key: cord-0845251-mqup3o1x
authors: Carvalho-Schneider, Claudia; Laurent, Emeline; Lemaignen, Adrien; Beaufils, Emilie; Bourbao-Tournois, Céline; Laribi, Saïd; Flament, Thomas; Ferreira-Maldent, Nicole; Bruyère, Franck; Stefic, Karl; Gaudy-Graffin, Catherine; Grammatico-Guillon, Leslie; Bernard, Louis
title: Follow-up of adults with non-critical COVID-19 two months after symptoms' onset
date: 2020-10-05
journal: Clin Microbiol Infect
DOI: 10.1016/j.cmi.2020.09.052
sha: 05722c74bd8dc6c34235d91fcc1fdd97cdc020d3
doc_id: 845251
cord_uid: mqup3o1x

OBJECTIVES: To describe the clinical evolution and predictors of symptom persistence during 2-month follow-up in adults with non-critical COVID-19. METHODS: Descriptive clinical follow-up (days 7, 30 [D30] and 60 [D60]) of 150 patients with non-critical COVID-19 confirmed by RT-PCR at Tours University Hospital from March 17 to June 3, 2020, including demographic, clinical and laboratory data collected from the electronic medical records and by phone call. Persisting symptoms were defined by the presence at D30 or D60 of at least one of the following: weight loss ≥ 5%, severe dyspnea or asthenia, chest pain, palpitations, anosmia/ageusia, headache, cutaneous signs, arthralgia, myalgia, digestive disorders, fever or sick leave. RESULTS: At D30, 68% (n=103/150) of patients presented at least one symptom and 66% (n=86/130) at D60, mainly anosmia/ageusia: (59% (n=89/150) at symptom onset, 28% (n=40/150) at D30 and 23% (n=29/130) at D60). Dyspnea concerned 36.7% (n=55/150) patients at D30 and 30% (n=39/130) at D60. Half of the patients (n=74/150) at D30 and 40% (n=52/130) at D60 reported asthenia. Persistent symptoms at D60 were significantly associated with age 40 to 60 years old, hospital admission and abnormal auscultation at symptom onset. At D30, severe COVID-19 and/or dyspnea at symptom onset were additional factors associated with persistent symptoms. CONCLUSIONS: Up to 2 months after symptom onset, two thirds of adults with non-critical COVID-19 had complaints, mainly anosmia/ageusia, dyspnea or asthenia. A prolonged medical follow-up of patients with COVID-19 seems essential, whatever the initial clinical presentation.

Tonnellé, 37000 Tours, France 23 presence at D30 or D60 of at least one of the following: weight loss ≥ 5%, severe dyspnea or 48 asthenia, chest pain, palpitations, anosmia/ageusia, headache, cutaneous signs, arthralgia, 49 myalgia, digestive disorders, fever or sick leave. 50

Results 51

At D30, 68% (n=103/150) of patients presented at least one symptom and 66% (n=86/130) at 52 D60, mainly anosmia/ageusia: (59% (n=89/150) at symptom onset, 28% (n=40/150) at D30 53 and 23% (n=29/130) at D60). Dyspnea concerned 36.7% (n=55/150) patients at D30 and 30% 54 (n=39/130) at D60. Half of the patients (n=74/150) at D30 and 40% (n=52/130) at D60 55 reported asthenia. Persistent symptoms at D60 were significantly associated with age 40 to 60 56 years old, hospital admission and abnormal auscultation at symptom onset. At D30, severe 57 COVID-19 and/or dyspnea at symptom onset were additional factors associated with 58 persistent symptoms. 59

Introduction 64

The most frequent symptoms of COVID-19 at disease onset are cough, fever, asthenia,

Demographic and initial clinical and laboratory data were collected from patients' electronic 113 medical records (consultation or hospitalization). The relevant comorbidities were those 114 considered at high risk for severe COVID-19 (i.e., obesity [body mass index > 30 kg/m 2 ], 115 chronic respiratory disease, dialysis, heart failure or previous cardiovascular event, liver 116 cirrhosis, insulin-dependent diabetes, immunosuppression, pregnancy) (11). 117

The follow-up information was collected by phone at D7, D30 and D60 with use of the 118 specific standardized CRF: 119

• Day 7, after symptom onset, by phone call for an outpatient or from the electronic 120 medical record for an inpatient: dyspnea, fever, weight loss, chest pain, influenza-like 121 symptoms (headache, asthenia, myalgia), digestive disorders (i.e., diarrhea, 122 vomiting), anosmia and ageusia (supplementary material S1). 123

• D30 and D60, after symptom onset, COVID-19 evolution was tracked by use of a 124 specific standardized CRF (supplementary material S2) by phone call: persistence or 125 emergence of sick leave, general condition (worse, same or better than before 126 COVID-19), dyspnea using the mMRC scale, chest pain and triggering factor, 127 palpitations, anosmia and ageusia on an analog scale (from 0, total anosmia/ageusia 128 to 10, normal) at the worse moment of the disease and at 1-month follow-up, 129 Over the first 6 weeks of the epidemic, 293 patients presented to our hospital, as in-or 156 outpatients with RT-PCR-confirmed COVID-19. After excluding 64 ICU patients, 36 157 residents of nursery home or long-term facilities or patients transferred to another healthcare 158 facility, 24 lost-to-follow-up at D30 and 19 deaths, we finally included 150 patients with non-159 critical COVID-19 presentation. Between D30 and D60, 20 more patients were lost-to-160 follow-up (Figure 1) . 161

The male/female ratio was 0.79 (females 56%, n=84/150); the mean age was 49 ± 15 years. 162

More than half of the patients (54%, n=80/150) had at least one comorbid condition and half 163 were healthcare professionals (n=75/150). Despite the 20 patients lost-to-follow-up, 164 demographic characteristics at D30 and D60 were similar (supplementary material S3). 165

The most common symptoms at disease onset were flu-like symptoms (87%, n=129/150), 166 anosmia/ageusia (59%, n=89/150) and fever (51%, n=76/150) ( Table I) . 167

For the follow-up at D30 and D60, phone calls were performed at a mean of 32.7 ± 2.5 days 168

(range 27 to 37) and 59.7 ±1.7 (range 57 to 67) after symptom onset. At D30, 103/150 (68%) 169 patients reported at least one symptom as compared with 86/130 (66%) at D60 (Table II) . 170

However, each symptom was less frequently reported at D60 than D30, except for arthralgia. 171

At D30, 46% (n=73/150) of patients felt still sick or in a worse clinical condition than at 172 COVID-19 onset versus 37% (n=48/130) at D60. 173

The most frequent symptom reported at D30 and D60 was anosmia/ageusia (Table I) . On an 174 analog scale (from 0, total anosmia/ageusia to 10,normal), at the worse moment of the 175 disease, the mean anosmia and ageusia scores were 1.5 ± 2.1 (range 0 to 8) and 1.9 ± 2.5 176 (range 0 to 8), respectively; at D30, the mean scores were 7 ± 2.9 (range 0 to 10) and 7.7 ± 177 2.3 (range 0 to 10); and at D60, they were 7.1 ± 2.3 (range 0 to 10) and 8.3 ± 1.6 (range 5 to 178 10), respectively. 179

Persisting symptoms at D30 were significantly associated with hospital admission at 180 symptom onset, initial clinical presentation, dyspnea and abnormal auscultation ( Figure 2 ). 181

Persisting clinical symptoms at D30 were associated with age class 40-60 years old but not 182 pre-existing comorbid conditions. At D60, the associations remained for hospital admission 183 and abnormal auscultation at symptom onset as well as the same age class 40-60 years old. 184

This study showed that the medium-term course of 150 patients with mild or moderate 187 COVID-19 was unfavorable: two-thirds of patients still reported symptoms at D30 and D60 188 and more than one-third felt still sick or in a worse clinical condition at D60 than at COVID-189 19 onset. These prolonged symptoms were significantly associated with age 40 to 60 years 190 old, hospital admission at symptom onset, severe COVID-19, and dyspnea or abnormal In our study, at D30, half of the patients still felt sick or in a worse clinical condition than 212 before symptom onset, and 7% reported severe asthenia (3.1% at D60). One-third of the 213 patients had dyspnea and approximately one-sixth had chest pain. This situation is 214 particularly frightening for patients. Rigorous studies with chest explorations seem necessary. 215

Indeed, the evaluation at D30 and D60 was declarative over a phone call, without available 216 physical, biological or imaging assessment. We controlled this potential reporting bias using 217 standardized questionnaires administrated by trained investigators (supplementary data S1 218 and S2). However, subjective complaints are worth the attention and focus of the medical 219 community and need to be taken into account in the medical care. Moreover, several 220 infectious diseases such as primary cytomegalovirus or Epstein-Barr virus infection are 221 known to be associated with persistent symptoms, without necessarily any obvious anomaly 222 on physical examination (20-22). 223

Heavy inflammatory response associated with symptomatic COVID-19 could promote such 224 prolonged convalescence and persisting symptoms. Some authors also suggest the possibility 225 of post-trauma stress disorder after COVID-19, which could contribute to a more prolonged 226 experience of symptoms such asthenia or poor well-being (23,24). These complex tardive 227 psychological disorders have already been shown after acute respiratory distress syndrome 228 (25,26). This hypothesis could not be detailed in our study due to the lack of a reproducible 229 psychological assessment, but should probably be explored. 230

We found prolonged symptoms significantly associated in bivariate analysis with age 40 to 231 60 years old, hospital admission at symptom onset, severe COVID-19, and dyspnea or 232 abnormal auscultation. As patients' baseline characteristics were partially retrospectively 233 collected, data for potentially contributive factors were missing, preventing multivariate 234 J o u r n a l P r e -p r o o f modelling, as the main contributive factors in bivariate analysis (dyspnea, abnormal 235 auscultation) had up to 29% of missing data. However, the findings of the bivariate analysis 236 were clinically relevant. The smoking status was not available, it would have been interesting 237 to look for an association with duration of symptoms (especially anosmia/ageusia or chronic 238 dyspnea). 239

With this observational study allowing the prospective follow-up of 150 patients with non-240 critical COVID-19, we were able to assess the evolution of the disease and demonstrate that 241 even the mildest presentation was associated with medium-term symptoms requiring follow-242 up. Thus, the COVID-19 pandemic will involve a care burden long after its end. 

Baseline 311 Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to 312 ICUs of the Lombardy Region

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