The main result of our study was the long duration of the disease. It took 31 days from the symptoms onset date, for symptomatic patients, or the laboratory confirmation date, for asymptomatic patients, until the second negative sample.
Our national cohort reached 1,030 COVID-19 infected patients. It is a relatively young population with almost patients under 55 years of age. In the literature, a mean age between 48 and 55 years was reported (6, 14-17). For the gender, there was no predominance of men or women. The number of imported cases was higher than the number of native cases until 03/18/2020. The trend reversal (native cases vs imported cases) was evident from 03/21/2020 which implied an increase in horizontal transmission (5).
Most of cases were mild as evidenced by relatively low ICU admissions and a high number of asymptomatic patients with mild symptoms that do not require treatment in a hospital structure. In fact, the proportion of mild and asymptomatic cases versus severe and fatal cases for COVID-19 infection is currently still unknown. According to a Chinese report publishing all confirmed, suspected, and asymptomatic cases in China, 80% of infections were mild and could recover at home (18). Concerning clinical presentation of COVID-19 disease, the common symptoms reported by symptomatic patients were cough, fatigue and fever in nearly half of cases and headache in 35 % of cases, which was consistent with general symptoms of viral infection. Similar symptoms were described in several case series (6, 15, 19). One out of three symptomatic patients reported loss of smell and/or taste. This type of disturbance was widely reported in the literature specially among patients with mild and moderate forms of coronavirus disease (20, 21).A multicenter European study showed that 85.6% and 88.0% of patients reported olfactory and gustatory dysfunctions (22).
The median duration of illness was estimated to be 31 days counting from the day of onset symptoms for symptomatic patients and from confirmation date for asymptomatic patients. This estimation for illness duration was long. In a recent Singapore study, similar results were recorded. It indicated that by day 15 from onset of illness, only 30% of all COVID-19 patients were PCR-negative by nasopharyngeal swab; this rose to 95% by day 33 (23). According to these results, the duration of viral shedding may extend to a month and sometimes longer for a small group of patients. Current guideline suggested two consecutive negative RT-PCR test results is one of the criteria for hospital discharge or discontinuation of isolation. However, a high false negative rate of viral test was reported and some patients experienced a “turn positive” of nucleic acid detection by RT-PCR test for SARS-CoV-2 after two consecutive negative results, which may be related to the false negative of RT-PCR test and prolonged nucleic acid conversion (24, 25). The Singapore study indicates also that viable virus was not found after the second week of illness despite the persistence of PCR detection of RNA(23). It is, then, important to note that traces of virus detected by RT-PCR were not necessarily correlated with the ability of transmission.
In addition, a recent Canadian study demonstrate that infectivity as defined by growth cell culture were most likely between days one and five (26). These data indicate that even viral RNA detection may persist in some patients, such persistent RNA detection represent non-viable virus and such patients are non-infectious(23). These findings are consistent with the new WHO recommendations for discontinue transmission-based precautions (including isolation) and release from the COVID-19 care pathway with 10 days after symptom onset, plus at least 3 days without symptoms for symptomatic patients and 10 days after test positive for asymptomatic patients (27). These new recommendations should be taken in a count to adapt strategy to discontinue isolation of COVID-19 patients in our country.
Cox regression model showed that younger patients recover faster compared to elderly patients. Similar findings were also reported in literature (28, 29). In fact, many studies found a high proportion of severe cases and fatality rate among elderly patients with COVID-19 (16, 30-33).
Based on the result of this study, being a healthcare worker was showed to be significantly associated to a lower median time to viral clearance after onset of symptoms. This finding could be explained by the fact that the healthcare workers' monitoring and control was different from that of other COVID-19 patients and that the deadlines for carrying out the control samples were shorter. Indeed, the COVID-19 monitoring and control protocol adopted by the Tunisian health authorities was inspired from the recovery criteria of the European center for disease prevention and control (ECDC) documents (34). This protocol consists in carrying out a control sample for asymptomatic patients after 14 days from the date of confirmation. For symptomatic ones, if the fever or any other signs persist beyond 14 days, the control sample was postponed for 3 days after the disappearance of the last sign. These deadlines are not respected for healthcare staff involved in the clinical management of COVID-19 patients. Healthcare workers infected with COVID-19 follow a closer control protocol, which may explain the faster time to viral clearance among them.
Results showed that the place of isolation is playing a significant role in survival time to recovery from COVID-19 infection. According to the output of the cox model, COVID-19 patients in self-isolation at home are almost three times more likely to recover faster than those in dedicated COVID-19 centers. In fact, the Tunisian strategy was based in the first phase of the epidemic on the isolation of confirmed COVID-19 cases at home or in dedicated centers and to hospitalize only serious cases requiring special care. Afterwards, given the registration of an increasing number of secondary cases among the close contacts of confirmed patients, the health authorities decided to create specialized centers to isolate COVID-19 patients in order to limit community transmission. The delay in recovery for COVID-19 patients isolated in COVID-19 centers compared to those in self-isolation at home could be explained by the fact that patients do not respect self-isolation inside these centers leading sometimes to mass gatherings. This promiscuity inside the dedicated centers for infected people may thus promote the maintenance of viral load. Symptomatic patients seem also to have slower recovery duration.
This study has some limitations. There was a lack in some clinical information such as comorbidities and vital signs (heart rate, respiration rate, blood pressure etc). In addition, since we used phone interview, information concerning, biological and radiological data were not available for patients who have been hospitalized.