On Reunion Island, a French overseas department of 860,000 inhabitants located in the Southwestern part of the Indian Ocean (SWIO), the first confirmed case of coronavirus disease 19 (COVID-19) was imported by March 11, 2020. Considering the intense air traffic, we hypothesized that importations would be a major source of COVID-19 cases on Reunion Island. It was even more likely given that high-level standard of care, regional organization and policies confer a central role to Reunion Island for receiving air-flight medical evacuations from the SWIO region (Mauritius, Madagascar, Mayotte, and The Comoros).
So far, limited information is available to describe the characteristics of inpatients from insular tropical settings. The Reunionese population is still relatively young but yet strongly affected by obesity (11%), diabetes (9.8%), and dengue, raising fear of increasing severe COVID-19 infections [1], [2], [3].
The purpose of this study was to describe the clinical severity of all COVID-19 inpatients presenting at the referral hospital of SWIO.
The COVID-EPI retrospective cohort study was conducted within Félix Guyon University Hospital, the only referral facility allowed to treat patients with COVID-19 on Reunion Island. Between March 11 and May 10, 2020, we enrolled all consecutive COVID-19 inpatients either diagnosed by a positive SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR) from a nasopharyngeal swab specimen or positive antibodies. We divided our study period into two periods: Stage-1 period (introduction of an emergent pathogen into the territory) for admissions between March 11 and March 24, 2020, and Stage-2 period (start of its autochthonous spread) between March 25 and May 10, 2020 (end of lockdown). Hospitalization policy changed to comply with national and local guidelines according to the stage of the outbreak.
Consent to participate was obtained orally for each patient before enrolment in the cohort after written information had been handed out.
Epidemiological, clinical, sociodemographic characteristics and outcomes were collected from electronic medical records. Length of stay was provided by the Medical Informatics Department, blood group by the French blood establishment, and health insurance status by the administrative department of the hospital.
Clinical outcomes included the length of hospital stay, intensive care unit (ICU) admission, vital status at discharge [4], type of discharge for patients discharged alive, readmission, and vital status on day 28 post admission.
Continuous variables were described using median and interquartile range (IQR) values and categorical variables as percentages. Comparison between Stage-1 and Stage-2 periods were performed using Student's t test or Mann-Whitney test or Chi2 or Fisher's exact test, as appropriate. Two-sided tests and a significance threshold set at p≤0.05 were used. All statistical analyses were performed using the SAS® software (v9.4, SAS Institute, Cary, NC, USA, 2013).
Out of 436 COVID-19 cases diagnosed on the island, 171 (39%) required hospitalization. Among these, 168 were enrolled in the COVID-EPI cohort.
The median age of inpatients was 50 years (IQR: 35-63, range 3-86 years). Half were females, of whom five were pregnant. Eighty-two inpatients (50%) had one or more comorbidities (including age and obesity), 70 (43%) excluding age. The most common comorbidities were hypertension, obesity, and diabetes mellitus (Table 1 ).
Table 1.
Epidemiological and clinical characteristics of 168 inpatients with coronavirus disease 2019 on Reunion Island (March 11–May 10, 2020).
| Total (n = 168) |
Stage 1 (n = 68) March 11- March 24 |
Stage 2 (n = 100) March 25–May 10 |
P-value | |
|---|---|---|---|---|
| Sociodemographic characteristics | ||||
| Age, yearsc | 0.466 | |||
| < 18 y | 4 (2) | 2 (3) | 2 (2) | |
| 18–44 y | 62 (37) | 27 (40) | 35 (35) | |
| 45–54 y | 27 (16) | 13 (19) | 14 (14) | |
| 55–64 y | 38 (23) | 14 (21) | 24 (24) | |
| 65–74 y | 21 (12) | 9 (13) | 12 (12) | |
| Aged ≥ 75 y | 16 (10) | 3 (4) | 13 (13) | |
| Male gender | 86 (51) | 31 (46) | 55 (55) | 0.231 |
| Health insurance (n = 167)b | 161 (96) | 67 (100) | 94 (94) | 0.082 |
| Supplemental health insurance (n = 162) | 0.150 | |||
| Yes | 115 (71) | 52 (78) | 63 (66) | |
| Social benefits for vulnerable population | 28 (17) | 7 (10) | 21 (22) | |
| No | 19 (12) | 8 (12) | 11 (12) | |
| Place of birth (n = 118)c | 0.088 | |||
| Reunion Island | 68 (58) | 26 (54) | 42 (60) | |
| Mainland France | 25 (21) | 15 (31) | 10 (14) | |
| Other Indian Ocean Island | 18 (15) | 4 (9) | 14 (20) | |
| Other | 7 (6) | 3 (6) | 4 (6) | |
| Place of residence (n = 167)c | 0.065 | |||
| Reunion Island | 143 (86) | 61 (91) | 82 (82) | |
| Mainland France | 17 (10) | 6 (9) | 11 (11) | |
| Other (Mayotte and Comoros Islands) | 7 (4) | 0 (0) | 7 (7) | |
| Epidemiological data | ||||
| Imported cases (n = 167) | 132 (79) | 61 (90) | 71 (72) | 0.005 |
| Of which medical evacuation (Yes) | 9 (7) | 0 (0) | 9 (13) | 0.004 |
| Healthcare workers (n = 154)b | 10 (6) | 7 (12) | 3 (3) | 0.048 |
| Contact with positive COVID-19 case (n = 158) | 69 (44) | 26 (39) | 43 (47) | 0.290 |
| Of which household transmission | 42 (61) | 13 (50) | 29 (67) | 0.150 |
| Comorbidities | ||||
| Hypertension | 41 (24) | 14 (21) | 27 (27) | 0.342 |
| Obesity (Body mass index ≥30 kg/m2)b | 23 (14) | 3 (4) | 20 (20) | 0.005 |
| Diabetes mellitus | 23 (14) | 6 (9) | 17 (17) | 0.130 |
| Cardiovascular disease (n = 167)b | 17 (10) | 2 (3) | 15 (15) | 0.017 |
| Cerebrovascular diseaseb | 8 (5) | 2 (3) | 6 (6) | 0.476 |
| Chronic respiratory disease (n = 167) | 22 (13) | 11 (16) | 11 (11) | 0.310 |
| Immunosuppression (n = 167)b | 4 (2) | 0 (0) | 4 (4) | 0.147 |
| Malignancyb | 7 (4) | 0 (0) | 7 (7) | 0.042 |
| Dementia and psychiatric disordersb | 7 (4) | 0 (0) | 7 (7) | 0.042 |
| Number of comorbidities (n = 164) | < 0.001 | |||
| None | 82 (50) | 46 (70) | 36 (37) | |
| ≥ 1 comorbidity | 82 (50) | 20 (30) | 62 (63) | |
| Smoking (n = 162) | 0.045 | |||
| Never | 118 (73) | 50 (75) | 68 (71) | |
| Past | 29 (18) | 15 (22) | 14 (15) | |
| Active | 15 (9) | 2 (3) | 13 (14) | |
| Blood group (n = 76) | 1 | |||
| Blood group O | 25 (33) | 9 (33) | 16 (33) | |
| Blood group A | 37 (49) | 13 (48) | 24 (49) | |
| Other blood groups (B, AB) | 14 (18) | 5 (19) | 9 (18) | |
| Clinical presentation | 0.022 | |||
| Symptomatic | 140 (84) | 61 (90) | 79 (79) | |
| Pauci-symptomatic | 19 (11) | 7 (10) | 12 (12) | |
| Fully asymptomatic | 9 (5) | 0 (0) | 9 (9) | |
| Symptoms at disease onset (n = 159) | ||||
| Fever | 104 (65) | 49 (72) | 55 (60) | 0.128 |
| Dry cough | 91 (54) | 37 (54) | 54 (59) | 0.534 |
| Asthenia | 52 (33) | 18 (26) | 34 (37) | 0.148 |
| Myalgia | 52 (33) | 23 (34) | 29 (32) | 0.795 |
| Headache | 49 (31) | 18 (26) | 31 (34) | 0.305 |
| Dyspnea | 43 (26) | 11 (16) | 32 (35) | 0.008 |
| Ageusia | 38 (23) | 11 (16) | 27 (30) | 0.048 |
| Diarrhea | 34 (21) | 8 (12) | 26 (29) | 0.011 |
| Symptom main locations (n = 159)c | 0.003 | |||
| Upper respiratory tract | 70 (42) | 41 (60) | 29 (32) | |
| Lower respiratory tract | 59 (35) | 18 (27) | 41 (45) | |
| Abdominal | 11 (7) | 2 (3) | 9 (10) | |
| Other | 28 (16) | 7 (10) | 12 (13) | |
| Coinfection with dengue feverb | 3 (2) | 0 (0) | 3 (3) | 0.273 |
| Time, median (IQR a), days | ||||
| between symptom onset and RT-PCR | 4 (2-7) | 3 (2-5) | 5 (2-9) | 0.013 |
| between symptom onset and admission | 5 (3-9) | 4 (3-6) | 7 (4-10) | 0.001 |
| Additional tests | ||||
| Chest X-ray (yes) (n = 167) | 65 (39) | 44 (65) | 21 (21) | < 0.001 |
| Abnormal (n = 59)b | 31 (53) | 20 (45) | 11 (73) | 0.078 |
| 1st chest CT scan (yes) | 68 (40) | 15 (22) | 53 (53) | < 0.001 |
| Abnormalb | 59 (87) | 13 (87) | 46 (87) | 1 |
| Bilateral distribution of patchy shadows or ground glass opacity (n = 67)b | 53 (79) | 12 (80) | 41 (79) | 1 |
| Injected chest CT scan (yes) (n = 166) | 46 (28) | 13 (19) | 33 (34) | 0.039 |
| At least one ECG (n = 166) | 107 (64) | 36 (55) | 71 (71) | 0.030 |
| At least one abnormal (n = 106) | 36 (34) | 7 (19) | 29 (41) | 0.023 |
| QTc on 1st ECG, median (IQRa), ms | 392 (367-420) | 380 (360-417) | 392 (374-420) | 0.313 |
Data is shown as n (column percentages) or median. All p-values refer to comparisons between the two periods using the Mann-Whitney U test for quantitative variables and the Chi2 test for categorical variables. RT-PCR, reverse-transcription polymerase chain reaction; CT scan, computed tomography; ECG, electrocardiogram.
Interquartile range.
Fisher's exact test.
Fisher-Freeman-Halton test.
Stage-2 inpatients were more likely autochthonous than Stage-1 inpatients. However, there were no significant differences between imported and autochthonous cases regarding age, comorbidities, severity of illness, and time from symptom onset to RT-PCR and from symptom onset to admission. Importantly, most imported cases (82%) were permanent residents of the island. Among 159 symptomatic people, the five most common symptoms at onset of illness were fever, dry cough, asthenia, myalgia, and headache.
Median time between fever onset and apyrexia was 9 days (IQR: 6-13 days).
Forty (23%) inpatients had a severe to critical COVID-19 presentation. There was a trend towards more severe forms of COVID-19 in Stage-2 compared with Stage-1 (P = 0.059). None of the patients have been included in an interventional research study protocol (Table 2 ).
Table 2.
Severity of illness, complications, therapeutic and clinical outcomes of 168 inpatients with coronavirus disease 2019 on Reunion Island (March 11–May 10, 2020).
| Total (n = 168) |
Stage 1 (n = 68) March 11- March 24 |
Stage 2 (n = 100) March 25–May 10 |
P-value | |
|---|---|---|---|---|
| Severity of illness (n = 159)b | 0.059 | |||
| Mild | 107 (64) | 49 (72) | 49 (54) | |
| Moderate | 21 (13) | 6 (9) | 15 (16) | |
| Severe | 36 (21) | 13 (19) | 23 (25) | |
| Critical | 4 (2) | 0 (0) | 4 (4) | |
| Complications | ||||
| Anemia | 18 (11) | 2 (3) | 16 (16) | 0.009 |
| Bacterial pneumonia (n = 167) | 15 (9) | 5 (7) | 10 (10) | 0.542 |
| Digestive complicationsa | 11 (7) | 3 (4) | 8 (8) | 0.528 |
| Acute renal failure or extra-renal purificationa | 10 (6) | 1 (2) | 9 (9) | 0.050 |
| ARDSa | 6 (4) | 1 (2) | 5 (5) | 0.403 |
| Pleural effusiona | 6 (4) | 1 (2) | 5 (5) | 0.403 |
| Altered mental statusa | 6 (4) | 2 (3) | 4 (4) | 1 |
| Cardiac rhythm disordersa | 4 (2) | 1 (2) | 3 (3) | 0.648 |
| Pulmonary embolisma | 3 (2) | 1 (2) | 2 (2) | 1 |
| Thrombosisa | 3 (2) | 0 (0) | 3 (3) | 0.273 |
| Cardiac ischemiaa | 3 (2) | 0 (0) | 3 (3) | 0.273 |
| Bacteremiaa | 3 (2) | 0 (0) | 3 (3) | 0.273 |
| Endocarditisa | 2 (1) | 1 (1) | 1 (1) | 1 |
| At least one complication (n = 167) | 50 (30) | 14 (21) | 36 (36) | 0.029 |
| Therapeutic outcomes | ||||
| Pharmaceutical treatment | ||||
| Anticoagulanta | 42 (25) | 4 (6) | 38 (38) | <0.001 |
| Antibiotics | 40 (24) | 10 (15) | 30 (30) | 0.022 |
| Antivirals | 33 (20) | 12 (18) | 21 (21) | 0.591 |
| Steroidsa | 16 (10) | 3 (4) | 13 (13) | 0.106 |
| Highest level of respiratory support (n = 165)b | 0.507 | |||
| None | 125 (76) | 55 (81) | 70 (72) | |
| Oxygen inhalation (nasal cannula/face mask) | 32 (19) | 12 (18) | 20 (21) | |
| High flow oxygen | 2 (1) | 0 (0) | 2 (2) | |
| NIV | 3 (2) | 1 (2) | 2 (2) | |
| IMV | 3 (2) | 0 (0) | 3 (3) | |
| Clinical outcomes | ||||
| ICU admissiona | 17 (10) | 4 (6) | 13 (13) | 0.193 |
| Vital status at discharge (at study end point)b | 1 | |||
| Discharged alive | 166 (99) | 68 (100) | 98 (98) | |
| Deceased | 1 (1) | 0 (0) | 1 (1) | |
| Currently hospitalized | 1 (1) | 0 (0) | 1 (1) | |
| Type of discharge for patients discharged alive (n = 166)a | 0.145 | |||
| Home | 162 (98) | 68 (100) | 94 (96) | |
| Facilities (rehabilitation) | 4 (2) | 0 (0) | 4 (4) | |
| GOS at discharge (n = 167)b | 0.875 | |||
| 1. Death | 1 (1) | 0 (0) | 1 (1) | |
| 2. Persistent vegetative state | 0 (0) | 0 (0) | 0 (0) | |
| 3. Severe disability | 1 (1) | 0 (0) | 1 (1) | |
| 4. Moderate disability | 4 (2) | 1 (1) | 3 (3) | |
| 5. Low disability | 161 (96) | 67 (99) | 94 (95) | |
| Readmitted | 13 (8) | 7 (10) | 6 (6) | 0.307 |
| Vital status at 28 days after admission (n = 167)a | 1 | |||
| Alive | 166 (99) | 68 (100) | 98 (99) | |
| Died | 1 (1) | 0 (0) | 1 (1) |
Data is shown as n (column percentages). All P-values refer to comparisons between the two periods using the Mann-Whitney U test for quantitative variables and the Chi2 test for categorical variables. ARDS, Acute Respiratory Distress Syndrome; NIV, Non-invasive ventilation; IMV, Invasive mechanical ventilation; ICU, Intensive Care Unit; GOS, Glasgow Outcome Scale.
Fisher's exact test.
Fisher-Freeman-Halton test.
The median length of stay was seven days (IQR: 3-13 days). Seventeen (10%) patients required admission to the ICU. One patient died in the ICU, 12 days after admission (death attributable to COVID-19). He was an 82-year-old man with hypertension and chronic kidney failure, who had been medically evacuated from Mayotte Island. Evacuated patients from Mayotte or Comoros Islands (n = 9) more frequently presented with comorbidities (89% vs. 47%; P = 0.034) and were more likely to be admitted to the ICU (33% vs. 9%; P = 0.050).
Our data highlight the low severity of the illness on our territory during the first wave of the COVID-19 epidemic (low infection fatality rate: 0.6%). Several factors may influence SARS-CoV-2 severity here. First, COVID-19 severity can be modulated by age [5]. Compared to some other European hospital-based studies, our population was about 10 to 20 years younger [6], [7], [8]. People under 20 years of age represent 31% of the Reunionese population [9]. Second, the health service has never been overburdened. Postponement of non-urgent care was implemented in the hospital as soon as March 11, 2020 (6 days prior to the national lockdown), thus increasing hospital bed capacity. Treatment has evolved during this period according to new scientific knowledge. In addition, early diagnosis at the time of travel return and systematic monitoring during Stage-1 may have contributed to prevent progression to severe disease.
We observed changes in the clinical presentation of COVID-19 over the study period and a non-significant trend towards more severe forms of the disease in the Stage-2 period that could be explained by an increase in the virulence as the transmission rate grew [10]. However, this hypothesis must be counterbalanced by the fact that hospitalization policy has also evolved over time, voluntarily selecting comorbid and severe patients who consulted later in hospital during the Stage-2 period.
This hospital-based study is one of the first to report exhaustive high-quality data about SARS-CoV-2 infection, from an insular tropical setting of the Indian Ocean. The study is still ongoing, which will allow us to follow the evolution of patients’ characteristics, especially for the South African variant
Ethical approval
An oral non-opposition to participate was obtained for each patient before inclusion in the study and a written information notice was handed out. Patients already discharged from hospital were called over the phone, and the information notice was sent at home. The study was registered at the National Institute for Health Data (French acronym INDS, No. MR0614010420) and was approved by an Institutional Review Board from the French infectious diseases ethics committee (CERC-MIT, No. 2020-043; N°IRB00011642). Collected data complied with the French data protection authority (CNIL MR-004). The review board approved this case series as minimal-risk research using data collected for routine clinical practice.
Consent to participate
An oral non-opposition to participate was obtained for each patient before inclusion in the study and a written information notice was handed out.
Availability of data and materials
The corresponding author (LB) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.
Funding
The authors did not receive any specific grant for this research from funding agencies in the public, commercial, or not-for-profit sectors.
Disclosure of interest
The authors declare that they have no competing interest. The corresponding author confirms that he had full access to all data in the study and had final responsibility for the decision to submit for publication.
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Associated Data
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Data Availability Statement
The corresponding author (LB) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.