The aim of this study was to describe the outcomes of patients with coronavirus disease 2019 (COVID-19) in the outpatient setting after early treatment with zinc, low-dose hydroxychloroquine and azithromycin (triple therapy) dependent on risk stratification. This was a retrospective case series study in the general practice setting. A total of 141 COVID-19 patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the year 2020 were included. The main outcome measures were risk-stratified treatment decision and rates of hospitalisation and all-cause death. A median of 4 days [interquartile range (IQR) 3–6 days; available for n = 66/141 patients] after the onset of symptoms, 141 patients (median age 58 years, IQR 40–67 years; 73.0% male) received a prescription for triple therapy for 5 days. Independent public reference data from 377 confirmed COVID-19 patients in the same community were used as untreated controls. Of 141 treated patients, 4 (2.8%) were hospitalised, which was significantly fewer (P < 0.001) compared with 58 (15.4%) of 377 untreated patients [odds ratio (OR) = 0.16, 95% confidence interval (CI) 0.06–0.5]. One patient (0.7%) in the treatment group died versus 13 patients (3.4%) in the untreated group (OR = 0.2, 95% CI 0.03–1.5; P = 0.12). No cardiac side effects were observed. Risk stratification-based treatment of COVID-19 outpatients as early as possible after symptom onset using triple therapy, including the combination of zinc with low-dose hydroxychloroquine, was associated with significantly fewer hospitalisations.
In accordance with available public reference data, 712 confirmed SARS-CoV-2 PCR-positive COVID-19 patients were reported for the respective community at the defined time point of the analysis. Of these 712 patients, 335 presented as outpatients at a general practice and 127 were treated with the triple combination therapy. Of these 127 patients, 104 met the risk stratification criteria and were included in the analysis . Of the 335 patients, 208 did not meet the defined risk stratification criteria and were treated with standard of care and recovered at home. The SARS-CoV-2 infection of 37 additional patients who were clinically diagnosed with COVID-19 who met the risk stratification criteria and who were also treated with triple therapy was later confirmed by IgG tests . These patients were included additionally in the analysis resulting in a total number of 141 patients, all with a confirmed SARS-CoV-2 infection by PCR or IgG tests. None of these patients were lost to follow-up for the defined outcome. The outcome of the remaining 377 positively tested but not treated COVID-19 patients, e.g. from other practices of the community, served as public reference . Analysis of the 141 patients in the treatment group showed that all of these patients (100%) received a prescription of HCQ, 136 (96.5%) of zinc sulfate and 133 (94.3%) of azithromycin, while 1 patient (0.7%) received doxycycline instead. Instead of triple therapy, 1 patient (0.7%) in the treatment group received HCQ only, 7 patients (5.0%) received HCQ and zinc, and 4 patients (2.8%) received HCQ and azithromycin.
Baseline characteristics of the patients
Above chart shows the baseline demographics and clinical characteristics of all 141 patients in the treatment group and for the risk stratification groups A, B and C. Of the 141 patients, 69 (48.9%) belonged to group A, 48 (34.0%) to group B and 24 (17.0%) to group C. The age ranged from 18–80 years and the median age was 58 years (IQR 40–67 years). The median age of patients in groups A, B and C was 67, 39 and 45 years, respectively. A total of 103 patients (73.0%) were male with a male-to-female ratio of 2.71. The most common co-morbidities included hypertension (28%), obesity (28%), hyperlipidaemia (23%) and diabetes mellitus (18%), whilst the least common co-morbidities were liver disease (2%), heart failure (1%) and stroke (1%). One patient (0.7%) was pregnant at initiation of treatment. There was a positive and significant correlation between age and hypertension (r = 0.3309, P = 0.001), hyperlipidaemia (r = 0.26306, P < 0.001) and cardiovascular disease (r = 0.16757, P < 0.05), whilst asthma was negatively correlated with age (r = –0.30867, P < 0.001).
Hospitalisations and all-cause death
In the treatment group, 4 (2.8%) of 141 patients were hospitalised, which was significantly fewer than the 58 (15.4%) of 377 patients in the untreated group [OR = 0.16, 95% confidence interval (CI) 0.06–0.5; P < 0.001] . Therefore, the odds of hospitalisation of treated patients was 84% less than in the untreated patients. All hospitalised patients were male, with one in his twenties, two in their forties and one in his seventies. Three (75%) of the four hospitalised patients belonged to risk stratification group B and one (25%) to group A. All patients (100%) reported SOB at the time of consultation. The median time from onset of symptoms to consultation was 4 days. In the treatment group, one patient had to stay only 1 day in hospital, two other patients were discharged as cured and one patient died (see below). No patient was on a ventilator.
Above charts Hospitalisation. Treatment with triple therapy of zinc, low-dose hydroxychloroquine and azithromycin was associated with significantly fewer hospitalisations compared with untreated patients of the public reference data. χ2 (1, N = 518) = 14.17; * P < 0.001.
Of the 141 patients, 1 (0.7%) in treatment group A died after being hospitalised. This patient had a history of cancer and only took one daily dose of the triple therapy before hospital admission. More patients (13/377; 3.4%) died in the untreated group (OR = 0.2, 95% CI 0.03–1.5) . Although the odds of all-cause death of treated patients was 80% less than in the untreated group, this difference did not reach statistical significance (P = 0.12).
All patients in the treatment group with the clinical outcome of hospitalisation or all-cause death received a prescription for the complete triple therapy including zinc, low-dose HCQ and azithromycin.
The outcome of the three different risk-stratified groups (A, B and C) was not significantly different.
The 208 patients presenting at the general practice who did not meet the risk stratification requirements and who were not treated with the triple therapy recovered at home and no hospital admissions or deaths were reported.
In general, triple therapy with zinc, low-dose HCQ and azithromycin was well tolerated. After initiation of treatment in the 141 patients, 30 (21.3%) reported weakness, 20 (14.2%) nausea, 15 (10.6%) diarrhoea and 2 (1.4%) rash . No patient reported palpitations or any cardiac side effects.
This study was approved by the Western Institutional Review Board and was exempt under 45 CFR § 46.104(d)(4). Ref. Number: D4-Excemption-Zelenko (06-16-2020).
Credited to -ELSEVIER & RolandDerwand
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