ABSTRACT
BackgroundA pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading over the world. However, the viral dynamics, host serologic responses, and their associations with clinical manifestations, have not been well described in prospective cohort. MethodsWe conducted a prospective cohort and enrolled 67 COVID-19 patients admitting between Jan 26 and Feb 5, 2020. Clinical specimens including nasopharyngeal swab, sputum, blood, urine and stool were tested periodically according to standardized case report form with final follow-up on February 27. The routes and duration of viral shedding, antibody response, and their associations with disease severity and clinical manifestations were systematically evaluated. Coronaviral particles in clinical specimens were observed by transmission electron microscopy (TEM). ResultsThe median duration of SARS-CoV-2 RNA shedding were 12 (3-38), 19 (5-37), and 18 (7-26) days in nasopharyngeal swabs, sputum and stools, respectively. Only 13 urines (5.6%) and 12 plasmas (5.7%) were viral positive. Prolonged viral shedding was observed in severe patients than that of non-severe patients. Cough but not fever, aligned with viral shedding in clinical respiratory specimens, meanwhile the positive stool-RNA appeared to align with the proportion who concurrently had cough and sputum production, but not diarrhea. Typical coronaviral particles could be found directly in sputum by TEM. The anti-nucleocapsid-protein IgM started on day 7 and positive rate peaked on day 28, while that of IgG was on day 10 and day 49 after illness onset. IgM and IgG appear earlier, and their titers are significantly higher in severe patients than non-severe patients (p<0.05). The weak responders for IgG had a significantly higher viral clearance rate than that of strong responders (p= 0.011). ConclusionsNasopharyngeal, sputum and stools rather than blood and urine, were the major shedding routes for SARS-CoV-2, and meanwhile sputum had a prolonged viral shedding. Symptom cough seems to be aligned with viral shedding in clinical respiratory and fecal specimens. Stronger antibody response was associated with delayed viral clearance and disease severity. Summary boxesO_ST_ABSWhat is already known on this topicC_ST_ABSAs a newly appearing infectious disease, early efforts have focused on virus identification, describing the epidemiologic characteristics, clinical course, prognostics for critically illed cases and mortality. Among COVID-19 cases reported in mainland China (72 314 cases, updated through February 11, 2020), 81% are mild, 14% are severe, and 5% are critical. The estimated overall case fatality rate (CFR) is 2.3%. Some case series reported had shown that SARS-CoV-2 could shed in upper/lower respiratory specimens, stools, blood and urines of patients. However, important knowledge gaps remain, particularly regarding full kinetics of viral shedding and host serologic responses in association with clinical manifestations and host factors. What this study addsThe incubation period has no change after spreading out of Wuhan, and has no sex or age differences, however, children had prolonged incubation period. Due to early recognition and intervention, COVID-19 illness of Chongqing cohort is milder than that of Wuhan patients reported. This prospective cohort study on SARS-CoV-2 infection shows clearly that the viral and serological kinetics were related in duration of infection, disease severity, and clinical manifestations of COVID-19. Our data demonstrate that nasopharyngeal, sputum and stools are major shedding routes for SARS-CoV-2, and stronger NP antibody response is associated with delayed viral clearance and disease severity.
ABSTRACT
BackgroundIn January 19, 2020, first case of 2019 novel coronavirus (2019-nCoV) pneumonia (COVID-19) was confirmed in Chongqing municipality, China. MethodsIn this retrospective, descriptive, multiple-center study, total of 267 patients with COVID-19 confirmed by real-time RT-PCR in Chongqing from Jan 19 to Feb 16, 2020 were recruited. Epidemiological, demographic, clinical, radiological characteristics, laboratory examinations, and treatment regimens were collected on admission. Clinical outcomes were followed up until Feb 16, 2020. Results267 laboratory-confirmed COVID-19 patients admitted to 3 designated-hospitals in Chongqing provincial municipality from January 19 to February 16, 2020 were enrolled and categorized on admission. 217 (81.27%) and 50 (18.73%) patients were categorized into non-severe and severe subgroups, respectively. The median age of patients was 48.0 years (IQR, 35.0-65.0), with 129 (48.3%) of the patients were more than 50 years of age. 149 (55.8%) patients were men. Severe patients were significantly older (median age, 71.5 years [IQR, 65.8-77.0] vs 43.0 years [IQR, 32.5-57.0]) and more likely to be male (110 [50.7%] vs 39 [78.0%]) and have coexisting disorders (15 [30.0%] vs 26 [12.0%]). 41 (15.4%) patients had a recent travel to Hubei province, and 139 (52.1%) patients had a history of contact with patients from Hubei. On admission, the most common symptoms of COVID-19 were fever 225(84.3%), fatigue (208 [77.9%]), dry cough (189 [70.8%]), myalgia or arthralgia (136 [50.9%]). Severe patients were more likely to present dyspnea (17 [34.0%] vs 26 [12.0%]) and confusion (10 [20.0%] vs 15 [6.9%]). Rales (32 [12.0%]) and wheezes (20 [7.5%]) are not common noted for COVID-19 patients, especially for the non-severe (11 [5.1%], 10 [4.6%]). 118 (44.2%). Most severe patients demonstrated more laboratory abnormalities. 231 (86.5%), 61 (22.8%) patients had lymphopenia, leukopenia and thrombocytopenia, respectively. CD4+T cell counts decrease was observed in 77.1 % of cases, especially in the severe patients (45, 100%). 53.1% patients had decreased CD+3 T cell counts, count of CD8+T cells was lower than the normal range in part of patients (34.4%). More severe patients had lower level of CD4+ T cells and CD+3 T cells (45 [100.0%] vs 29[56.9%], 31 [68.9%] vs 20 [39.2%]). Most patients had normal level of IL-2, IL-4, TNF- and INF-{gamma}, while high level of IL-6 and IL-17A was common in COVID-19 patients (47 [70.1%], 35 [52.2%]). Level of IL-6, IL-17A and TNF- was remarkably elevated in severe patients (32 [84.2%] vs 15 [51.7%], 25 [65.8%] vs 10 [34.5%], 17 [44.7%] vs 5 [17.2%]). All patients received antiviral therapy (267, 100%). A portion of severe patients (38, 76.0%) received systemic corticosteroid therapy. Invasive mechanical ventilation in prone position, non-invasive mechanical ventilation, high-flow nasal cannula oxygen therapy was adopted only in severe patients with respiratory failure (5[10.0%], 35[70.0%], 12[24.0%]). Traditional Chinese medicine was adopted to most of severe patients (43,86.0%). ConclusionOur study firstly demonstrated the regional disparity of COVID-19 in Chongqing municipality and further thoroughly compared the differences between severe and non-severe patients. The 28-day mortality of COVID-19 patients from 3 designed hospitals of Chongqing is 1.5%, lower than that of Hubei province and mainland China including Hubei province. However, the 28-mortality of severe patients was relatively high, with much higher when complications occurred. Notably, the 28-mortality of critically severe patients complicated with severe ARDS is considerably as high as 44.4%. Therefore, early diagnosis and intensive care of critically severe COVID-19 cases, especially those combined with ARDS, will be considerably essential to reduce mortality.
