Coronavirus Disease 2019 Hospitalization Research Articles

Impact of COVID-19 Towards Antibiotic Consumption in a Major Specialist Hospital: A Non-COVID-19 Hospital Perspective

The Coronavirus disease 2019 (COVID-19) pandemic heavily affected healthcare services and medication supply. Literatures showed that the consumption of antibiotics was significantly increased during the pandemic especially in COVID-19 hospitals, however, little is known about the collateral impact of the pandemic in non-COVID-19 healthcare settings, such as Hospital Queen Elizabeth II (HQEII) based in Malaysia. This study aimed to compare the prevalence of antibiotic consumption before (2018 & 2019) and during (2020 & 2021) the pandemic, and to explore its impact on antibiotic-acquired cost and bacterial resistance. This is a descriptive observational study where the antibiotic consumption from 1st January 2018 to 31st December 2021 in HQEII was reviewed. The antibiotics selected were Meropenem, Vancomycin, Piperacillin-tazobactam, Ceftazidime and Ceftriaxone. The antibiotic consumption, antibiotic-acquired cost and cases of multidrug resistant organism (MRO) before (2018 & 2019) and during (2020 & 2021) the COVID-19 pandemic were compared, with combined 2 years data for comparison. The overall consumption of the selected antibiotics significantly increased by 45.2% (34.8 vs 50.5, p<0.001) during the COVID-19 pandemic. Intensive care unit had the highest increase in antibiotic consumption (+114.3%, p<0.001). There was a raising trend for the use of Vancomycin, Meropenem, Ceftazidime and Piperacillin-Tazobactam (p<0.005). All these contributed to a significant increase in antibiotic-acquired cost by 64.4% during the COVID-19 pandemic (RM909,898.80 vs RM1,486,791.20, p<0.001). Notably, cases of multidrug resistant organisms also increased, especially MRO Acinetobacter (+197%) and Carbapenem-resistant Enterobacterales (+92%). High antibiotic consumption, antibiotic-acquired cost and MRO cases were observed in non-COVID-19 healthcare setting during the pandemic, but the factors contributing to the surge were not explored in this study.

Systematic review and meta-analysis of COVID-19 mRNA vaccine effectiveness against hospitalizations in adults

Abstract Background During the Coronavirus disease 2019 (COVID-19) pandemic, Pfizer/BioNTech BNT162b2 and Moderna mRNA-1273 vaccines were central to the global pandemic control measures. Methods Here we conducted a systematic review and meta-analysis to evaluate their real-world vaccine effectiveness (VE). Our study focussed on those that reported the efficacy of these vaccines against COVID-19 hospitalization. Hospitalization was chosen as the primary outcome as it directly reflects the ability of the vaccine in preventing severe disease. A literature search was undertaken using Medline and Embase on 25/2/2024. From this, 50 studies out of 18,347 articles were included for further analysis. Results High VE against hospitalization was reported for both the BNT162b2 and mRNA-1273 COVID-19 vaccines when used either as a primary vaccination series (2-dose) or following an additional booster dose (3-dose). Meta-analysis indicated that the pooled VE estimates for each of these vaccination protocols ranged from 84% to 86%, suggesting strong protectiveness. Our data also imply that booster doses can restore waning effectiveness, with no significant differences observed in VE between the 2-dose and 3-dose protocols. However, subgroup analysis revealed an association between the presence of the Omicron variant and a drop in VE, indicating that future emerging SARS-CoV-2 virus variants could similarly affect VE. Conclusions Our review underscores the importance of ongoing research to ensure vaccine strategies remain effective against evolving variants. Our study also identified the need for expanding data collection to include underrepresented populations.

High Colchicine Doses Are Really Silver Bullets Against COVID-19

Abstract The numerous attempts to prove a therapeutic effect of low-dose colchicine for the treatment of Coronavirus disease-2019 (COVID-19) have been discouraging. Increase of doses, however, leads to accumulation in leukocytes and inhibition of the cytokine storm thus preventing COVID-19 complications and hospitalizations. Hospital mortality drops up to 7-fold, while outpatients practically do not reach hospitalization.

SARS-CoV-2 surveillance in US wastewater: Leading indicators and data variability analysis in 2023–2024

Wastewater-Based Epidemiology (WBE) has become a powerful tool for assessing disease occurrence in communities. This study investigates the coronavirus disease 2019 (COVID-19) epidemic in the United States during 2023–2024 using wastewater data from 189 wastewater treatment plants in 40 states and the District of Columbia. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and pepper-mild mottle virus normalized SARS-CoV-2 RNA concentration data were compared with COVID-19 hospitalization admission data at both national and state levels. We further investigate temporal features in wastewater viral RNA abundance, with peak timing and cross-correlation lag analyses indicating that wastewater SARS-CoV-2 RNA concentrations precede hospitalization admissions by 2 to 12 days. Lastly, we demonstrate that wastewater treatment plant size has a significant effect on the variability of measured SARS-CoV-2 RNA concentrations. This study highlights the effectiveness of WBE as a non-invasive, timely and resource-efficient disease monitoring strategy, especially in the context of declining COVID-19 clinical reporting.

Poor correlation between diaphragm ultrasound and invasive gold standard technique derived respiratory muscle strength assessment in patients after hospitalization for COVID-19.

Individuals who survive acute coronavirus disease 2019 (COVID-19) might experience diaphragm muscle weakness. Diaphragm ultrasound may be an easy-to-obtain bedside tool for determining diaphragm function. However, twitch transdiaphragmatic pressure (twPdi) following magnetic stimulation (MS) of the phrenic nerves is the gold standard for non-volitional assessment of diaphragm strength. This study investigated whether diaphragm thickening ratio (DTR) measured on diaphragm ultrasound reflects diaphragm strength as measured by twPdi following MS of the phrenic nerves or other (volitional) invasively obtained pressure values and could therefore be used to accurately diagnose diaphragm weakness. One year after discharge, 50 individuals (14 female, age 58±12 years) who had been hospitalised and treated for moderate-severe COVID-19 underwent standard spirometry and diaphragm ultrasound. TwPdi following cervical MS of the phrenic nerve and volitional inspiratory manoeuvres (Sniff and Mueller manoeuvre) were measured using oesophageal and gastric balloon catheters after transnasal placement. At follow-up, no clinically meaningful restrictive lung function impairment was evident on spirometry. On diaphragm ultrasound, diaphragm dysfunction, i. e. an impaired diaphragm thickening ratio was detected in 24% (12/50) of participants. An objective diagnosis of diaphragm dysfunction, defined as twPdi <16 cmH2O, was made in 60% (30/50) of participants. The measurement results of the two methods did not agree, given that there were many false negative, but also false positive results, so diaphragm ultrasound diagnosed in parts other patients with diaphragm dysfunction than TwPdi. Diaphragm ultrasound had a sensitivity of 26.67% and a specificity of 80.0% in the detection of diaphragm dysfunction (Positive predictive value 66.67%, negative predictive value 42.10%). Diagnosis of diaphragm weakness in individuals who have recovered from COVID-19 cannot be made accurately on diaphragm ultrasound (via DTR), but requires twPdi as the gold standard for assessment of diaphragm strength.

Impact of Frailty on COVID-19 Hospitalizations: Results from the California State Inpatient Database.

Frail patients are at greater risk of experiencing adverse clinical outcomes in any critical illness due to decreased physiologic reserves, greater susceptibility to the adverse effects of treatment, and greater needs for intensive care. In this study, we sought to assess the prevalence of frailty and associated adverse in-hospital outcomes among coronavirus disease 2019 (COVID-19) hospitalizations using the 2020 California State Inpatient Database (SID). For this study, we conducted a retrospective analysis of data from all COVID-19 hospital patients aged 18 years and older. We identified hospitalizations that were at high risk of frailty using the Hospital Frailty Risk Score. The primary outcome of our study was in-hospital mortality, and the secondary outcomes were prolonged length of stay, vasopressor use, mechanical ventilation, and intensive care unit admission. The prevalence of frailty was 44.3% among COVID-19 hospitalizations. Using propensity score matching analysis, we found that the odds of mortality (odds ratio [OR] 4.54, 95% confidence interval [CI] 4.28-4.82), prolonged length of stay (OR 2.81, 95% CI 2.70-2.90), vasopressor use (OR 8.65, 95% CI 7.45-10.03), mechanical ventilation (OR 6.90, 95% CI 6.47-7.35), and intensive care unit admission (OR 7.17, 95% CI 6.71-7.66) were significantly higher among the group of frail patients. Our findings show that frailty could be used for assessing and risk stratifying patients for improved hospital outcomes.

Community-level variability in Bronx COVID-19 hospitalizations associated with differing population immunity during the second year of the pandemic.

The Bronx, New York, exhibited unique peaks in the number of coronavirus disease 2019 (COVID-19) cases and hospitalizations compared to national trends. To determine which features of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus might underpin this local disease epidemiology, we conducted a comprehensive analysis of the genomic epidemiology of the four dominant strains of SARS-CoV-2 (Alpha, Iota, Delta, and Omicron) responsible for COVID-19 cases in the Bronx between March 2020 and January 2023. Genomic analysis revealed similar viral fitness for Alpha and Iota variants in the Bronx despite nationwide data showing higher cases of Alpha. However, Delta and Omicron variants had increased fitness within the borough. While the transmission dynamics of most variants in the Bronx corresponded with mutational fitness-based predictions of transmissibility, the Delta variant presented as an exception. Epidemiological modeling confirms Delta's advantages of higher transmissibility in Manhattan and Queens, but not the Bronx; wastewater analysis suggests underdetection of cases in the Bronx. The Alpha variant had slightly faster growth but a lower carrying capacity compared to Iota and Delta in all four boroughs, suggesting stronger limitations on Alpha's growth in New York City (NYC). The founder effect of Iota varied between higher vaccinated and lower vaccinated boroughs with longer delay, shorter duration, and lower fitness of the Alpha variant in lower vaccinated boroughs. Amino acid changes in T-cell and antibody epitopes revealed Delta and Iota having larger antigenic variability and antigenic profiles distant from local previously circulating lineages compared to Alpha. In concert with transmission modeling, our data suggest that the limited spread of Alpha may be due to a lack of adaptation to immunity in NYC. Overall, our study demonstrates that localized analyses and integration of orthogonal community-level datasets can provide key insights into the mechanisms of transmission and immunity patterns associated with regional COVID-19 incidence and disease severity that may be missed when analyzing broader datasets.

Use of proton pump inhibitors and risk of severe COVID-19: A case-control study in United States Medicare beneficiaries.

Concerns have been raised regarding proton pump inhibitor (PPI) use and risk of severe coronavirus disease 2019 (COVID-19). Observational studies have yielded heterogeneous results and were subject to important methodological limitations. To examine the association between the receipt of PPIs and risk of COVID-19 hospitalizations and severe in-hospital outcomes or death. Case-control study among Medicare fee-for-service beneficiaries 66+ years old with gastroesophageal reflux disorder (GERD). Within this population, we identified cases by an incident hospital discharge diagnosis of COVID-19 from April 1 to December 11, 2020, using the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) U07.1, and randomly selected up to 10 controls per case, matched on date and neighborhood. We defined PPI use as a prescription providing ≥15 days of supply in the 30 days before admission, with H2-receptor antagonist (H2RA) use as the reference to account for indication. We analyzed uncomplicated hospitalizations and hospitalizations with severe outcomes (intensive/coronary care unit admission, invasive mechanical ventilation, or death), estimating odds ratios (ORs), and 95% confidence intervals (CIs) with multinomial conditional logistic regression adjusted for demographics, comorbidities, chronic medications, and health care utilization. We matched 25,867 uncomplicated and 12,954 severe hospitalized COVID-19 cases to 146,972 and 73,104 controls, respectively. Cases tended to be older and have more comorbidities. Relative to H2RA use, we found no association of PPI use with uncomplicated COVID-19 hospitalization (OR 0.99, 95% CI 0.93-1.06) or severe COVID-19 hospitalization (OR 1.00, 95% CI 0.91-1.10). Relative to H2RA use, PPI use was not associated with uncomplicated or severe COVID-19 hospitalizations among Medicare beneficiaries with GERD.

Development and Validation of Claims-based Algorithms for Identifying Hospitalized Patients With COVID-19 and Their Severity in 2020 and 2021.

This study aimed to develop and validate claims-based algorithms for identifying hospitalized patients with coronavirus disease 2019 (COVID-19) and disease severity. We used claims data including all patients at the National Center for Global and Medicine Hospital between January 1, 2020, and December 31, 2021. The claims-based algorithms for three statuses with COVID-19 (hospitalizations, moderate or higher status, and severe status) were developed using diagnosis codes (International Classification of Diseases, 10th revision code: U07.1, B34.2) and relevant medical procedure code. True cases were determined using the COVID-19 inpatient registry and electronic health records. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each algorithm at 6-month intervals. Of the 75,711 total patients, the number of true cases was 1,192 for hospitalizations, 622 for moderate or higher status, and 55 for severe status. The diagnosis code-only algorithm for hospitalization had sensitivities 90.4% to 94.9% and PPVs 9.3% to 19.4%. Among the algorithms consisting of both diagnosis codes and procedure codes, high sensitivity and PPV were observed during the following periods: 93.9% and 97.1% for hospitalization (January-June 2021), 90.4% and 87.5% for moderate or higher status (July-December 2021), and 92.3% and 85.7% for severe status (July-December 2020), respectively. Almost all algorithms had specificities and NPVs of approximately 99%. The diagnosis code-only algorithm for COVID-19 hospitalization showed low validity throughout the study period. The algorithms for hospitalizations, moderate or higher status, and severe status with COVID-19, consisting of both diagnosis codes and procedure codes, showed high validity in some periods.

8772 Impact of Stress Hyperglycemia on Individuals Hospitalized for COVID-19 with and without Diabetes

Abstract Disclosure: E. Burguera-Couce: None. V.O. Cheng: None. J.G. Monteiro: None. G. Gopalakrishnan: None. Background: Stress hyperglycemia (SH), the physiologic increase in blood glucose during severe illness, has been linked with poor outcomes in certain disease states1. Hyperglycemia in the setting of diabetes (DM) has been well established as a predictor of poor outcomes in Coronavirus disease 2019 (COVID-19) infection2-4. The impact of SH on health outcomes for individuals without DM (NoDM) hospitalized with COVID-19 infection is less clear with studies reporting variable outcomes in this population4-6. Objective: To evaluate the impact of SH on health outcomes among hospitalized individuals with COVID-19Methods: Data from 1001 individuals with SH (defined as ≥ 2 instances of BG above 180 mg/dL) admitted in Rhode Island with COVID-19 infection during the first-wave (March 1-June 30, 2020) and second-wave (July 1, 2020-February 28, 2021) was analyzed. Multivariate logistic regression was conducted to compare DM status for length of stay (LOS), ICU admission, mechanical ventilation (MV) and in-hospital mortality, and was adjusted for age, race/ethnicity, gender, insurance, and wave. Model investigating risk factors associated with poor outcomes (ICU admission, MV or in-hospital mortality) in hospitalized individuals with SH was additionally adjusted to include BMI, Chronic kidney disease (CKD), hypertension (HTN), pulmonary disease, and cardiovascular diseases. Results: 17.0% (170) of the cohort had NoDM. Average age (67.6±13.9), gender (57.1% male) and race/ethnicity (Caucasian/White 48.9%, Hispanic 28.0%, Black 13.2% and Other 10.0%) noted in the overall cohort. Individuals with NoDM were more likely to be Caucasian/White (57.7 vs 47.1%, p-value=0.0122), and more likely to require LOS ≥1-week (OR 2.32[1.57-3.44]), ICU admission (2.26[1.60-3.20]) and MV (3.39[2.35-4.89]). NoDM was also associated with higher in-hospital mortality (3.44[2.39-4.96]). The risk of poor outcomes was significantly higher in NoDM compared to DM (ICU admission 47.7 vs 28.6%, MV 45.3 vs 20.1%, Mortality 41.8 vs. 18.2%). In multivariate analysis, Caucasians/Whites (0.50[0.29-0.87]) were less likely to have poor outcomes than the other races. NoDM (3.55[2.40-5.25]), male gender (1.57[1.16-2.13]), CKD stage 5 (1.94[1.40-2.68]), and admission during the first-wave (2.64[1.89-3.70]) were identified as independent risk factors for poor outcomes in SH associated with COVID-19. Conclusion: Our study showed that individuals without a known diagnosis of diabetes hospitalized with COVID-19 who experienced SH during their hospital course had worse outcomes when compared to individuals with diabetes and hyperglycemia. NoDM, male gender, nonwhite race/ethnicity, CKD stage 5 and admission during the first wave were identified as independent risk factors for poor outcomes in COVID-19 hospitalizations with hyperglycemia. Presentation: 6/1/2024

Clinicopathological presentations of eyelid malignancy in COVID era versus pre-COVID era.

The coronavirus disease 2019 (COVID-19) pandemic led to overall interrupted medical care, resulting in disease progression and morbidity. The study aimed to evaluate clinicopathological presentations and severity of eyelid malignancy during the COVID era, comparing the results with patients presented during pre-COVID era and evaluating the reasons for delayed presentation in patients with advanced eyelid malignancy in the COVID-era. This was a comparative, ambispective observational study. Data regarding demographic, clinical, histopathology, and treatment modalities of confirmed cases of eyelid malignancy admitted during the period from March 2020 to September 2022 (defined as COVID era group) were collected and compared with retrospectively collected data from March 2017 to March 2020 (defined as pre-COVID era group). COVID era patients were further categorized as localized and advanced disease. Patients with advanced eyelid malignancy during COVID era were further subjected to a questionnaire to evaluate the reasons for delayed presentation. In total, 115 patients of eyelid malignancy were studied [COVID era group 40 (35%) and pre-COVID era group 75 (65%)]. A statistically significant increase in the duration of disease (P = 0.0001) and advanced tumor T-stage (P = 0.03) was noticed in the COVID era group. Demographic, histopathology, and ocular morbidity details were similar in both groups. The common reasons that led to delay in presentation and treatment in advanced T-stage patients during the COVID era were fear of acquiring COVID, lockdown, and lack of medical facilities. During the COVID-19 pandemic, both hospital- and patient-related factors contributed to delay in presentation, leading to advanced-stage disease indicating need of triaging of eyelid malignancy in the event of such pandemics in future.

Viral load dynamics in asymptomatic and symptomatic patients during Omicron BA.2 outbreak in Shanghai, China, 2022: A longitudinal cohort study

The SARS-CoV-2 virus, particularly the Omicron BA.2 variant, led to a significant surge in Shanghai, 2022. However, the viral load dynamic in Omicron infections with varying clinical severities remain unclear. This prospective cohort included 48,830 hospitalized coronavirus disease 2019 (COVID-19) patients across three hospitals in Shanghai, China, between 23 March and 15 May, 2022. Systematic nucleic acid testing was performed using RT-PCR Cycle threshold (Ct) value as a proxy of viral load. We analyzed the kinetic characteristics of viral shedding by clinical severity and identified associated risk factors. The study comprised 31.06% asymptomatic cases, 67.66% mild-moderate cases, 1.00% severe cases, 0.29% critical and fatal cases. Upon admission, 57% of patients tested positive, with peak viral load observed at 4 days (median Ct value 27.5), followed by a decrease and an average viral shedding time (VST) of 6.1 days (Interquartile range, 4.0–8.8 days). Although viral load exhibited variation by age and clinical severity, peak Ct values occurred at similar times. Unvaccinated status, age exceeding 60, and comorbidities including hypertension, renal issues kidney dialysis and kidney transplantation, neurological disorders, rheumatism, and psychotic conditions were found to correlate with elevated peak viral load and extended VST. Asymptomatic cases demonstrated a 40% likelihood of contagiousness within 6 days of detection, while mild-moderate and severe cases exhibited post-symptom resolution infectious probabilities of 27% and over 50%, respectively. These findings revealed that the initial Ct values serve as a predictive indicator of severe outcomes. Unvaccinated elderly individuals with particular comorbidities are at high-risk for elevated viral load and prolonged VST.

The effectiveness of COVID-19 vaccination in preventing hospitalisation and mortality: A nationwide cross-sectional study in Iran.

The pandemic of the coronavirus disease 2019 (COVID-19) led to a global health crisis, prompting widespread vaccination efforts to reduce severe outcomes. In this study, we assessed the impact of mass COVID-19 vaccination on hospitalisation and mortality rates in Iran, where over 83% of the vaccinated population received inactivated virus vaccines. Using retrospective, cross-sectional analysis, we examined data from the Iran Health Insurance Organisation, covering 41 million individuals from 20 February 2020 to 20 March 2022. We analysed hospital records from 956 Iranian hospitals, focusing on inpatient stays, short-term hospitalisations, and emergency department visits. Study outcomes included COVID-19 hospital admissions and associated mortality. We used negative binomial regression to compare hospital admission rates between periods, while we used a poison regression model with a log link to assess mortality risks before and after vaccination. Among 806 076 hospital admissions, 57 599 deaths were recorded. COVID-19 hospitalisations increased with age, and women had slightly higher admission rates than men. Advanced age and male sex correlated with higher mortality rates. Hospital admissions rose to 1178.66 per million population per month post-vaccination compared to 459.78 pre-vaccination. The incidence rate ratio was 2.09 (95% confidence interval (CI) = 1.90-2.32, P < 0.001), mainly due to the Delta variant. In contrast, post-vaccination mortality rates decreased from 111.33 to 51.66 per 1000 admissions per month. Post-vaccination, COVID-19 mortality significantly decreased, with a relative risk being 0.61 (95% CI = 0.60-0.62, P < 0.001) across all age groups and sexes. The Delta variant increased hospital admissions among vaccinated individuals, but widespread vaccination significantly reduced COVID-19-related mortality.

Frequency of exposure incidents in hospital workers before and during the COVID-19 pandemic based on the hospital status and the use of personal protective equipment: a descriptive study with a historical comparison group

BackgroundAn occupational exposure, i.e. exposure incident (EI), is contact with potentially contaminated material that may contain bloodborne pathogens and that occurs during occupational activities inside or outside a health care facility, either during direct work with a patient or during contact with a patient’s body fluids and tissues. This study aimed to compare the frequency of EIs in a university hospital before and during the Coronavirus Disease 2019 (COVID-19) pandemic.MethodsThis was a descriptive study with a historical comparison group conducted at the Dubrava University Hospital (DUH) in Zagreb, Croatia. We compared the frequency of EIs among healthcare and non-healthcare workers before (from March 11, 2018, to March 10, 2020) and during (from March 11, 2020, to March 11, 2022) the COVID-19 pandemic, expressed as the number of EIs per number of hospitalized patients and the total number of hospital activities. We analyzed data based on the status of the hospital (a COVID-19 hospital or not) and the use of personal protective equipment (PPE) as recommended by the World Health Organization.ResultsDuring the total analyzed period, 241 EIs were reported in DUH. Before the pandemic, 128 EIs were reported, compared to 113 during the pandemic. Before the pandemic, 91% of EIs were recorded in healthcare workers, while during the pandemic, 96% of EIs were recorded in healthcare workers. Slightly more EIs were recorded during the period of mixed work form and de-escalation of PPE. The rate of EIs relative to the total number of hospital patients was significantly higher during the pandemic (3.9/1000) than in the pre-pandemic period (2.5/1000). The rate of EIs relative to the total number of hospital activities was significantly higher during the pandemic (0.4/1000) than in the pre-pandemic period (0.2/1000).ConclusionThe rate of EIs relative to the total number of hospitalized patients and the total number of hospital activities in DUH was significantly higher during the pandemic, and the rate of total EIs increased among healthcare workers during the COVID-19 pandemic. The results of this study show that it is necessary to constantly and effectively work on the prevention of EI.

Prevalence of Potential Drug Interactions With Direct-Acting Antivirals for COVID-19 Among Hospitalized Patients

PurposeClinicians consider polypharmacy, comorbidities, and other factors including the potential for drug-drug interactions (DDIs) when evaluating therapeutic options for specific clinical diagnoses. Contemporary treatment for coronavirus disease 2019 (COVID-19) includes direct-acting antivirals (DAAs). We sought to characterize patients’ characteristics, comorbidities, and medications received during their hospitalization for COVID-19 and quantify potential DDIs that clinicians consider in selecting appropriate DAAs. MethodsPatients hospitalized with a primary diagnosis of COVID-19 between May 2020 and December 2022 from the PINC AI Healthcare Database were identified. Medications administered during the hospitalization with the potential to cause DDIs with nirmatrelvir/ritonavir, remdesivir, or molnupiravir (per the Emergency Use Authorization factsheet or package insert) were assessed. For DDIs with nirmatrelvir/ritonavir, medications are categorized as “Contraindicated,” “Avoid Concomitant Use,” or “Other DDIs” (includes recommendation for dose modification or clinical and laboratory monitoring). For remdesivir, coadministration with chloroquine phosphate and hydroxychloroquine sulfate was not recommended. For molnupiravir, no drugs are listed as having potential DDIs. In a subset of patients, a multivariable logistic regression model was used to examine the association between documented patient/hospital characteristics and the likelihood of being “Contraindicated” to receive nirmatrelvir/ritonavir. FindingsOf the 788,238 patients hospitalized for COVID-19 in 920 hospitals, 53% were ≥ 65 years old, and 31% had Charlson Comorbidity Index (CCI) ≥ 3. During the study period, about half of the patients received medications categorized as “Contraindicated” (11%) and/or “Avoid Concomitant Use” (41%) with nirmatrelvir/ritonavir. The frequency of administered drugs was higher in those aged ≥ 65 years (68%), CCI ≥ 3 (78%), with high-risk underlying conditions (55%). About 1% of patients received medications that were not recommended to be coadmistered with remdesivir. Among a subset of patients hospitalized for COVID-19 in 2022, those who were older, had higher CCI, high-risk underlying conditions, severe hepatic impairment, Medicare insurance, and hospitalized in larger hospitals were significantly more likely to be categorized as “Contraindicated” when considering nirmatrelvir/ritonavir as a therapeutic option to manage COVID-19. ImplicationsA significant proportion of patients hospitalized for COVID-19 receive medications for other conditions that have the potential to result in DDIs with DAAs; most predominantly with nirmatrelvir/ritonavir, a strong CYP3A enzyme inhibitor, fewer with remdesivir, and none with molnupiravir. Higher age and comorbidity burden were significantly associated with a higher likelihood of receiving medications that are “Contraindicated” with nirmatrelvir/ritonavir. In the evolving COVID-19 era, these findings provide insights into patients hospitalized for COVID-19, and the polypharmacy evaluations that clinicians may encounter when selecting among DAAs to manage COVID-19.

Clinical profiles and mortality predictors of hospitalized patients with COVID-19 in Ethiopia

BackgroundStudying the characteristics of hospitalized Coronavirus Disease 2019 (COVID-19) patients is vital for understanding the disease and preparing for future outbreaks. The aim of this study was to analyze and describe the clinical profiles and factors associated with mortality among COVID-19 patients admitted to Jimma Medical Center COVID-19 Treatment Center (JMC CTC) in Ethiopia.MethodsAll confirmed COVID-19 patients admitted to JMC CTC between 17 April 2020 and 05 March 2022 were included in this study. Socio-demographic data, clinical information, and outcome variables were collected retrospectively from medical records and COVID-19 database at the hospital. Bivariable and multivariable analyses were performed to determine factors associated with COVID-19 severity and mortality. A P-value < 0.05 was considered statistically significant.ResultsA total of 542 confirmed COVID-19 patients were admitted to JMC CTC, of which 322 (59.4%) were male. Their median age was 48 years (IQR 32–64). About 51% (n = 277) of them had severe COVID-19 upon admission. Patients with hypertension [AOR: 2.8 (95% CI: 1.02–7.7, p = 0.046)], diabetes [AOR: 8.8 (95% CI: 1.2–17.3, p = 0.039)], and underlying respiratory diseases [AOR: 18.8 (95% CI: 2.06–71.51, p = 0.009)] were more likely to present with severe COVID-19 cases. Overall, 129 (23.8%) died in the hospital. Death rate was higher among patients admitted with severe disease [AHR = 5.5 (3.07–9.9) p < 0.001)] and those with comorbidities such as hypertension [AHR = 3.5 (2.28–5.41), p < 0.001], underlying respiratory disease [AHR = 3.4 (1.97–5.94), p < 0.001], cardiovascular disease (CVDs) [AHR = 2.8 (1.73–4.55), p < 0.001], and kidney diseases [AHR = 3.7 (2.3–5.96), p < 0.001].ConclusionAbout half of COVID-19 cases admitted to the hospital had severe disease upon admission. Comorbidities such as hypertension, diabetes, and respiratory diseases were linked to severe illness. COVID-19 admissions were associated with high inpatient mortality, particularly among those with severe disease and comorbidities.

Protecting effects of smoking against COVID-19: a community-based retrospective cohort study in middle- and older-aged adults

On December 7, 2022, China switched from dynamic zeroing strategy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to reopening. A nationwide SARS-CoV-2 epidemic emerged rapidly. The effect of smoking on SARS-CoV-2 infection remains unclear. We aimed to retrospectively investigate the relationship between smoking and coronavirus disease 2019 (COVID-19) using a community-based cohort of smokers and non-smokers. We included participants from a pre-pandemic cohort with a prolonged follow-up period. Data on smoking status, body mass index, and history of other diseases were collected from health examination and consultation clinic records. Cox regression analysis was used to identify the relationship between groups and SARS-CoV-2 infection over time. We analysed 218 male patients with varied smoking statuses (46.3% current or ex-smokers; average age 68.63 ± 9.81 years). Two peaks in the epidemic were observed following the December 2022 outbreak. At the end of the second peak, non-smokers, current smokers, and ex-smokers had primary infection rates increase to 88.0%, 65.1%, and 81.0%, respectively, with a significant difference between the groups. Current smoking significantly protected against SARS-CoV-2 infection (HR 0.625, 95% CI 0.402–0.970, p = 0.036). Further analyses showed that the prevalence of pneumonia in the unvaccinated, older, diabetic, and non-smoking groups was significantly higher than that in the other groups (p < 0.05). Our study suggests a potential association between smoking and a reduced risk of SARS-CoV-2 infection and pneumonia. This indicates that nicotine and ACE2 play important roles in preventing COVID-19 and its progression. We suggest smokers use nicotine replacement therapy during hospitalization for COVID-19.

The Relationship Between Pre-Pandemic Comorbidities With SARS-CoV-2 Infections and Hospitalizations in Black Versus White Military Service Members: A Retrospective Study.

Comorbidities such as hypertension, diabetes mellitus, asthma, and cardiovascular conditions have been reported to worsen the clinical progression of coronavirus disease 2019 (COVID-19) and related hospitalizations. Furthermore, the COVID-19 pandemic has disproportionately affected the historically marginalized groups, i.e., Black, Hispanic, and Asian individuals have substantially higher rates of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection, COVID-19 hospitalization, and death compared to White individuals. Despite these findings in civilian populations, the impact of comorbidities and race in SARS-CoV-2 infection and COVID-19 hospitalizations in military populations is unknown. We evaluated the relationship of pre-selected pre-pandemic comorbidities and race with SARS-CoV-2 infections and COVID-19 hospitalizations in U.S. military service members (SMs). We conducted a systematic review of Military Health System beneficiaries' records by accessing the Defense Medical Epidemiological Database. Our inclusion criteria were being an active duty SM and having at least one pre-COVID-19 pandemic comorbidity. Retired as well as uninfected healthy active duty SMs and beneficiaries were excluded from the study. A total population of 1.334 million active duty SM records was drawn from Defense Medical Epidemiological Database. The data were stratified, by race (primary outcome), as well as gender, age, and military service branches (secondary outcomes). We found higher trends in SARS-CoV-2 infection and COVID-19 hospitalization rates in Black compared to White SMs. This seamless inequality was also seen in other viral infections affecting SMs including human immunodeficiency virus and viral hepatitis. We hypothesized this disparity to some extent be associated with the presence of pre-pandemic comorbidities that is affecting this military subpopulation. Supporting our hypothesis, we found trends toward the higher pre-pandemic prevalence of diabetes mellitus, asthma, hypertension, and ischemic heart disease, in Black compared to White military SMs, especially in Black older male adults. Our results highlight the role of pre-pandemic comorbidities and race likely enhancing the frequency of SARS-CoV-2 infections and COVID-19 hospitalizations in military SMs. These preliminary findings underscore the need for future retrospective studies using additional Military Health System data bases reporting data on this military subpopulation, especially in the setting of future pathogens outbreaks or pandemics affecting military populations.

Large-scale genetic correlation studies explore the causal relationship and potential mechanism between gut microbiota and COVID-19-associated risks

Recent observational studies suggest that gut microorganisms are involved in the onset and development of coronavirus disease 2019 (COVID-19), but the potential causal relationship behind them remains unclear. Exposure data were derived from the MiBioGen consortium, encompassing 211 gut microbiota (n = 18,340). The outcome data were sourced from the COVID-19 host genetics initiative (round 7), including COVID-19 severity (n = 1,086,211), hospitalization (n = 2,095,324), and susceptibility (n = 2,597,856). First, a two-sample Mendelian randomization (TSMR) was performed to investigate the causal effect between gut microbiota and COVID-19 outcomes. Second, a two-step MR was used to explore the potential mediators and underlying mechanisms. Third, several sensitivity analyses were performed to verify the robustness of the results. Five gut microbes were found to have a potential causality with COVID-19 severity, namely Betaproteobacteria (beta = 0.096, p = 0.034), Christensenellaceae (beta = -0.092, p = 0.023), Adlercreutzia (beta = 0.072, p = 0.048), Coprococcus 1 (beta = 0.089, p = 0.032), Eisenbergiella (beta = 0.064, p = 0.024). Seven gut microbes were found to have a potential causality with COVID-19 hospitalization, namely Victivallaceae (beta = 0.037, p = 0.028), Actinomyces (beta = 0.047, p = 0.046), Coprococcus 2 (beta = -0.061, p = 0.031), Dorea (beta = 0.067, p = 0.016), Peptococcus (beta = -0.035, p = 0.049), Rikenellaceae RC9 gut group (beta = 0.034, p = 0.018), and Proteobacteria (beta = -0.069, p = 0.035). Two gut microbes were found to have a potential causality with COVID-19 susceptibility, namely Holdemanella (beta = -0.024, p = 0.023) and Lachnospiraceae FCS020 group (beta = 0.026, p = 0.027). Multi-omics mediation analyses indicate that numerous plasma proteins, metabolites, and immune factors are critical mediators linking gut microbiota with COVID-19 outcomes. Sensitivity analysis suggested no significant heterogeneity or pleiotropy. These findings revealed the causal correlation and potential mechanism between gut microbiota and COVID-19 outcomes, which may improve our understanding of the gut-lung axis in the etiology and pathology of COVID-19 in the future.

A real-world study of the differences in Traditional Chinese Medicine diagnosis and treatment rules for coronavirus disease 2019 between Northern and Southern China.

To explore the differences in Traditional Chinese Medicine (TCM) diagnosis and treatment rules for coronavirus disease 2019 (COVID-19) between Northern and Southern China based on the real-world data from 982 COVID-19 patients. All consecutive cases of COVID-19 admitted to the TCM department of designated COVID-19 hospitals in eight provinces and cities were retrospectively analyzed. Patients were divided into a Northern and a Southern group according to the location of the admitting hospital. The symptoms, syndrome elements, syndrome distribution and herbal treatments were analyzed. The core prescriptions were extracted using the multiscale backbone-based network comparison algorithm (msbNC). The distribution of syndrome elements showed that dampness was common in Northern and Southern China, wind and heat were more often present in the South, while fire toxin and spleen deficiency were more often encountered in the North. The distribution of syndromes showed that the South was dominated by heat dampness accumulating in the lung (55.69%), while the North was dominated by dampness-toxin stagnating in the lung (44.90%).The results of core prescription mining showed that dispelling dampness, dispersing wind, clearing heat and strengthening spleen were the common treatment methods in Northern and Southern China. For mild cases, Jinyinhua (Flos Lonicerae) and Lianqiao (Fructus Forsythiae Suspensae) were often used in the South to clear heat and relieve exterior symptoms, while Chaihu (Radix Bupleuri Chinensis) and Huangqin (Radix Scutellariae Baicalensis) were often used in the North to relieve muscles by expelling heat. For moderate cases, Chaihu (Radix Bupleuri Chinensis), Qinghao (Herba Artemisiae Annuae), and Shigao (Gypsum Fibrosum) were often used to clear heat of Tri-jiao Channel and stomach in the South, while Fuling (Poria), Chenpi (Pericarpium Citri Reticulatae), and Dangshen (Radix Codonopsis) were often used to invigorate spleen and remove dampness in the North. For severe cases, spleen invigoration and dampness removal as well as relaxing the bowels and discharging heat were often used in the North. There were certain North-South differences in terms of symptoms, syndrome elements and syndrome distribution of COVID-19, as well as differences in core prescriptions during different periods of the disease. The regional differences in the rules of TCM diagnosis and treatment for COVID-19 should be further considered in the process of optimization and revision of relevant treatment guidance.