Retrospective Analysis of Clostridioides difficile Infection Rates in Hospitalized Patients during COVID-19 Pandemic. A Unicenter Study in Reus, Spain (preprint)

.Background: Clostridioides difficile infections (CDI) vary in severity from mild diarrhea to life-threatening conditions like pseudomembranous colitis or toxic megacolon, often leading to sepsis and death. The COVID-19 pandemic prompted changes in healthcare practices, potentially affecting CDI incidence, though reported data are inconclusive. We studied factors influencing CDI incidence and outcomes at a university hospital throughout the COVID-19 pandemic years. Methods: We conducted a retrospective study on all adult hospitalized CDI cases from January 1, 2020, to December 31, 2022. We collected demographic information, comorbid conditions, and concurrent infections. Results: While overall CDI and COVID-19 rates decreased in 2022, a nota-ble increase in CDI infections was observed among oncological patients and those undergoing some aggressive treatments, such as colon or gastroscopies. The prevalence of comorbidities remained unmodified, and there were declines in prior gastrointestinal surgeries and proton pump inhibitor prescriptions. Factors associated with patient fatality or prolonged hospitaliza-tion included older age, cancer, chronic kidney disease, higher Charlson and McCabe indices, elevated C-reactive protein, and low albumin concentrations. Conclusion: Our study shows the evolving landscape of CDI during the COVID-19 pandemic and emphasizes the impact of de-layed diagnoses and treatments exacerbated by telemedicine adoption. Identified risk factors for CDI-related mortality or prolonged hospital stays underscore the importance of targeted inter-ventions in high-risk populations.

Similarities between long COVID and cognitive impairment and potential implications; Results from the 2022 BRFSS (preprint)

BackgroundCOVID has been linked to cognitive issues with brain fog a common complaint among adults reporting long COVID (symptoms lasting 3 or more months). ObjectiveTo study similarities and differences between cognitive impairment (CI) (the cognitive disability measure) and long COVID. MethodsUsing 2022 BRFSS data from 50 states and 169,894 respondents in 29 states with COVID vaccine data, respondents with CI and long COVID were compared in unadjusted analysis and logistic regression. Apparent vaccine effectiveness was compared in the 29 states. ResultsPrevalence of long COVID was 7.4% (95% CI 7.3-7.6) and CI was 13.4% (13.2-13.6) with both rates higher among women, ages 18-64 years, Hispanics, American Indians, ever smokers, those with depression, e-cigarette users, and those with more of the co-morbidities of diabetes, asthma, COPD, and obesity. The strong association between long COVID and CI was confirmed. Apparent vaccine effectiveness of 3 or more doses vs <3 was 38% for long COVID and 35% for CI, in both cases reducing rates for 3 or more doses to those comparable to adults with 0 comorbidities and showing dose response gradients. For CI, apparent vaccine effectiveness was similar for respondents with or without long COVID. Logistic regression confirmed most results except the magnitude of vaccine effectiveness on CI was reduced in some models while vaccine effectiveness for long COVID was confirmed. ConclusionsMore research is needed to understand the apparent effectiveness of COVID vaccines on CI but, if confirmed, results could expand the list of non-infectious outcomes for which mRNA vaccines can be effective.

Preoperative COVID-19 Vaccination is Associated with Decreased Perioperative Mortality after Major Vascular Surgery (preprint)

Background: The objective of this study was to examine the effect of COVID-19 vaccination on perioperative outcomes after major vascular surgery. Methods: This is a multicenter retrospective study of patients who underwent major vascular surgery between December 2021 through August 2023. The primary outcome was all-cause mortality within 30 days of index operation or prior to hospital discharge. Multivariable models were used to examine the association between vaccination status and the primary outcome. Results: Of the total 85,424 patients included, 19161 (22.4%) were unvaccinated. Unvaccinated patients were younger compared to vaccinated patients (mean age 68.44 +/- 10.37 years vs 72.11 +/- 9.20 years, p <.001) and less likely to have comorbid conditions, including hypertension (87.2% vs 89.7%, p <.001), congestive heart failure (14.5% vs 15.9%, p <.001), chronic obstructive pulmonary disease (35.7% vs 36.3, p <.001) and renal failure requiring hemodialysis (1.4% vs 1.7%, p = .005). After risk factor adjustment, vaccination was associated with decreased mortality (OR 0.7, 95% CI 0.62 - 0.81, p <.0001). Stratification by procedure type demonstrated that vaccinated patients had decreased odds of mortality after open AAA (OR 0.6, 95% CI 0.42-0.97, p = 0.03), EVAR (OR 0.6, 95% CI 0.43-0.83, p 0.002), CAS (OR 0.7, 95% CI 0.51-0.88, p = 0.004) and infra-inguinal lower extremity interventions (OR 0.7, 95% CI 0.48-0.96, p = 0.03). Conclusions: COVID-19 vaccination is associated with reduced perioperative mortality in patients undergoing vascular surgery. This association is most pronounced for patients undergoing aortic aneurysm repair, carotid stenting and infrainguinal bypass.

Duration of effectiveness of the COVID-19 vaccine in Japan: A retrospective cohort study using large- scale population-based registry data (preprint)

Background Most evidence of the waning of vaccine effectiveness is limited to a relatively short period after vaccination.Methods Data obtained from a linked database of healthcare administrative claims and vaccination records maintained by the municipality of a city in the Kanto region of Japan were used in this study. The study period extended from April 1, 2020, to December 31, 2022. The duration of the effectiveness of the COVID-19 vaccine was analyzed using a time-dependent piecewise Cox proportional hazard model using the age, sex and history of cancer, diabetes, chronic obstructive pulmonary disease, asthma, chronic kidney disease, and cardiovascular disease as covariates.Results Among the 174,757 eligible individuals, 14,416 (8.3%) were diagnosed with COVID-19 and 936 (0.54%) were hospitalized for COVID-19. Multivariate analysis based on the time-dependent Cox regression model revealed a lower incidence of COVID-19 in the one-dose group (hazard ratio, 0.76 [95% confidence interval, 0.63–0.91]), two-dose (0.89 [0.85–0.93]), three-dose (0.80 [0.76–0.85]), four-dose (0.93 [0.88–1.00]), and five-dose (0.72 [0.62–0.84]) groups. A lower incidence of COVID-19-related hospitalization was observed in the one-dose group (0.42 [0.21–0.81]), two-dose (0.44 [0.35–0.56]), three-dose (0.38 [0.30–0.47]), four-dose (0.20 [0.14–0.28]), and five-dose (0.11 [0.014–0.86]) groups. Multivariable analyses based on the time-dependent piecewise Cox proportional hazard model revealed significant preventive effects of the vaccine at 0–1, 1–2, 2–3, 3–4, 7–8, ≥ 12 months for the incidence of COVID-19 and 0–1, 1–2, 2–3, 3–4, 4–5, 5–6, 7–8, and 9–10 months for hospitalization.Conclusions Vaccine effectiveness showed gradual attenuation with time after vaccination; however, protective effects against the incidence of COVID-19 and hospitalization were maintained for 4 months and ≥ 6 months, respectively. These results may aid in formulating routine vaccination plans after the COVID-19 pandemic.

Changes of respiratory pathogen and clinical features of in acute exacerbation of chronic obstructive pulmonary disease after COVID-19 pandemic (preprint)

Respiratory infections are common causes of acute exacerbation of chronic obstructive lung disease (AECOPD). We explored whether the pathogens causing AECOPD and clinical features changed from before to after the coronavirus disease 2019 (COVID-19) outbreak. We reviewed the medical records of patients hospitalized with AECOPD at four university hospitals between January 2017 and December 2018 and between January 2021 and December. We evaluated 1,180 patients with AECOPD for whom medication histories were available. After the outbreak, the number of patients hospitalized with AECOPD was almost 44% lower compared with before the outbreak. Patients hospitalized with AECOPD after the outbreak were younger (75 vs. 77 years, p = 0.003) and more often stayed at home (96.6% vs. 88.6%, p < 0.001) than patients of AECOPD before the outbreak. Hospital stay was longer after the outbreak than before the outbreak (10 vs. 8 days. p < 0.001). After the COVID-19 outbreak, the identification rates of S. pneumoniae (15.3 vs. 6.2%, p < 0.001) and Hemophilus influenzae (6.4 vs. 2.4%, p = 0.002) decreased, whereas the identification rates of P. aeruginosa (9.4 vs. 13.7%, p = 0.023), Klebsiella pneumoniae (5.3 vs. 9.8%, p = 0.004), and methicillin-resistant Staphylococcus aureus (1.0 vs. 2.8%, p = 0.023) increased. After the outbreak, the identification rate of influenza A decreased (10.4 vs. 1.0%, p = 0.023). After the outbreak, the number of patients hospitalized with AECOPD was lower and the identification rates of community-transmitted pathogens tended to decrease, whereas the rates of pathogens capable of chronic colonization tended to increase. During the period of large-scale viral outbreaks that require quarantine, patients with AECOPD should consider treatment against strains that can colonize chronic respiratory disease rather than community acquired pathogens.

Can COVID-19 Lead to Differences in COPD Patients' Exacerbations and Clinical Evolution? (preprint)

Background COPD patients show higher mortality and worse prognosis in the acute phase of COVID-19, and survivors may suffer persistent symptoms that could make them more vulnerable to exacerbations.Objectives We aimed to evaluate the impact of COVID-19 on the exacerbations, symptoms, quality of life, and mental health of a cohort of COPD patients.Methods Retrospective case-control single-centre study including all COPD patients from the pulmonary consultation of University Hospital Santa Maria (Lleida, Spain) surviving COVID-19 between March 2020 and September 2021, and similar propensity-score-matched (1:2) COPD patients. Differences in COPD exacerbations, COPD clinical evolution (lung function, dyspnoea, CAT and symptoms), long COVID-19 symptoms, quality of life, and mental health, were assessed at the end of 2021.Results We included 39 COVID-19 COPD patients and 78 similar non-COVID-19. No differences were found on exacerbations (46(59%) vs 27(69.2%), p = 0.380), dyspnoea (2 [1; 3] vs 2 [1; 3], p = 0.921) CAT (14.5 [10.0; 18.8] vs 13.0 [10.0; 16.0], p = 0.432). Only the prevalence of smell or taste disorders, hair loss and tingling was higher in COVID-19 patients. No differences were found in quality of life or mental health.Conclusions COPD patients surviving COVID-19 were not at a higher risk of COPD exacerbations nor showed significant changes in COPD clinical evolution, and only showed differences in a few very specific COVID-19 symptoms. These unexpected results suggest that the conditions triggered by the pandemic and its management could have affected COPD patients as much as actually having had COVID-19.

Comparing surveyed adults with long COVID and those with just a positive test helps put COVID into perspective (preprint)

Introduction: Among adults who test positive for COVID-19, some develop long COVID (symptoms lasting [≥]3 months), and some do not. We compared 3 groups on selected measures to help determine strategies to reduce COVID impact. Methods: Using Stata and data for 385,617 adults from the 2022 Behavioral Risk Factor Surveillance System, we compared adults reporting long COVID, those with just a positive test, and those who never tested positive, on several health status and risk factor measures plus vaccination rates (data for 178,949 adults in 29 states). Results: Prevalence of just COVID was 26.5% (95% CI 26.2-26.8) and long COVID was 7.4% (7.3-7.6). Compared with adults with just COVID those with long COVID had worse rates for 13 of 17 measures of chronic disease, disability, and poor health status, while those with just COVID had the best results for 15 of the 17 measures among all 3 groups. The 5 risk factors (obesity, diabetes, asthma, cardiovascular disease, and COPD) previously associated with COVID deaths, increased long COVID but not just COVID rates, which were highest among younger and higher income adults. Adults with long COVID had the highest rate among the 3 groups for any COVID risk factors and data from 29 states showed they had the lowest rates for [≥]3 vaccine doses of 35.6%, vs. 42.7% and 50.3% for those with just a positive test, and neither, respectively. Vaccination with [≥]3 vaccines vs. <3 reduced long COVID rates by 38%, and just COVID rates by 16%. Conclusions: Results show the seriousness of long COVID vs. just a positive test and that increasing vaccine coverage by targeting adults with risk factors shows promise for reducing COVID impact.

Hematological Features and Risk Factors of Hospitalized COVID-19 Patients: A Retrospective Analysis (preprint)

Background: Coronavirus disease 2019 (COVID-19) has become pandemic in 2020 and recently mutated coronavirus has emerged in many countries. This study firstly identified the clinical characteristics and risk factors for COVID-19 patients in Zhengzhou for clinical prevention and management. Methods: A total of 70 patients hospitalized with COVID-19 were enrolled between 21th January and 29th February 2020, in Zhengzhou, China. Clinical characteristics, hematological findings, neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR) and inflammatory index on admission were selected from medical records and the comparison between COVID-19 patients with different outcomes were evaluated. Results : The median age was 55 years. Forty-three (43%) patients were classified as severe or critical cases. Eighteen (12.8%) patients died in hospital and the remaining fifty-two were discharged. Patients who died tend to old aged, expectoration, with chronic obstructive pulmonary disease. Compared to survivor, non-survivor has significantly higher leucocytes, neutrophils, NLR, AST, GGT, TBIL, DBIL, LDH, PT, D-dimer, CRP, and decreased platelet, lymphocyte, UA, ALB, CHE, PTA. Multiple logistic regression analysis identified leucocytes, platelet, PLR, NLR, AST, and ALB as independent factors for poor outcomes. The AUC of combination of leucocyte, PLR, NLR, and AST have the largest area under curve at 0.87, with the sensitivity of 0.83 and specificity of 0.81. Conclusion : Our results identified the risk factors among COVID-19 patients in-hospital fatality. Leucocyte, PLR, NLR, and AST could have important reference value for prognostic prediction and early intervention.

An Approach to Identifying Spatial Variability in Observed Infectious Disease Spread in a Prospective Time-Space Series with Applications to COVID-19 and Dengue Incidence (preprint)

Most of the growing prospective analytic methods in space-time disease surveillance and intended functions of disease surveillance systems focus on earlier detection of disease outbreaks, disease clusters, or increased incidence. The spread of the virus such as SARS-CoV-2 has not been spatially and temporally uniform in an outbreak. With the identification of an infectious disease outbreak, recognizing and evaluating anomalies (excess and decline) of disease incidence spread at the time of occurrence during the course of an outbreak is a logical next step.  We propose and formulate a hypergeometric probability model that investigates anomalies of infectious disease incidence spread at the time of occurrence in the timeline for many geographically described populations (e.g., hospitals, towns, counties) in an ongoing daily monitoring process. It is structured to determine whether the incidence grows or declines more rapidly in a region on the single current day or the most recent few days compared to the occurrence of the incidence during the previous few days relative to elsewhere in the surveillance period. The new method uses a time-varying baseline risk model, accounting for regularly (e.g., daily) updated information on disease incidence at the time of occurrence, and evaluates the probability of the deviation of particular frequencies to be attributed to sampling fluctuations, accounting for the unequal variances of the rates due to different population bases in geographical units.    We attempt to present and illustrate a new model to advance the investigation of anomalies of infectious disease incidence spread by analyzing subsamples of spatiotemporal disease surveillance data from Taiwan on dengue and COVID-19 incidence which are mosquito-borne and contagious infectious diseases, respectively. Efficient R programs for computation are available to implement the two approximate formulae of the hypergeometric probability model for large numbers of events. 

Mild and moderate COVID-19 during Alpha, Delta and Omikron pandemic waves in urban Maputo, Mozambique, December 2020-March 2022: a population-based surveillance study (preprint)

In sub-Saharan Africa, reported COVID-19 numbers have been lower than anticipated, even when considering populations younger age. The extent to which risk factors, established in industrialised countries, impact the risk of infection and of disease in populations in sub-Saharan Africa, remains unclear. We estimated the incidence of mild and moderate COVID-19 in urban Mozambique and analysed factors associated with infection and disease in a population-based surveillance study. During December 2020-March 2022, households of a population cohort in Polana Canico, Maputo, Mozambique, were contacted biweekly. Residents reporting any respiratory sign, anosmia, or ageusia, were asked to self-administer a nasal swab, for SARS-CoV-2 PCR testing. Of a subset of 1400 participants, dried blood spots were repeatedly collected three-monthly from finger pricks at home. Antibodies against SARS-CoV-2 spike glycoprotein and nucleocapsid protein were detected using an in-house developed multiplex antibody assay. We estimated the incidence of respiratory illness and COVID-19, and SARS-CoV-2 seroprevalence. We used Cox regression models, adjusting for age and sex, to identify factors associated with first symptomatic COVID-19 and with SARS-CoV-2 sero-conversion in the first six months. During 11925 household visits in 1561 households, covering 6049 participants (median 21 years, 54.8% female, 7.3% disclosed HIV positive), 1895.9 person-years were followed up. Per 1000 person-years, 364.5 (95%CI 352.8-376.1) respiratory illness episodes of which 72.2 (95%CI 60.6-83.9) COVID-19 confirmed, were reported. Of 1412 participants, 2185 blood samples were tested (median 30.6 years, 55.2% female). Sero-prevalence rose from 4.8% (95%CI 1.1-8.6%) in December 2020 to 34.7% (95%CI 20.2-49.3%) in June 2021, when 3.0% were vaccinated. Increasing age (strong gradient in hazard ratio, HR, up to 15.70 in [≥]70 year olds, 95%CI 3.74-65.97), leukaemia, chronic lung disease, hypertension, and overweight increased risk of COVID-19. We found no increased risk of COVID-19 in people with HIV or tuberculosis. Risk of COVID-19 was lower among residents in the lowest socio-economic quintile (HR 0.16, 95%CI 0.04-0.64), with no or limited handwashing facilities, and who shared bedrooms (HR 0.42, 95%CI 0.25-0.72). Older age also increased the risk of SARS-CoV-2 seroconversion (HR 1.57 in 60-69 year olds, 95%CI 1.03-2.39). We found no associations between SARS-CoV-2 infection risk and socio-economic, behavioural factors and comorbidities. Active surveillance in an urban population cohort confirmed frequent COVID-19 underreporting, yet indicated that the large majority of cases were mild and non-febrile. In contrast to industrialised countries, deprivation did not increase the risk of infection nor disease.

Effects of Pulmonary Rehabilitation on Functional and Psychological Parameters in Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) Patients (preprint)

Background COVID-19 survivors may develop long-term symptoms of fatigue, dyspnea, mental health issues, and functional limitations: a condition termed post-acute sequelae of COVID-19 (PASC). Pulmonary rehabilitation (PR) is a recommended treatment for PASC; however, there is a lack of data regarding PR’s effect on multiple health indices and the factors that influence patient outcomes.Methods We extracted patient demographic, comorbidity, and outcome data from Allegheny Health Network’s electronic medical records. Functionality test results were compared before and after PR, including 6-minute walk test (6MWT), chair rise repetitions (CR reps), timed up and go test (TUG), gait speed (Rehab gait), modified medical research council scale (MMRC), shortness of breath questionnaire (SOBQ), hospital anxiety and depression scale (HADS) and chronic obstructive pulmonary disease assessment test (CAT) scores. Multiple regression analysis was done to evaluate the effect of comorbidities and patient factors on patient responses to PR.Results The 55 patients included in this study had a mean time of 3.8 months between the initial COVID-19 diagnosis and the subsequent PASC diagnosis. Post-PR, patients signficantly improved in 6MWT, CR reps, TUG, Rehab gait, MMRC, SOBQ, HADS, and CAT scores. However, hypertension, diabetes, chronic lung diseases, being an outpatient, and receiving pharmacologic treatments (decadron, decadron + remdesivir, and decadron + remdesivir + tocilizumab) were associated with a poor response to PR.Conclusion Our study supports PR as an integrated model of care for PASC patients to improve several physical and mental health indices. The long-term effects of PR on patients’ functional status should be investigated in the future.

Prevalence of COVID-19 and long COVID - Results from the 2022 Behavioral Risk Factor Surveillance System, 50 states. (preprint)

Recent MMWR results estimate long COVID prevalence at 6.0% in June 2023, while the percentage of those with COVID reporting long COVID was 11.0%. The 2022 Behavioral Risk Factor Surveillance System addressed COVID (positive test) and long COVID (symptoms lasting [≥]3 months) in a population-based sample from each state and DC. Results for 385,617 adults indicated 34.4% had ever had COVID, 21.9% of whom reported long COVID, representing 7.4% of all adults. State rates ranged from 25.4% - 40.8% for COVID and 4.1%-11.1% for long COVID. Groups with high rates for both included women, younger adults, those with children in the household, plus those reporting obesity, asthma, chronic obstructive pulmonary disease (COPD), diabetes, or cardiovascular disease (CVD). Highest adjusted odds ratios for COVID were 2.34 (95% CI 2.20-2.49) for age 18-24 years vs. age 65+ while for long COVID it was 2.81 (2.53-3.13) for 3+ of the 5 conditions. Most frequently reported problems for those with long COVID were fatigue (26.0%), shortness of breath (18.8%), loss of taste or smell (17.2%), and memory problems (9.9%). Results show the need for state-based data and suggest a focus on younger adults is needed to address COVID and long COVID.

Risk Factors for Post-Traumatic Stress Disorder (PTSD) in COVID Survivors A Cross-Sectional Study (preprint)

The study aimed to investigate the impact of demographic, socio-economic, health, and lifestyle variables on the development of PTSD symptoms in COVID survivors. The study used a cross-sectional design, and data were collected via a standard set of questionnaires from 228 COVID survivors, who required oxygen support and were admitted to Damak COVID hospital from April to October 2021. Descriptive statistics such as frequency and percentage were used to summarize the data and inferential statistics such as chi-square test, Fishers exact test, and Binary logistic regression were used to analyze the data and to infer the overall result from the taken sample. The study found that only three variables, i.e., gender, diabetes, and chronic obstructive pulmonary disorder (COPD), were significant factors that posed a higher threat of PTSD in COVID survivors. Additionally, the study uses model adequacy tests such as Pseudo R2 test, Reliability test and Hosmer and Lemeshow test to validate the model fitted. The study found that only three variables had significant impact PTSD symptoms in COVID survivors. Male patients were more likely to have PTSD symptoms than female patients. The presence of diabetes before or after the infection increased the risk of PTSD. The patients with high blood pressure before COVID and those who developed chronic obstructive pulmonary disorder (COPD) after COVID were more likely to experience PTSD symptoms. The study provides valuable information on the risk factors for developing PTSD symptoms in COVID survivors. This study can contribute to the understanding and growing body of research on the psychological impact of COVID and help healthcare professionals identify patients who are at risk of developing PTSD and provide them with appropriate interventions to prevent or treat PTSD.

Infant and Neonatal Mortality During the Covid-19 Pandemic: An Interrupted Time Series Analysis From Five Low- and Middle-Income Countries (preprint)

Background: The Covid-19 pandemic led to widespread changes to health and social institutions. The effects of the pandemic on neonatal and infant health outcomes in low- and middle-income countries (LMICs) are poorly understood, and nationally representative data characterizing changes to health care and outcomes is only now emerging. Methods: We used nationally representative survey data with vital status and perinatal care information on 2,959,203 children born in India, Madagascar, Cambodia, Nepal, and the Philippines. Using interrupted time series models, we estimated the change in neonatal mortality (death in first 30 days of life) and infant mortality (death in first year of life) following the start of the Covid-19 pandemic, controlling for granular location fixed-effects and seasonality. Findings: We analyzed 2,935,052 births (146,820 deaths) before March 2020 and 24,151 births (799 deaths) after March 2020. We estimated that infant mortality increased by 9.9 deaths per 1,000 live births after March 2020 (95% CI 5.0, 15.0; p<0.01; 22% increase) and neonatal mortality increased by 6.7 deaths per 1,000 live births (95% CI 2.4, 11.1; p<0.01; 27% increase). We observe increased mortality in all study countries. We also estimated a 3.8 percentage point reduction in antenatal care use (95% CI -4.9, -2.7; p<0.01) and a 5.6 percentage point reduction in facility deliveries (95% CI -7.2, -4.0; p<0.01) during the pandemic. Interpretation: Since the start of the Covid-19 pandemic, neonatal and infant mortality are higher than expected in five LMICs. Helping LMICs resume pre-pandemic declines in neonatal and infant mortality should be a major global priority. Funding: National Institute of Child Health and Development (R01HD104835 PI Wagner)

Effectiveness and Optimal Timing of Azvudine in COVID-19 Patients: A Multi-center Retrospective Study in Beijing, China (preprint)

Background: Clinical effectiveness of Azvudine against coronavirus infection and optimal time for initiation of Azvudine treatment to hospitalized COVID-19 patients are not fully understood. Methods: This is a multi-center retrospective cohort study, and five clinical centers of the Chinese People’s Liberation Army General Hospital participated. From omicron pandemics, 6218 hospitalized patients confirmed with COVID-19 from December 10, 2022, to February 20, 2023, were retrieved for this study. After exclusions and propensity score matching , 428 Azvudine recipients and 428 controls were included with a follow-up of 28 days. The primary outcome was all-cause mortality during 28 days of hospitalization, and the secondary outcome was the proportion of patients with clinical improvement up to day 28. Results: The Azvudine group had a lower crude all-cause death rate when compared to the control group (2.82 per 1000 person-days vs. 4.52 per 1000 person-days; HR: 0.63, 95%CI: 0.40-1.00; P=0.038). Notably, the incidence rate of clinical improvement outcome was significantly higher in patients who received Azvudine within 5 days from the onset of symptoms, compared to the control group (Median days: 9 vs. 10; P=0.007). Subgroup analyses showed that chronic lung disease and corticosteroid treatment acted as protective factors (P=0.010; P=0.050). Conclusions: Clinical effectiveness of Azvudine in improving all-cause mortality in COVID-19 patients was seen, and initiation of Azvudine treatment within 5 days of the onset of symptoms was found to be significant. Additionally, the findings revealed the protective effect of Azvudine in COVID-19 patients with chronic lung disease.

[Connotation of Xiao Chaihu Decoction combined with Maxing Shigan Decoction based on severe cases and modern pathophysiological mechanism and application for severe pulmonary infection and acute exacerbation of chronic obstructive pulmonary disease in critical care medicine].

Xiao Chaihu Decoction combined with Maxing Shigan Decoction is a classic herbal formula. All of them are derived from Treatise on Cold Damage(Shang Han Lun) by ZHANG Zhong-jing. This combination has the effects of harmonizing lesser yang, relieving exterior syndrome, clearing lung heat, and relieving panting. It is mainly used for treating the disease involving the triple-Yang combination of diseases and accumulation of pathogenic heat in the lung. Xiao Chaihu Decoction combined with Maxing Shigan Decoction is a classic combination for the treatment of exogenous diseases involving the triple-Yang combination. They are commonly used in exogenous diseases, especially in the north of China. This combination is also the main treatment strategy for coronavirus disease 2019(COVID-19) accompanied by fever and cough. Maxing Shigan Decoction is a classical herbal formula for treating the syndrome of phlegm-heat obstructing the lung. "Dyspnea after sweating" suggests the accumulation of pathogenic heat in the lung. Patients with mild symptoms may develop cough and asthma along with forehead sweating, and those in critical severe may develop whole-body sweating, especially the front chest. Modern medicine believes that the above situation is related to lung infection. "Mild fever" refers to syndromes rather than pathogenesis. It does not mean that the heat syndrome is not heavy, instead, it suggests that severe heat and inflammation have occurred. The indications of Xiao Chaihu Decoction combined with Maxing Shigan Decoction are as follows.(1) In terms of diseases, it is suitable for the treatment of viral pneumonia, bronchopneumonia, lobar pneumonia, mycoplasma pneumonia, COVID-19 infection, measles with pneumonia, severe acute respiratory syndrome(SARS), avian influenza, H1N1 influenza, chronic obstructive pulmonary disease with acute exacerbation, pertussis, and other influenza and pneumonia.(2) In terms of syndromes, it can be used for the syndromes of bitter mouth, dry pharynx, vertigo, loss of appetite, vexation, vomiting, and fullness and discomfort in the chest and hypochondrium. It can also be used to treat alternate attacks of chill and fever and different degrees of fever, as well as chest tightness, cough, asthma, expectoration, dry mouth, wanting cold drinks, feeling agitated, sweating, yellow urine, dry stool, red tongue, yellow or white fur, and floating, smooth, and powerful pulse, especially the right wrist pulse.

[Clinic and functional features of chronic obstructive pulmonary disease after virus-induced acute exacerbations.]

AIM: To establish symptoms, lung function and to evaluate subsequent exacerbations of chronic obstructive pulmonary disease (COPD) during a year after virus-induced COPD exacerbations. MATERIALS AND METHODS: Patients hospitalized with viral (n=60), bacterial (n=60) and viral-bacterial (n=60) COPD exacerbations were enrolled to single-center prospective observational study. COPD was diagnosed according spirography criteria. Viral infection was established in bronchoalveolar lavage fluid or sputum by real-time reverse transcription-polymerase chain reaction for RNA of influenza A and B virus, rhinovirus, respiratory syncytial virus and SARS-CoV-2. Symptoms, lung function, COPD exacerbations were assessed. Patients were investigated at the hospitalization onset and then 4 and 52 weeks following the discharge from the hospital. RESULTS: After 52 weeks in viral and viral-bacterial COPD exacerbations groups the rate of forced expiratory volume in one second (FEV1) decline were maximal - 71 (68; 73) ml/year and 69 (67; 72) ml/year versus 59 (55; 62) ml/year after bacterial exacerbations. Low levels of diffusion lung capacity for carbon monoxide (DLco/Va) - 52.5% (45.1%; 55.8%), 50.2% (44.9%; 56.0%) and 75.3% (72.2%; 80.1%) respectively, of 6-minute walk distance; p<0.001 in relation to bacterial exacerbations. In Cox proportional hazards regression analyses viral and viral-bacterial exacerbations were associated with increased risk of subsequent COPD exacerbations by 2.4 times independent of exacerbations rate before index event and FEV1. In linear regression models the relationships between airflow limitation and respiratory syncytial virus, rhinovirus and influenza virus infection, between low DLco/Va and rhinovirus, influenza virus and SARS-CoV-2 infection. CONCLUSION: COPD after virus-induced exacerbations were characterized by progression of airflow limitation, low DLco/Va, low 6-minute walking test distance, subsequent COPD exacerbations risk.