A case report of moderate COVID-19 with an extremely long-term viral shedding period in China

Background An ongoing outbreak of novel coronavirus disease 2019 (COVID-19) from Wuhan, China, is currently recognized as a global public health emergency, which has subsequently spread to the rest of China and other countries. The WHO raised the COVID-19 alert to the highest level. The virus is a new highly contagious via human-to-human transmission. The median duration of viral shedding is 20.0 days. We report that the longest duration of viral shedding was 32.0 days from illness onset in a patient with moderate COVID-19 admitted to QianJiang Central Hospital. and including and All clinical symptoms and CT imaging manifestation abnormalities resolved during the course of therapy.


Background
Since the outbreak of coronavirus disease 2019 (COVID-19, previously known as SARS-CoV-2), which was rst reported from Wuhan, China, on 31 December 2019, the causative pathogen has rapidly spread throughout China and around the world in a relatively short period of time. This virus is a positive-sense single-stranded RNA virus belonging to the family Coronaviridae, which is distributed broadly among humans, other mammals, and birds. Most coronaviruses cause a range of mild upper respiratory infections, inducing symptoms of fever, fatigue, and dry cough; some patients present with nasal congestion, runny nose, diarrhoea and shortness of breath [1], but sometimes they exhibit severe acute respiratory syndrome (SARS), coagulation disorders and metabolic acidosis [2].
As of March 7, 2020, the cumulative incidence in mainland China, Hong Kong, and Macau is 80735 cases, of which 67592 cases were diagnosed in Hubei. Additionally, 3045 deaths have been linked to the outbreak, and 19903 cases have been reported in South Korea, Iran, Italy, France, Japan, the United States and other countries [3].
China health authorities posted the full COVID-19 genome sequence on January 10, 2020, and the Chinese Center for Disease Control and Prevention (CDC) approved a real-time reverse transcriptasepolymerase chain reaction(RT-PCR) test that can diagnose COVID-19 clinical respiratory specimens [4], including upper (nasopharyngeal and throat swabs) and lower (sputum and bronchial lavage uid) respiratory tract specimens, anal swabs and faecal samples. Hence, RT-PCR is widely deployed in diagnosis of COVID-19. According to the Chinese management guideline for COVID-19 (standard version 6) [5], negative RT-PCR results from at least 2 consecutive sets of specimens collected at least 24 hours apart from a patient with COVID-19 indicate release from quarantine. Thus far, the onset and viral shedding duration of COVID-19 are not yet known. We report here a rare case in which consecutively positive RT-PCR test results were separated by more than one month.

Case Presentations
A 37-year-old male had a history of travel from affected geographic areas (Wuhan) on January 26, 2020 and then presented symptoms of fever (38.5 °C), dry cough, fatigue, dizziness, runny nose and diarrhoea 5 days later. Physical examination revealed increased respiratory (25/min) and heart rates (115/min), and lung auscultation revealed a few moist rales in the right lower lobe. On admission, the patient had positive RT-PCR test results, and chest computed tomography (CT) images showed multiple nodules and In this retrospectively analysed case, the hospitalized patient with COVID-19 was treated at QianJiang Central Hospital of ChongQing, which is a designated hospital for COVID-19 pneumonia and Public Health Clinical Center, from February 2, 2020, to March 6, 2020, and evaluated with consecutive RT-PCR tests for COVID-19 nucleic acid. The patient was diagnosed with moderate COVID-19 pneumonia according to the China Health Authority's interim criteria. Informed consent for the therapeutic regimen was obtained from the patient prior to treatment.
The patient received antiviral treatment, including arbidol (0.2 g, tid, po), Kaletra (lopinavir 400 mg/ritonavir 100 mg, q12h, po), IFN-α(interferon-α 50 µg, q12h, hypo), and traditional Chinese medicine, and was started on supplemental oxygen by nasal cannula after admission to the hospital. The duration of antiviral treatment was 9 days and IFN-α was 13 days. (Fig. 1). Routine blood analysis showed an increased lymphocyte count, indicating recovery and restoration of immune function. Arterial blood gas analysis showed no hypoxia. The fever, fatigue, diarrhea and rhinorrhea disappeared after four days of treatment.The cough lasted for 25 days from the illness onset. A CT scan on February 7 showed that bilateral pneumonia remained, but the appearance of the left lower lobe mildly worsened. On February 28, a chest CT scan demonstrated bilateral multiple nodules and mixed ground-glass opaci cation with consolidation, which were obviously improved compared with those observed on February 4, 2020 (Fig. 2). Throat and nasopharyngeal swab nucleic acid testing, COVID-19-speci c antibody detection (IgG and IgM), and CD4 + lymphocyte counts were evaluated regularly during the period of hospitalization (Fig. 3). The results of two continuous COVID-19 virus tests were negative for throat swabs and nasopharyngeal swabs, and the patient was thus discharged on March 6, 2020. The necleic acid test was negative from throat-swab follow up to two weeks.

Discussion And Conclusions
We report here a rare case with COVID-19, for which the longest duration of viral shedding was 32.0 days from illness onset with moderate COVID-19 pneumonia. The time from symptom onset to recovery was 36 days. Feiz et al [6] reported that the median duration of viral shedding was 20.0 days (IQR 17.0-24.0 days) in survivors, but the COVID-19 virus was detectable in patients who unfortunately died, and the longest shedding time was 37 days. That study showed that the duration of viral shedding was affected by the severity of the disease and noted that all patients in the study were hospitalized. Furthermore, prolonged viral shedding suggests that patients may still be able to transmit the new coronavirus, and prolonged shedding of the virus has important guiding signi cance for isolation prevention measures.
Hence, non-symptomatic infected persons or recovered patients should be in in-home quarantine for an extended period of time of more than 14 days. prolonged shedding of the virus has important guiding signi cance for the isolation prevention measures.
Recently, many cases were positive upon RT-PCR retesting during the period of isolation and observation after discharge [7]. These ndings indicated that some recovered patients may still be virus carriers.
However, Nancy Knight, an o cer of the CDC's Division of Global Health Protection, said that it is possible that the oral and nasal swab positive tests detected pieces of dead virus, which would not be transmissible [8]. In the present case, consecutively positive RT-PCR tests were veri ed for the upper respiratory tract. The lymphocyte count from routine blood testing and CD4 + count from peripheral blood increased gradually. IgM and IgG antibodies are known to be important indicators of current, recent and past infection [9]. New coronavirus-speci c IgG and IgM antibody levels changed in this case throughout the entire course of infection and recovery period. The recovery period of IgG antibodies is 3 times longer than that of the acute period. Therefore, the patient's upper respiratory tract swab positive test may have been caused by a piece of inactive virus.
The therapeutic procedure for this COVID-19 patient consisted of comprehensive therapy. The antiviral treatment regimen included arbidol, lopinavir/ritonavir, and interferon-α1b. The combination of therapeutic strategies is currently recommended in the latest version of China's National Health Commission-issued (version 7) o cial guidance. Aralen (chloroquine phosphate) is an effective antimalarial drug used to treat and prevent malaria [10]. Aralen demonstrated effectiveness against COVID-19 in a randomized multicentre controlled clinical trial (ChiCTR2000029559) [11].
In conclusion, the patient was given combination medicine treatment. All clinical symptoms and CT imaging manifestation abnormalities resolved during the course of therapy. New coronavirus-speci c IgG antibody levels signi cantly increased by more than 3 times above those at illness onset, accompanied by decreased IgM levels. Even though the positive RT-PCR tests were veri ed in the upper respiratory specimens, SARS-CoV-2 may have actually changed from active to inactive, at which point it is not easily transmissible among humans and moderate COVID-19 patients. However, the shedding period of the virus is not clear in severely or extremely ill COVID-19 patients. The results warrant further independent veri cation in future studies; if con rmed, this information can reduce hospital bed occupancy and save medical resources.  Temporal changes in laboratory markers from illness onset in this patient hospitalised with COVID-19.