Early cidofovir administration might be associated with a lower probability of respiratory failure in treating human adenovirus pneumonia: a retrospective cohort study

Ko, Jae-Hoon; Lim, Jihyang; Choi, Joon Young; Oh, Hong Sang; Yoo, Hyuk Sang; Jhun, Byung Woo; Huh, Kyungmin; Peck, Kyong Ran

doi:10.1016/j.cmi.2019.10.012

Cited by 20 publications

(24 citation statements)

References 27 publications

(28 reference statements)

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“…The search for an effective treatment of COVID-19 also needs to consider the optimal time to start the use of effective drugs, taking advantage of the emerging data concerning the pathogenetic mechanisms underlying different stages of the disease. As it has been shown that the pathogenesis of COVID-19 includes a viremic phase that peaks 5-6 days after infection, followed by an immunemediated phase characterised by an aggressive inflammatory response that is largely responsible for airway damage [4], it is possible to hypothesise that the early use of effective antiviral drugs would reduce the progression and mortality of COVID-19, as has been observed in the case of other acute viral respiratory illnesses [17][18][19][20].…”

Section: Discussionmentioning

confidence: 99%

Early administration of lopinavir/ritonavir plus hydroxychloroquine does not alter the clinical course of SARS-COV-2 infection: a retrospective cohort study

Giacomelli

Pagani

Ridolfo

et al. 2020

Preprint

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Background The potential benefit of a combination therapy with lopinavir/ritonavir (LPV/r) and hydroxychloroquine (HCQ) on COVID-19 has been speculated. We explored the effect of the timing of LPV/r + HCQ initiation on the outcome of patients with COVID-19. Methods A retrospective cohort study was conducted on patients with COVID-19 who started treatment with LPV/r plus HCQ between February 21 and March 20, 2020, at Luigi Sacco Hospital in Milan, Italy. Over time cumulative incidence of clinical improvement was compared between patients who started treatment less than 5 days from the onset of symptoms [early treatment group (ET)] and those who initiated it later [delayed treatment group (DT)]. The association of LPV/r plus HCQ initiation timing on 30-day mortality was also assessed by univariate and multivariate logistic models. Results The study included 172 patients, prevalently males (72%) in their sixties, with a moderate (53.4%) or severe (34.9%) disease. Fourty-three (25%) patients were included in the ET group and and 129 (75%) in the DT group. Severity of disease did not significantly differ between the two groups. Conclusion Timing of LPV/r + HCQ initiation seems to have no impact on COVID-19 clinical course in terms of improvement and 30-day mortality. These findings rise doubts on the clincial efficacy of this regimen.

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Section: Discussionmentioning

confidence: 99%

Early administration of lopinavir/ritonavir plus hydroxychloroquine does not alter the clinical course of SARS-COV-2 infection: a retrospective cohort study

Giacomelli

Pagani

Ridolfo

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…The search for an effective treatment of COVID‐19 also needs to consider the optimal time to start the use of effective drugs, taking advantage of the emerging data concerning the pathogenetic mechanisms underlying different stages of the disease. As it has been shown that the pathogenesis of COVID‐19 includes a viremic phase that peaks 5 to 6 days after infection, followed by an immune‐mediated phase characterized by an aggressive inflammatory response that is largely responsible for airway damage, 4 it is possible to hypothesize that the early use of effective antiviral drugs would reduce the progression and mortality of COVID‐19, as has been observed in the case of other acute viral respiratory illnesses 17‐20 …”

Section: Discussionmentioning

confidence: 99%

“…In particular, one randomized controlled trial comparing the efficacy of LPV/r with that of standard of care in patients with severe COVID‐19 did not find any significant differences in mortality, clinical improvement or viral shedding, 15 and an observational study carried out in New York did not find any difference in mortality between severely ill patients with COVID‐19 who received HCQ and those who did not 16 . However, neither of these studies considered the possible effect of the timing of the start of treatment, although there is evidence that early treatment is crucial when assessing efficacy against acute respiratory infections 17‐20 …”

Section: Introductionmentioning

confidence: 99%

“…16 However, neither of these studies considered the possible effect of the timing of the start of treatment, although there is evidence that early treatment is crucial when assessing efficacy against acute respiratory infections. [17][18][19][20] The aim of this study was to analyze the combined effect of LPV/r and HCQ treatment on the course of COVID-19 by examining the differences in clinical outcomes of patients who started treatment within 5 days of the onset of symptoms and those who started later. In accordance with the SIMIT drug protocol, all patients with COVID-19 pneumonia admitted to our hospital during the study period were offered off-label treatment with LPV/r 400/100 mg (tablet or oral solution) twice daily plus HCQ 200 mg twice daily for a minimum of five and a maximum of 20 days depending on patients' clinical response.…”

mentioning

confidence: 99%

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Early administration of lopinavir/ritonavir plus hydroxychloroquine does not alter the clinical course of SARS‐CoV‐2 infection: A retrospective cohort study

Giacomelli

Pagani

Ridolfo

et al. 2020

Journal of Medical Virology

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Background As it has been shown that lopinavir (LPV) and hydroxychloroquine (HCQ) have in vitro activity against coronaviruses, they were used to treat COVID‐19 during the first wave of the epidemic in Lombardy, Italy. Methods To compare the rate of clinical improvement between those who started LPV/ritonavir (LPV/r)+HCQ within five days of symptom onset (early treatment, ET) and those who started later (delayed treatment, DT). This was a retrospective intent‐to‐treat analysis of the hospitalized patients who started LPV/r+HCQ between 21 February and 20 March 2020. The association between the timing of treatment and the probability of 30‐day mortality was assessed using uni‐ and multivariable logistic models. Results The study involved 172 patients: 43 (25%) in the ET and 129 (75%) in the DT group. The rate of clinical improvement increased over time to 73.3% on day 30, without any significant difference between the two groups (Gray's test P =0.213). After adjusting for potentially relevant clinical variables, there was no significant association between the timing of the start of treatment and the probability of 30‐day mortality (adjusted odds ratio [aOR] ET vs DT=1.45, 95% confidence interval 0.50‐4.19). Eight percent of the patients discontinued the treatment because of severe gastrointestinal disorders attributable to LPV/r. Conclusion The timing of the start of LPV/r+HCQ treatment does not seem to affect the clinical course of hospitalised patients with COVID‐19. Together with the severe adverse events attributable to LPV/r, this raises concerns about the benefit of using this combination to treat COVID‐19. This article is protected by copyright. All rights reserved.

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“…151,152 As an example, in a recent report of 89 patients in Korean military hospitals with severe HAdV pneumonia who were treated with cidofivir, drug administration within 7 days was associated with a reduced risk of respiratory failure. 153 However, the use of cidofivir is limited by significant side effects including nephrotoxicity and neutropenia. 154,155 Brincidovifir, a lipid conjugate of cidofivir associated with less nephrotoxicity, is a promising alternative, although its administration has been associated with significant diarrhea.…”

Section: Treatmentmentioning

confidence: 99%

Other Respiratory Viruses as a Cause of Community-Acquired Pneumonia

Walter

2020

Semin Respir Crit Care Med

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AbstractCommunity-acquired pneumonia (CAP) is a major cause of morbidity and mortality worldwide. There is growing appreciation of the burden of noninfluenza viral pathogens in CAP. Due to multiple factors including pneumococcal vaccination programs, declining rates of cigarette smoking, an aging population, and increasingly sensitive diagnostic tests, respiratory viruses are now the most common pathogens detected in CAP, outpacing Streptococcus pneumoniae. Noninfluenza respiratory pathogens are widely accepted as causal pathogens in CAP including in immunocompetent patients. This review provides an overview of five noninfluenza respiratory viral pathogens commonly implicated in CAP pathogenesis: rhinovirus, human metapneumovirus, respiratory syncytial virus, human parainfluenza virus, and human adenoviruses. Nucleic acid amplification testing platforms and their impact on antimicrobial stewardship efforts are also considered.

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Early cidofovir administration might be associated with a lower probability of respiratory failure in treating human adenovirus pneumonia: a retrospective cohort study

Cited by 20 publications

References 27 publications

Early administration of lopinavir/ritonavir plus hydroxychloroquine does not alter the clinical course of SARS-COV-2 infection: a retrospective cohort study

Early administration of lopinavir/ritonavir plus hydroxychloroquine does not alter the clinical course of SARS-COV-2 infection: a retrospective cohort study

Early administration of lopinavir/ritonavir plus hydroxychloroquine does not alter the clinical course of SARS‐CoV‐2 infection: A retrospective cohort study

Other Respiratory Viruses as a Cause of Community-Acquired Pneumonia

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