Inhaled CO2 concentration while wearing face masks: a pilot study using capnography.

None of the available evaluations of the inhaled air carbon dioxide (CO2) concentration, while wearing face masks, used professional, real-time capnography with water-removal tubing. We measured the end-tidal CO2 using professional side-stream capnography, with water-removing tubing (Rad-97 capnograph), at rest, (1) without masks, (2) wearing a surgical mask, and (3) wearing a FFP2 respirator, in 102 healthy volunteers aged 10-90 years, from the general population of Ferrara province, Italy. The inhaled air CO2 concentration was then computed as: ((mask volume x end-tidal CO2) + ((tidal volume - mask volume) x ambient air CO2)) / tidal volume). The mean CO2 concentration was 4965{+/-}1047 ppm with surgical masks, and 9396{+/-}2254 ppm with FFP2 respirators. The proportion of the sample showing a CO2 concentration higher than the 5000 ppm acceptable exposure threshold recommended for workers was 40.2% while wearing surgical masks, 99.0% while wearing FFP2 respirators. The mean blood oxygen saturation remained >96%, and the mean end-tidal CO2 <33 mmHg. Adjusting for age, gender, BMI, and smoking, the inhaled air CO2 concentration significantly increased with increasing respiratory rate (with a mean of 10,143{+/-}2782 ppm among the participants taking 18 or more breaths per minute, while wearing FFP2 respirators), and was higher among the minors, who showed a mean CO2 concentration of 12,847{+/-}2898 ppm, while wearing FFP2 respirators. If these results will be confirmed, the current guidelines on mask-wearing could be updated to integrate recommendations for slow breathing and a more targeted use when contagion risk is low.

Risk of SARS-CoV-2 reinfection 18 months after primary infection: population-level observational study.

Current data suggest that SARS-CoV-2 reinfections are rare, but uncertainties remain on the duration of the natural immunity, its protection against Omicron variant, finally the impact of vaccination to reduce reinfection rates. In this retrospective cohort analysis of the entire population of an Italian Region, we followed 1,293,941 subjects from the beginning of the pandemic to the current scenario of Omicron predominance (up to mid-January 2022). After an average of 334 days, we recorded 260 reinfections among 84,907 previously infected subjects (overall rate: 0.31%), two hospitalizations (2.4 x100,000), and one death. Importantly, the incidence of reinfection did not vary substantially over time: after 18-22 months from the primary infection, the reinfection rate was still 0.32%, suggesting that protection conferred by natural immunity may last beyond 12 months. The risk of reinfection was significantly higher among the unvaccinated subjects, and during the Omicron wave.

The impact of COVID-19 on the oncologic outcomes of 3236 patients undergoing ColoRectal Cancer surgery in Northern Italy in 2019 and 2020 (COVID-CRC): results of a multicentric comparative cohort study.

ObjectiveThis study compared all patients undergoing surgery for colorectal cancer in 20 hospitals of Northern Italy in 2019 versus 2020, in order to evaluate whether COVID-19-related delays in the execution of colorectal cancer screening resulted in more advanced cancers at diagnosis and worse clinical outcomes. DesignA retrospective multicentric cohort analysis of patients who underwent surgery for colorectal cancer in March-December 2019 (2019) versus March-December 2020 (2020). The independent predictors of disease stage (oncologic stage, associated symptoms, clinical T4 stage, metastasis) and postoperative outcome (surgical complications, palliative surgery, 30-day death) were evaluated using logistic regression. ResultsThe sample consisted of 1755 patients operated in 2019, and 1481 in 2020 (both mean ages 69.6 years). The proportions of cancers with symptoms, clinical T4 stage, liver and lung metastases in 2019 and 2020 were, respectively: 80.8% vs 84.5%; 6.2% vs 8.7%; 10.2% vs 10.3%; and 3.0% vs 4.4%. The proportions of surgical complications, palliative surgery, and death in 2019 and 2020 were, respectively: 34.4%vs 31.9%; 5.0% vs 7.5%; and 1.7% vs 2.4%. At multivariate analysis, as compared with 2019, cancers in 2020 were significantly more likely to be symptomatic (Odds Ratio - OR: 1.36, 95% Confidence Interval - CI: 1.09-1.69), in clinical T4 stage (OR: 1.38; 1.03-1.85), with multiple liver metastases (OR: 2.21; 1.24-3.94), but less likely to cause surgical complications (OR: 0.79; 0.68-0.93). ConclusionsColorectal cancer patients who had surgery between March and December 2020 had an increased risk of more advanced disease in terms of associated symptoms, cancer location, clinical T4 stage, and number of liver metastases. SHORT SUMMARY BOX What is already known about this subject?A specific search regarding the correlation between colorectal cancer oncologic outcomes and COVID-19 showed a few modeling studies which reported the predictions of the potential impact of the diagnostic delays (due to the reduction of the screening programs) on the survival of patients affected by colorectal cancer. However, no study reported any real-life evidence regarding the correlation between the COVID-19 outbreak and the deteriorations of the oncologic outcomes of patients with colorectal cancer. What are the new findings?The present study showed that patients who had surgery for colorectal cancer between March and December 2020 had an increased risk of more advanced disease in terms of associated symptoms, cancer location, clinical T4 stage, and number of liver metastases, than patients who had surgery between March and December 2019. How might it impact on clinical practice in the foreseeable future?The present study confirmed that the backlogs of the screening programs have had, and probably will have, detrimental effects on the oncologic outcomes of patients affected by colorectal cancer. Increased resources should be placed in order to reactivate and enhance the screening programs, and to reduce the risk of colorectal cancer patients to be diagnosed with advanced cancer in the next future.

Magnitude and time-course of excess mortality during COVID-19 outbreak: population-based empirical evidence from highly impacted provinces in northern Italy

BackgroundThe real impact of SARS-CoV-2 on overall mortality remains uncertain and surveillance reports attributed to COVID-19 a limited amount of deaths during the outbreak. Aim of this study is to assess the excess mortality (EM) during COVID-19 outbreak in highly impacted areas of northern Italy. MethodsWe analyzed data on deaths occurred in the first four months of 2020 in health protection agencies (HPA) of Bergamo and Brescia (Lombardy), building a time-series of daily number of deaths and predicting the daily standardized mortality ratio (SMR) and cumulative number of excess deaths (ED) through a Poisson generalized additive model of the observed counts in 2020, using 2019 data as a reference. ResultsWe estimated 5740 (95% Credible Set (CS): 5552-5936) ED in the HPA of Bergamo and 3703 (95% CS: 3535 - 3877) in Brescia, corresponding to 2.55 (95% CS: 2.50-2.61) and 1.93 (95% CS: 1.89-1.98) folds increase in the number of deaths. The ED wave started a few days later in Brescia, but the daily estimated SMR peaked at the end of March in both HPAs, roughly two weeks after the introduction of lock-down measures, with significantly higher estimates in Bergamo (9.4, 95% CI: 9.1-9.7). ConclusionEM was significantly larger than that officially attributed to COVID-19, disclosing its hidden burden likely due to indirect effects on health system. Time-series analyses highlighted the impact of lockdown restrictions, with a lower EM in the HPA where there was a smaller delay between the epidemic outbreak and their enforcement.

SARS-CoV-2 lethality decreased over time in two Italian Provinces

BackgroundSome experts recently reported that SARS-CoV-2 lethality decreased considerably, but no evidence is yet available. This retrospective cohort study aimed to evaluate whether SARS-CoV-2 case-fatality rate decreased with time, adjusting for several potential confounders. MethodsWe included all subjects diagnosed with SARS-CoV-2 infection in Ferrara and Pescara provinces, Italy. Information were collected from local registries, clinical charts, and electronic health records. We compared the case-fatality rate (after [≥]28 days of follow-up) of the subjects diagnosed during April and March, 2020. We used Cox proportional hazards analysis and random-effect logistic regression, adjusting for age, gender, hypertension, type II diabetes, major cardiovascular diseases (CVD), chronic obstructive pulmonary diseases (COPD), cancer and renal disease. ResultsThe sample included 2493 subjects (mean age 58.6y; 47.7% males). 258 persons deceased, after a mean of 16.1 days of follow-up. The mean age of those who died substantially increased from March (78.1{+/-}11.0y) to April (84.3{+/-}10.2y). From March to April, the case-fatality rate did not decrease in the total sample (9.5% versus 12.1%; adjusted hazard ratio 0.93; 95% Confidence Interval: 0.71-1.21; p=0.6), and in any age-class. ConclusionsIn this sample, SARS-CoV-2 case-fatality rate did not decrease over time, in contrast with recent claims of a substantial improvement of SARS-CoV-2 clinical management. The findings require confirmation from larger datasets. Author summaryO_ST_ABSWhy was this study done?C_ST_ABSO_LISome experts recently reported that SARS-CoV-2 lethality decreased considerably, but no evidence is yet available. C_LI What did the researchers do and find?O_LIWe carried out a retrospective cohort study on 2493 SARS-CoV-2 infected subjects from two Italian provinces, evaluating the potential variation of the case-fatality rate over time. C_LIO_LIFrom March to April, SARS-CoV-2 case-fatality rate did not decrease, overall and in any age-class. C_LI What do these findings mean?O_LIThe therapies and clinical management of SARS-CoV-2 infected subjects did not determine a substantial change of the clinical course of the disease from March to April, 2020. C_LI

Predictors of severe or lethal COVID-19, including Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers, in a sample of infected Italian citizens

AimsThis retrospective case-control study was aimed at identifying potential independent predictors of severe/lethal COVID-19, including the treatment with Angiotensin-Converting Enzyme inhibitors (ACEi) and/or Angiotensin II Receptor Blockers (ARBs). Methods and ResultsAll adults with SARS-CoV-2 infection in two Italian provinces were followed for a median of 24 days. ARBs and/or ACEi treatments, and hypertension, diabetes, cancer, COPD, renal and major cardiovascular diseases (CVD) were extracted from clinical charts and electronic health records, up to two years before infection. The sample consisted of 1603 subjects (mean age 58.0y; 47.3% males): 454 (28.3%) had severe symptoms, 192 (12.0%) very severe or lethal disease (154 deaths; mean age 79.3 years; 70.8% hypertensive, 42.2% with CVD). The youngest deceased person aged 44 years. Among hypertensive subjects (n=543), the proportion of those treated with ARBs or ACEi were 88.4%, 78.7% and 80.6% among patients with mild, severe and very severe/lethal disease, respectively. At multivariate analysis, no association was observed between therapy and disease severity (Adjusted OR for very severe/lethal COVID-19: 0.87; 95% CI: 0.50-1.49). Significant predictors of severe disease were older age (with AORs largely increasing after 70 years of age), male gender (AOR: 1.76; 1.40-2.23), diabetes (AOR: 1.52; 1.05-2.18), CVD (AOR: 1.88; 1.32-2.70) and COPD (1.88; 1.11-3.20). Only gender, age and diabetes also predicted very severe/lethal disease. ConclusionNo association was found between COVID-19 severity and treatment with ARBs and/or ACEi, supporting the recommendation to continue medication for all patients unless otherwise advised by their physicians.