The primary endpoints were: 

- an aggressive clinical course requiring oxygen therapy or transfer to the ICU after at least three days of treatment
- contagiousness as assessed by PCR and culture
- length of stay in the ID ward

University of South Florida

- Clinical classification and clinical follow-up
- Chest computed tomography (LDCT) 
- PCR assay 
- Culture 
- COVID treatment
- Criteria for discharge 
- Criteria for contagiousness 
- Outcomes

Methods: Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study

Gautret, P., Lagier, J., Parola, P., Hoang, V. T., Meddeb, L., Sevestre, J., et al.  (2020). Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study. Travel Medicine and Infectious Disease, 34(SI), 101663. doi:10.1016/j.tmaid.2020.101663
https://www.sciencedirect.com/science/article/pii/S1477893920301319

Clinical and microbiological effect of a combination of Hydroxychloroquine and Azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study

Patients grouped into two categories upon admission: those with an upper respiratory tract infection (URTI), and those with a lower respiratory tract infection (LRTI). 

The time between the onset of symptoms and admission, and the time between the onset of symptoms and treatment was documented. Risk factors for severe COVID-19 were also documented.

The national early warning score (NEWS) for patients was also collected upon admission and during follow ups. Three risk  categories for clinical deterioration were defined: low score (NEWS 0–4), medium score (NEWS 5–6), and high score (NEWS≥7) for COVID patients.

Lastly, the need for oxygen therapy, transfer to the intensive care unit (ICU), death, and length of stay in the ID ward were documented.

Clinical classification and clinical follow-up

Patients regularly underwent an unenhanced chest low-dose computed tomography (LDCT) upon admission or soon after, using a single CT machine. All images were analyzed by experienced chest radiologists, then classified as compatible or not compatible with pneumonia. Images were considered to be compatible in the presence of peripheral multifocal ground-glass opacities with or without reticulations, or in the presence of alveolar consolidation or crazy paving pattern.

Chest computed tomography (LDCT)

Patients were administered nasopharyngeal swabbing daily until discharge, with some exceptions. SARS-CoV-2 RNA was assessed by real-time reverse transcription- PCR using a hydrolysis probe-based system that targets the gene encoding the envelope (E) protein. Negative results for viral RNA detection were defined as those with a cycle threshold (Ct) value ≥ 35.

PCR assay

Cultures were attempted in a selected convenience sample of patients. A 500 μL aliquot of the liquid collected from the nasopharyngeal swab were passed through 0.22-μm pore sized centrifugal filter and were then inoculated in wells on 96-well culture microplates, of which four wells contained Vero E6 cells (ATCC CRL-1586) in Minimum Essential Medium culture medium with 4% foetal calf serum and 1% glutamine. After centrifugation at 4000 g, microplates were incubated at 37 °C. Plates were observed every day for evidence of a cytopathogenic effect. The presumptive detection of the virus in supernatant was performed using SU5000 SEM (Hitachi) scanning electronic microscope and then confirmed by specific RT-PCR.

Culture

Patients with no contraindications  were offered a combination of 200 mg of oral HCQ sulfate, three times per day for ten days combined with AZM (500 mg on D1 followed by 250 mg per day for the next four days). For patients with pneumonia and NEWS score ≥ 5, a broad spectrum antibiotic (ceftriaxone) was added to HCQ and AZM. Twelve-lead electrocardiograms (ECG) were performed on each patient before treatment and two days after treatment began. All ECGs were reviewed by senior cardiologists. The treatment was either not started or discontinued when the QTc (Bazett's formula) was > 500 ms.  Symptomatic treatments, including oxygen, were added when needed. An ionogram and verification of serum potassium levels were regularly performed upon admission. When needed, standard blood chemistry was checked.

COVID-19 Treatment

Initially, patients with two successive negative nasopharyngeal samples resulting from PCR assay (CT value ≥ 35) were discharged. From 18 March, patients with a single nasopharyngeal sample with a PCR CT value ≥ 34 were discharged to their homes or transferred to other units for continuing treatment. Ultimately, because of a crucial need to admit new, untreated inpatients, inpatients already receiving treatment with a PCR CT value < 34, with good clinical outcome and good adherence to treatment were also discharged. When possible, further follow-up was continued in other units or through out-patient consultations.

Criteria for discharge

Patients with a PCR CT value of < 34 were considered presumably contagious based on results of a study showing that culture are positive under this condition. 

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