Comparison of safety and efficacy between therapeutic or intermediate versus prophylactic anticoagulation for thrombosis in COVID-19 patients: a systematic review and meta-analysis.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) infections often have macrovascular or microvascular thrombosis and inflammation, which are known to be associated with a poor prognosis. Heparin has been hypothesized that administration of heparin with treatment dose rather than prophylactic dose for prevention of deep vein thrombosis in COVID-19 patients. METHODS: Studies comparing therapeutic or intermediate anticoagulation with prophylactic anticoagulation in COVID-19 patients were eligible. Mortality, thromboembolic events, and bleeding were the primary outcomes. PubMed, Embase, the Cochrane Library, and KMbase were searched up to July 2021. A meta-analysis was performed using random-effect model. Subgroup analysis was conducted according to disease severity. RESULTS: Six randomized controlled trials (RCTs) with 4,678 patients and four cohort studies with 1,080 patients were included in this review. In the RCTs, the therapeutic or intermediate anticoagulation was associated with significant reductions in the occurrence of thromboembolic events (5 studies, n=4,664; relative risk [RR], 0.72; P=0.01), and a significant increase in bleeding events (5 studies, n=4,667; RR, 1.88; P=0.004). In the moderate patients, therapeutic or intermediate anticoagulation was more beneficial than prophylactic anticoagulation in terms of thromboembolic events, but showed significantly higher bleeding events. In the severe patients, the incidence of thromboembolic and bleeding events in the therapeutic or intermediate. CONCLUSIONS: The study findings suggest that prophylactic anticoagulant treatment should be used in patients with moderate and severe COVID-19 infection groups. Further studies are needed to determine more individualized anticoagulation guidance for all COVID-19 patients.

COVID-19 Vaccine-Associated Pneumonitis in the Republic of Korea: A Nationwide Multicenter Survey.

BACKGROUND: Recent reports have suggested that pneumonitis is a rare complication following vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, its clinical features and outcomes are not well known. The aim of this study was to identify the clinical characteristics and outcomes of patients with vaccine-associated pneumonitis following vaccination against SARS-CoV-2. METHODS: In this nationwide multicenter survey study, questionnaires were distributed to pulmonary physicians in referral hospitals. They were asked to report cases of development or exacerbation of interstitial lung disease (ILD) associated with the coronavirus disease 2019 vaccine. Vaccine-associated pneumonitis was defined as new pulmonary infiltrates documented on chest computed tomography within 4 weeks of vaccination and exclusion of other possible etiologies. RESULTS: From the survey, 49 cases of vaccine-associated pneumonitis were identified between February 27 and October 30, 2021. After multidisciplinary discussion, 46 cases were analyzed. The median age was 66 years and 28 (61%) were male. The median interval between vaccination and respiratory symptoms was 5 days. There were 20 (43%), 17 (37%), and nine (19%) patients with newly identified pneumonitis, exacerbation of pre-diagnosed ILD, and undetermined pre-existing ILD, respectively. The administered vaccines were BNT162b2 and ChAdOx1 nCov-19/AZD1222 each in 21 patients followed by mRNA-1273 in three, and Ad26.COV2.S in one patient. Except for five patients with mild disease, 41 (89%) patients were treated with corticosteroid. Significant improvement was observed in 26 (57%) patients including four patients who did not receive treatment. However, ILD aggravated in 9 (20%) patients despite treatment. Mortality was observed in eight (17%) patients. CONCLUSION: These results suggest pneumonitis as a potentially significant safety concern for vaccines against SARS-CoV-2. Clinical awareness and patient education are necessary for early recognition and prompt management. Additional research is warranted to identify the epidemiology and characterize the pathophysiology of vaccine-associated pneumonitis.

Efficacy and safety of prone position in COVID-19 patients with respiratory failure: a systematic review and meta-analysis.

BACKGROUND: Prone position has already been demonstrated to improve survival in non-COVID acute respiratory distress syndrome and has been widely performed in COVID-19 patients with respiratory failure, both in non-intubated and intubated patients. However, the beneficial effect of the prone position in COVID-19 pneumonia still remains controversial. Therefore, we aimed to evaluate the effectiveness and safety of the prone position compared with the non-prone in non-intubated and intubated COVID-19 patients, respectively. METHODS: We searched the MEDLINE, EMBASE, and Cochrane databases, as well as one Korean domestic database, on July 9, 2021, and updated the search 9 times to September 14, 2022. Studies that compared prone and non-prone positions in patients with COVID-19 were eligible for inclusion. The primary outcomes were mortality, need for intubation, and adverse events. RESULTS: Of the 1259 records identified, 9 randomized controlled trials (RCTs) and 23 nonrandomized studies (NRSs) were eligible. In the non-intubated patients, the prone position reduced the intubation rate compared with the non-prone position in 6 RCTs (n = 2156, RR 0.81, P = 0.0002) and in 18 NRSs (n = 3374, RR 0.65, P = 0.002). In the subgroup analysis according to the oxygen delivery method, the results were constant only in the HFNC or NIV subgroup. For mortality, RCTs reported no difference between prone and non-prone groups, but in NRSs, the prone position had a significant advantage in mortality [18 NRSs, n = 3361, relative risk (RR) 0.56, P < 0.00001] regardless of the oxygen delivery methods shown in the subgroup analysis. There was no RCT for intubated patients, and mortality did not differ between the prone and non-prone groups in NRSs. Adverse events reported in both the non-intubated and intubated groups were mild and similar between the prone and non-intubated groups. CONCLUSION: For non-intubated patients with COVID-19, prone positioning reduced the risk of intubation, particularly in patients requiring a high-flow oxygen system. However, the survival benefit was unclear between the prone and non-prone groups. There was insufficient evidence to support the beneficial effects of prone positioning in intubated patients. Trial registration This study was registered in the Prospective Register of Systematic Reviews on February 16, 2022 (Registration No.: CRD42022311150 ).

Early intubation and clinical outcomes in patients with severe COVID-19: a systematic review and meta-analysis.

BACKGROUND: Evidence regarding the timing of the application of mechanical ventilation among patients with severe coronavirus disease (COVID-19) is insufficient. This systematic review and meta-analysis aimed to evaluate the effectiveness of early intubation compared to late intubation in patients with severe and critical COVID-19. METHODS: For this study, we searched the MEDLINE, EMBASE, and Cochrane databases as well as one Korean domestic database on July 15, 2021. We updated the search monthly from September 10, 2021 to February 10, 2022. Studies that compared early intubation with late intubation in patients with severe COVID-19 were eligible for inclusion. Relative risk (RR) and mean difference (MD) were calculated as measures of effect using the random-effects model for the pooled estimates of in-hospital mortality, intensive care unit (ICU) length of stay (LOS), duration of mechanical ventilation (MV), hospital LOS, ICU-free days, and ventilator-free days. Subgroup analysis was performed based on the definition of early intubation and the index time. To assess the risk of bias in the included studies, we used the Risk of Bias Assessment tool for Non-randomized studies 2.0. RESULTS: Of the 1523 records identified, 12 cohort studies, involving 2843 patients with severe COVID-19 were eligible. There were no differences in in-hospital mortality (8 studies, n = 795; RR 0.91, 95% CI 0.75-1.10, P = 0.32, I2 = 33%), LOS in the ICU (9 studies, n = 978; MD -1.77 days, 95% CI -4.61 to 1.07 days, P = 0.22, I2 = 78%), MV duration (9 studies, n = 1,066; MD -0.03 day, 95% CI -1.79 to 1.72 days, P = 0.97, I2 = 49%), ICU-free days (1 study, n = 32; 0 day vs. 0 day; P = 0.39), and ventilator-free days (4 studies, n = 344; MD 0.94 day, 95% CI -4.56 to 6.43 days, P = 0.74, I2 = 54%) between the early and late intubation groups. However, the early intubation group had significant advantage in terms of hospital LOS (6 studies, n = 738; MD -4.32 days, 95% CI -7.20 to -1.44 days, P = 0.003, I2 = 45%). CONCLUSION: This study showed no significant difference in both primary and secondary outcomes between the early intubation and late intubation groups. Trial registration This study was registered in the Prospective Register of Systematic Reviews on 16 February, 2022 (registration number CRD42022311122).

Comparison of the clinical characteristics and mortality of adults infected with human coronaviruses 229E and OC43.

The purpose of the study was to compare clinical characteristics and mortality among adults infected with human coronaviruses (HCoV) 229E and OC43. We conducted a retrospective cohort study of adults (≥ 18 years) admitted to the ward of a university teaching hospital for suspected viral infection from October 2012 to December 2017. Multiplex real-time polymerase chain reaction (PCR) was used to test for respiratory viruses. Multivariate logistic regression was used to compare mortality among patients with HCoV 229E and HCoV OC43 infections. The main outcome was 30-day all-cause mortality. Of 8071 patients tested, 1689 were found to have a respiratory virus infection. Of these patients, 133 had HCoV infection, including 12 mixed infections, 44 HCoV 229E infections, and 77 HCoV OC43 infections. HCoV 229E infections peaked in January and February, while HCoV OC43 infections occurred throughout the year. The 30-day all-cause mortality was 25.0% among patients with HCoV 229E infection, and 9.1% among patients with HCoV OC43 infection (adjusted odds ratio: 3.58, 95% confidence interval: 1.19-10.75). Infections with HCoVs 229E and OC43 appear to have different seasonal patterns, and HCoV 229E might be more virulent than HCoV OC43.