key: cord-0840639-mfsdj70s
authors: Chen, J.; Xu, X.; Hu, J.; Chen, Q.; Xu, F.; Liang, H.; Liu, N.; Zhu, H.; Lan, J.; Zhou, L.; Xing, J.; Pu, N.; Cai, Z.
title: Clinical Course and Risk Factors for Recurrence of Positive SARS-CoV-2 RNA: A Retrospective Cohort Study from Wuhan, China
date: 2020-05-12
journal: nan
DOI: 10.1101/2020.05.08.20095018
sha: 27722c0a52e7cbe22703f976aa4a061d62bf4ac4
doc_id: 840639
cord_uid: mfsdj70s

Background Coronavirus Disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has developed into a full-blown global pandemic. It has been reported that patients with COVID-19 meeting the criteria for hospital discharge (including two consecutive negative RT-PCR results) have experienced recurrent PCR positivity. However, the clinical course and risk factors for these patients have not been well described. Methods In this retrospective cohort study, consecutive patients with COVID-19 confirmed by RT-PCR from the Guanggu Branch of Hubei Province Maternity and Childcare Hospital from February 24, 2020 to March 31, 2020 were enrolled. The epidemiological, radiographic, laboratory, treatment, and outcome data were extracted from medical records. Univariate and multivariable logistic regression methods were used to elucidate risk factors for patients with recurrence of positive SARS-CoV-2 RNA. Results 1087 COVID-19 patients were included in this study. Of these, 20 (1.8%) died and 1067 (98.2%) were discharged from the hospital. Among the discharged cases, there were 81 (7.6%) patients found to develop a repeat positive SARS-Cov-2 RNA result. Older age was obviously associated with death. For patients with recurrent RT-PCR positivity, the median duration from illness onset to onset of complete RNA negative was 33.0 days (range, 6.0-82.0 days; IQR, 20.0-41.0 days), while that from illness onset to recurrence was 50.0 days (range, 21.0-95.0 days; IQR, 36.5-59.5 days). Multivariate regression analysis identified recurrence of positive SARS-Cov-2 RNA was associated with elevated IL-6 levels (P=0.004, OR=3.050; 95% CI, 1.432-6.499), increased lymphocyte count (P=0.038, OR=2.321; 95% CI, 1.048-5.138) and CT imaging features of lung consolidation (P=0.038, OR=1.641; 95% CI, 1.028-2.620) during hospitalization. Conclusion Elevated lymphocyte counts and IL-6 levels in blood, and consolidation features on CT imaging are useful risk factors for clinicians to identify patients at risk of developing recurrent positivity of SARS-CoV-2 RNA. This is speculated to be caused by a balance in immune regulation when fighting virus toxicity. For patients with a high risk of recurrent positivity, a prolonged observation and additional preventative measures should be implemented for at least 50 days after illness onset to prevent future outbreaks.

Coronavirus Disease 2019 , caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported in Wuhan, China and has been spreading globally. 1, 2 As of April 18, 2020, there have been 2,121,675 confirmed cases of COVID-19 and 142,299 related deaths from a total of 213 different countries according to the World Health Organization (WHO). 3 Undoubtedly, COVID-19 has caused a global pandemic. Thus far, many studies have reported and summarized the epidemiological and clinical features of patients infected with SARS-CoV-2. [4] [5] [6] Furthermore, the pathogenicity and mechanism of SARS-CoV-2 are being wrestled at full stretch and the mystery of SARS-CoV-2 is gradually being unraveled. However, the exact origin species that carried SARS-CoV-2 remains a controversial issue, which is a potential threat to a new outbreak. 7, 8 As we learn more about the origins and course of this disease, we must appropriately looking into the mechanisms of its eradication. Until now, very little know about how the human body regulates and clears a SARS-CoV-2 infection which, in turn, makes it difficult to assess a complete recovery with no risk of infectivity to others. This is essential to halt the COVID-19 spread, "flatten the curve" and prevent additional outbreaks.

In the early stages of the COVID-19 outbreak located in Wuhan, China, the severe shortage and limitations in the detection and accuracy of the RT-PCR test was severely problematic in identifying infected patients. Thankfully, this has since improved drastically with the support of national medical teams from every other provinces comprising of nationwide medical experts and nurses. 9 This experience gave meaningful insight into the false negative rates of RT-PCR tests and possibility of recurrence of positive SARS-CoV-2 RNA. To counteract the potential probability of false negative rate of RT-PCR tests, patients have been routinely undergone two or more multipoint throat-swabs over 24 hours apart before discharge. 10 Lan L et al. 11 reported that four medical professionals with COVID-19 who met criteria for hospital discharge (including two consecutive negative RT-PCR results) experienced repeat RT-PCR positivity, implying potential asymptomatic carrier states. Although it has not been demonstrated that patients with recurrent SARS-CoV-2 RNA positive remain infectious after discharge, this is an inevitable matter that must be addressed.

Furthermore, our understanding of clinical and radiological characteristics of the patients with COVID-19 who experience recurrence of positive SARS-CoV-2 RNA is very limited.

Herein, we report on 1087 patients with confirmed COVID 19 and further explore a population with repeat positivity of SARS-CoV-2 RNA on RT-PCR during post-hospital isolation and after at least two negative RT-PCR tests from one hospital in Wuhan, China. We aim to present outcomes All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 12, 2020. . https://doi.org/10.1101/2020.05.08.20095018 doi: medRxiv preprint on this large sample and provide further insight into a unique and understudied population by exploring their clinical course and risk factors.

This is a retrospective analysis of 1087 consecutive COVID-19 pneumonia patients at the 

An experienced team of front-line medical personnel reviewed and collected the epidemiological, radiographic, laboratory, treatment, and outcome data from medical records to establish a database for COVID-19 pneumonia patients. All patients received follow-up to April 15, 2020 from discharge. The confidential information of patients was protected by assigning a new specific record number. All collected data were checked by two authors (JC and QC) and finally adjudicated by a third researcher (NP) for any differences in interpretation.

In concordance with standard procedure, throat-swab specimens were obtained and tested using real-time RT-PCR methods to identify SARS-CoV-2 infection. 12 The Academy of Military Medical Sciences and the hospital laboratory were responsible for SARS-CoV-2 detection in respiratory specimens. During the hospital stay and after clinical remission of symptoms, SARS-CoV-2 PCR re-examination by throat-swab specimens was performed at 24-hour intervals.

During hospitalization, regular laboratory blood examinations were performed comprising of complete blood counts (including white blood cells, neutrophils, lymphocytes, monocytes and platelets), serum biochemical tests (including liver function tests, renal function indicators and electrolytes), coagulation indices, high-sensitivity C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin, myocardial enzymes, D-dimer and interleukin-6 (IL-6). At All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 12, 2020. . https://doi.org/10.1101/2020.05.08.20095018 doi: medRxiv preprint an appropriate time determined by the attending physician, computed tomography (CT) scans were routinely performed for inpatients.

The criteria for discharge were as follows: 1) no fever for at least three days; 2) remission of clinical respiratory symptoms; 3) substantial improvement of pulmonary inflammation on chest CT scan; 4) two negative SARS-CoV-2 RNA tests at least 24 hours apart; 5) good general condition.

The illness severity of COVID-19 was defined according to the Chinese management guideline for COVID-19 (version 6.0). 10 Fever was defined as axillary temperature of at least 37.3°C.

Comorbid conditions included hypertension, diabetes and other internal visceral dysfunction during hospitalization (including hypoproteinaemia, coagulopathy, hyperuricemia, anemia, respiratory failure, liver injury, renal injury and cardiac injury).

Hypoproteinaemia was defined as blood albumin of less than 25 g/L, coagulopathy was defined as a 3-second increase in prothrombin time or a 5-second increase of activated partial thromboplastin time, and hyperuricemia was defined as blood trioxypurine greater than 420 umol/L (male) or 360 umol/L (female). Anemia was determined according to WHO guidelines. 13 Acute respiratory distress syndrome (ARDS) was diagnosed according to the Berlin Definition. 14 Acute liver failure was diagnosed according to EASL Clinical Practical Guidelines 15 , acute kidney injury was diagnosed according to the KDIGO clinical practice guidelines 16 , and acute cardiac injury was diagnosed as previously reported. 6

Descriptive analyses of continuous and categorical variables were presented as a median with interquartile range (IQR) and counts with column percentages, respectively. The differences between recurrence and non-recurrence were compared using the Pearson Chis-quared test, Fisher's exact test or Mann-Whitney U test as appropriate. To explore the risk indicators associated with recurrence of positive SARS-Cov-2 RNA, univariate and multivariate logistic regression models were implemented. Variables with P value <0.2 were selected for multivariable analysis on the basis of previous findings and clinical constraints. Missing data was not imputed and presented as is in Table 4 and 5, and analyses regarding different indicators were based on non-missing data.

A two-sided P value less than 0.05 was considered statistically significant. All statistical analyses were performed using the SPSS v21.0 software (IBM Corporation, Armonk, NY, USA), and figures were plotted by GraphPad Prism 8.0 software (GraphPad Software, La Jolla, CA, USA).

A total of 1087 consecutive COVID-19 pneumonia patients with positive SARS-CoV-2 RNA were enrolled in this study. In this cohort, the median patient age was 60.0 years ranging from 9.0 to 100.0 years (IQR, 49.0-69.0 years) and 635 (58.4%) were women. The proportion of general cases was 83.1%, and that of severe and critical cases were 13.2% and 3.7%, respectively. Other general features, inpatient laboratory examinations and imaging findings were shown in Table 1 . and 20 patients died during hospitalization, while 1067 were discharged. The total mortality was 1.8% and discharge rate was 98.2%. Within these fatalities, 5 patients were graded as severe cases where the mortality was 3.5%, and 15 were labeled critical cases where the mortality rose to 37.5%.

The total mortality of severe and critical cases was 10.6%. The median age of death was 83.0 years ranging from 65.0 to 92.0 years (IQR, 79.3-87.8 years). All of these patients died from multiple organ failure (MOSF), most commonly from lungs, heart, liver and kidneys.

Among the discharged cases, there were 81 (7.6%) patients found to develop a repeat positive SARS-Cov-2 RNA result during their post-discharge isolation and after two negative RT-PCR tests to warrant initial discharge. In these recurrent cases, the median age was 62.0 years (range, years; IQR, 50.5-68.0 years), and 51 (63.0%) patients were female. Twenty (24.7%) patients had comorbid disease of hypertension and 9 (11.1%) patients had diabetes. Divided by clinical severity, general, severe and critical cases accounted for 84.0% (68 cases), 14.8 (12 cases) and 1.2% (1 case), respectively. Most of these patients had initial symptoms before initial COVID-19 diagnosis.

However, 15 (18.5%) patients were asymptomatic when first diagnosed by positive SARS-Cov-2 RNA. Before hospitalization, 70 patients were confirmed to harbor pulmonary infection via CT scan, and 65 (65.3%) patients have received therapeutic anti-viral agents.

Laboratory and CT imaging results from the inpatient hospital-stay are summarized in Table 2 .

Of these patients, 7 (8.6%) patients had lymphocytopenia, and only 4 (4.9%) patients had neutrophilia. High sensitivity CRP was elevated in 8 (9.9%) patients, increased ESR was found in 27 (33.3%) patients and increased procalcitonin in 14 (17.3%) patients. Additionally, the increased inflammatory factor of IL-6 was found in 11 (13.6%) patients. Regarding organ dysfunction, 10 (12.3%) patients developed liver injury with elevated ALT, 4 (4.9%) patients demonstrated All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 12, 2020. Amongst these 81 patients, oxygen support was administrated in 37 (45.7%), however, no invasive mechanical ventilation (IMV) or IMV with extracorporeal membrane oxygenation (ECMO) was used. The optimal antiviral therapy was administrated in 69 (85.2%) patients; these included abidor hydrochloride (40 patients, 49.4%), interferon alfa (17 patients, 21.0%), entecavir/tenofovir (7 patients, 8.6%) and oseltamivir (5 patients, 6.2%). More than half of patients (51, 63.0%) were treated with Chinese patent drugs, such as Lianhuaqingwen capsule. Vitamin C was given to 41 (50.6%) patients, and immunomodulators, such as thymopentin and immunoglobulin, were administrated in 8 (9.9%) patients. Table 3 (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 12, 2020. . https://doi.org/10.1101/2020.05.08.20095018 doi: medRxiv preprint of SARS-Cov-2 RNA positivity ( Table 4 ). Multivariate analysis concluded that elevated lymphocyte count (P=0.038, OR=2.321; 95% CI, 1.048-5.138), serum IL-6 level (P=0.004, OR=3.050; 95% CI, 1.432-6.499) and consolidation features on CT imaging (P=0.038, OR=1.641; 95% CI, 1.028-2.620) remained as independent risk predictors for recurrence ( Table 5 ).

In this study, we provide comprehensive data on the demographic and clinical characteristics of 1087 consecutive patients with COVID-19 from Wuhan, China. According to the degree of severity of COVID 19, the enrolled patients were categorized as 903 (83.1%) general cases, 144 (13.2%) severe cases and 40 (3.7%) critical cases on admission. The total mortality of severe and critical cases was 10.6%. The mortality of the all patients with COVID-19 pneumonia was 1.8%, which was similar to that of a previous study 4 , but lower than that reported in another studies. 5, 17 This difference may be partly attributed to the fact that the majority proportion of cases were classified as general severity and that more medical resources were made available in the later stages of this pandemic which matches our window of enrollment into this study. Liang WH et al. 18 reported that the mortality of COVID-19 patients out of the Hubei Province was limited to 0.3%, as strict public health interventions were initiated in order to prevent further outbreak outside Hubei and medical resources were adequately provided for treatment. Additionally, previous studies indicated that older age was an important independent predictor for mortality in COVID-19 patients. 6, 12 Our findings support this claim; the median age of death was 83.0 years, distinctly higher than that of the discharged patients, which further suggests that increased age was associated with an increased risk of mortality.

Of 1067 discharged patients, we identified 81 (7.6%) patients that experienced recurrence of positive SARS-Cov-2 RNA after meeting criteria for discharge. This is similar to findings in previous case reports. 11, 19, 20 However, Yuan J et al. 20 reported a higher repeat positivity rate of 14.5% after discharge, which may be due to a small cohort of enrolled patients. This group of patients may pose a potential risk for further disease spread as persistent asymptomatic viral carriers. This not so rare phenomenon threatens potential future outbreaks of COVID-19 that seems to have been temporarily controlled in China after a series of unprecedented public health interventions. 21 Thus, we aimed to explore the clinical course and risk predictors for recovered COVID-19 patients with recurrent PCR positivity to provide insight into this population and help guide clinical practice in order to help halt future outbreaks.

Various studies have reported on infectivity and viral shedding. Zhou F et al. 6 showed that the All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 12, 2020. . https://doi.org/10.1101/2020.05.08.20095018 doi: medRxiv preprint median duration of viral shedding was 20.0 days in survivors and the longest observed duration was 37 days. Moreover, Zhou B et al. 22 reported that the median duration of viral shedding was 31.0 days from illness onset in severe COVID-19 patients. Xu K et al. 23 reported that almost 3 in every 4 patients had viral RNA clearance within 21 days of illness onset, and male gender, older age, hypertension, delayed hospital admission after illness onset, severe illness upon admission, invasive mechanical ventilation and corticosteroid treatment were risk factors for extended viral RNA clearance. In our study, the median duration of viral shedding for patients with recurrence of positive SARS-CoV-2 RNA was 33.0 days from illness onset to onset of complete RNA negative.

However, the median duration from illness onset to recurrent SARS-CoV-2 RNA positive was 50.0 days. Thus, our findings underscore the importance of a prolonged treatment or isolation for patients at increased risk of recurrence of SARS-CoV-2 RNA positivity.

Amongst the 81 discharged patients with recurrence of positive SARS-CoV-2 RNA, we found that age and comorbid diseases, which were previously described to be risk factors for mortality 12 , were not significant risk factors when compared with patients with no recurrence. However, three independent predictors were identified for patients with recurrence of positive SARS-Cov-2 RNA after treatment and hospital discharge. Elevated serum IL-6 level, lymphocyte count greater than 1.1*10 8 /L and consolidation on CT imaging during hospitalization were associated with higher likelihoods of recurrent SARS-Cov-2 RNA positivity after discharged. Partly similar to previous study, it showed that lymphocyte concentrations before discharge were significantly positively correlated with the time interval for virus reappearing, which confirmed the role of lymphocytes in the potential recurrence of SARS-CoV-2 RNA positivity. 20 No significant differences were found in other factors in our cohort, including clinical severity of disease, CRP, D-dimer level, etc. IL-6, one of the main pro-inflammatory factors of the immune system, plays an important role in host defense against infections. However, due to the ability of SARS-CoV-2 to infect the lower respiratory tract and rapidly replicated leads to excessive IL-6 release inducing an acute severe systemic inflammatory response known as cytokine release syndrome (CRS). 24 Previously, increased serum IL-6 level was reported to be observed in severe and critical patients with COVID-19 and to be associated with poor outcomes 25, 26 , which is a similar finding during severe acute respiratory syndrome (SARS) outbreak. 27 Concurrently, lymphopenia was also commonly noted in patients with COVID-19, especially in severe and critical cases 5, 26, 28 , suggesting dysregulated immune responses in this sub-cohort. However in our study, only 175 (16.1%) of 1087 cases showed a decrease in lymphocyte count, which again may be due to the fact that the cohort is largely comprised of general cases. Interestingly, we discovered that the discharged patients with All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 12, 2020. . https://doi.org/10.1101/2020.05.08.20095018 doi: medRxiv preprint recurrence of positive SARS-CoV-2 RNA may potentially have an elevated serum IL-6 level and lymphocyte count than those with no recurrence, implying that the immune responses against SARS-CoV-2 might still be attempting to clear the infection. Perhaps the immune system could suppress but not eradicate SARS-CoV-2 completely, which may have led to the false-negative results due to lower viral loads. Theoretically, at some point further down the line, the virus started replicating again to cause recurrent positive RT-PCR test results in the already discharged patients with COVID-19.

The characteristics of chest CT imaging features of COVID-19 pneumonia are very useful for preliminary judgment and have contributed to a lower rate of missed diagnoses. 29 Patients with features of consolidation on CT imaging were reported to associated with more critical cases. 30 Progression of consolidation might represent further infiltration of the lung parenchyma and lung interstitium, indicating that the virus has invaded the respiratory epithelium which is characterized by diffuse alveolar damage and necrotizing bronchitis. This leads to alveoli being completely filled by inflammatory exudate. 31, 32 Thus, during the recovery process of COVID-19 patients with lung consolidation, a potentially undetectable amount of SARS-CoV-2 may persist in the respiratory epithelium. This may result in the recurrence of positive SARS-CoV-2 RNA after discharge.

Interestingly, we found that most patients with recurrence of positive SARS-CoV-2 RNA had fluctuating positive and negative results in the course of the disease, typically in cases 7, 8, 41 amongst others (Figure 1) . This, in itself, may partially reflect another potential sign for recurrent positivity after discharge. Also, such fluctuations in one case partly ruled out the randomly error probability in RT-PCR detection. Thus, individuals may have already had immunity to eradicate the virus, so a period of duration was needed for complete recovery yet. However, if the individual immunity cannot deal with the recurrence, further treatment may be still needed.

This study has a few notable limitations. First, this study was conducted at a single-center (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 12, 2020. . https://doi.org/10.1101/2020.05.08.20095018 doi: medRxiv preprint Figure 2A shows the median duration from illness onset to initial RT-PCR confirmed, onset of complete RNA negative and recurrent RT-PCR positivity after discharge, and from discharge to recurrence. Figure 2B shows the median duration from initial RT-PCR confirmed to onset of complete RNA negative and recurrent RT-PCR positivity after discharge, and from onset of complete RNA negative to recurrence. SARS-CoV-2=severe acute respiratory syndrome coronavirus 2. RT-PCR=reverse transcription-polymerase chain reaction. All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 12, 2020. . (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 12, 2020. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 12, 2020 (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 12, 2020. . https://doi.org/10.1101/2020.05.08.20095018 doi: medRxiv preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 12, 2020. . https://doi.org/10.1101/2020.05.08.20095018 doi: medRxiv preprint

A Novel Coronavirus from Patients with Pneumonia in China

The Novel Coronavirus Originating in Wuhan, China: Challenges for Global Health Governance

Clinical Characteristics of Coronavirus Disease 2019 in China. The New England journal of medicine

Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

The proximal origin of SARS-CoV-2. Nature medicine

Phylogenetic network analysis of SARS-CoV-2 genomes

Stability issues of RT-PCR testing of SARS-CoV-2 for hospitalized patients clinically diagnosed with COVID-19

National Health Commission of the People's Republic of China

Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease

Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Vitamin and Mineral Nutrition Information System

Acute respiratory distress syndrome: the Berlin Definition

Clinical Practical Guidelines on the management of acute (fulminant) liver failure

KDIGO clinical practice guidelines for acute kidney injury

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

Clinical characteristics and outcomes of hospitalised patients with COVID-19 treated in Hubei (epicenter) and outside Hubei (non-epicenter): A Nationwide Analysis of China

Recurrence of positive SARS-CoV-2 RNA in COVID-19: A case report

PCR Assays Turned Positive in 25 Discharged COVID-19 Patients

Association of Public Health Interventions With the Epidemiology of the COVID-19 Outbreak in Wuhan, China

The duration of viral shedding of discharged patients with severe COVID-19

Factors associated with prolonged viral RNA shedding in patients with COVID-19

Detectable serum SARS-CoV-2 viral load (RNAaemia) is closely correlated with drastically elevated interleukin 6 (IL-6) level in critically ill COVID-19 patients

Clinical and immunological features of severe and moderate coronavirus disease 2019

Analysis of serum cytokines in patients with severe acute respiratory syndrome

Epidemiological and clinical features of COVID-19 patients with and without pneumonia in Beijing, China. medRxiv

COVID-19): Role of Chest CT in Diagnosis and Management

The performance of chest CT in evaluating the clinical severity of COVID-19 pneumonia: identifying critical cases based on CT characteristics

CT Features of Coronavirus Disease

Pneumonia in 62 Patients in Wuhan, China

Radiographic and CT Features of Viral Pneumonia

Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples from the Hong Kong Cohort and Systematic Review and Meta-analysis