Analysis of 394 COVID-19 cases infected with Omicron variant in Shenzhen: impact of underlying diseases to patient's symptoms.

OBJECTIVES: The emergence of new variants of SARS-CoV-2 is continuously posing pressure to the epidemic prevention and control in China. The Omicron variant of SARS-CoV-2 having stronger infectivity, immune escape ability, and capability causing repetitive infection spread to many countries and regions all over the world including South Africa, United States and United Kingdom etc., in a short time. The outbreaks of Omicron variant also occurred in China. The aim of this study is to understand the epidemiological characteristics of Omicron variant infection in Shenzhen and to provide scientific basis for effective disease control and prevention. METHODS: The clinical data of 394 imported COVID-19 cases infected with Omicron variant from 16 December 2021 to 24 March 2022 admitted to the Third People's hospital of Shenzhen were collected and analyzed retrospectively. Nucleic acid of SARS-CoV-2 of nasopharyngeal swabs and blood samples was detected using 2019-nCoV nucleic acid detection kit. Differences in Ct values of N gene were compared between mild group and moderate group. The specific IgG antibody was detected using 2019-nCoV IgG antibody detection kit. Statistical analysis was done using SPSS software and graphpad prism. RESULTS: Patients were categorized into mild group and moderate group according to disease severity. The data on the general conditions, underlying diseases, COVID-19 vaccination and IgG antibody, viral load, laboratory examination results, and duration of hospitalization, etc., were compared among disease groups. Mild gorup had higher IgG level and shorter nucleic acid conversion time. Patients with underlying diseases have 4.6 times higher probability to progress to moderate infection. CONCLUSION: In terms of epidemic prevention, immunization coverage should be strengthened in the population with underlying diseases. In medical institutions, more attention needs to be paid to such vulnerable population and prevent further deterioration of the disease.

Low-to-Moderate Dosage and Short-Term Use of Corticosteroids Benefit Patients With Severe COVID-19 Infections.

Although the FDA has given emergency use authorization (EUA) for some antiviral drugs for the treatment of COVID-19, no direct antiviral drugs have been identified for the treatment of critically ill patients, the most important treatment is suppression of the hyperinflammation. The purpose of this study was to evaluate the role of corticosteroids in hospitalized severe or critical patients positive for COVID-19. This is a retrospective single-center descriptive study. Patients classified as having severe or critical COVID-19 infections with acute respiratory dysfunction syndrome in Shenzhen Third People's Hospital were enrolled from January 11th to March 30th, 2020. Ninety patients were classified as having severe or critical COVID-19 infections. The patients were treated with methylprednisolone with a low-to-moderate dosage and short duration. The days from the symptom onset to methylprednisolone were about 8 days. Eighteen patients were treated with invasive ventilation and intensive care unit (ICU) care. All the patients in the severe group and ten in the critical group recovered and were discharged. Three critical cases with invasive ventilation died. Although cases were much more severe in the corticosteroid-treated group, the mortality was not significantly increased. Early use of low-to-moderate dosage and short duration of corticosteroid may be the more accurate immune-modulatory treatment and brings more benefits to severe patients with COVID-19.

Low-to-Moderate Dosage and Short-Term Use of Corticosteroids Benefit Patients With Severe COVID-19 Infections

Although the FDA has given emergency use authorization (EUA) for some antiviral drugs for the treatment of COVID-19, no direct antiviral drugs have been identified for the treatment of critically ill patients, the most important treatment is suppression of the hyperinflammation. The purpose of this study was to evaluate the role of corticosteroids in hospitalized severe or critical patients positive for COVID-19. This is a retrospective single-center descriptive study. Patients classified as having severe or critical COVID-19 infections with acute respiratory dysfunction syndrome in Shenzhen Third People’s Hospital were enrolled from January 11th to March 30th, 2020. Ninety patients were classified as having severe or critical COVID-19 infections. The patients were treated with methylprednisolone with a low-to-moderate dosage and short duration. The days from the symptom onset to methylprednisolone were about 8 days. Eighteen patients were treated with invasive ventilation and intensive care unit (ICU) care. All the patients in the severe group and ten in the critical group recovered and were discharged. Three critical cases with invasive ventilation died. Although cases were much more severe in the corticosteroid-treated group, the mortality was not significantly increased. Early use of low-to-moderate dosage and short duration of corticosteroid may be the more accurate immune-modulatory treatment and brings more benefits to severe patients with COVID-19.

Antiviral Efficacy and Safety of Molnupiravir Against Omicron Variant Infection: A Randomized Controlled Clinical Trial.

Background: The rapid worldwide spread of the Omicron variant of SARS-CoV-2 has unleashed a new wave of COVID-19 outbreaks. The efficacy of molnupiravir, an approved drug, is still unknown in patients infected with the Omicron variant. Objective: Evaluated the antiviral efficacy and safety of molnupiravir in patients infected with SARS-CoV-2 Omicron variant, with symptom duration within 5 days. Methods: We conducted a randomized, controlled trial involving patients with mild or moderate COVID-19. Patients were randomized to orally receive molnupiravir (800 mg) plus basic treatment or only basic treatment for 5 days (BID). The antiviral efficacy of the drug was evaluated using reverse transcriptase polymerase chain reaction. Results: Results showed that the time of viral RNA clearance (primary endpoint) was significantly decreased in the molnupiravir group (median, 9 days) compared to the control group (median, 10 days) (Log-Rank p = 0.0092). Of patients receiving molnupiravir, 18.42% achieved viral RNA clearance on day 5 of treatment, compared to the control group (0%) (p = 0.0092). On day 7, 40.79%, and 6.45% of patients in the molnupiravir and control groups, respectively, achieved viral RNA clearance (p = 0.0004). In addition, molnupiravir has a good safety profile, and no serious adverse events were reported. Conclusion: Molnupiravir significantly accelerated the SARS-CoV-2 Omicron RNA clearance in patients with COVID-19. Clinical Trial Registration: [chictr.org.cn], identifier [ChiCTR2200056817].

Amphiphilic Dendrimer Vectors for RNA Delivery: State-of-the-Art and Future Perspective.

Dendrimers, a special family of polymers, are particularly promising materials for various biomedical applications by virtue of their well-defined dendritic structure and cooperative multivalency. Specifically, in this Account, we present state-of-the-art amphiphilic dendrimers for nucleic acid delivery. Ribonucleic acid (RNA) molecules are fast becoming an important drug modality, particularly since the recent success of mRNA vaccines against COVID-19. Notably, RNA therapeutics offer the unique opportunity to treat diseases at the gene level and address "undruggable" targets. However, RNA therapeutics are not stable and have poor bioavailability, imposing the need for their protection and safe delivery by vectors to the sites-of-action to allow the desired therapeutic effects. Currently, the two most advanced nonviral vectors are based on lipids and polymers, with lipid vectors primarily exploiting the membrane-fusion mechanism and polymer vectors mainly endocytosis-mediated delivery. Notably, only lipid vectors have been advanced through to their clinical use in the delivery of, for example, the first siRNA drug and the first mRNA vaccine. The success of lipid vectors for RNA delivery has motivated research for further innovative materials as delivery vectors. Specifically, we have pioneered lipid/dendrimer conjugates, referred to as amphiphilic dendrimers, for siRNA delivery with the view to harnessing the delivery advantages of both lipid and polymer vectors while enjoying the unique structural features of dendrimers. These amphiphilic dendrimer vectors are lipid/dendrimer hybrids and are thus able to mimic lipid vectors and exploit membrane-fusion-mediated delivery, while simultaneously retaining the multivalent properties of polymer vectors that allow endocytosis-based delivery. In addition, they have precisely controllable and stable nanosized chemical structures and offer nanotechnology-based delivery. Effective amphiphilic dendrimer vectors share two important elements: chemical hydrophilic entities to bind RNA and RNA complex-stabilizing hydrophobicity. These two combined features allow the encapsulation of RNA within a stable complex before its release into the cytosol following endocytosis. This hydrophilic/hydrophobic balance permitted by the structural features of amphiphilic dendrimers plays a determining role in RNA delivery success. In this Account, we provide a conceptual overview of this exciting field with the latest breakthroughs and key advances in the design of amphiphilic dendrimers for the delivery of siRNA and mRNA. Specifically, we start with a short introduction to siRNA- and mRNA-based therapeutics and their delivery challenges. We then outline the pioneering and representative studies on amphiphilic dendrimer vectors to highlight their historical development and promising features that offer to facilitate the once challenging RNA delivery. We conclude by offering perspectives for the future of amphiphilic dendrimer vectors for nucleic acid delivery in general.

Global Burden of Respiratory Diseases Attributable to Ambient Particulate Matter Pollution: Findings From the Global Burden of Disease Study 2019.

Background: Exposure to ambient particulate matter pollution (APMP) is a global health issue that directly affects the human respiratory system. Thus, we estimated the spatiotemporal trends in the burden of APMP-related respiratory diseases from 1990 to 2019. Methods: Based on the Global Burden of Disease Study 2019, data on the burden of APMP-related respiratory diseases were analyzed by age, sex, cause, and location. Joinpoint regression analysis was used to analyze the temporal trends in the burden of different respiratory diseases over the 30 years. Results: Globally, in 2019, APMP contributed the most to chronic obstructive pulmonary disease (COPD), with 695.1 thousand deaths and 15.4 million disability-adjusted life years (DALYs); however, the corresponding age-standardized death and DALY rates declined from 1990 to 2019. Similarly, although age-standardized death and DALY rates since 1990 decreased by 24% and 40%, respectively, lower respiratory infections (LRIs) still had the second highest number of deaths and DALYs attributable to APMP. This was followed by tracheal, bronchus, and lung (TBL) cancer, which showed increased age-standardized death and DALY rates during the past 30 years and reached 3.78 deaths per 100,000 persons and 84.22 DALYs per 100,000 persons in 2019. Among children aged < 5 years, LRIs had a huge burden attributable to APMP, whereas for older people, COPD was the leading cause of death and DALYs attributable to APMP. The APMP-related burdens of LRIs and COPD were relatively higher among countries with low and low-middle socio-demographic index (SDI), while countries with high-middle SDI showed the highest burden of TBL cancer attributable to APMP. Conclusions: APMP contributed substantially to the global burden of respiratory diseases, posing a significant threat to human health. Effective actions aimed at air pollution can potentially avoid an increase in the PM2.5-associated disease burden, especially in highly polluted areas.

Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma.

Importance: Coronavirus disease 2019 (COVID-19) is a pandemic with no specific therapeutic agents and substantial mortality. It is critical to find new treatments. Objective: To determine whether convalescent plasma transfusion may be beneficial in the treatment of critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Design, Setting, and Participants: Case series of 5 critically ill patients with laboratory-confirmed COVID-19 and acute respiratory distress syndrome (ARDS) who met the following criteria: severe pneumonia with rapid progression and continuously high viral load despite antiviral treatment; Pao2/Fio2 <300; and mechanical ventilation. All 5 were treated with convalescent plasma transfusion. The study was conducted at the infectious disease department, Shenzhen Third People's Hospital in Shenzhen, China, from January 20, 2020, to March 25, 2020; final date of follow-up was March 25, 2020. Clinical outcomes were compared before and after convalescent plasma transfusion. Exposures: Patients received transfusion with convalescent plasma with a SARS-CoV-2-specific antibody (IgG) binding titer greater than 1:1000 (end point dilution titer, by enzyme-linked immunosorbent assay [ELISA]) and a neutralization titer greater than 40 (end point dilution titer) that had been obtained from 5 patients who recovered from COVID-19. Convalescent plasma was administered between 10 and 22 days after admission. Main Outcomes and Measures: Changes of body temperature, Sequential Organ Failure Assessment (SOFA) score (range 0-24, with higher scores indicating more severe illness), Pao2/Fio2, viral load, serum antibody titer, routine blood biochemical index, ARDS, and ventilatory and extracorporeal membrane oxygenation (ECMO) supports before and after convalescent plasma transfusion. Results: All 5 patients (age range, 36-65 years; 2 women) were receiving mechanical ventilation at the time of treatment and all had received antiviral agents and methylprednisolone. Following plasma transfusion, body temperature normalized within 3 days in 4 of 5 patients, the SOFA score decreased, and Pao2/Fio2 increased within 12 days (range, 172-276 before and 284-366 after). Viral loads also decreased and became negative within 12 days after the transfusion, and SARS-CoV-2-specific ELISA and neutralizing antibody titers increased following the transfusion (range, 40-60 before and 80-320 on day 7). ARDS resolved in 4 patients at 12 days after transfusion, and 3 patients were weaned from mechanical ventilation within 2 weeks of treatment. Of the 5 patients, 3 have been discharged from the hospital (length of stay: 53, 51, and 55 days), and 2 are in stable condition at 37 days after transfusion. Conclusions and Relevance: In this preliminary uncontrolled case series of 5 critically ill patients with COVID-19 and ARDS, administration of convalescent plasma containing neutralizing antibody was followed by improvement in their clinical status. The limited sample size and study design preclude a definitive statement about the potential effectiveness of this treatment, and these observations require evaluation in clinical trials.

Characteristics and outcomes of COVID-19 infection in 45 patients with breast cancer: A multi-center retrospective study in Hubei, China.

BACKGROUND: The COVID-19 pandemic is a significant worldwide health crisis. Breast cancer patients with COVID-19 are fragile and require particular clinical care. This study aimed to identify the clinical characteristics of breast cancer patients with COVID-19 and the risks associated with anti-cancer treatment. METHODS: The medical records of breast cancer patients with laboratory-confirmed COVID-19 were collected among 9559 COVID-19 patients from seven designated hospitals from 13th January to 18th March 2020 in Hubei, China. Univariate and multivariate analyses were performed to assess risk factors for COVID-19 severity. RESULTS: Of the 45 breast cancer patients with COVID-19, 33 (73.3%) developed non-severe COVID-19, while 12 (26.7%) developed severe COVID-19, of which 3 (6.7%) patients died. The median age was 62 years, and 3 (6.7%) patients had stage IV breast cancer. Univariate analysis showed that age over 75 and the Eastern Cooperative Oncology Group (ECOG) score were associated with COVID-19 disease severity (P < 0.05). Multivariate analysis showed that patients who received chemotherapy within 7 days had a significantly higher risk for severe COVID-19 (logistic regression model: RR = 13.886, 95% CI 1.014-190.243, P = 0.049; Cox proportional hazards model: HR = 13.909, 95% CI 1.086-178.150, P = 0.043), with more pronounced neutropenia and higher LDH, CRP and procalcitonin levels than other patients (P < 0.05). CONCLUSIONS: In our breast cancer cohort, the severity of COVID-19 could be associated with baseline factors such as age over 75 and ECOG scores. Chemotherapy within 7 days before symptom onset could be a risk factor for severe COVID-19, reflected by neutropenia and elevated LDH, CRP and procalcitonin levels.

Biomimetic Design and Mass Production of Sustainable Multiscale Cellulose Fibers‐Based Hierarchical Filter Materials for Protective Clothing

As a core part of personal protective equipment (PPE), filter materials play a key role in individual protection, especially in the fight against the COVID‐19. Here, a high‐performance multiscale cellulose fibers‐based filter material is introduced for protective clothing, which overcomes the limitation of mutual exclusion of filtration and permeability in cellulose‐based filter materials. With the hierarchical biomimetic structure design and the active surface of multiscale cellulose fibers, high PM2.5 removal efficiency of ≈92% is achieved with the high moisture transmission rate of 8 kg m−2 d−1. Through a simple and effective dip‐coating and roll‐to‐roll process, the hierarchical filter materials can be made on a large scale and further fabricated into high‐quality protective clothing by industrial production equipment. [ABSTRACT FROM AUTHOR] Copyright of Advanced Materials Technologies is the property of John Wiley & Sons, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Laboratory Diagnosis and Monitoring the Viral Shedding of SARS-CoV-2 Infection.

The worldwide epidemic of coronavirus disease 2019 (COVID-19) is ongoing. Rapid and accurate detection of the causative virus SARS-CoV-2 is vital for the treatment and control of COVID-19. In this study, the comparative sensitivity of different respiratory specimen types were retrospectively analyzed using 3,552 clinical samples from 410 COVID-19 patients confirmed by Guangdong CDC (Center for Disease Control and Prevention). Except for bronchoalveolar lavage fluid (BALF), the sputum possessed the highest positive rate (73.4%-87.5%), followed by nasal swabs (53.1%-85.3%) for both severe and mild cases during the first 14 days after illness onset (d.a.o.). Viral RNA could be detected in all BALF samples collected from the severe group within 14 d.a.o. and lasted up to 46 d.a.o. Moreover, although viral RNA was negative in the upper respiratory samples, it was also positive in BALF samples in most cases from the severe group during treatment. Notably, no viral RNA was detected in BALF samples from the mild group. Despite typical ground-glass opacity observed via computed tomographic scans, no viral RNA was detected in the first three or all upper respiratory tract specimens from some COVID-19 patients. In conclusion, sputum is most sensitive for routine laboratory diagnosis of COVID-19, followed by nasal swabs. Detection of viral RNA in BALF improves diagnostic accuracy in severe COVID-19 patients.

Inflammatory indexes and T lymphocyte subsets in patients with severe coronavirus disease 2019 pneumonia

Objective: To analyze inflammatory indicators and T lymphocyte subsets in severe patients with coronavirus disease-19 (COVID-19).

Risk factors for Coronavirus disease 2019 pneumonia after admission outside Wuhan, China.

Coronavirus disease 2019 (COVID-19) has spread worldwide, causing significant stress on the medical system. We explored the risk factors for condition changes in COVID-19 pneumonia patients after admission.The patients diagnosed with COVID-19 pneumonia at 2 medical centers in Hunan Province were studied, and those whose conditions changed after admission were compared. Their clinical characteristics and experimental indicators were compared using SPSS software and R language to build a disease risk prediction model.Patients with condition changes after admission were older and had more blood cell abnormalities and impaired organ function (decreased albumin, elevated D-dimer) than normal patients. We found that age, neutrophil ratio, D-dimer, chest Computed tomograpgy (CT) changes, and glucocorticoid use were risk factors for COVID-19 pneumonia after admission.Elderly patients are more susceptible to disease changes after COVID-19 pneumonia; COVID-19 pneumonia patients who develop disease changes after admission have higher neutrophil ratios, increased D-dimer levels, chest imaging changes, and glucocorticoid usage. Additional research is needed.

Elevated plasma levels of selective cytokines in COVID-19 patients reflect viral load and lung injury.

A recent outbreak of pneumonia in Wuhan, China was found to be caused by a 2019 novel coronavirus (2019-nCoV or SARS-CoV-2 or HCoV-19). We previously reported the clinical features of 12 patients with 2019-nCoV infections in Shenzhen, China. To further understand the pathogenesis of COVID-19 and find better ways to monitor and treat the disease caused by 2019-nCoV, we measured the levels of 48 cytokines in the blood plasma of those 12 COVID-19 patients. Thirty-eight out of the 48 measured cytokines in the plasma of 2019-nCoV-infected patients were significantly elevated compared to healthy individuals. Seventeen cytokines were linked to 2019-nCoV loads. Fifteen cytokines, namely M-CSF, IL-10, IFN-α2, IL-17, IL-4, IP-10, IL-7, IL-1ra, G-CSF, IL-12, IFN-γ, IL-1α, IL-2, HGF and PDGF-BB, were strongly associated with the lung-injury Murray score and could be used to predict the disease severity of 2019-nCoV infections by calculating the area under the curve of the receiver-operating characteristics. Our results suggest that 2019-nCoV infections trigger extensive changes in a wide array of cytokines, some of which could be potential biomarkers of disease severity of 2019-nCoV infections. These findings will likely improve our understanding of the immunopathologic mechanisms of this emerging disease. Our results also suggest that modulators of cytokine responses may play a therapeutic role in combating the disease once the functions of these elevated cytokines have been characterized.

A real-world disproportionality analysis of FDA Adverse Event Reporting System (FAERS) events for baricitinib.

BACKGROUND: Baricitinib is approved for the treatment of rheumatoid arthritis (RA). The authors retrospectively investigated adverse events (AEs) by data-mining a self-reporting database to better understand toxicities, especially since it has been used during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: A reporting odds ratio (ROR) was used to detect the risk signals from the data in the US Food and Drug Administration (FDA) adverse event reporting system database (FAERS). The definition relied on system organ class (SOCs) and preferred terms (PTs) by the Medical Dictionary for Regulatory Activities (MedDRA). RESULTS: The search retrieved 1,598 baricitinib-associated cases within the reporting period: 86 PTs with significant disproportionality were retained. Infections including 'herpes zoster,' 'oral herpes,' and 'herpes virus infection' were found at a similar rate to those reported in trials, and such events were rare. Reports emerged for several thrombotic adverse events, while these events were also rare. Unexpected safety signals as opportunistic infections were detected. Serious outcomes as death and life-threatening outcomes accounted for 9.76% of the reported cases. CONCLUSIONS: The incidence of these AEs does not appear above the background expected. These data are consistent with routine clinical observations and suggest the importance of pharmacovigilance.

Clinical characteristics, outcomes, and risk factors for mortality in patients with cancer and COVID-19 in Hubei, China: a multicentre, retrospective, cohort study.

BACKGROUND: Patients with cancer are a high-risk population in the COVID-19 pandemic. We aimed to describe clinical characteristics and outcomes of patients with cancer and COVID-19, and examined risk factors for mortality in this population. METHODS: We did a retrospective, multicentre, cohort study of 205 patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and with a pathological diagnosis of a malignant tumour in nine hospitals within Hubei, China, from Jan 13 to March 18, 2020. All patients were either discharged from hospitals or had died by April 20, 2020. Clinical characteristics, laboratory data, and cancer histories were compared between survivors and non-survivors by use of χ2 test. Risk factors for mortality were identified by univariable and multivariable logistic regression models. FINDINGS: Between Jan 13 and Mar 18, 2020, 205 patients with cancer and laboratory-confirmed SARS-CoV-2 infection were enrolled (median age 63 years [IQR 56-70; range 14-96]; 109 [53%] women). 183 (89%) had solid tumours and 22 (11%) had haematological malignancies. The median duration of follow-up was 68 days (IQR 59-78). The most common solid tumour types were breast (40 [20%] patients), colorectal (28 [14%]), and lung cancer (24 [12%]). 54 (30%) of 182 patients received antitumour therapies within 4 weeks before symptom onset. 30 (15%) of 205 patients were transferred to an intensive care unit and 40 (20%) died during hospital admission. Patients with haematological malignancies had poorer prognoses than did those with solid tumours: nine (41%) of 22 patients with haematological malignancies died versus 31 (17%) of 183 patients with solid tumours (hazard ratio for death 3·28 [95% CI 1·56-6·91]; log rank p=0·0009). Multivariable regression analysis showed that receiving chemotherapy within 4 weeks before symptom onset (odds ratio [OR] 3·51 [95% CI 1·16-10·59]; p=0·026) and male sex (OR 3·86 [95% CI 1·57-9·50]; p=0·0033) were risk factors for death during admission to hospital. INTERPRETATION: Patients with cancer and COVID-19 who were admitted to hospital had a high case-fatality rate. Unfavourable prognostic factors, including receiving chemotherapy within 4 weeks before symptom onset and male sex, might help clinicians to identify patients at high risk of fatal outcomes. FUNDING: National Natural Science Foundation of China.

Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 was first reported in Wuhan, December 2019, and continuously poses a serious threat to public health, highlighting the urgent need of identifying biomarkers for disease severity and progression. OBJECTIVE: We sought to identify biomarkers for disease severity and progression of COVID-19. METHODS: Forty-eight cytokines in the plasma samples from 50 COVID-19 cases including 11 critically ill, 25 severe, and 14 moderate patients were measured and analyzed in combination with clinical data. RESULTS: Levels of 14 cytokines were found to be significantly elevated in COVID-19 cases and showed different expression profiles in patients with different disease severity. Moreover, expression levels of IFN-γ-induced protein 10, monocyte chemotactic protein-3, hepatocyte growth factor, monokine-induced gamma IFN, and macrophage inflammatory protein 1 alpha, which were shown to be highly associated with disease severity during disease progression, were remarkably higher in critically ill patients, followed by severe and then the moderate patients. Serial detection of the 5 cytokines in 16 cases showed that continuously high levels were associated with deteriorated progression of disease and fatal outcome. Furthermore, IFN-γ-induced protein 10 and monocyte chemotactic protein-3 were excellent predictors for the progression of COVID-19, and the combination of the 2 cytokines showed the biggest area under the curve of the receiver-operating characteristics calculations with a value of 0.99. CONCLUSIONS: In this study, we report biomarkers that are highly associated with disease severity and progression of COVID-19. These findings add to our understanding of the immunopathologic mechanisms of severe acute respiratory syndrome coronavirus 2 infection, and provide potential therapeutic targets and strategies.

The novel coronavirus (COVID-19) pneumonia with negative detection of viral ribonucleic acid from nasopharyngeal swabs: a case report.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) outbreak started in Wuhan, Hubei, China since Dec 2019 and cases of infection have been continuously reported in various countries. It is now clear that the SARS-COV-2 coronavirus is transmissible from human to human. Nucleic acid detection is considered as the gold standard for the diagnosis of COVID-19. In this case report, we describe our experience in detection of SARS-COV-2 from a confirmed patient using nucleic acid test of bronchoalveolar-lavage fluid (BALF) samples but not nasopharyngeal swabs. CASE PRESENTATION: We present a case of severely ill SARS-COV-2 infected 46-year-old man with fever, coughing and chest tightness. We performed viral detection using his BALF samples and imaging method (CT) for confirmation. The patient received combination of interferonalfa-1b and ribavirin, lopinavir and ritonavir for antiviral treatment at different stages. Other medication was also given to him in combination for anti-inflammation, intestinal microbial regulation, phlegm elimination, liver protection and pulmonary fibrosis prevention purposes. We provided oxygen supply to him using BIPAP ventilator and high-flow humidification oxygen therapy instrument to facilitate respiration. The patient was cured and discharged. CONCLUSION: This case report described an effective supportive medication scheme to treat SARS-COV-2 infected patient and emphasized the necessity of detection of the viral genome using BALF samples and its significance in the diagnosis and prognosis of the disease.