responsible for proteolytic cleavage of the replicase polyprotein to release non-structural proteins 1, 2 & 3 (Nsp1, Nsp2 and Nsp3) all essential for viral replication. [19];

3) potential to inhibit 3C-like main protease (3CLpro) or Nsp5 which is cleaved from the polyproteins causes further cleavage of Nsp4-16 and mediates maturation of Nsps which is essential in the virus lifecycle. [19];

4) act as an ionophore help transport Zinc intracellularly, increasing cellular concentrations of Zinc to inhibit viral replication. [6, 15];

5) inhibit Nf-kB which may lower inflammatory response to COVID-19 infection, and lower risk of viral entry due to decreasing DPP4 cell surface receptor. [20, 21];

6) inhibits (specifically low-dose doxycycline) expression of CD147/EMMPRIN that may be necessary for SARS-CoV-2 entry into T lymphocytes [22, 23].

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From the PDF:

Inclusion: Confirmed cases of Covid-19 by RT-PCR test

Procedure

100 patients RT-PCR confirmed cases of SARS CoV-2 met the selection criteria and was enrolled in the study. They were given a combination treatment of Tab Ivermectin and Cap Doxycycline along with supportive treatment. The dose of ivermectin was 0.2 mg/kg single dose. Doxycycline 100 mg daily was given to patients aged 8 years and above for 10 days. Patients were given the choice to go to a COVID 19 designated hospital but they went home and continued treatment. Follow up was done every day for all symptomatic patients over telephone about remission of symptoms. RT-PCR test was repeated with sample of nasal swab for all patients according to availability of testing centers between 4 to 18 days. Six weeks after testing negative, we plan to follow up on the patient about their health conditions

The results section from the PDF has more details, which contradict the rosy summary from the abstract:

All patients tested negative and their symptoms improved within 72 hours.

Nonetheless, the fact that 100 out of 100 tested negative for the virus is very positive.

Result:

This observational study, consisting of 64 males and 36 females was conducted from April to May 2020 (Figure 2) in Bangladesh Medical College. The oldest patient was 84 years and the youngest one was 8 years with most patients between the ages of 21 to 40 years (Figure 3). Patients were divided in 3 groups: Mild (73), Moderate (20) and Severe (7), based on their symptoms. From the severe patients, three had fever more than 103 Fahrenheit for seven days with severe cough and lung infiltrates, three had severe loose motion and one had uncontrolled diabetes. Out of the rest, 20 patients had moderate symptoms of mild fever (100 Fahrenheit) and mild cough. Moreover, 73 had mild symptoms of malaise, sore throat, loss of smell, loss of taste, and body ache.

Fifty percent symptomatic improvement of mild to moderate patients was seen between 3rd to 5th day after starting treatment. All 7 severe patients' symptoms subsided by 50 percent by 7th day of treatment. Retesting was done between 4 to 18 days of starting medication (Figure 4). Twenty five patients underwent retesting between 4th to 8th days, 51 between 9th to 13th days and 24 between 14th to 18th days from starting medication. All of the patients tested negative. None needed intensive care admission and no deaths were reported.

It doesn't say anything about who was tested when. Were the severe patients tested last? Did they test when symptoms had gone down 50%? What does that mean, symptoms down 50%?

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Doxy is one weird antibiotic. They had me on it. I swear it actually made breathing worse and if you google it, there are noted esophagus problems so that makes sense.

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Not sure if this is good or bad. Many people still tested positive 2 weeks after treatment started.

Edit: see fig 4. Edit 2: looks like some late testings were due to resources availability. Can’t infer much from that.

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