Comparison of the first and second waves of coronavirus disease in Toulouse, France.

We conducted a retrospective Covid-clinic-Toul cohort study at Toulouse university hospital, in southern France (2800 beds, tertiary hospital covering an area of about 3 million inhabitants) and selected hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia from September 1st, 2020 to October 31st, 2020. We compared their demographics, clinical, biological and radiological features, as well as unfavorable outcome (admission in an intensive care unit, mechanical ventilation, death) at Day 14 after admission to those of hospitalized patients during the 1st wave (March 11, 2020 to April 20, 2020).

Like many other European countries, France faced a second wave of Coronavirus 2019 (COVID-19) pandemic from September to November 2020 [1]. A number of studies have compared the epidemiological and clinical features of hospitalized patients with COVID-19 during the first and second wave, mostly in Italy [2], [3], [4], [5], [6]. In addition, a few studies have assessed whether the characteristics and outcomes of hospitalized patients with COVID-19 changed in the second phase of the epidemic due to the evolution of healthcare system organization, patient demographics, and/or progress in disease management in France/other European countries. In particular, several randomized controlled trials conducted during the first wave highlighted the beneficial effects of early administration of glucocorticoids for critically ill COVID-19 patients [7].

The Covid-clinic-Toul cohort records data about all patients hospitalized for SARS-CoV-2 infection at Toulouse University hospital. The first group consisted of all hospitalized patients with SARS-CoV-2 infection confirmed by real-time polymerase chain reaction (RT-PCR) between March 11th 2020 and April 20th 2020 [8]. The second group consisted of all patients hospitalized with COVID-19 from September 1st to October 31st 2020. All patients, or their representatives for those not able to understand the purpose of the study, were informed by a letter given at admission to hospital and/or sent to their place of residency. The cohort was approved by institutional review board (n°RnIPH 2020-31), in accordance with the French data protection authority (MR004, Commission Nationale de l’Informatique et des Libertés, CNIL).

We collected demographics, clinical, laboratory, radiological (description of chest computed tomography–CT scans), treatment data within the first 24 hours after admission, exposure to corticosteroids during the first 14 days after admission, as well as outcome at Day 14 after admission. The primary outcome was composite, including admission to ICU, need for mechanical ventilation and death occurring during the 14 days after admission to the hospital.

The results of comparison between the first (n  = 263) and the second (n  = 340) wave regarding patient characteristics, comorbidities, biological data and outcome are detailed in Table 1 . During the second wave, patients were older (median age: 73 vs. 65 years, P  < 0.0001). They were also more likely to have comorbidities (92.9% had at least 1 comorbidity vs. 86.3%, P  = 0.007), such as hypertension (58.5% vs. 39.5%, P  < 0.0001), diabetes (30.3% vs. 19.8%, P  = 0.003) and cardiovascular diseases (25.9% vs. 13.3%, P  = 0.0001). Duration of symptoms from onset to admission was shorter in the second phase of the epidemic (median duration 5.0 vs. 7.0 days, P  < 0.0001). Need for oxygen therapy at admission was more frequent (69.4% vs. 44.8%, P  < 0.0001).

Table 1

Comparison of patients hospitalized for a SARS-CoV-2 infection proven by RT-PCR included in the Covid-Clinic-Toul cohort between March 6th, 2020 and April 21th, 2020 (first wave) and between September 1st, 2020 and October 30th, 2020 (second wave).

Variables	All patients included in the cohort			Patients with aggravation criteria at day 14 after hospital admission
	First wave n = 263	Second wave 2020 n = 340	P-value	First wave n = 122	Second wave n = 140	P-value
Age
Median (IQR), years	65 (54–76)	73 (58–85)	<0.0001	68 (58 – 78)	71 (59–82)	0.2
Age ≥ 65 years, n (%)	132 (50.2)	220 (64.7)	0.0003	69 (56.6)	89 (63.6)	0.2
Men, n (%)	155 (58.9)	202 (59.4)	0.9	40 (32.8)	45 (32.1)	0.9
Comorbidities
≥1 comorbidity, n (%)	227 (86.3)	316 (92.9)	0.007	109 (89.3)	133 (95.0)	0.09
Overweight (BMI: 25–30 kg/m2), n (%)a	88/244 (36.1)	103/310 (33.2)	–	43 (36.4)	38 (30.2)	–
Obesity (BMI > 30 kg/m2), n (%)a	69/244 (28.3)	101/310 (32.6)	–	40 (33.9)	48 (38.1)	–
Overweight or obesity, n (%)a	157/244 (64.3)	204/310 (65.8)	0.7	83 (68.0)	86 (61.4)	0.7
Hypertension, n (%)	104 (39.5)	199 (58.5)	<0.0001	56 (45.9)	94 (67.1)	0.0005
Diabetes, n (%)	52 (19.8)	103 (30.3)	0.003	30 (24.6)	46 (32.9)	0.1
Cardiovascular disease, n (%)	35 (13.3)	88 (25.9)	0.0001	19 (15.6)	42 (30.0)	0.006
Cerebrovascular disease, n (%)	17 (6.5)	29 (8.5)	0.3	8 (6.6)	11 (7.9)	0.7
Chronic lung disease, n (%)	57 (21.6)	76 (22.4)	0.8	30 (24.6)	35 (25.0)	0.9
Chronic kidney disease, n (%)	24 (9.1)	45 (13.2)	0.1	12 (9.8)	23 (16.4)	0.1
Chronic liver disease, n (%)	2 (0.8)	2 (0.6)	–	2 (1.6)	1 (0.7)	–
Malignancy <5 years, n (%)	27 (10.3)	34 (10.0)	0.9	15 (12.3)	14 (10.0	0.6
Immunosuppression, n (%)	25 (9.5)	32 (9.4)	1	16 (13.1)	19 (13.6)	0.9
Current smokers, n (%)a	11/115 (9.3)	15/174 (8.6)	–	7/51 (13.7)	7/69 (10.1)	–
Signs and symptoms
Crackling, n (%)a	156 (62.9)	234 (72.2)	0.018	77 (68.1)	94 (72.9)	0.4
Time from first symptoms to admissiona, median (IQR), days	7 (4–10)	5 (2–8)	<0.0001	7 (4 –10)	5 (2–8)	<0.0001
Vital signs at admissiona
Temperature, median (IQR), Celsius degreesa	37.8 (37.0–38.5)	37.6 (36.9–38.4)	–	37.9 (37.1–38.7)	38.0 (37.1–38.6)	–
Respiratory rate, median (IQR), by minutea	22 (19–27)	22 (18–28)	–	24 (20–30)	24 (20–30)	–
Respiratory rate ≥22 by minute, n (%)	147 (58.6)	167 (54.2)	0.3	80 (66.7)	78 (62.9)	0.5
Oxygen saturation ≤ 92% (without oxygen therapy), n (%)a	58/202 (28.7)	58/160 (36.3)	–	41/78 (52.6)	29/80	–
Oxygen saturation measured with oxygen therapy before admission, n (%)a	59/261 (22.6)	173/333 (52.0)	–	43/121 (35.5)	80/135 (59.3)	–
Oxygen saturation ≤ 92% or measured with oxygen therapy before the admission, n (%)	117/261 (44.8)	231/333 (69.4)	<0.0001	84/121 (69.4)	109/135 (80.7)	0.045
Laboratory findings at admissiona
Platelet count, median (IQR), × 109/La	186 (150–233)	194 (155–244)	–	178 (136–226)	188 (149–230)	–
Platelet count < 150 × 109/L, n (%)	63 (24.9)	70 (20.9)	0.3	43 (35.8)	35 (25.4)	0.0068
C-reactive protein level, median (IQR), mg/La	52.4 (27.0–107.6)	72.7 (35.6–122.0)	–	86.7 (40.0–140.0)	81.0 (47.0–134.0)	–
C-reactive protein level > 50 mg/L, n (%)	131 (51.6)	215 (65.2)	0.0009	77 (65.3)	96 (73.3)	0.2
Creatinine level, median (IQR), μmol/La	80 (66–97)	83 (67 –112)	–	84 (69–111)	89 (71–123)	–
Chest CT scan at admission	253 (96.2)	332 (97.6)	–	120 (100)	135 (96.4)	–
Chest CT scan severity score
Uninterpretable, n (%)	0 (0)	1 (0.3)	–	0 (0)	1 (0.7)
No typical sign of COVID–19, n (%)	10 (4.0)	20 (5.8)	0.001	4 (3.3)	6 (4.4)	0.4
Mild, n (%)	34 (13.4)	86 (25.3)		13 (10.8)	26 (19.3)
Moderate, n (%)	139 (54.9)	139 (40.9)		46 (38.3)	45 (33.3)
Severe, n (%)	64 (25.3)	82 (24.1)		51 (42.5)	53 (39.3)
Critical, n (%)	6 (2.4)	4 (1.2)		6 (5.0)	4 (3.0)
Treatment administered during the first 24 hours after admission
Oxygen therapy, n (%)	212 (80.6)	292 (85.9)	0.08	116 (95.1)	132 (94.3)	0.8
Antibiotics, n (%)	165 (62.7)	246 (72.4)	0.01	103 (84.4)	110 (78.6)	0.2
Corticosteroids, n (%)	–	99 (29.2)	–	–	51 (36.4)	–
Remdesivir, n (%)	1 (1.9)	4 (1.2)	–	1 (0.8)	5 (3.6)	–
Corticosteroids administered during the first 14 days after admission, n (%)	–	225 (66.4)	–	–	120 (85.7)	–
Detailed outcomes at Day 14 after admission
Composite outcome, n (%)	122 (46.4)	140 (41.2)	0.2	122 (100)	140 (100)	–
Admission to ICU, n (%)	111 (42.2)	120 (35.3)	0.08	111 (91.0)	120 (85.7)	–
Mechanical ventilation, n (%)	61 (23.2)	35 (10.3)	<0.0001	61 (50.0)	35 (25.0)	–
Death, n (%)	19 (7.2)	33 (9.7)	0.3	19 (15.6)	33 (23.6)	–
Discharged, n (%)	154 (58.6)	223 (65.6)	0.08	34 (27.9)	50 (35.7)	0.2

BMI: body mass index; CT: computed tomography; ICU: intensive care unit; IQR: interquartile range; RT–PCR: reverse transcriptase polymerase chain reaction.

Missing values: For patients included between 6th March to 21st April 2020: Body Mass Index, n = 19; current smoker, n = 148; time from first symptoms to admission, n = 2; temperature, n = 7; respiratory rate, n = 12; oxygen saturation, n = 2; platelet count, n = 10; C-reactive protein, n = 9; creatinine level, n = 6. Missing values: For patients included between 1st September 2020 and 30th October 2020: Body Mass Index, n = 30; current smoker, n = 166; crackling, n = 16; time from first symptoms to admission, n = 6; temperature, n = 19; respiratory rate, n = 12; oxygen saturation, n = 7; platelet count, n = 5; C-reactive protein, n = 10; creatinine level, n = 5.

Patients of the second wave more frequently had a C-reactive protein level > 50 mg/L (65.2% vs. 51.6%, P  = 0.0009). Patients admitted during the second wave more frequently received antibiotic treatment during the first 24 hours after admission (72.4% vs. 62.7%, P  = 0.01). Two hundred and twenty-five patients (66.4%) received corticosteroids within the first 14 days after admission.

Compared to the first wave, we observed a trend toward a lower proportion of patients requiring ICU admission because of the development of organ dysfunction and/or acute respiratory distress syndrome during the first 14 days of hospitalization (35.3% vs. 42.2%, P  = 0.08) and a significant decrease in the proportion of patients who received invasive mechanical ventilation (10.3% vs. 23.2%, P  < 0.0001). However, case-fatality at D14 was similar between the two waves (9.7% vs. 7.2%, P  = 0.3).

Data from the second wave indicated a demographic shift toward an older population with more comorbidities, and no decrease of mortality rate in comparison with the first wave, despite a shorter time from disease onset to admission. These changes in demographics may explain the lower frequency of ICU hospitalizations and mechanical ventilation due to treatment limitations in old and comorbid patients.

The differences between the two COVID-19 waves could be influenced by other factors. In the first phase of the epidemic, hospitals were overwhelmed, and some of oldest and most severely impaired patients were neither tested nor admitted to hospital and died at home or in long-term care facilities. The organization of care improved in the second phase of the epidemic, as did knowledge about COVID-19 diagnosis and treatment, potentially leading to more accurate diagnosis and better treatment. During the first period, patients were less likely to be treated with steroids and more likely to receive antivirals that may not have been effective against COVID-19, and could have been harmful [9]. Similarly, the use of high-flow nasal oxygen therapy was less prevalent in the first wave [10] and prevention of blood clots had changed. All these factors may have improved survival in COVID-19 patients and led to a stable mortality rate despite increased admission of older and more vulnerable patients.

This cohort exhibits a number of epidemiological results: higher frequency of comorbidities and older patients in comparison with the first wave. Interestingly, the need for mechanical ventilation and ICU admission was less frequent, but due to the aforementioned demographic shift, no decrease of mortality was observed.

Human and animal rights

The authors declare that the work described has not involved experimentation on humans or animals.

Informed consent and patient details

The authors declare that this report does not contain any personal information that could lead to the identification of the patient(s) and/or volunteers.

Disclosure of interest

The authors declare that they have no competing interest.

Funding

This work did not receive any grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author contributions

All authors attest that they meet the current International Committee of Medical Journal Editors (ICMJE) criteria for Authorship

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Margaux Lafaurie and Aurelie Jourdes. The first draft of the manuscript was written by Aurelie Jourdes and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.