Duration of SARS-CoV-2 RNA Shedding Is Significantly Influenced by Disease Severity, Bilateral Pulmonary Infiltrates, Antibiotic Treatment, and Diabetic Status: Consideration for Isolation Period.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) ribonucleic acid (RNA) shedding is an important parameter for determining the optimal length of isolation period required for coronavirus disease 2019 (COVID-19) patients. However, the clinical (i.e., patient and disease) characteristics that could influence this parameter have yet to be determined. In this study, we aim to explore the potential associations between several clinical features and the duration of SARS-CoV-2 RNA shedding in patients hospitalized with COVID-19. A retrospective cohort study involving 162 patients hospitalized for COVID-19 in a tertiary referral teaching hospital in Indonesia was performed from June to December 2021. Patients were grouped based on the mean duration of viral shedding and were compared based on several clinical characteristics (e.g., age, sex, comorbidities, COVID-19 symptoms, severity, and therapies). Subsequently, clinical factors potentially associated with the duration of SARS-CoV-2 RNA shedding were further assessed using multivariate logistic regression analysis. As a result, the mean duration of SARS-CoV-2 RNA shedding was found to be 13 ± 8.44 days. In patients with diabetes mellitus (without chronic complications) or hypertension, the duration of viral shedding was significantly prolonged (≥13 days; p = 0.001 and p = 0.029, respectively). Furthermore, patients with dyspnea displayed viral shedding for longer durations (p = 0.011). The multivariate logistic regression analysis reveals that independent risk factors associated with the duration of SARS-CoV-2 RNA shedding include disease severity (adjusted odds ratio [aOR] = 2.94; 95% CI = 1.36-6.44), bilateral lung infiltrates (aOR = 2.79; 95% CI = 1.14-6.84), diabetes mellitus (aOR = 2.17; 95% CI = 1.02-4.63), and antibiotic treatment (aOR = 3.66; 95% CI = 1.74-7.71). In summary, several clinical factors are linked with the duration of SARS-CoV-2 RNA shedding. Disease severity is positively associated with the duration of viral shedding, while bilateral lung infiltrates, diabetes mellitus, and antibiotic treatment are negatively linked with the duration of viral shedding. Overall, our findings suggest the need to consider different isolation period estimations for specific clinical characteristics of patients with COVID-19 that affect the duration of SARS-CoV-2 RNA shedding.

Antiviral Treatment in COVID-19 Outpatients: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: Most COVID-19 patients have mild or moderate illnesses that can progress to severe illness, leading to hospitalization and/or mortality. The use of antivirals to prevent the progression of COVID-19 in non-hospitalized patients shows conflicting result and efficacy remain unclear. This study evaluates the efficacy and safety of antivirals therapy in COVID-19 outpatients. METHODS: Search were conducted in Pubmed, ScienceDirect, Cochrane Library, Springer, medRxiv, Journal Storage [JSTOR], and Directory of Open Access Journals [DOAJ] for articles investigating antivirals in COVID-19 outpatients. In addition, clinical and virological outcomes, COVID-19 hospitalization, all caused mortality, and adverse events were assessed. RESULTS: Thirteen studies were included in this review. The consecutive data from these studies suggested that favipiravir is more optimally used in early disease, but improvement in symptoms shows inconsistent results. Meanwhile, molnupiravir shows consistent results, which can reduce hospitalization and mortality risk. In addition, remdesivir and nirmatrelvir-ritonavir have the potential to prevent the progression of COVID-19 in outpatients, but the data provided in this study are very limited. Finally, there is no significant difference in serious and non-serious adverse events, highlighting that antivirals have a good safety profile. CONCLUSION: This study provides an overview of the role of various antivirals therapy in COVID-19 outpatients. Molnupiravir, remdesivir, and nirmatrelvir-ritonavir have shown potential to prevent the progression of COVID-19 in early disease. However, this review was based on very limited data. Therefore, further clinical trials are needed to confirm this finding.

Effectiveness of COVID-19 Vaccines against SARS-CoV-2 Omicron Variant (B.1.1.529): A Systematic Review with Meta-Analysis and Meta-Regression.

Vaccine effectiveness (VE) and the urgency of booster vaccination against SARS-CoV-2 Omicron variant need evaluation. A systematic search was conducted from 1−6 April, 2022. VE difference (VED) estimates were assessed using random-effects and meta-regression analyses were performed for evaluating VE over time. Compared to full dose, booster dose of overall vaccines provided better protection against any and severe Omicron infections within 3 months (p < 0.001), and within 3 months or more in any, severe, and symptomatic infections (p < 0.001). From meta-regression analysis of overall vaccines, the full-dose VE against any and symptomatic Omicron infections reduced per month by 2.45% and 5.5%, respectively; whereas booster dose effectiveness against any and symptomatic Omicron infections reduced per month by 1.79% and 1.14%, respectively. The VE estimates of booster dose provide excellent protection against symptomatic infection compared to full dose. The VE estimates of Ad26.COV2.S, BNT162b2, ChAdOx1 nCov-19, and mRNA-1273 against Omicron infection are generally moderate, despite the VE estimates declining over time.

Prolonged fever and exaggerated hypercoagulopathy in malaria vivax relapse and COVID-19 co-infection: a case report.

BACKGROUND: Coronavirus disease 2019 (COVID-19) often causes atypical clinical manifestations similar to other infectious diseases. In malaria-endemic areas, the pandemic situation will very likely result in co-infection of COVID-19 and malaria, although reports to date are still few. Meanwhile, this disease will be challenging to diagnose in areas with low malaria prevalence because the symptoms closely resemble COVID-19. CASE PRESENTATION: A 23-year-old male patient presented to the hospital with fever, anosmia, headache, and nausea 1 week before. He was diagnosed with COVID-19 and treated for approximately 10 days, then discharged to continue self-quarantine at home. 2 weeks later, he returned to the hospital with a fever raised intermittently every 2 days and marked by a chilling-fever-sweating cycle. A laboratory test for malaria and a nasopharyngeal swab for SARS CoV-2 PCR were conducted, confirming both diagnoses. The laboratory examination showed markedly elevated D-dimer. He was treated with dihydroartemisinin-piperaquine (DHP) 4 tablets per day for 3 days and primaquine 2 tablets per day for 14 days according to Indonesian National Anti-malarial Treatment Guidelines. After 6 days of treatment, the patient had no complaints, and the results of laboratory tests had improved. This report describes the key points in considering the differential diagnosis and prompt treatment of malaria infection during the pandemic of COVID-19 in an endemic country to prevent the worse clinical outcomes. COVID-19 and malaria may also cause a hypercoagulable state, so a co-infection of those diseases may impact the prognosis of the disease. CONCLUSION: This case report shows that considering the possibility of a co-infection in a COVID-19 patient who presents with fever can prevent delayed treatment that can worsen the disease outcome. Paying more attention to a history of travel to malaria-endemic areas, a history of previous malaria infection, and exploring anamnesis regarding the fever patterns in patients are important points in making a differential diagnosis of malaria infection during the COVID-19 pandemic.

Predictive Value of Sequential Organ Failure Assessment, Quick Sequential Organ Failure Assessment, Acute Physiology and Chronic Health Evaluation II, and New Early Warning Signs Scores Estimate Mortality of COVID-19 Patients Requiring Intensive Care Unit.

Introduction: Various mortality predictive score models for coronavirus disease-2019 (COVID-19) have been deliberated. We studied how sequential organ failure assessment (SOFA), quick sequential organ failure assessment (qSOFA), acute physiology and chronic health evaluation II (APACHE II), and new early warning signs (NEWS-2) scores estimate mortality in COVID-19 patients. Materials and methods: We conducted a prospective cohort study of 53 patients with moderate-to-severe COVID-19. We calculated qSOFA, SOFA, APACHE II, and NEWS-2 on initial admission and re-evaluated on day 5. We performed logistic regression analysis to differentiate the predictors of qSOFA, SOFA, APACHE II, and NEWS-2 scores on mortality. Result: qSOFA, SOFA, APACHE II, and NEWS-2 scores on day 5 exhibited a difference between survivors and nonsurvivors (p <0.05), also between ICU and non-ICU admission (p <0.05). The initial NEWS-2 revealed a higher AUC value than the qSOFA, APACHE II, and SOFA score in estimating mortality (0.867; 0.83; 0.822; 0.794). In ICU, APACHE II score revealed a higher AUC value than the SOFA, NEWS-2, and qSOFA score (0.853; 0.832; 0.813; 0.809). Concurrently, evaluation on day 5 showed that qSOFA AUC had higher scores than the NEWS-2, APACHE II, and SOFA (0.979; 0.965; 0.939; 0.933) in predicting mortality, while SOFA and APACHE II AUC were higher in ICU admission than NEWS-2 and qSOFA (0.968; 0.964; 0.939; 0.934). According to the cutoff score, APACHE II on day 5 revealed the highest sensitivity and specificity in predicting the mortality (sensitivity 95.7%, specificity 86.7%). Conclusion: All scores signify good predictive values on COVID-19 patients mortality following the evaluation on the day 5. Nonetheless, APACHE-II appears to be the best at predicting mortality and ICU admission rate. How to cite this article: Asmarawati TP, Suryantoro SD, Rosyid AN, Marfiani E, Windradi C, Mahdi BA, et al. Predictive Value of Sequential Organ Failure Assessment, Quick Sequential Organ Failure Assessment, Acute Physiology and Chronic Health Evaluation II, and New Early Warning Signs Scores Estimate Mortality of COVID-19 Patients Requiring Intensive Care Unit. Indian J Crit Care Med 2022;26(4):464-471.

National early warning score (NEWS) 2 predicts hospital mortality from COVID-19 patients.

Background: COVID-19 has a high risk of mortality, especially in patients with comorbid diseases such as cardiac disease, type 2 diabetes mellitus, chronic kidney disease, and hypertension. The National Early Warning Score (NEWS) is a tool that helps in identifying changes in patient conditions that require intensive treatment. Objective: Analyzing NEWS-2 to identify the risk of death in COVID-19 patients. Methods: This research was conducted from June to July 2020 by using quota sampling. The number of participants in this study was 112 participants (case group = 56 participants and control group = 56 participants). Participants were assessed for NEWS-2 and evaluated for their treatment outcomes. The analysis used in this study was the Chi-squared test and logistic regression with p < 0.05. Results: 45 participants died of having NEWS-2 score >5, and as many as 50 participants showed an improvement in their condition by having NEWS-2 score 5 (OR = 34.091; p < 0.001). The accuracy of NEWS-2's assessment of mortality of COVID-19 patients had a sensitivity of 80.4% and a specificity of 89.3%. There were several comorbid diseases that had a significant relationship on mortality of COVID-19 patients such as cardiac disease (ß = 5.907; 1.107-31.527 95% CI; p = 0.038), T2DM (ß = 3.143; 1.269-7.783 95% CI; p = 0.013), CKD (ß = 3.851; 1.195-12.416 95% CI; p = 0.024), and hypertension (ß = 2.820; 1.075-7.399 95% CI; p = 0.035). Conclusion: The NEWS-2 can be used to identify the risk of death of COVID-19 patients.

An in vitro study of dual drug combinations of anti-viral agents, antibiotics, and/or hydroxychloroquine against the SARS-CoV-2 virus isolated from hospitalized patients in Surabaya, Indonesia.

A potent therapy for the infectious coronavirus disease COVID-19 is urgently required with, at the time of writing, research in this area still ongoing. This study aims to evaluate the in vitro anti-viral activities of combinations of certain commercially available drugs that have recently formed part of COVID-19 therapy. Dual combinatory drugs, namely; Lopinavir-Ritonavir (LOPIRITO)-Clarithromycin (CLA), LOPIRITO-Azithromycin (AZI), LOPIRITO-Doxycycline (DOXY), Hydroxychloroquine (HCQ)-AZI, HCQ-DOXY, Favipiravir (FAVI)-AZI, HCQ-FAVI, and HCQ-LOPIRITO, were prepared. These drugs were mixed at specific ratios and evaluated for their safe use based on the cytotoxicity concentration (CC50) values of human umbilical cord mesenchymal stem cells. The anti-viral efficacy of these combinations in relation to Vero cells infected with SARS-CoV-2 virus isolated from a patient in Universitas Airlangga hospital, Surabaya, Indonesia and evaluated for IC50 24, 48, and 72 hours after viral inoculation was subsequently determined. Observation of the viral load in qRT-PCR was undertaken, the results of which indicated the absence of high levels of cytotoxicity in any samples and that dual combinatory drugs produced lower cytotoxicity than single drugs. In addition, these combinations demonstrated considerable effectiveness in reducing the copy number of the virus at 48 and 72 hours, while even at 24 hours, post-drug incubation resulted in low IC50 values. Most combination drugs reduced pro-inflammatory markers, i.e. IL-6 and TNF-α, while increasing the anti-inflammatory response of IL-10. According to these results, the descending order of effective dual combinatory drugs is one of LOPIRITO-AZI>LOPIRITO-DOXY>HCQ-AZI>HCQ-FAVI>LOPIRITO-CLA>HCQ-DOX. It can be suggested that dual combinatory drugs, e.g. LOPIRITO-AZI, can potentially be used in the treatment of COVID-19 infectious diseases.

A Randomized, Double-Blind, Multicenter Clinical Study Comparing the Efficacy and Safety of a Drug Combination of Lopinavir/Ritonavir-Azithromycin, Lopinavir/Ritonavir-Doxycycline, and Azithromycin-Hydroxychloroquine for Patients Diagnosed with Mild to Moderate COVID-19 Infections.

BACKGROUND: At the present time, COVID-19 vaccines are at the testing stage, and an effective treatment for COVID-19 incorporating appropriate safety measures remains the most significant obstacle to be overcome. A strategic countermeasure is, therefore, urgently required. AIM: This study aims to evaluate the efficacy and safety of a combination of lopinavir/ritonavir-azithromycin, lopinavir/ritonavir-doxycycline, and azithromycin-hydroxychloroquine used to treat patients with mild to moderate COVID-19 infections. Setting and Design. This study was conducted at four different clinical study sites in Indonesia. The subjects gave informed consent for their participation and were confirmed as being COVID-19-positive by means of an RT-PCR test. The present study constituted a randomized, double-blind, and multicenter clinical study of patients diagnosed with mild to moderate COVID-19 infection. MATERIALS AND METHODS: Six treatment groups participated in this study: a Control group administered with a 500 mg dose of azithromycin; Group A which received a 200/50 mg dose of lopinavir/ritonavir and 500 mg of azithromycin; Group B treated with a 200/50 mg dose of lopinavir/ritonavir and 200 mg of doxycycline; Group C administered with 200 mg of hydroxychloroquine and 500 mg of azithromycin; Group D which received a 400/100 mg dose of lopinavir/ritonavir and 500 mg of azithromycin; and Group E treated with a 400/100 mg dose of lopinavir/ritonavir and 200 mg of doxycycline. RESULTS: 754 subjects participated in this study: 694 patients (92.4%) who presented mild symptoms and 57 patients (7.6%) classified as suffering from a moderate case of COVID-19. On the third day after treatment, 91.7%-99.2% of the subjects in Groups A-E were confirmed negative by a PCR swab test compared to 26.9% in the Control group. Observation of all groups which experienced a significant decrease in virus load between day 1 and day 7 was undertaken. Other markers, such as CRP and IL-6, were significantly lower in all treatment groups (p < 0.05 and p < 0.0001) than in the Control group. Furthermore, IL-10 and TNF-α levels were significantly elevated in all treatment groups (p < 0.0001). The administration of azithromycin to the Control group increased CRP and IL-6 levels, while reduced IL-10 and TNF-α on day 7 (p < 0.0001) compared with day 1. Decreases in ALT and AST levels were observed in all groups (p < 0.0001). There was an increase in creatinine in the serum level of the Control, C, D, and E groups (p < 0.05), whereas the BUN level was elevated in all groups (p < 0.0001). CONCLUSIONS: The study findings suggest that the administration of lopinavir/ritonavir-doxycycline, lopinavir/ritonavir-azithromycin, and azithromycin-hydroxychloroquine as a dual drug combination produced a significantly rapid PCR conversion rate to negative in three-day treatment of mild to moderate COVID-19 cases. Further studies should involve observation of older patients with severe clinical symptoms in order to collate significant amounts of demographic data.