Effectiveness and Safety of Normoxic Allogenic Umbilical Cord Mesenchymal Stem Cells Administered as Adjunctive Treatment in Patients with Severe COVID-19 (preprint)

Inflammatory response in COVID-19 contributes greatly to disease severity. Mesenchymal Stem Cells (MSCs) have the potential to alleviate inflammation and reduce mortality and length of stay in COVID-19 patients. We investigated the safety and effectiveness of normoxic-allogenic umbilical cord (NA-UC)-MSCs as an adjunctive treatment in severe COVID-19 patients. A double-blind, multicentric, randomized, placebo-controlled trial involving severe COVID-19 patients was performed from January–June 2021 in three major hospitals across Java, Indonesia. Eligible participants (n = 42) were randomly assigned to two groups (1:1), namely the intervention (n = 21) and control (n = 21) groups. Either NA-UC-MSCs or NaCl placebo were administered daily. The primary outcome was the duration of hospitalization. Meanwhile, the secondary outcomes were radiographical progression (Brixia score), respiratory and oxygenation parameters, and inflammatory markers, in addition to the safety profile of NA-UC-MSCs. NA-UC-MSC administration did not affect the length of hospital stay of severe COVID-19 patients, nor did it improve the Brixia score or mMRC dyspnoea scale better than placebo. Nevertheless, NA-UC-MSCs led to a better recuperation in oxygenation index (120.80 ± 72.70 baseline vs 309.63 ± 319.30 D + 22, p = 0.038) and oxygen saturation (97.24 ± 4.10% vs 96.19 ± 3.75% in placebo, p = 0.028). Additionally, compared to the placebo group, the treatment group had a significantly smaller increase in PCT level at D + 22 (1.43 vs. 12.76, p = 0.011). No adverse effects, including serious ones, were recorded until D + 91. NA-UC-MSC therapy is a very safe adjunct for COVID-19 patients. It improves the oxygenation profile and carries potential to suppress inflammation.

Perioperative Factors Impact on Mortality and Survival Rate of Geriatric Patients Undergoing Surgery in the COVID-19 Pandemic: A Prospective Cohort Study in Indonesia.

Background: The COVID-19 pandemic continues to have an impact on geriatric patients worldwide since geriatrics itself is an age group with a high risk due to declined physiological function and many comorbidities, especially for those who undergo surgery. In this study, we determine the association between perioperative factors with 30-day mortality and a survival rate of geriatric patients undergoing surgery during COVID-19 pandemic. Methods: A prospective cohort study was conducted at 14 central hospitals in Indonesia. The recorded variables were perioperative factors, 30-day mortality, and survival rate. Analyses of associations between variables and 30-day mortality were performed using univariate/multivariable logistic regression, and survival rates were determined with Kaplan-Meier survival analysis. Results: We analyzed 1621 elderly patients. The total number of patients who survived within 30 days of observation was 4.3%. Several perioperative factors were associated with 30-day mortality (p < 0.05) is COVID-19 (OR, 4.34; 95% CI, 1.04-18.07; p = 0.04), CCI > 3 ( odds ratio [OR], 2.33; 95% confidence interval [CI], 1.03-5.26; p = 0.04), emergency surgery (OR, 3.70; 95% CI, 1.96-7.00; p ≤ 0.01), postoperative ICU care (OR, 2.70; 95% CI, 1.32-5.53; p = 0.01), and adverse events (AEs) in the ICU (OR, 3.43; 95% CI, 1.32-8.96; p = 0.01). Aligned with these findings, COVID-19, CCI > 3, and comorbidities have a log-rank p < 0.05. The six comorbidities that have log-rank p < 0.05 are moderate-to-severe renal disease (log-rank p ≤ 0.01), cerebrovascular disease (log-rank p ≤ 0.01), diabetes with chronic complications (log-rank p = 0.03), metastatic solid tumor (log-rank p = 0.02), dementia (log-rank p ≤ 0.01), and rheumatology disease (log-rank p = 0.03). Conclusions: Having at least one of these conditions, such as COVID-19, comorbidities, emergency surgery, postoperative ICU care, or an AE in the ICU were associated with increased mortality in geriatric patients undergoing surgery during the COVID-19 pandemic.

Comorbidities and COVID-19 status influence the survival rate of geriatric patients in intensive care units: a prospective cohort study from the Indonesian Society of Anaesthesiology and Intensive Therapy.

BACKGROUND: With the more advanced science in the field of medicine and disease management, the population of geriatric intensive care patients is increasing. The COVID-19 pandemic has impacted healthcare management around the globe, especially on critically-ill elderly patients. We aim to analyse the relationship between underlying illnesses, including COVID-19, and the survival rate of elderly patients who are treated in the intensive care setting. METHODS: We conducted a prospective cohort study at 14 teaching hospitals for Anaesthesiology and Intensive Therapy Education in Indonesia. We selected all subjects with 60 years of age or older in the period between February to May 2021. Variables recorded included subject characteristics, comorbidities, and COVID-19 status. Subjects were followed for 30-day mortality as an outcome. We analysed the data using Kaplan-Meier survival analysis. RESULTS: We recruited 982 elderly patients, and 728 subjects were in the final analysis (60.7% male; 68.0 ± 6.6 years old). The 30-day mortality was 38.6%. The top five comorbidities are hypertension (21.1%), diabetes (16.2%), moderate or severe renal disease (10.6%), congestive heart failure (9.2%), and cerebrovascular disease (9.1%). Subjects with Charlson's Comorbidity Index Score > 5 experienced 66% death. Subjects with COVID-19 who died were 57.4%. Subjects with comorbidities and COVID-19 had lower survival time than subjects without those conditions (p < 0.005). Based on linear correlation analysis, the more comorbidities the geriatric patients in the ICU had, the higher chance of mortality in 30 days (p < 0.005, R coefficient 0.22). CONCLUSION: Approximately one in four elderly intensive care patients die, and the number is increasing with comorbidities and COVID-19 status.

Ko-infeksi jamur pada COVID-19 dengan terapi steroid

Ko-infeksi jamur pada pasien Coronavirus Disease 2019 (COVID-19) acapkali terjadi. Hal itu dikarenakan kegagalan sistem imun karena infeksi COVID-19 maupun karena pengobatan anti inflamasi yang diberikan.Kasus: Seorang laki-laki 39 tahun dengan acute respiratory distress syndrome (ARDS) berat akibat infeksi COVID-19 dan disertai dengan ko-infeksi jamur. Pasien ini mendapatkan pengobatan steroid dari awal masuk dan pada hari ke-6 hasil kultur sputumnya menunjukkan adanya ko-infeksi jamur. Pasien ini memiliki komorbid berupa riwayat diabetes mellitus. Dari pemeriksaan fisik ditemukan dispnea takipnea takikardia sejak hari pertama. Dari hasil laboratorium menunjukkan angka leukosit high sensitivity c-reactive protein (HsCRP) serum glutamic oxaloacetic (SGOT) gula darah d-dimmer lactat dehydrogenase (LDH) dan limfosit netrophyl ratio (LNR) yang tinggi. Pada pasien ini didapatkan rasio PaO2 / FiO2 rendah dan procalcitonin (PCT) yang normal. Dari kultur sputum ditemukan adanya infeksi jamur dan dari hasil rontgen toraks (CXR) menunjukkan pneumonia bilateral. Pasien ini dirawat dengan terapi standar dan mendapatkan dexametason 5 mg / 8 jam setelah kultur sputum menunjukkan infeksi jamur pasien juga mendapat mycafungin untuk pengobatan jamurnya. Diskusi: Kecurigaan terhadap ko-infeksi jamur pada pasien COVID-19 yang mendapatkan terapi steroid dalam jangka waktu lama maupun adanya penyerta diabetes harus dipikirkan. Penggunaan terapi anti jamur empiris pun acapkali diperlukan untuk mengurangi morbiditas dan mortalitas. Kesimpulan: Infeksi COVID-19 memiliki risiko terjadinya ko-infeksi salah satunya adalah infeksi jamur. Insiden koinfeksi jamur diperberat dengan pemberian pengobatan steroid dan riwayat diabetes mellitus. 

Comorbidities and COVID-19 Status Influence the Survival Rate of Geriatric Patients in Intensive Care Units: a Prospective Cohort Study From the Indonesian Society of Anaesthesiology and Intensive Therapy (preprint)

Background: With the more advanced science in the field of medicine and disease management, the population of geriatric intensive care patients is increasing. The COVID-19 pandemic has impacted healthcare management around the globe, especially on critically-ill elderly patients. We aim to analyse the relationship between underlying illnesses, including COVID-19, and the survival rate of elderly patients who are treated in the intensive care setting. Methods: : We conducted a prospective cohort study at 14 teaching hospitals for Anaesthesiology and Intensive Therapy Education in Indonesia. We selected all subjects with 60 years of age or older in the period between February to May 2021. Variables recorded included subject characteristics, comorbidities, and COVID-19 status. Subjects were followed for 30-day mortality as an outcome. We analysed the data using Kaplan-Meier survival analysis. Results: : We recruited 982 elderly patients, and 728 subjects were in the final analysis (60.7% male; 68.0 ± 6.6 years old). The 30-day mortality was 38.6%. The top five comorbidities are hypertension (21.1%), diabetes (16.2%), moderate or severe renal disease (10.6%), congestive heart failure (9.2%), and cerebrovascular disease (9.1%). Subjects with Charlson's Comorbidity Index Score >5 experienced 66% death. Subjects with COVID-19 who died were 57.4%. Subjects with comorbidities and COVID-19 had lower survival rates than subjects without those conditions (p < 0.005). Conclusion: Approximately one in four elderly intensive care patients die, and the number is increasing with comorbidities and COVID-19 status.