Secondary Infection in Severe and Critical COVID-19 Patients in China: A Multicenter Retrospective Study (preprint)

Background. Since 2020 COVID-19 pandemic became an emergent public sanitary incident. The epidemiology data and the impact on prognosis of secondary infection in severe and critical COVID-19 patients in China remained largely unclear.Methods. We retrospectively reviewed medical records of all adult patients with laboratory-confirmed COVID-19 who were admitted to ICUs from January 18th 2020 to April 26th 2020 at two hospitals in Wuhan, China and one hospital in Guangzhou, China. We measured the frequency of bacteria and fungi cultured from respiratory tract, blood and other body fluid specimens. The risk factors for and impact of secondary infection on clinical outcomes were also assessed. Results. Secondary infections were very common (86.6%) when patients were admitted to ICU for >72 hours. The majority of infections were respiratory, with the most common organisms being Klebsiella pneumoniae (24.5%), Acinetobacter baumannii (21.8%), Stenotrophomonas maltophilia (9.9%), Candida albicans (6.8%), and Pseudomonas spp. (4.8%). Furthermore, the proportions of multidrug resistant (MDR) bacteria and carbapenem resistant Enterobacteriaceae (CRE) were high. We also found that age ≥60 years and mechanical ventilation ≥13days independently increased the likelihood of secondary infection. Finally, patients with positive cultures had reduced ventilator free days in 28 days and patients with CRE and/or MDR bacteria positivity showed lower 28 day survival rate.Conclusions. In a retrospective cohort of severe and critical COVID-19 patients admitted to ICUs in China, the prevalence of secondary infection was high, especially with CRE and MDR bacteria, resulting in poor clinical outcomes.

Decrease of exercise endurance in critically ill COVID-19 survivors: 4 case reports (preprint)

Background: The Coronavirus Disease 2019 (COVID-19) already have been as a pandemic. However, knowledge about the sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains limited. Here we descirbe the pulmonary function test (PFT) and cardiopulmonary exercise test (CPET) of critically ill COVID-19 in four cases with sereve acute respiratory distress syndrome (ARDS) after discharge.Case presentation: We introduce four patients who complained of fever, cough, chest tightness and other symptoms, all of them were confirmed as SARS-CoV-2 infection by real-time reverse transcription polymerase chain reaction (RT-PCR). They were treated with mechanical ventilation because of severe ARDS. After respiratory support, antiviral and anti-infective treatment, they were weaned from mechanic ventilation with the improvement of hypoxemia. All patients were discharged from the hospital after completion of treatment and had no mortality. Around 1-month post-discharge, they were followed up for chest computed tomography (CT) scan, and performed PFT and CPET. Peak oxygen uptake of predicted (peakVO2% pred) decreased in all four cases, although spirometry were in the normal range, and only 2 cases had mild decline in carbon monoxide diffusion capacity of predicted (DLCO%pred).Conclusions: We found reduced exercise endurance in all four COVID-19 survivors, even parts of them with normal or slightly abnormal static lung function. We also believe that exercise endurance impairment of COVID-19 convalescents is more likely affected by extrapulmonary factors. Taken the above into consideration, our study highlights that the combination of PFT and CPET are important tests for tracking the development and recovery of COVID-19 survivors.

The incidence, risk factors and prognosis of acute kidney injury in severe and critically ill patients with COVID-19 in mainland China: a retrospective study (preprint)

Background: Since the clinical correlates, prognosis and determinants of AKI in patients with Covid-19 remain largely unclear, we perform a retrospective study to evaluate the incidence, risk factors and prognosis of AKI in severe and critically ill patients with Covid-19.Methods: We reviewed medical records of all adult patients (>18 years) with laboratory-confirmed Covid-19 who were admitted to the intensive care unit (ICU) between January 23rd 2020 and April 6th 2020 at Wuhan JinYinTan Hospital and The First Affiliated Hospital of Guangzhou Medical University. The clinical data, including patient demographics, clinical symptoms and signs, laboratory findings, treatment [including respiratory supports, use of medications and continuous renal replacement therapy (CRRT)] and clinical outcomes, were extracted from the electronic records, and we access the incidence of AKI and the use of CRRT, risk factors for AKI, the outcomes of renal diseases, and the impact of AKI on the clinical outcomes.Results: Among 210 subjects, 131 were males (62.4%). The median age was 64 years (IQR: 56-71). Of 92 (43.8%) patients who developed AKI during hospitalization, 13 (14.1%), 15 (16.3%) and 64 (69.6%) patients were classified as stage 1, 2 and 3, respectively. 54 cases (58.7%) received CRRT. Age, sepsis, Nephrotoxic drug, IMV and elevated baseline Scr were associated with AKI occurrence. The renal recover during hospitalization among 16 AKI patients (17.4%), who had a significantly shorter time from admission to AKI diagnosis, lower incidence of right heart failure and higher P/F ratio. Of 210 patients, 93 patients deceased within 28 days of ICU admission. AKI stage 3, critical disease, greater age and minimum P/F <150mmHg independently associated with it.Conclusions: Among patients with Covid-19, the incidence of AKI was high. age , sepsis, nephrotoxic drug, IMV and baseline Scr were strongly associated with the development of AKI. Time from admission to AKI diagnosis, right heart failure and P/F ratio were independently associated with the potential of renal recovery. Finally, AKI KIDGO stage 3 independently predicted the risk of death within 28 days of ICU admission.

Rapid Screening Diagnosis of SARS-COV-2 Infection With IgM-igG Combined Antibody Test Using Peripheral Blood (preprint)

Background Rapid and convenient screening for identification of SARS-CoV-2 infected individuals are key to prevent and control this pandemic.Methods The peripheral blood samples were collected from coronavirus disease 2019 (COVID-19) patients and asymptomatic carriers to evaluate the test characteristics of the IgM-IgG combined assay for SARS-CoV-2 compared to that of serum samples and enzyme-linked immuno sorbent assay (ELISA). Close contacts, healthcare workers and workforces were recruited and screened using this assay.Results The sensitivity of the rapid IgM-IgG combined antibody test for SARS-CoV-2 using peripheral blood (sued as a POCT) was 97.0% and the specificity was 99.2%, which was consistent with the result obtained using serum sample (consistency is about 100%). Furthermore, this POCT assay also can detect IgM and IgG antibodies of SARS-CoV‐2 in asymptomatic carriers, with 19 of the 20 RT-PCR confirmed asymptomatic carriers testing positive. Therefore, this POCT assay was used for population screening of SARS-CoV-2 infection diagnosis. First, it found 4 positive close contacts among the 10 cases, and there were three IgM positive cases and one IgG positive case among them. It is worth noting that the IgM positive cases also tested positive for the nucleic acid of the SARS-CoV-2. Second, there was one IgM positive assay among the 63 healthcare workers, but RT-PCR of SARS CoV-2 was negative. Third, for workforces screening, there were no positive cases.Conclusions The IgM-IgG combined antibody test of SARS-CoV-2 can be used as a POCT for rapid screening of SARS-CoV-2 infection.

Clinical symptoms, comorbidities and complications features in severe and non-severe patients with COVID-19: a systematic review and meta-analysis without cases duplication (preprint)

Background: The pandemic of COVID-19 posed a challenge to global healthcare. The mortality rates of severe cases range from 8.1% to 31.8%, and it is particularly important to identify risk factors that aggravate the disease.Methods: We performed a systematic review of the literature with meta-analysis, using 7 databases to assess clinical characteristics, comorbidities and complications in severe and non-severe patients with COVID-19. All the observational studies were included. We performed a random or fixed effects model meta-analysis to calculate the pooled proportion and 95% CI. Measure of heterogeneity was estimated by Cochran’s Q statistic, I2 index and P value.Results: 4881 cases from 25 studies related to COVID-19 were included. The most prevalent comorbidity was hypertension (severe: 33.4%, 95% CI: 25.4% - 41.4%; non-severe 21.6%, 95% CI: 9.9% - 33.3%), followed by diabetes (severe: 14.4%, 95% CI: 11.5% - 17.3%; non-severe: 8.5%, 95% CI: 6.1% - 11.0%). The prevalence of ARDS, AKI and shock were all higher in severe cases, with 41.1% (95% CI: 14.1% - 68.2%), 16.4% (95% CI: 3.4% - 29.5%) and 19.9% (95% CI: 5.5% - 34.4%), rather than 3.0% (95% CI: 0.6% - 5.5%), 2.2% (95% CI: 0.1% - 4.2%) and 4.1% (95% CI -4.8% - 13.1%) in non-severe patients, respectively. The death rate was higher in severe cases (30.3%, 95% CI: 13.8% - 46.8%) than non-severe cases (1.5%, 95% CI: 0.1% - 2.8%).Conclusions: Hypertension, diabetes and cardiovascular diseases may be risk factors for COVID-19 patients to develop into severe cases.

Evaluation of recombinant nucleocapsid and spike proteins for serological diagnosis of novel coronavirus disease 2019 (COVID-19) (preprint)

Background: The colloidal gold immunochromatography assay (GICA) is a rapid diagnostic tool for novel coronavirus disease 2019 (COVID-19) infections. However, with significant numbers of false negatives, improvements to GICA are needed. Methods: Six recombinant HCoV-19 nucleocapsid and spike proteins were prepared and evaluated. The optimal proteins were employed to develop a sandwich-format GICA strip to detect total antibodies (IgM and IgG) against HCoV-19. GICA performance was assessed with comparison of viral RNA detection. Results: Recombinant HCoV-19 proteins were obtained, including three prokaryotically expressed rN, rN1, rN2 nucleocapsid proteins, and three eukaryotically expressed rS1, rS-RBD, rS-RBD-mFc spike proteins. The recombinant proteins with the highest ELISA titers (rS1 and rS-RBD-mFc) against coronavirus-specific IgM and IgG were chosen for GICA development. The GICA has a sensitivity and specificity of 86.89% (106/122) and 99.39% (656/660), respectively. Furthermore, 65.63% (21/32) of the clinically confirmed but RT-PCR negative samples were GICA positive. Conclusions: The eukaryotically-expressed spike proteins (rS1and rS-RBD-mFc) are more suitable than the prokaryotically expressed nucleocapsid proteins for HCoV-19 serological diagnosis. The GICA sandwich used to detect total antibodies is a powerful complement to the current standard RNA-based tests.