Favipiravir in patients hospitalised with COVID-19 (PIONEER trial): a multicentre, open-label, phase 3, randomised controlled trial of early intervention versus standard care.

BACKGROUND: COVID-19 has overwhelmed health services globally. Oral antiviral therapies are licensed worldwide, but indications and efficacy rates vary. We aimed to evaluate the safety and efficacy of oral favipiravir in patients hospitalised with COVID-19. METHODS: We conducted a multicentre, open-label, randomised controlled trial of oral favipiravir in adult patients who were newly admitted to hospital with proven or suspected COVID-19 across five sites in the UK (n=2), Brazil (n=2) and Mexico (n=1). Using a permuted block design, eligible and consenting participants were randomly assigned (1:1) to receive oral favipiravir (1800 mg twice daily for 1 day; 800 mg twice daily for 9 days) plus standard care, or standard care alone. All caregivers and patients were aware of allocation and those analysing data were aware of the treatment groups. The prespecified primary outcome was the time from randomisation to recovery, censored at 28 days, which was assessed using an intention-to-treat approach. Post-hoc analyses were used to assess the efficacy of favipiravir in patients aged younger than 60 years, and in patients aged 60 years and older. The trial was registered with clinicaltrials.gov, NCT04373733. FINDINGS: Between May 5, 2020 and May 26, 2021, we assessed 503 patients for eligibility, of whom 499 were randomly assigned to favipiravir and standard care (n=251) or standard care alone (n=248). There was no significant difference between those who received favipiravir and standard care, relative to those who received standard care alone in time to recovery in the overall study population (hazard ratio [HR] 1·06 [95% CI 0·89-1·27]; n=499; p=0·52). Post-hoc analyses showed a faster rate of recovery in patients younger than 60 years who received favipiravir and standard care versus those who had standard care alone (HR 1·35 [1·06-1·72]; n=247; p=0·01). 36 serious adverse events were observed in 27 (11%) of 251 patients administered favipiravir and standard care, and 33 events were observed in 27 (11%) of 248 patients receiving standard care alone, with infectious, respiratory, and cardiovascular events being the most numerous. There was no significant between-group difference in serious adverse events per patient (p=0·87). INTERPRETATION: Favipiravir does not improve clinical outcomes in all patients admitted to hospital with COVID-19, however, patients younger than 60 years might have a beneficial clinical response. The indiscriminate use of favipiravir globally should be cautioned, and further high-quality studies of antiviral agents, and their potential treatment combinations, are warranted in COVID-19. FUNDING: LifeArc and CW+.

Early treatment of Favipiravir in COVID-19 patients without pneumonia: a multicentre, open-labelled, randomized control study.

We investigated Favipiravir (FPV) efficacy in mild cases of COVID-19 without pneumonia and its effects towards viral clearance, clinical condition, and risk of COVID-19 pneumonia development. PCR-confirmed SARS-CoV-2-infected patients without pneumonia were enrolled (2:1) within 10 days of symptomatic onset into FPV and control arms. The former received 1800 mg FPV twice-daily (BID) on Day 1 and 800 mg BID 5-14 days thereafter until negative viral detection, while the latter received only supportive care. The primary endpoint was time to clinical improvement, defined by a National Early Warning Score (NEWS) of ≤1. 62 patients (41 female) comprised the FPV arm (median age: 32 years, median BMI: 22 kg/m²) and 31 patients (19 female) comprised the control arm (median age: 28 years, median BMI: 22 kg/m²). The median time to sustained clinical improvement, by NEWS, was 2 and 14 days for FPV and control arms, respectively (adjusted hazard ratio (aHR) of 2.77, 95% CI 1.57-4.88, P < .001). The FPV arm also had significantly higher likelihoods of clinical improvement within 14 days after enrolment by NEWS (79% vs. 32% respectively, P < .001). 8 (12.9%) and 7 (22.6%) patients in FPV and control arms developed mild pneumonia at a median (range) of 6.5 (1-13) and 7 (1-13) days after treatment, respectively (P = .316). All recovered well without complications. We can conclude that early treatment of FPV in symptomatic COVID-19 patients without pneumonia was associated with faster clinical improvement.Trial registration: Thai Clinical Trials Registry identifier: TCTR20200514001.

Patient perception of voxelotor treatment benefit in sickle cell disease.

Patients with sickle cell disease (SCD) experience a range of clinical symptoms, including acute and chronic pain, fatigue, and respiratory problems, as well as chronic organ complications that can lead to disability and accelerated mortality. Voxelotor is a first-in-class therapy that targets sickle hemoglobin polymerization, the root cause of SCD. It is approved by the US Food and Drug Administration for treatment of SCD in patients aged 4 years and older and in the European Union and United Arab Emirates for the treatment of SCD in patients aged 12 years and older. Here, we report the single-center experience of both clinician-determined and patient-reported benefits of voxelotor in 27 consecutive patients treated for at least 8 weeks. Clinical Global Impression of Change and Patient Global Impression of Change rating scales were used to capture clinicians' and patients' perceptions of change in overall patient health-related quality-of-life with voxelotor treatment. Laboratory data were also collected to assess clinical response to treatment. As observed in previous clinical studies, hemoglobin concentrations and markers of hemolysis were improved in patients treated with voxelotor. Most patients reported marked improvement in disease symptoms, which correlated well with the clinicians' assessments. Although limited by the retrospective open-label study design, these findings suggest that voxelotor use has a positive impact on outcomes in patients with SCD.

Analytical Performance and Greenness Evaluation of Five Multi-Level Design Models Utilized for Impurity Profiling of Favipiravir, a Promising COVID-19 Antiviral Drug.

In 2018, the discovery of carcinogenic nitrosamine process related impurities (PRIs) in a group of widely used drugs led to the recall and complete withdrawal of several medications that were consumed for a long time, unaware of the presence of these genotoxic PRIs. Since then, PRIs that arise during the manufacturing process of the active pharmaceutical ingredients (APIs), together with their degradation impurities, have gained the attention of analytical chemistry researchers. In 2020, favipiravir (FVR) was found to have an effective antiviral activity against the SARS-COVID-19 virus. Therefore, it was included in the COVID-19 treatment protocols and was consequently globally manufactured at large-scales during the pandemic. There is information indigence about FVR impurity profiling, and until now, no method has been reported for the simultaneous determination of FVR together with its PRIs. In this study, five advanced multi-level design models were developed and validated for the simultaneous determination of FVR and two PRIs, namely; (6-chloro-3-hydroxypyrazine-2-carboxamide) and (3,6-dichloro-pyrazine-2-carbonitrile). The five developed models were classical least square (CLS), principal component regression (PCR), partial least squares (PLS), genetic algorithm-partial least squares (GA-PLS), and artificial neural networks (ANN). Five concentration levels of each compound, chosen according to the linearity range of the target analytes, were used to construct a five-level, three-factor chemometric design, giving rise to twenty-five mixtures. The models resolved the strong spectral overlap in the UV-spectra of the FVR and its PRIs. The PCR and PLS models exhibited the best performances, while PLS proved the highest sensitivity relative to the other models.

Favipiravir for the treatment of COVID-19 in elderly patients-what do we know after 2 years of COVID-19?

Since the appearance of coronavirus disease 2019 (COVID-19), numerous studies have been conducted to find effective therapeutics. Favipiravir (FVP) is one of the repurposed drugs which has been authorized in a few countries on an emergency basis to treat COVID-19. Elderly individuals especially 65 years or older are more prone to develop severe illness. We aim to provide a short summary of the current knowledge of the antiviral efficacy of favipiravir with respect to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected elderly patients. We found that it is rather controversial whether favipiravir is effective against SARS-CoV-2 infection. Data regarding patients 65 years or older is not sufficient to support or reject the usage of favipiravir for COVD-19 treatment. Further studies would be advisable to elicit the efficiency of favipiravir in elderly COVID-19 patients.

Longitudinal Analysis of Neutralizing Potency against SARS-CoV-2 in the Recovered Patients after Treatment with or without Favipiravir.

The effect of treatment with favipiravir, an antiviral purine nucleoside analog, for coronavirus disease 2019 (COVID-19) on the production and duration of neutralizing antibodies for SARS-CoV-2 was explored. There were 17 age-, gender-, and body mass index-matched pairs of favipiravir treated versus control selected from a total of 99 patients recovered from moderate COVID-19. These subjects participated in the longitudinal (>6 months) analysis of (i) SARS-CoV-2 spike protein's receptor-binding domain IgG, (ii) virus neutralization assay using authentic virus, and (iii) neutralization potency against original (WT) SARS-CoV-2 and cross-neutralization against B.1.351 (beta) variant carrying triple mutations of K417N, E484K, and N501Y. The results demonstrate that the use of favipiravir: (1) significantly accelerated the elimination of SARS-CoV-2 in the case vs. control groups (p = 0.027), (2) preserved the generation and persistence of neutralizing antibodies in the host, and (3) did not interfere the maturation of neutralizing potency of anti-SARS-CoV-2 and neutralizing breadth against SARS-CoV-2 variants. In conclusion, treatment of COVID-19 with favipiravir accelerates viral clearance and does not interfere the generation or maturation of neutralizing potency against both WT SARS-CoV-2 and its variants.

Auxora vs. placebo for the treatment of patients with severe COVID-19 pneumonia: a randomized-controlled clinical trial.

BACKGROUND: Calcium release-activated calcium (CRAC) channel inhibitors block proinflammatory cytokine release, preserve endothelial integrity and may effectively treat patients with severe COVID-19 pneumonia. METHODS: CARDEA was a phase 2, randomized, double-blind, placebo-controlled trial evaluating the addition of Auxora, a CRAC channel inhibitor, to corticosteroids and standard of care in adults with severe COVID-19 pneumonia. Eligible patients were adults with ≥ 1 symptom consistent with COVID-19 infection, a diagnosis of COVID-19 confirmed by laboratory testing using polymerase chain reaction or other assay, and pneumonia documented by chest imaging. Patients were also required to be receiving oxygen therapy using either a high flow or low flow nasal cannula at the time of enrolment and have at the time of enrollment a baseline imputed PaO2/FiO2 ratio > 75 and ≤ 300. The PaO2/FiO2 was imputed from a SpO2/FiO2 determine by pulse oximetry using a non-linear equation. Patients could not be receiving either non-invasive or invasive mechanical ventilation at the time of enrolment. The primary endpoint was time to recovery through Day 60, with secondary endpoints of all-cause mortality at Day 60 and Day 30. Due to declining rates of COVID-19 hospitalizations and utilization of standard of care medications prohibited by regulatory guidance, the trial was stopped early. RESULTS: The pre-specified efficacy set consisted of the 261 patients with a baseline imputed PaO2/FiO2≤ 200 with 130 and 131 in the Auxora and placebo groups, respectively. Time to recovery was 7 vs. 10 days (P = 0.0979) for patients who received Auxora vs. placebo, respectively. The all-cause mortality rate at Day 60 was 13.8% with Auxora vs. 20.6% with placebo (P = 0.1449); Day 30 all-cause mortality was 7.7% and 17.6%, respectively (P = 0.0165). Similar trends were noted in all randomized patients, patients on high flow nasal cannula at baseline or those with a baseline imputed PaO2/FiO2 ≤ 100. Serious adverse events (SAEs) were less frequent in patients treated with Auxora vs. placebo and occurred in 34 patients (24.1%) receiving Auxora and 49 (35.0%) receiving placebo (P = 0.0616). The most common SAEs were respiratory failure, acute respiratory distress syndrome, and pneumonia. CONCLUSIONS: Auxora was safe and well tolerated with strong signals in both time to recovery and all-cause mortality through Day 60 in patients with severe COVID-19 pneumonia. Further studies of Auxora in patients with severe COVID-19 pneumonia are warranted. Trial registration NCT04345614.

Efficacy and safety of favipiravir plus interferon-beta versus lopinavir/ritonavir plus interferon-beta in moderately ill patients with COVID-19: A randomized clinical trial.

Favipiravir (FVP), lopinavir/ritonavir (LPV/RTV), and interferon-beta (INF-beta) are considered as potential treatments for COVID-19. We examined the efficacy and safety of FVP and INF-beta compared to LPV/RTV and INF-beta combinations for the treatment of SARS-CoV-2. It was a single-center randomized clinical trial. Eligible patients were randomized to receive FVP plus INF-beta versus LPV/RTV plus INF-beta. The primary endpoint was the viral clearance after seven days of randomization. ICU admission, length of stay (LOS) in hospital, in-hospital mortality, and the incidence of adverse events were also measured. This trial was registered on the Iranian Registry of Clinical Trials (IRCT20200506047323N3). Patients were randomly allocated to the FVP (n = 33) and LPV/RTV (n = 33) groups. The viral clearance on Day seven was not significantly different between the FVP (31.1%) and the LPV/RTV groups (16.1%). The rate of ICU admission and likewise the in-hospital mortality in the FVP group (12.5% and 6.3%, respectively) were similar to the LPV/RTV groups (19.4% and 19.4%, respectively). The median LOS in the hospital was also not different (6.8 days [interquartile range; IQR = 5.0-11.0] in the FVP and (8.0 days [IQR = 5.5-12.5]) in LPV/RTV groups (p = 0.140). Adverse events were observed in 25.0% of FVP and 32.3% of LPV/RTV groups. The combination therapy with FVP did not exert a higher efficacy compared to the combination regimen of LPV/RTV. However, both treatment regimens demonstrated a mild profile of adverse events.

Core-shell nanocomposite of flower-like molybdenum disulfide nanospheres and molecularly imprinted polymers for electrochemical detection of anti COVID-19 drug favipiravir in biological samples.

A novel electrochemical sensor is reported for the detection of the antiviral drug favipiravir based on the core-shell nanocomposite of flower-like molybdenum disulfide (MoS2) nanospheres and molecularly imprinted polymers (MIPs). The MoS2@MIP core-shell nanocomposite was prepared via the electrodeposition of a MIP layer on the MoS2 modified electrode, using o-phenylenediamine as the monomer and favipiravir as the template. The selective binding of target favipiravir at the MoS2@MIP core-shell nanocomposite produced a redox signal in a concentration dependent manner, which was used for the quantitative analysis. The preparation process of the MoS2@MIP core-shell nanocomposite was optimized. Under the optimal conditions, the sensor exhibited a wide linear response range of 0.01 ~ 100 nM (1.57*10-6 ~ 1.57*10-2 µg mL-1) and a low detection limit of 0.002 nM (3.14*10-7 µg mL-1). Application of the sensor was demonstrated by detecting favipiravir in a minimum amount of 10 µL biological samples (urine and plasma). Satisfied results in the recovery tests indicated a high potential of favipiravir monitoring in infectious COVID-19 samples.

Favipiravir in the Battle with Respiratory Viruses.

Among antiviral drugs, the vast majority targets only one or two related viruses. The conventional model, one virus - one drug, significantly limits therapeutic options. Therefore, in the strategy of controlling viral infections, there is a necessity to develop compounds with pleiotropic effects. Favipiravir (FPV) emerged as a strong candidate to become such a drug. The aim of the study is to present up-to-date information on the role of favipiravir in the treatment of viral respiratory infections. The anti-influenza activity of favipiravir has been confirmed in cell culture experiments, animal models, and clinical trials. Thoroughly different - from the previously registered drugs - mechanism of action suggests that FVP can be used as a countermeasure for the novel or re-emerging influenza virus infections. In recent months, favipiravir has been broadly investigated due to its potential efficacy in the treatment of COVID-19. Based on preclinical and clinical studies and a recently published meta-analysis it seems that favipiravir may be a promising antiviral drug in the treatment of patients with COVID-19. FPV is also effective against other RNA respiratory viruses and may be a candidate for the treatment of serious infections caused by human rhinovirus, respiratory syncytial virus, metapneumovirus, parainfluenza viruses and hantavirus pulmonary syndrome.

Therapeutic dilemmas in addressing SARS-CoV-2 infection: Favipiravir versus Remdesivir.

Coronavirus disease 2019 (COVID-19) represents an unmet clinical need, due to a high mortality rate, rapid mutation rate in the virus, increased chances of reinfection, lack of effectiveness of repurposed drugs and economic damage. COVID-19 pandemic has created an urgent need for effective molecules. Clinically proven efficacy and safety profiles have made favipiravir (FVP) and remdesivir (RDV) promising therapeutic options for use against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Even though both are prodrug molecules with an antiviral role based on a similar mechanism of action, differences in pharmacological, pharmacokinetic and pharmacotoxicological mechanisms have been identified. The present study aims to provide a comprehensive comparative assessment of FVP and RDV against SARS-CoV-2 infections, by centralizing medical data provided by significant literature and authorized clinical trials, focusing on the importance of a better understanding of the interactions between drug molecules and infectious agents in order to improve the global management of COVID-19 patients and to reduce the risk of antiviral resistance.

The incidence, clinical characteristics, and outcome of COVID-19 in a prospectively followed cohort of patients with Behçet's syndrome.

Initial case series of small number of patients at the beginning of the pandemic reported a rather guarded prognosis for Behçet's syndrome (BS) patients infected with SARS-CoV-2. In this prospective study, we describe the incidence, clinical characteristics, disease course, management, and outcome in a large cohort of BS patients with laboratory-confirmed infection of SARS-CoV-2. We defined a cohort of 1047 registered BS patients who were aged between 16 and 60 years and seen routinely before the pandemic at the multidisciplinary outpatient clinic. We followed prospectively this cohort from beginning of April 2020 until the end of April 2021. During 13 months of follow-up, of the 1047 (599 M/448 F) patients, 592 (56.5%) were tested for SARS-CoV-2 PCR at least once and 215 (20.5%; 95% CI 0.18-0.23) were tested positive. We observed 2 peaks which took place in December 2020 and April 2021. Of the 215 PCR positive patients, complete information was available in 214. Of these 214, 14 (6.5%) were asymptomatic for COVID-19. In the remaining, the most common symptoms were anosmia, fatigue, fever, arthralgia, and headache. A total of 40 (18.7%) had lung involvement, 25 (11.7%) were hospitalized, 1 was admitted to the intensive care unit while none died. Favipiravir was the most prescribed drug (74.3%), followed by colchicine (40.2%), and hydroxychloroquine (20.1%) in the treatment of COVID-19. After COVID-19, 5 patients (2.3%) were given supplemental O2 and 31 (14.5%) antiaggregant or anticoagulants. During COVID-19, of the 214 PCR positive patients, 116 (54.2%) decreased the dose of their immunosuppressives or stopped taking completely; 36 (16.8%) experienced a BS flare which was mostly oral ulcers (10.3%). None of the patients reported a thrombotic event. A total of 93 (43.5%) patients reported BS flares after a median 45 days of COVID-19 infection and this was found to be significantly associated with immunosuppressive drug discontinuation. Multiple regression analysis adjusted for age and gender indicated that smoking and using interferon-alpha decreased the likelihood of getting COVID-19. The incidence and severity of COVID-19 did not differ between those who were using colchicine or not. The cumulative incidence of COVID-19 in this prospectively followed cohort of BS patients was almost two folds of that estimated for the general population living in Istanbul, Turkey, however, the clinical outcome of COVID-19 was not severe and there was no mortality. The protective effect of smoking and interferon deserves further investigation. On the other hand, colchicine did not have any positive or negative effect against COVID-19. Significant number of patients flared after COVID-19, however, this was significantly associated with immunosuppressive discontinuation during the infection. Contrary to our previous observations, COVID-19 did not seem to exacerbate thrombotic events during or after the infection.

Human genetic risk of treatment with antiviral nucleoside analog drugs that induce lethal mutagenesis: The special case of molnupiravir.

This review considers antiviral nucleoside analog drugs, including ribavirin, favipiravir, and molnupiravir, which induce genome error catastrophe in SARS-CoV or SARS-CoV-2 via lethal mutagenesis as a mode of action. In vitro data indicate that molnupiravir may be 100 times more potent as an antiviral agent than ribavirin or favipiravir. Molnupiravir has recently demonstrated efficacy in a phase 3 clinical trial. Because of its anticipated global use, its relative potency, and the reported in vitro "host" cell mutagenicity of its active principle, ß-d-N4-hydroxycytidine, we have reviewed the development of molnupiravir and its genotoxicity safety evaluation, as well as the genotoxicity profiles of three congeners, that is, ribavirin, favipiravir, and 5-(2-chloroethyl)-2'-deoxyuridine. We consider the potential genetic risks of molnupiravir on the basis of all available information and focus on the need for additional human genotoxicity data and follow-up in patients treated with molnupiravir and similar drugs. Such human data are especially relevant for antiviral NAs that have the potential of permanently modifying the genomes of treated patients and/or causing human teratogenicity or embryotoxicity. We conclude that the results of preclinical genotoxicity studies and phase 1 human clinical safety, tolerability, and pharmacokinetics are critical components of drug safety assessments and sentinels of unanticipated adverse health effects. We provide our rationale for performing more thorough genotoxicity testing prior to and within phase 1 clinical trials, including human PIG-A and error corrected next generation sequencing (duplex sequencing) studies in DNA and mitochondrial DNA of patients treated with antiviral NAs that induce genome error catastrophe via lethal mutagenesis.

Visual classification of three computed tomography lung patterns to predict prognosis of COVID-19: a retrospective study.

BACKGROUND: Quantitative evaluation of radiographic images has been developed and suggested for the diagnosis of coronavirus disease 2019 (COVID-19). However, there are limited opportunities to use these image-based diagnostic indices in clinical practice. Our aim in this study was to evaluate the utility of a novel visually-based classification of pulmonary findings from computed tomography (CT) images of COVID-19 patients with the following three patterns defined: peripheral, multifocal, and diffuse findings of pneumonia. We also evaluated the prognostic value of this classification to predict the severity of COVID-19. METHODS: This was a single-center retrospective cohort study of patients hospitalized with COVID-19 between January 1st and September 30th, 2020, who presented with suspicious findings on CT lung images at admission (n = 69). We compared the association between the three predefined patterns (peripheral, multifocal, and diffuse), admission to the intensive care unit, tracheal intubation, and death. We tested quantitative CT analysis as an outcome predictor for COVID-19. Quantitative CT analysis was performed using a semi-automated method (Thoracic Volume Computer-Assisted Reading software, GE Health care, United States). Lungs were divided by Hounsfield unit intervals. Compromised lung (%CL) volume was the sum of poorly and non-aerated volumes (- 500, 100 HU). We collected patient clinical data, including demographic and clinical variables at the time of admission. RESULTS: Patients with a diffuse pattern were intubated more frequently and for a longer duration than patients with a peripheral or multifocal pattern. The following clinical variables were significantly different between the diffuse pattern and peripheral and multifocal groups: body temperature (p = 0.04), lymphocyte count (p = 0.01), neutrophil count (p = 0.02), c-reactive protein (p < 0.01), lactate dehydrogenase (p < 0.01), Krebs von den Lungen-6 antigen (p < 0.01), D-dimer (p < 0.01), and steroid (p = 0.01) and favipiravir (p = 0.03) administration. CONCLUSIONS: Our simple visual assessment of CT images can predict the severity of illness, a resulting decrease in respiratory function, and the need for supplemental respiratory ventilation among patients with COVID-19.

Effects of hydroxychloroquine and favipiravir on clinical course in outpatients with COVID-19

Background/aim: Due to the importance of early outpatient treatment to prevent hospitalization and disease progression, we examined the effects of hydroxychloroquine and favipiravir, which were initiated in early period, on the clinical course of COVID-19 outpatients. Materials and methods: Data of confirmed COVID-19 outpatients over a 4-month period were analyzed retrospectively. Public Health Management System (HSYS) was used for the case-based follow-up. Patients on antiviral therapy for at least five days, including hydroxychloroquine and / or favipiravir and patients who were followed-up for 30 days were included in this analysis. Results: We enrolled 1489 patients in this study. Overall, 775 (52%) patients were male and a mean age of patients was 38.9 ± 11.1 years. Of these patients, 537 of them were received favipiravir, 545 of them were received hydroxychloroquine and 407 of them were received both favipiravir and hydroxychloroquine. Symptoms improvement on the 14th day of follow-up was 1.8 times higher in the group of patients receiving hydroxychloroquine compared to patients who received favipiravir (p = 0.003). On the 3rd day of follow- up, PCR negativity rate was higher in patients who received hydroxychloroquine (p = 0.004). Hospitalization rates were similar in patients receiving favipiravir and hydroxychloroquine (p = 0.144). However, in the presence of pneumonia at the time of diagnosis, the hospitalization rate was 6.6 times higher in patients who received favipiravir than those who received hydroxychloroquine. Conclusion: The subgroups of patients treated with hydroxychloroquine and/or favipiravir did not have similar disease severities in our study. Therefore, further studies with homogeneous patient groups to be arranged prospectively are needed.

Comparison of demographic and clinical characteristics of hospitalized COVID-19 patients with severe/critical illness in the first wave versus the second wave.

Due to current advances and growing experience in the management of coronavirus Disease 2019 (COVID-19), the outcome of COVID-19 patients with severe/critical illness would be expected to be better in the second wave compared with the first wave. As our hospitalization criteria changed in the second wave, we aimed to investigate whether a favorable outcome occurred in hospitalized COVID-19 patients with only severe/critical illness. Among 642 laboratory-confirmed hospitalized COVID-19 patients in the first wave and 1121 in the second wave, those who met World Health Organization (WHO) definitions for severe or critical illness on admission or during follow-up were surveyed. Data on demographics, comorbidities, C-reactive protein (CRP) levels on admission, and outcomes were obtained from an electronic hospital database. Univariate analysis was performed to compare the characteristics of patients in the first and second waves. There were 228 (35.5%) patients with severe/critical illness in the first wave and 681 (60.7%) in the second wave. Both groups were similar in terms of age, gender, and comorbidities, other than chronic kidney disease. Median serum CRP levels were significantly higher in patients in the second wave compared with those in the first wave [109 mg/L (interquartile range [IQR]: 65-157) vs. 87 mg/L (IQR: 39-140); p < 0.001]. However, intensive care unit admission and mortality rates were similar among the waves. Even though a lower mortality rate in the second wave has been reported in previous studies, including all hospitalized COVID-19 patients, we found similar demographics and outcomes among hospitalized COVID-19 patients with severe/critical illness in the first and second wave.