Beneficial impact of Baricitinib in COVID-19 moderate pneumonia; multicentre study
Authors: Fabrizio Cantini, Laura Niccoli, Carlotta Nannini, Daniela Matarrese, Massimo Edoardo Di Natale, Pamela Lotti, Donatella Aquilini, Giancarlo Landini, Barbara Cimolato, Massimo Antonio Di Pietro, Michele Trezzi, Paolo Stobbione, Gabriele Frausini, Assunta Navarra, Emanuele Nicastri, Giovanni Sotgiu, Delia Goletti
Journal: Journal of Infection (2020)

•Baricitinib, an anti-JAK1/JAK2, reduces cytokine release and SARS-Co-V2 entry.•In a retrospective multicenter study baricitinib reduces COVID-19 mortality rate.•Baricitinib reduces intensive care unit admissions of COVID-19 pneumonia.•Baricitinb reduces SARS-CoV-2 viral burden detected by nasopharyngeal swab.•Baricitinib used for 2 weeks was not associated with serious adverse events. As recently discussed in the Journal,1Cantini F. Niccoli L. Matarrese D. Nicastri E. Stobbione P. Goletti D Baricitinib therapy in COVID-19: a pilot study on safety and clinical impact.J Infect. 2020; (Apr 23Epub ahead of print])https://doi.org/10.1016/j.jinf.2020.04.017Abstract Full Text Full Text PDF PubMed Scopus (343) Google Scholar baricitinib was safe and improved the clinical conditions in 12 patients with mild-moderate Coronavirus Disease 2019 (COVID-19) pneumonia. It is known that severe symptoms of COVID-19 may develop after a median of 8-days from illness-onset, with a median time to Intensive Care Unit (ICU) admission of 5 days from the dyspnea occurrence.2Huang C. Wang Y. Li X. Ren L. Zhao J. Hu Y. et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; 395: 497-506Abstract Full Text Full Text PDF PubMed Scopus (32450) Google Scholar Currently, no antiviral therapies or vaccines are available. An uncontrolled immune response3Sun X. Wang T. Cai D. et al.Cytokine storm intervention in the early stages of COVID-19 pneumonia.Cytokine Growth Factor Rev. 2020; (Apr. 25)https://doi.org/10.1016/j.cytogfr.2020.04.002Crossref PubMed Scopus (349) Google Scholar is observed and is likely involved in tissues injury.4Adachi T. Chong J.M. Nakajima N. et al.Clinicopathological and immunohistochemical findings from autopsy of patient with COVID-19, Japan.Emerg Infect Dis. 2020; 26 (May 15[Epub ahead of print])https://doi.org/10.3201/eid2609.201353Crossref PubMed Scopus (102) Google Scholar Baricitinib is an anti-Janus kinase inhibitor-1 and −2, and has a dual action on COVID-19 therapy including the inhibition of cytokine release and SARS-CoV-2 endocytosis.5Stebbing J. Phelan A. Griffin I. Tucker C. Oechsle O. Richardson P COVID-19: combining antiviral and anti-inflammatory treatments.Lancet Infect Dis 2020. 2020; (Published online February 27https//doi.org/)https://doi.org/10.1016/51473-3099(20)30132-8Crossref Google Scholar Based on this evidence, we conducted an observational, retrospective, longitudinal multicenter-study in consecutive-hospitalized patients with COVID-19 moderate pneumonia to evaluate the 2-week effectiveness and safety of baricitinib combined with antivirals (lopinavir/ritonavir) compared with the standard of care therapy which was hydroxychloroquine and lopinavir/ritonavir. Primary aim was to evaluate the mortality rate; secondary aims were to evaluate the rate of ICU transfer, hospital discharge, improvement of respiratory parameters, adverse events (AEs) occurrence. Moreover, associations between therapy and modification of respiratory parameters and C-Reactive Protein (CRP), interleukin-6 (IL-6), lymphocyte percentage were evaluated. Clinical charts of patients with moderate COVID-19 pneumonia from 7 Italian hospitals (Hospital of Prato, Hospital of Pistoia, Hospital S.Maria Nuova, Florence, Hospital of Alessandria, Hospital of Fano, Hospital of Pesaro, Hospital of Ariano Irpino (Avellino) were reviewed. Baricitinib-treated arm included consecutive-hospitalized patients,18 years-older, SARS-CoV-2 naso-pharingeal swab-positive, with a moderate pneumonia characterized by typical symptoms, radiological findings of pneumonia, SpO2 >92% on room air,and PaO2/FiO2 100–300 mmHg, admitted between March 15th-May 5th, 2020. Baricitinib 4 mg/day was provided orally associated with lopinavir/ritonavir tablets 250 mg/bid for 2 weeks. Control-arm included all consecutive-hospitalized patients from February 20th-March 15th, 2020 with moderate COVID-19 pneumonia, 18 years-older, treated with hydroxychloroquine (HCLR) and lopinavir/ritonavir. Exclusion criteria were: history of thrombophlebitis, latent tuberculosis infection,6QuantiFERONⓇ-TB Gold Plus, ELISA package insert, quiagen. http://www.quantiferon.com/irm/content/PI/QFT/PLUS/2PK-Elisa/UK.pdf.Google Scholar,7Goletti D. Lee M.R. Wang J.Y. Walter N. Ottenhoff T.H.M Update on tuberculosis biomarkers: from correlates of risk, to correlates of active disease and of cure from disease.Respirology. 2018; 23: 455-466Crossref PubMed Scopus (121) Google Scholar HBV or HCV infection, current varicella zoster or bacterial infection, pregnancy, lactation, contraceptive pills intake, previous (last 5 years) or current malignancy, neutrophil count<1.0 × 109/L, lymphocyte count<0.2 × 109/L, platelets count<50 × 109/L, transaminases values 4-fold higher than the upper normal limit. Prophylactic anti-thrombotic therapy with low-weight molecular heparin wasadministered. Patients had supportive therapy (O2 supply, rehydration, diuretics, anti-hypertensive, antibiotics) if needed. Corticosteroids were not allowed. If patients were discharged earlier than 2 weeks, they were requested to continue the ongoing therapy until the scheduled 14-days. Temperature, respiratory and pulse rate, arterial blood gas analysis, blood pressure, blood cell count, liver and kidney tests function were daily assessed. IL-6 serum levels of (RayBioⓇ Human IL-6 ELISA Kit, RayBiotech Co.,USA) were tested at baseline, week 1 and 2. Since low lymphocyte percentage can predict a poor prognosis6QuantiFERONⓇ-TB Gold Plus, ELISA package insert, quiagen. http://www.quantiferon.com/irm/content/PI/QFT/PLUS/2PK-Elisa/UK.pdf.Google Scholar, patients were stratified at baseline as: lymphocytes >20%, >5% to <20%, and <5%. Patients provided a written-informed consent. The off-label use of baricitinib was approved by the Hospital-Committee and Ethical-Committee of Toscana-Region (Code: BARIC-off; 17,261; approval date: May 5th 2020). Mann-Whitney U test was used to compare quantitative variables; Wilcoxon test for paired data; Chi-squared or Fisher's exact test for categorical variables. A two-tailed p-value <0.05 was considered significant. At baseline, 113 patients were in the baricitinib-arm, and 78 in the control-arm (Table 1). The results indicate that the 2-week case fatality rate was significantly lower in the baricitinib-arm compared with controls [0% (0/113) vs 6.4% (5/78) (p-value: 0.010; 95%CI 0.0000–0.4569)] (Table 2). ICU admission was requested in 0.88% (1/113) vs 17.9% (14/78) patients in the baricitinib-arm compared to the control-arm (week 1, p-value: 0.019; 95%CI 0.0092–0.6818), (week 2, p-value: <0.0001; 95%CI 0.0038–0.2624). Discharge rate was significantly higher in the baricitinib-arm at week 1 [9.7% (11/113) vs 1.3% (1/78) (p-value: 0.039; 95%CI: 1.41–90.71)], and at week 2 [77.8% (88/113) vs 12.8% (10/78) (p:<0.0001; 95%CI 10.79–51.74)].Table 1Baseline demographic, clinical, and laboratory characteristics of COVID-19 patients treated with lopinavir/ritonavir and either baricitinib or with standard of care therapy.FeatureBaricitinibCombined with lopinavir/ritonavir treated arm aBaricitinib-treated arm: Baricitinib-therapy was given 4 mg/day orally combined with lopinavir/ritonavir tablets 250 mg/bid.HydroxychloroquineCombined with lopinavir/ritonavir treated arm(standard of care-treated arm) bConsecutive patients treated with standard of care therapy (hydroxychloroquine 200 mg/bid with lopinavir/ritonavir tablets 250 mg/bi) during the previous weeks before the first baricitnib-treated patient served as controls.P valuePatient number, No (%)113 (100)78 (100)Male/female, No (%)73/40 (64.6/35.4)46/32 (59/41)0.524Age years, median (IQR)68 (57–76)63 (55.5–69.5)0.602Interval from symptoms onset and therapy starting, days, No7 (5–10)6.5 (4–9)0.915Cough, No (%)75/113 (66.4)53/78 (67.9)0.943Dyspnea, No (%)84/113 (74.3)58/78 (74.4)0.869Sputum production, No (%)41/113 (36.2)29/78 (37.2)0.979Headache, No (%)56/113 (49.5)31/78 (39.7)0.234Diarrhea, No (%)26/113 (23)11/78 (14.1)0.179Ageusia/anosmia, No (%)44/113 (38.9)29/78 (37.1)0.925Hypertension, No (%)32/113 (28.3)21/78 (26.9)0.962Diabetes, No (%)18/113 (15.9)13/78 (16.6)0.949COPD, No (%)16/113 (14.1)14/78 (17.9)0.613CVD, No (%)10/113 (8.5)5/78 (6.4)0.732Fever °C, median (IQR)37.9 (36.7–38.3)37.8 (37.7–38.7)0.915Breath rate n/min, median (IQR),20 (17–22)21 (19–24)0.825SpO2 (%),median (IQR)95 (92–98)93 (92–97)0.234PaO2/FiO2, median (IQR)265.7 (202–330)267.5 (263.1–301)0.522Pulse rate, median (IQR)80 (70–90)85 (79–92)0.129SBP mm/hg, median (IQR)125 (112–135)115 (105–130)0.121DBP mm/hg, median (IQR)70 (65–80)65 (60–72)0.232WBC (x109/l), median (IQR)6.5 (4.9–8.3)7.2 (5.8–8.6)0.708Neutrophils (x109/l), median (IQR)4.7 (3.5–6.5)4.9 (4.4–6.9)0.911Lymphocytes (x109/l), median (IQR)0.93 (0.7–1.2)0.88 (0.7–0.9)0.728Lymphocyte percentage>20 N (%)39 (34.5)24 (30.8)0.701>5-<2070 (61.9)51 (65.4)0.740<54 (3.6)3 (3.8)0.779Hemoglobin (g/l), median (IQR)118 (101–134)125 (108–133)0.426Platelets (x109/l), median (IQR)213 (167–308)268 (156–392)0.234Alt (u/l), median (IQR)29 (19–49)34 (25–52)0.168Ast (u/l), median (IQR)34 (25–51)40 (34–47)0.628Creatinine (mg/dl), median (IQR)0.9 (0.7–1.1)1.00 (0.9–1.2)0.925Crp (mg/dl), median (IQR)8.2 (4.1–14.5)6.3 (2.8–13.6)0.129IL-6 (PG/ML), MEDIAN (IQR) cIL-6 values were available in 58 patients of the baricitinib-treated group and in 36 controls.29.4 (16–45)32.6 (25–61)0.225Procalcitonin (ng/ml), median (IQR)0.6 (0.3–1.2)0.9 (0.8–2.1)0.802Mews, median (IQR)1 (0–2)2 (1–3)0.225Abbreviations and symbols: No= number;%= percentage; °C: grade Celsius; min= minute; SpO2= peripheral capillary oxygen saturation; PaO2/FiO2= ratio of arterial oxygen partial pressure to fractional inspired oxygen; SBP= systolic blood pressure; DBP= diastolic blood pressure; WBC= white blood cells; AST= serum glutamic oxaloacetic transaminase; ALT= serum alanine aminotransferase; MEWS= Modified Early Warning Score; IQR: Interquartile range.a Baricitinib-treated arm: Baricitinib-therapy was given 4 mg/day orally combined with lopinavir/ritonavir tablets 250 mg/bid.b Consecutive patients treated with standard of care therapy (hydroxychloroquine 200 mg/bid with lopinavir/ritonavir tablets 250 mg/bi) during the previous weeks before the first baricitnib-treated patient served as controls.c IL-6 values were available in 58 patients of the baricitinib-treated group and in 36 controls. Open table in a new tab Table 2Clinical, laboratory and respiratory parameters of COVID-19 patients after 1- or 2-week treatment in the baricitinib-treated group and in the standard-treated group: comparison within the same treatment group and between the 2 different treatment groups.Baricitinibcombined with lopinavir/ritonavir treated arm113 patientsHydroxychloroquinecombined with lopinavir/ritonavir treated arm(Standard of care-treated arm)78 patientsBaricitinib-based therapy arm vsstandard of care therapy armClinical, laboratory, respiratory parametersBaselineWeek 1Week 2P valueBaseline values vsWeek 1 aDifferences between the values at baseline and after 1 week. orvs Week 2 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir. valuesBaselineWeek 1Week 2P valueBaseline values vsWeek 1 aDifferences between the values at baseline and after 1 week. orvs Week 2 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir. valuesP valueWeek 1 aDifferences between the values at baseline and after 1 week.Week 2 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.Cough, No (%)75 (66.4)25 (22.1)4 (3.5)0.000 aDifferences between the values at baseline and after 1 week.0.000 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.53 (67.9)39 (50)15 (19.2)0.034 aDifferences between the values at baseline and after 1 week.0.000 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.0.000 aDifferences between the values at baseline and after 1 week.0.014 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.Dyspnea, No (%)84 (74.3)20 (1.7)4 (3.5)0.000 aDifferences between the values at baseline and after 1 week.0.000 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.58 (74.4)51 (65.3)39 (50)0.295 aDifferences between the values at baseline and after 1 week.0.003 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.0.000 aDifferences between the values at baseline and after 1 week.0.000 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.Sputum production, No (%)41 (36.2)15 (13.2)10 (8.8)0.000 aDifferences between the values at baseline and after 1 week.0.000 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.29 (37.2)18 (23)12 (15.3)0.081aDifferences between the values at baseline and after 1 week.0.004 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.0.117 aDifferences between the values at baseline and after 1 week.0.246 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.Headache, No (%)56 (49.5)12 (10.6)2 (1.7)0.000 aDifferences between the values at baseline and after 1 week.0.000 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.31 (39.7)24 (30.7)10 (12.8)0.315 aDifferences between the values at baseline and after 1 week.0.002 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.0.000 aDifferences between the values at baseline and after 1 week.0.005 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.Diarrhea, No (%)26 (23)2 (1.7)00.000 aDifferences between the values at baseline and after 1 week.0.000 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.11 (14.1)1 (1.3)00.007 aDifferences between the values at baseline and after 1 week.0.002 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.0.745 aDifferences between the values at baseline and after 1 week.NA bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.Ageusia/Anosmia, No (%)44 (38.9)32 (28.3)24 (21.2)0.121 aDifferences between the values at baseline and after 1 week.0.006 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.29 (37.1)25 (32)19 (24.3)0.614 aDifferences between the values at baseline and after 1 week.0.118 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.0.694 aDifferences between the values at baseline and after 1 week.0.740 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.Fever °C, median (IQR)38(37.4–38.2)36.1(36–36.4)36(36–36.1)0.001 aDifferences between the values at baseline and after 1 week.0.001 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.38(37.7–38.7)37.5(36.5–38.1)37(36.3–37.4)0.516 aDifferences between the values at baseline and after 1 week.0.129 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.0.000 aDifferences between the values at baseline and after 1 week.0.000 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.Breath, N/min, median (IQR)20 (17–22)18(15–20)16(14–18)0.003 aDifferences between the values at baseline and after 1 week.0.002 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.21 (19–24)19(18–22)17(16–21.7)0.083 aDifferences between the values at baseline and after 1 week.0.058 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.0.724 aDifferences between the values at baseline and after 1 week.0.225 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.SpO2%, median (IQR)95 (92–98)96(95–98)97(96–98)0.191 aDifferences between the values at baseline and after 1 week.0.0018 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.93 (92–97)93.8(91.8–94.7)93.6(86.7–94.3)0.678 aDifferences between the values at baseline and after 1 week.0.715 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.0.000 aDifferences between the values at baseline and after 1 week.0.000 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.PaO2/FiO2 value, median (IQR)265.7 (202–330)336.5(245.5–452)395(320–452.3)0.0016 aDifferences between the values at baseline and after 1 week.0.0000 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.267.5 (263.1–301)278.2(258.3–302.4)293.5(244.2–315.1)0.514 aDifferences between the values at baseline and after 1 week.0.376 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.0.001 aDifferences between the values at baseline and after 1 week.0.000 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.Pulse rate, No/min. median (IQR)80 (70–90)76(68.5–81)74.5(68–80)0.433 aDifferences between the values at baseline and after 1 week.0.177 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.85 (79–92)82.5(76.5–91)83(77–96.4)0.433 aDifferences between the values at baseline and after 1 week.0.903 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.0.129 aDifferences between the values at baseline and after 1 week.0.004 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.WBC, x109/L, median (IQR)6.5 (4.9–8.3)7.0 (5.7–9.2)7.0 (5.8–8.6)0.481 aDifferences between the values at baseline and after 1 week.0.225 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.7.2 (5.8–8.6)6.9(6.5–7.4)7.2(6.4–8.6)0.789 aDifferences between the values at baseline and after 1 week.0.922 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.0.389 aDifferences between the values at baseline and after 1 week.0.533 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.Neutrophils, x109/L, median (IQR)4.7 (3.5–6.5)5 (3.3–7)4.4(3.2–6.9)0.720 aDifferences between the values at baseline and after 1 week.0.876 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.4.9 (4.4–6.9)5.4(5.1–6.2)6.7 (6.3–7.3)0.054 aDifferences between the values at baseline and after 1 week.0.002 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.0.136 aDifferences between the values at baseline and after 1 week.0.068 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.Lymphocytes, x109/L, median (IQR)0.93 (0.7–1.2)1.11 (0.8–1.9)1.3 (1–2.1)0.0023 aDifferences between the values at baseline and after 1 week.0.0017 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.0.88 (0.7–0.9)0.86 (0.5–1)0.9 (0.69–1.0)0.524 aDifferences between the values at baseline and after 1 week.0.836 bDifferences between the values at baseline and after 2 weeks. Standard of care therapy-treated group: COVID-19 patients under standard respiratory therapy and lopinavir/ritonavir and hydroxychloroquine treatment that were admitted in the hospital the week before starting the therapy with baricitinib and lopinavir/ritonavir.0.023 *0.004 †Lymphocytes, No (%)>2