Key PointsQuestionCould administration of convalescent plasma transfusion be beneficial in the treatment of critically ill patients with coronavirus disease 2019 (COVID-19)?FindingsIn this uncontrolled case series of 5 critically ill patients with COVID-19 and acute respiratory distress syndrome (ARDS), administration of convalescent plasma containing neutralizing antibody was followed by an improvement in clinical status.MeaningThese preliminary findings raise the possibility that convalescent plasma transfusion may be helpful in the treatment of critically ill patients with COVID-19 and ARDS, but this approach requires evaluation in randomized clinical trials.

1 BackgroundThe outbreak of novel coronavirus pneumonia (NCP) caused by

Background: The outbreak of coronavirus disease 2019 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-g-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-g-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 outbreak of Coronavirus Disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, December 2019, and continuously poses a serious threat to public health. Our previous study has shown that cytokine storm occurred during SARS-CoV-2 infection, while the detailed role of cytokines in the disease severity and progression remained unclear due to the limited case number. In this study, we examined 48 cytokines in the plasma samples from 53 COVID-19 cases, among whom 34 were severe cases, and the others moderate. Results showed that 14 cytokines were significantly elevated upon admission in COVID-19 cases. Moreover, IP-10, MCP-3, and IL-1ra were significantly higher in severe cases, and highly associated with the PaO2/FaO2 and Murray score. Furthermore, the three cytokines were independent predictors for the progression of COVID-19, and the combination of IP-10, MCP-3 and IL-1ra showed the biggest area under the curve (AUC) of the receiver-operating characteristics (ROC) calculations. Serial detection of IP-10, MCP-3 and IL-1ra in 14 severe cases showed that the continuous high levels of these cytokines were associated with disease deterioration and fatal outcome. In conclusion, we report three cytokines that closely associated with disease severity and outcome of COVID-19. These findings add to our understanding of the immunopathologic mechanisms of SARS-CoV-2 infection, which suggested novel therapeutic targets and strategy.

The global pandemic of Coronavirus Disease 2019 (COVID-19) is now 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 specimens were retrospectively analyzed using 3552 clinical samples from 410 Guangdong CDC (Center for Disease Control and Prevention) confirmed COVID-19 patients. Except for 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 from the severe group collected as early as 4 days after illness onset (d.a.o) and lasted up to 46 d.a.o., while none of BALF samples from mild group. Moreover, although viral RNA was negative in the upper respiratory samples, it was also positive in BALF samples in most cases from severe group during treatment. Despite of typical ground-glass opacity observed via computed tomographic (CT) scans, no viral RNA was detected in the first 3 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 RNAs in BLAF improves diagnostic accuracy in severe COVID-19 patients.

The number of annotated protein coding genes in the genome of Caenorhabditis elegans is similar to that of other animals, but the extent of its non-protein-coding transcriptome remains unknown. Expression profiling on whole-genome tiling microarrays applied to a mixed-stage C. elegans population verified the expression of 71% of all annotated exons. Only a small fraction (11%) of the polyadenylated transcription is non-annotated and appears to consist of ∼3200 missed or alternative exons and 7800 small transcripts of unknown function (TUFs). Almost half (44%) of the detected transcriptional output is non-polyadenylated and probably not protein coding, and of this, 70% overlaps the boundaries of protein-coding genes in a complex manner. Specific analysis of small non-polyadenylated transcripts verified 97% of all annotated small ncRNAs and suggested that the transcriptome contains ∼1200 small (<500 nt) unannotated noncoding loci. After combining overlapping transcripts, we estimate that at least 70% of the total C. elegans genome is transcribed.

Our results support that H5N6 virus could potentially be a major public health threat, and suggest it is possible that the earlier acquisition of cellular immunity and lower concentrations of cytokines/chemokines contributed to survival in our patient. Analysis of more patient samples will be needed to draw concrete conclusions.

BackgroundPrimary amoebic meningoencephalitis (PAM), caused by Naegleria fowleri, is a rare protozoan infectious disease in China. A fatality rate of over 95% had been reported due to extremely rapid disease progression in the USA and other countries. Rapid and precise identification of the causative agent is very important to clinicians for guiding their choices for administering countermeasures in the clinic. In this report, we applied the next-generation sequencing (NGS) method to rapidly show that N. fowleri was the causative agent of a fatal case involving a 42-year-old man with severe PAM disease, the first reported in mainland China.Case presentationA 42-year old male in a deep coma was admitted to Shenzhen Third People’s Hospital, a special medical care unit with expertise in infectious diseases. Increased intracranial pressure was detected. The cerebrospinal fluid (CSF) sample was found to be red and cloudy with increased leukocyte and protein levels. While bacterial cultures with CSF were negative, N. fowleri was determined to be the causative agent with NGS. Amphotericin B (AmB), a drug with anti-amoeba activity, was used immediately, but the treatment came too late and the patient died 2 days after the NGS confirmation.ConclusionIn this paper, we reported a case of PAM disease for the first time in mainland China. NGS was used for rapid diagnosis and provided guidance for prescribing medications. However, the patient died due to a late admission amid advanced PAM disease. Early detection of N. fowleri is necessary in order to select effective drug treatments and control the disease progression. Despite the negative survival outcome, NGS was shown to be a promising method of rapid and precise identification of N. fowleri.Electronic supplementary materialThe online version of this article (10.1186/s12879-018-3261-z) contains supplementary material, which is available to authorized users.