Evaluation of the Prophylactic Effect of Hydroxychloroquine on People in Close-Contact with Patients with Covid-19

Shabani et al., Pulmonary Pharmacology & Therapeutics, doi:10.1016/j.pupt.2021.102069, IRCT20130917014693N10, Aug 2021
Symp. case, PCR+ 59% improvement lower risk ← → higher risk Symp. case 19% Case -6% Case b -22% HCQ for COVID-19  Shabani et al.  PROPHYLAXIS Is post-exposure prophylaxis with HCQ beneficial for COVID-19? Prospective study of 113 patients in Iran Study underpowered to detect differences c19early.org Shabani et al., Pulmonary Pharmacology.., Aug 2021 0 0.5 1 1.5 2+ RR
HCQ for COVID-19
1st treatment shown to reduce risk in March 2020, now with p < 0.00000000001 from 424 studies, used in 59 countries.
No treatment is 100% effective. Protocols combine treatments.
6,400+ studies for 210+ treatments. c19early.org
Small non-randomized PEP study with 51 HCQ patients, showing no significant difference in cases.
This paper contains multiple data inconsistencies and mathematical impossibilities.
The number of COVID-19 cases in the control group is reported inconsistently across the manuscript. The abstract states 8 (12.90%) contacts in the control group contracted COVID-19, which is mathematically consistent (8/62 = 12.90%). However, the results section states '[7 (12.90%) vs. 7 (13.72%), p=0.625]', giving 7 for the control group. Table 2 also reports 7. The percentage 12.90% is then applied to 7, but 7/62 = 11.29%, not 12.90%.
The text states '113 participants (51[82.25%] and 62[75.60%] participants in the HCQ and control groups, respectively) completed the study.' For the HCQ group, 51/62 = 82.26%, which matches 82.25% (minor rounding). However, for the control group, all 62 allocated participants completed the study (62/62 = 100%), not 75.60%. The value 75.60% would require a denominator of approximately 82 (62/82 = 75.61%), but the CONSORT diagram shows only 62 were allocated to the control group. This percentage is mathematically impossible given the reported allocation and completion numbers.
Authors report a hazard ratio of 1.5 (95% CI: 1.372-1.642) for RT-PCR positivity in the entire study population after exposure, then state 'no differences were seen between the control group and those treated with hydroxychloroquine.' Several problems exist: (1) The confidence interval excludes 1.0, which indicates statistical significance, yet the authors interpret this as showing no difference. (2) The CI is remarkably narrow (range of only 0.27) for a study of 113 participants with few events. (3) The HR appears to describe overall infection risk post-exposure rather than a between-group comparison, but this is poorly explained, and it is not clear how this is calculated. The sentence structure conflates the overall HR with the group comparison, creating confusion about what is actually being reported.
Table 1 headers read 'MEAN-IQR' but the methods section states that descriptive results were reported as 'medians and interquartile ranges.' The parenthetical values are single numbers rather than the standard Q1-Q3 range format (e.g., '41 (43.5)' rather than '41 (30-52)').
In Table 1, the 'Control Group - Negative' column has a stated header denominator of n=54. However, the sum of the patients in the 'Blood Group' categories is 62. Percentages within this subsection are calculated inconsistently, with some using 54 as the denominator and others using 62.
The albumin IQR for control-negative participants is reported as 4.50 (4.30-40.70) g/dL. The upper bound of 40.70 is physiologically unrealistic (normal: 3.5-5.0 g/dL); this is likely a typo for 4.70. Additionally, multiple lab values for the control-positive subgroup (N=8) show identical Q1 and Q3 values (e.g., AST: 14.00 (14.00-14.00), ALT: 12.00 (12.00-12.00)), suggesting these values come from only 1 patient rather than the stated N=8. This suggests substantial unreported missing lab data. CRP values are entirely absent for COVID-positive participants in both groups, despite being the most clinically relevant inflammatory marker.
18% of HCQ patients were excluded post-allocation, while none were excluded from the control group. Authors conducted a per-protocol analysis rather than intention-to-treat, introducing significant attrition bias.
This study is excluded in the after exclusion results of meta-analysis: multiple potential data reliability issues.
risk of symptomatic case, 59.5% lower, RR 0.41, p = 0.63, treatment 1 of 51 (2.0%), control 3 of 62 (4.8%), NNT 35, day 7, PCR+ symptomatic cases.
risk of symptomatic case, 19.0% lower, RR 0.81, p = 1.00, treatment 2 of 51 (3.9%), control 3 of 62 (4.8%), NNT 109, day 7, symptomatic cases.
risk of case, 6.4% higher, RR 1.06, p = 1.00, treatment 7 of 51 (13.7%), control 8 of 62 (12.9%), day 7, PCR+ or symptomatic.
risk of case, 21.6% higher, RR 1.22, p = 0.78, treatment 7 of 51 (13.7%), control 7 of 62 (11.3%), day 7, PCR+ only.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Shabani et al., 10 Aug 2021, prospective, Iran, peer-reviewed, 16 authors, trial IRCT20130917014693N10.
$0 $500 $1,000+ Efficacy vs. cost for COVID-19 treatment protocols c19early.org February 2026 Iran United Kingdom USA Russia Sudan Angola Colombia Kenya Mozambique Pakistan Peru Philippines Argentina Vietnam Spain Brazil Italy France Japan China Uzbekistan Nepal Ethiopia Mexico South Korea Ghana Germany Bangladesh Saudi Arabia Algeria Morocco Yemen Poland India DR Congo Madagascar Thailand Uganda Venezuela Nigeria Egypt Bolivia Taiwan Zambia Fiji Bosnia-Herzegovina Ukraine Côte d'Ivoire Bulgaria Greece Slovakia Singapore Iceland New Zealand Mongolia Czechia Israel Trinidad and Tobago Hong Kong Belarus North Macedonia Qatar Panama Serbia CAR Iran favored high-profit treatments.The average efficacy of treatments was moderate.High-cost protocols reduce early treatment, andforgo complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
$0 $500 $1,000+ Efficacy vs. cost for COVID-19treatment protocols worldwide c19early.org February 2026 Iran United Kingdom USA Russia Sudan Angola Colombia Kenya Mozambique Pakistan Peru Philippines Argentina Vietnam Spain Brazil Italy France Japan China Uzbekistan Nepal Ethiopia Mexico South Korea Ghana Germany Bangladesh Saudi Arabia Algeria Morocco Yemen Poland India DR Congo Madagascar Thailand Uganda Venezuela Nigeria Egypt Bolivia Taiwan Zambia Fiji Bosnia-Herzegovina Côte d'Ivoire Bulgaria Greece Slovakia Iceland Mongolia Czechia Israel Trinidad and Tobago Hong Kong Belarus North Macedonia Qatar Panama Serbia Syria Iran favored high-profit treatments.The average efficacy was moderate.High-cost protocols reduce early treatment,and forgo complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
Evaluation of the prophylactic effect of hydroxychloroquine on people in close-contact with patients with COVID-19
Minoosh Shabani, Mehdi Totonchi, Omidvar Rezaeimirghaed, Latif Gachkar, Mohammadreza Hajiesmaeili, Ali Khoshkar, Mahdi Amirdosara, Ali Saffaei, Shervin Shokouhi, Masoud Mardani, Ilad Alavi Darazam, Alireza Karami, Milad Sharifi, Mana Zaman, Elham Abedheydari, Dr Zahra Sahraei
Pulmonary Pharmacology & Therapeutics, doi:10.1016/j.pupt.2021.102069
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Yao, Ye, Zhang, Cui, Huang et al., Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Clinical Infectious Diseases
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