key: cord-1048992-dg3murwy
authors: Zayet, Souheil; Gendrin, Vincent; Klopfenstein, Timothee
title: Natural history of COVID-19: Back to the Basics
date: 2020-11-13
journal: New Microbes New Infect
DOI: 10.1016/j.nmni.2020.100815
sha: 50ee8929b9ab0508703066b8ee40b86a355fe63e
doc_id: 1048992
cord_uid: dg3murwy

nan

Countries across Europe and especially France are seeing a resurgence in coronavirus disease 2019 (COVID-19) cases after successfully slowing down outbreaks earlier this year.

We recently published a study comparing clinical features of COVID-19 and seasonal influenza A/B (1) . In front of this second 'wave', we want to focus only in the natural history of COVID-19, so we present in this correspondence a retrospective and observational study in NFC (Nord Franche-Comté) Hospital as a major French cluster of COVID-19 began on February, the 26th in the near-by Grand-Est region. Between February, 26 th and March, 14 th 2020, we enrolled all adult patients (≥18 years) with confirmed COVID-19. Diagnosis was confirmed by real-time RT-PCR on respiratory samples, mainly nasopharyngeal swabs, sputum, bronchial aspirates or broncho-alveolar lavage fluids for SARS-CoV-2.

We reconstituted the history of evolution and onset of the main symptoms of COVID-19 in 70 patients ([29 males, 41%] with a mean age of 56.7± 19.3 [19-96] years). The mean incubation period (time from contact symptomatic case to illness onset) was 6 ±2.1 [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] days.

Firstly, pain syndrome defined by headache and/or myalgia and/or arthralgia (87%, n=61) appeared as the first manifestation 1.6 day after the onset of the illness (Figure) . Secondly, fever (76%, n=53), followed by cough (80%, n=56) and diarrhea (40%, n=28). In 5 th position, anosmia was described in 37 patients (53%) and began 4.7 (± 1.9 [1-8]) days after infection onset. In our patients, all symptoms persisted 10 (± 4.9 ) days and the duration of fever was 5.5± 4.4 [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] days, however, the mean duration of cough and anosmia was respectively 7.7± 4.3 [1-18] and 7.3± 5 [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] days.

Out of the 70 patients, 28 (40%) had diarrhea. Diarrhea began 4.5 (± 1.8 [1] [2] [3] [4] [5] [6] [7] ) days after infection onset. Only 2 patients (2.8%) had a past history of inflammatory bowel disease. Of these patients with diarrhea, 25 (89.3%) had at least one simultaneous gastrointestinal (GI) symptom other than diarrhea. Twenty-two patients (31.4%) had nausea, 14 patients (20%) had abdominal pain and 2 (2.8%) had vomiting.

Concerning the assessment of this disease, hospitalization and clinical aggravation appeared in the second week. Thirty three patients (47.1%) were hospitalized on day 7 (±3) with a mean duration of hospitalization of 6.9 (± 5.8 ) days. On admission, the mean oxygen saturation was 93.16 ±3.46 [85-98] %. In our case study, 23 patients (32.9%) required oxygen therapy 6.7 (± 4.1 [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] ) days from illness onset. The recommended target saturation range for these patients was 94 (±2) and 94 (±2) in patients with COPD.

Fifteen patients had a respiratory rate ≥22/min on day 9 (±0.8) and only 8 patients (15%) were admitted or transferred in an ICU on day 10 (±2.7) with a mean duration of hospitalization in ICU of 7.9 (± 6.6 [2-21]) days. The mean of oxygen therapy flow was 10.5 L/min in patients admitted in ICU and all of them needed invasive mechanical ventilation.

Among patients with COVID-19, general symptoms appeared in the first plan followed by respiratory, rhinolaryngological and GI symptoms (1) . Actually, most reports so far have put anosmia (new loss of smell in COVID-19) to neurological symptoms instead of rhinolaryngological symptoms (2) . Mucosal inflammation due to SARS-CoV-2 with acute rhinosinusitis can participate in the pathogenesis of anosmia. However, in anosmia related to COVID-19, a neurotropism of SARS-CoV-2 should was proven; the assumptions include an invasion of the olfactory receptors or damage of the first cranial nerves in the nasal cavity cell membrane and/or central lesion.

The timeline of symptoms onset is explained by the pathophysiology of this coronavirus. The entry of SARS-CoV-2 into human host cells is mediated mainly by a cellular receptor angiotensin-converting enzyme 2 (ACE2), which is expressed in human airway epithelia, lung parenchyma and secondary in small intestine cells, sensory receptors and neural system (3).

In a systematic review and meta-analysis, Cheung et al. showed that SARS-CoV-2 RNA was detected in stool samples from 48% patients -even in stool collected after respiratory samples tested negative, which concludes that stool samples are highly contagious in patients with COVID-19-even during patient recovery (4).

Finally, medical publications reported a 'second-week crash' among COVID-19 patients. SARS-CoV-2 induces excessive and prolonged cytokine/chemokine responses in some infected individuals, known as the cytokine storm (5). The severe deterioration of these patients requires monitoring during the second week of COVID-19 course. 

Clinical features of COVID-19 and influenza: a comparative study on Nord Franche-Comte cluster. Microbes Infect

Can symptoms of anosmia and dysgeusia be diagnostic for COVID-19? Brain Behav

Renin-Angiotensin-Aldosterone System Inhibitors in Patients with Covid-19