An Updated Systematic Review of the Therapeutic Role of Hydroxychloroquine in Coronavirus Disease-19 (COVID-19)

Das, Saibal; Bhowmick, Subhrojyoti; Tiwari, Sayali C; Sen, Sukanta

doi:10.1007/s40261-020-00927-1

Cited by 77 publications

(105 citation statements)

References 57 publications

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“…Hydroxychloroquine was largely used in the early period of COVID-19 pandemic owing to its in vitro activity against the virus and relatively safe profile. However, an observational study of 811 patients treated with hydroxychloroquine failed to show any clinical benefit compared with standard of care [38], and a systematic review raised concerns about the quality of published studies [39]. Interim results of the Solidarity Trial showed no significant reduction in mortality of hospitalized COVID-19 patients treated with either hydroxychloroquine or lopinavir/ritonavir compared to standard of care, and these arms of the study were discontinued.…”

Section: Discussionmentioning

confidence: 99%

Compassionate use of JAK1/2 inhibitor ruxolitinib for severe COVID-19: a prospective observational study

et al. 2020

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Overwhelming inflammatory reactions contribute to respiratory distress in patients with COVID-19. Ruxolitinib is a JAK1/ JAK2 inhibitor with potent anti-inflammatory properties. We report on a prospective, observational study in 34 patients with COVID-19 who received ruxolitinib on a compassionate-use protocol. Patients had severe pulmonary disease defined by pulmonary infiltrates on imaging and an oxygen saturation ≤ 93% in air and/or PaO2/FiO2 ratio ≤ 300 mmHg. Median age was 80.5 years, and 85.3% had ≥ 2 comorbidities. Median exposure time to ruxolitinib was 13 days, median dose intensity was 20 mg/day. Overall survival by day 28 was 94.1%. Cumulative incidence of clinical improvement of ≥2 points in the ordinal scale was 82.4% (95% confidence interval, 71-93). Clinical improvement was not affected by low-flow versus highflow oxygen support but was less frequent in patients with PaO2/FiO2 < 200 mmHg. The most frequent adverse events were anemia, urinary tract infections, and thrombocytopenia. Improvement of inflammatory cytokine profile and activated lymphocyte subsets was observed at day 14. In this prospective cohort of aged and high-risk comorbidity patients with severe COVID-19, compassionate-use ruxolitinib was safe and was associated with improvement of pulmonary function and discharge home in 85.3%. Controlled clinical trials are necessary to establish efficacy of ruxolitinib in COVID-19.

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Section: Discussionmentioning

confidence: 99%

Compassionate use of JAK1/2 inhibitor ruxolitinib for severe COVID-19: a prospective observational study

et al. 2020

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“…However, opposite findings have been reported [30] and the role of HCQ in the development of AKI has still to be fully elucidated, and larger randomized clinical trials are warranted to address this issue. Use of HCQ in COVID-19 patients is largely debated [31].…”

Section: Discussionmentioning

confidence: 99%

Kidney disease and all-cause mortality in patients with COVID-19 hospitalized in Genoa, Northern Italy

et al. 2020

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Background The prevalence of kidney involvement during SARS-CoV-2 infection has been reported to be high. Nevertheless, data are lacking about the determinants of acute kidney injury (AKI) and the combined effect of chronic kidney disease (CKD) and AKI in COVID-19 patients. Methods We collected data on patient demographics, comorbidities, chronic medications, vital signs, baseline laboratory test results and in-hospital treatment in patients with COVID-19 consecutively admitted to our Institution. Chronic kidney disease was defined as eGFR < 60 mL/min per 1.73 m2 or proteinuria at urinalysis within 180 days prior to hospital admission. AKI was defined according to KDIGO criteria. The primary and secondary outcomes were the development of AKI and death. Results Of 777 patients eligible for the study, acute kidney injury developed in 176 (22.6%). Of these, 79 (45%) showed an acute worsening of a preexisting CKD, and 21 (12%) required kidney replacement therapy. Independent associates of AKI were chronic kidney disease, C-reactive protein (CRP) and ventilation support. Among patients with acute kidney injury, 111 died (63%) and its occurrence increased the risk of death by 60% (HR 1.60 [95% IC 1.21–2.49] p = 0.002) independently of potential confounding factors including hypertension, preexisting kidney damage, and comorbidities. Patients with AKI showed a significantly higher rate of deaths attributed to bleeding compared to CKD and the whole population (7.5 vs 1.5 vs 3.5%, respectively). Conclusion Awareness of kidney function, both preexisting CKD and development of acute kidney injury, may help to identify those patients at increased risk of death.

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“…Hydroxychloroquine was at the disposal for ICU intensivists at any time because this drug is in stock for chronic disease such as patients with systemic lupus erythematosus. When doubts were raised regarding effectiveness of hydroxychloroquine, this antiviral strategy was replaced by administration of camostat mesylate by mid of March ( 3 , 4 ). The following doses were used: hydroxychloroquine was administered with a loading dose of 400 mg on day 1 followed by 200 mg days 2–5 and camostat mesylate at the maximum dose of 3 × 200 mg daily for 5 days according to information based on a protocol of a larger trial in Denmark (clinical trials reference: NCT04321096).…”

Section: Methodsmentioning

confidence: 99%

Camostat Mesylate May Reduce Severity of Coronavirus Disease 2019 Sepsis: A First Observation

Hofmann-Winkler

Moerer

Alt-Epping

et al. 2020

Critical Care Explorations

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Objectives: Severe acute respiratory syndrome coronavirus 2 cell entry depends on angiotensin-converting enzyme 2 and transmembrane serine protease 2 and is blocked in cell culture by camostat mesylate, a clinically proven protease inhibitor. Whether camostat mesylate is able to lower disease burden in coronavirus disease 2019 sepsis is currently unknown. Design: Retrospective observational case series. Setting: Patient treated in ICU of University hospital Göttingen, Germany. Patients: Eleven critical ill coronavirus disease 2019 patients with organ failure were treated in ICU. Interventions: Compassionate use of camostat mesylate (six patients, camostat group) or hydroxychloroquine (five patients, hydroxychloroquine group). Measurements and Main Results: Clinical courses were assessed by Sepsis-related Organ Failure Assessment score at days 1, 3, and 8. Further, viral load, oxygenation, and inflammatory markers were determined. Sepsis-related Organ Failure Assessment score was comparable between camostat and hydroxychloroquine groups upon ICU admission. During observation, the Sepsis-related Organ Failure Assessment score decreased in the camostat group but remained elevated in the hydroxychloroquine group. The decline in disease severity in camostat mesylate treated patients was paralleled by a decline in inflammatory markers and improvement of oxygenation. Conclusions: The severity of coronavirus disease 2019 decreased upon camostat mesylate treatment within a period of 8 days and a similar effect was not observed in patients receiving hydroxychloroquine. Camostat mesylate thus warrants further evaluation within randomized clinical trials.

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An Updated Systematic Review of the Therapeutic Role of Hydroxychloroquine in Coronavirus Disease-19 (COVID-19)

Cited by 77 publications

References 57 publications

Compassionate use of JAK1/2 inhibitor ruxolitinib for severe COVID-19: a prospective observational study

Compassionate use of JAK1/2 inhibitor ruxolitinib for severe COVID-19: a prospective observational study

Kidney disease and all-cause mortality in patients with COVID-19 hospitalized in Genoa, Northern Italy

Camostat Mesylate May Reduce Severity of Coronavirus Disease 2019 Sepsis: A First Observation

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