Lombardy, Italy: COVID-19 second wave less severe than the rst? A preliminary investigation

Andrea Borghesi (  andrea.borghesi@unibs.it ) Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, ASST Spedali Civili of Brescia https://orcid.org/0000-0002-4761-2923 Salvatore Golemi Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, ASST Spedali Civili of Brescia Nicola Carapella Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, ASST Spedali Civili of Brescia Angelo Zigliani Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, ASST Spedali Civili of Brescia Davide Farina Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, ASST Spedali Civili of Brescia Roberto Maroldi Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, ASST Spedali Civili of Brescia


Introduction
Italy is one of the countries that has been most affected by the coronavirus disease  pandemic, and Lombardy is the region of Italy with the highest number of infected patients [1]. On October 30, 2020, the overall number of con rmed COVID-19 cases in Lombardy was 186825, corresponding to about 30% of all cases in Italy [1].
During the COVID-19 rst wave, the peak incidence in Italy was reached on March 21, 2020 [1]. After a progressive and signi cant descent, since late August 2020, the infections have started to rise again.
On March 21, 2020, the number of new severe acute respiratory syndrome coronavirus 2 (SARS-  infections in Italy was 6557. On October 30, 2020, the number of new SARS-CoV-2 infections was 31084 [1]. However, on March 21, the number of newly hospitalized patients with SARS-CoV-2 infection was 1890, with a hospitalization rate (HR) of 28.8% (10.7% in intensive care units), whereas the number of new hospitalized patients with SARS-CoV-2 infection on October 30 was 1125 with a HR of 3.6% (8.4% in intensive care units) [1]. In addition, while on March 21, the number of new deaths was 793 with a daily case fatality rate (dCFR, calculated as the reported number of new COVID-19 deaths divided by the total number of positive cases) of 1.8 %, the number of new deaths on October 30 was 199 with a dCFR of 0.06% [1].
Similarly, on March 21, the daily HR and dCFR in Lombardy were 17.4% and 3%, respectively, whereas the daily HR and dCFR on October 30 were 4.1% and 0.06%, respectively [1].
The thing worth highlighting is that Lombardy had a signi cantly higher dCFR than the rest of Italy only in the rst COVID-19 wave.
According to these preliminary data, it would appear that in Italy, especially in Lombardy, the COVID-19 second wave is less severe (reduced daily HR) and deadly (reduced dCFR) than the rst one was. In particular, it should be stressed that in Lombardy the dCFR in the COVID-19 second wave (calculated on October 30) was about 50 times lower than in the rst one (calculated on March 21). However, this difference could be affected by several factors, including the different number of swabs performed in the two waves. In fact, while on March 21, the number of nasal/pharyngeal swabs was 26336 (with a 24.9% positivity rate), the number of nasal/pharyngeal swabs on October 30 was 215085 (with a 14.5% positivity rate) [1]. Therefore, it is not yet clear whether the COVID-19 second wave in Italy, speci cally in Lombardy, is less severe and deadly than the rst one.
Considering the close relationship between pulmonary involvement, in-hospital mortality [2,3], and the need for ventilatory support [3,4], the main purpose of this study was to quantify the radiographic severity of COVID-19 pneumonia during the second wave and compare it with that of the rst one. In addition, to further test whether the severity of the second wave is indeed lower than that of the rst wave, we also compared the use of mechanical ventilation (MV) in the two waves.

Materials And Methods
To quantify and compare the radiographic severity of COVID-19 pneumonia in both waves, we selected two independent groups of hospitalized patients with SARS-CoV-2 infection (con rmed by real-time polymerase chain reaction). The rst group consisted of the rst 100 male patients with COVID-19 admitted to our hospital during the rst wave. The second group consisted of 100 consecutive male patients with COVID-19 admitted to our hospital during the second wave, from August 21 to October 26, 2020. For this study, we decided to enlist only Caucasian male patients over the age of fty, as the literature reports that this subgroup of the population is more likely to develop severe lung disease [5]. Patients with previous interstitial lung disease or lung resection were excluded from this analysis. The selected patients, retrospectively obtained through a search on our departmental digital archive, were also divided into four groups according to age: 50-59 years (group A), 60-69 years (group B), 70-79 years (group C), and ≥ 80 years (group D).
The radiographic severity of COVID-19 pneumonia was assessed using a dedicated chest X-ray (CXR) scoring system (Brixia score) [6]. For each patient, only the CXR examination showing the worst pneumonia was considered for comparison. The frontal chest projection of these examinations was independently evaluated by a thoracic radiologist (A.B.) with 15 years of experience in thoracic imaging who assigned the appropriate Brixia score. In addition, we also compared the use of MV in the two waves.

Statistical analysis
The data are presented as numbers (%) or as median and interquartile range (IQR), because the Brixia scores in both waves were not normally distributed. The Mann-Whitney U test was used to compare the Brixia scores between the rst and second waves. The chi-square test was used to analyze signi cant differences in the frequency of MV use between the two waves. In addition, the Mann-Whitney U test was also used to compare the Brixia scores in the group of patients who needed MV. Statistical analysis was performed using MedCalc® Statistical Software version 19.5.1 (MedCalc Software Ltd, Ostend, Belgium), and p values <0.05 were considered statistically signi cant.

Results
In the rst wave, the Brixia score ranged from 1 to 16 (median, 10; IQR, 7.5-13). In the second wave, the Brixia score ranged from 0 to 14 (median 5; IQR, 2-8). The Brixia score was signi cantly higher in the rst wave than in the second wave (p < 0.001). The Brixia scores of groups A, B, C, and D were also signi cantly higher in the rst wave than in the second wave (Table 1, and Fig. 1).
In addition, in the rst wave 35/100 (35%) patients required the MV, whereas 21/100 (21%) patients required MV in the second wave (p = 0.028). With regard to this group of COVID-19 patients, the Brixia score was signi cantly higher in the rst wave than in the second wave (p < 0.001) ( Table 1).

Discussion
The much-heralded second wave of COVID-19 has arrived in Italy [7][8][9]. Right now, one of the most challenging questions about COVID-19 in Italy is whether the second wave will be less severe than the rst. Currently, the answer to this question remains open, as the published data on COVID-19 in Italy were obtained almost exclusively from the rst wave [10].
To the best of our knowledge, this is the rst study to assess and compare the radiographic severity of COVID-19 pneumonia and the use of MV in the two waves.
In our study sample, we found that the CXR severity index of COVID-19 pneumonia and the frequency of MV use was signi cantly lower in the second wave than in the rst wave.
Of course, we realize that the differences between the two COVID-19 waves could be in uenced by several factors, such as the different number of swabs performed, the improved patient treatment, the different season (late winter/early spring for the rst wave, late summer/early autumn for the second wave), and the widespread use of face masks [14]. However, in our opinion, these factors cannot fully justify the results of this preliminary investigation.
Another thing worth pointing is that, in our study, the patients who required MV had a signi cantly lower Brixia score in the second wave than in the rst wave. From a clinical point of view, this could indicate a different (improved) management of patients with acute respiratory failure for the increased availability of ventilators.
Our study has some limitations. First, the retrospective nature of our analysisSecond, the relatively large sample (100 patients per group); however, we enrolled only hospitalized male patients over the age of 50.
Third, the lack of comparison with the nal outcome (since we are at the beginning of the COVID-19 second wave), and the fact that in the second patient group this data was collected in a relatively small number of cases.
In conclusion, this study seems to con rm that the COVID-19 second wave is less severe than the rst one. Although preliminary, this information is of particular interest not only for clinicians but also for the general population in Italy, as it allows us to look to the near future with less pessimism.

Declarations Funding
The author states that this work has not received any funding Compliance with ethical standards

Con ict of interest/Competing interests
The authors declare that they have no con ict of interest Ethical standards All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation and with the 2013 version of the Declaration of Helsinki. This preliminary investigation was noti ed to our local ethics committee (Ethics Committee of Brescia) as a retrospective analysis. Given the retrospective nature of this analysis, performed with data collected in an anonymous manner, and in accordance with the current legislation, the need for informed consent was waived.  MV, group of patients who needed mechanical ventilation