An acute respiratory disease, caused by a novel coronavirus (SARS-CoV-2, previously known as 2019-nCoV), the coronavirus disease 2019 (COVID-19) has spread throughout China and received worldwide attention. On 30 January 2020, World Health Organization (WHO) officially declared the COVID-19 epidemic as a public health emergency of international concern. The emergence of SARS-CoV-2, since the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, marked the third introduction of a highly pathogenic and large-scale epidemic coronavirus into the human population in the twenty-first century. As of 1 March 2020, a total of 87,137 confirmed cases globally, 79,968 confirmed in China and 7169 outside of China, with 2977 deaths (3.4%) had been reported by WHO. Meanwhile, several independent research groups have identified that SARS-CoV-2 belongs to β-coronavirus, with highly identical genome to bat coronavirus, pointing to bat as the natural host. The novel coronavirus uses the same receptor, angiotensin-converting enzyme 2 (ACE2) as that for SARS-CoV, and mainly spreads through the respiratory tract. Importantly, increasingly evidence showed sustained human-to-human transmission, along with many exported cases across the globe. The clinical symptoms of COVID-19 patients include fever, cough, fatigue and a small population of patients appeared gastrointestinal infection symptoms. The elderly and people with underlying diseases are susceptible to infection and prone to serious outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm. Currently, there are few specific antiviral strategies, but several potent candidates of antivirals and repurposed drugs are under urgent investigation. In this review, we summarized the latest research progress of the epidemiology, pathogenesis, and clinical characteristics of COVID-19, and discussed the current treatment and scientific advancements to combat the epidemic novel coronavirus.

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The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status.

Importance The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an unprecedented challenge to identify effective drugs for prevention and treatment. Given the rapid pace of scientific discovery and clinical data generated by the large number of people rapidly infected by SARS-CoV-2, clinicians need accurate evidence regarding effective medical treatments for this infection. Observations No proven effective therapies for this virus currently exist. The rapidly expanding knowledge regarding SARS-CoV-2 virology provides a significant number of potential drug targets. The most promising therapy is remdesivir. Remdesivir has potent in vitro activity against SARS-CoV-2, but it is not US Food and Drug Administration approved and currently is being tested in ongoing randomized trials. Oseltamivir has not been shown to have efficacy, and corticosteroids are currently not recommended. Current clinical evidence does not support stopping angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in patients with COVID-19. Conclusions and Relevance The COVID-19 pandemic represents the greatest global public health crisis of this generation and, potentially, since the pandemic influenza outbreak of 1918. The speed and volume of clinical trials launched to investigate potential therapies for COVID-19 highlight both the need and capability to produce high-quality evidence even in the middle of a pandemic. No therapies have been shown effective to date.

https://jamanetwork.com/journals/jama/articlepdf/2764727/jama_sanders_2020_rv_200005.pdf

Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review.

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 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/Fio2increased 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.

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

Currently, there are no approved specific antiviral agents for novel coronavirus disease 2019 (COVID-19). In this study, 10 severe patients confirmed by real-time viral RNA test were enrolled prospectively. One dose of 200 mL of convalescent plasma (CP) derived from recently recovered donors with the neutralizing antibody titers above 1:640 was transfused to the patients as an addition to maximal supportive care and antiviral agents. The primary endpoint was the safety of CP transfusion. The second endpoints were the improvement of clinical symptoms and laboratory parameters within 3 d after CP transfusion. The median time from onset of illness to CP transfusion was 16.5 d. After CP transfusion, the level of neutralizing antibody increased rapidly up to 1:640 in five cases, while that of the other four cases maintained at a high level (1:640). The clinical symptoms were significantly improved along with increase of oxyhemoglobin saturation within 3 d. Several parameters tended to improve as compared to pretransfusion, including increased lymphocyte counts (0.65 × 109/L vs. 0.76 × 109/L) and decreased C-reactive protein (55.98 mg/L vs. 18.13 mg/L). Radiological examinations showed varying degrees of absorption of lung lesions within 7 d. The viral load was undetectable after transfusion in seven patients who had previous viremia. No severe adverse effects were observed. This study showed CP therapy was well tolerated and could potentially improve the clinical outcomes through neutralizing viremia in severe COVID-19 cases. The optimal dose and time point, as well as the clinical benefit of CP therapy, needs further investigation in larger well-controlled trials.

https://www.pnas.org/content/pnas/117/17/9490.full.pdf

Effectiveness of convalescent plasma therapy in severe COVID-19 patients.

Coronavirus disease 2019 (COVID-19) is currently a global pandemic, but human immune responses to the virus remain poorly understood. We used high-dimensional cytometry to analyze 125 COVID-19 patients and compare them with recovered and healthy individuals. Integrated analysis of ~200 immune and ~50 clinical features revealed activation of T cell and B cell subsets in a proportion of patients. A subgroup of patients had T cell activation characteristic of acute viral infection and plasmablast responses reaching >30% of circulating B cells. However, another subgroup had lymphocyte activation comparable with that in uninfected individuals. Stable versus dynamic immunological signatures were identified and linked to trajectories of disease severity change. Our analyses identified three immunotypes associated with poor clinical trajectories versus improving health. These immunotypes may have implications for the design of therapeutics and vaccines for COVID-19.

Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications

398 www.thelancet.com/infection Vol 20 April 2020 Control and Nursing in Guangdong Second Provincial General Hospital, have undergone intensive training to become familiar with the requirements for infection control in the negative pressure isolation wards. Herein, cameras cover the entire ward except for the privacy area. The infection control observer monitors medical staff in real time via computer monitors in a separate area (figure). The main responsibilities of the observer are to maintain the normal operation of the negative pressure isolation wards, supervise the implementation of disinfection, ensure a sufficient supply of protective materials, arrange specimens for inspection, and relieve anxiety of the medical personnel while treating patients. The observers pay attention to the medical staff not only during their time in the negative pressure ward, but also during the putting on or taking off of protective equipment when they enter or leave the ward. Although the health-care providers have attended multiple training sessions and emergency drills, in operation (especially in high-stress negative pressure wards) some steps might be omitted or overlooked, thus incurring potential exposure to nosocomial infection. For example, when a nurse helped an elderly patient pull up a zipper in the negative pressure ward, the zipper unexpectedly ripped the nurse’s glove. The nurse became nervous, and anxious to continue her procedures. Discovering this situation on screen, the observer immediately soothed the nurse and sent another staff member into the ward to assist. Following the occupational exposure process, the observer then instructed the nurse to remove her gloves carefully, disinfect her hands, and dispose of the ripped gloves. The observer also systematically assessed the risks for the nurse and arranged a quarantine room for medical observation to ensure full safety before she was allowed to return to the negative pressure ward. The observing system, as a proactive infection control tool, provides immediate prevention against nosocomial infection in negative pressure isolation wards, which offers creative assistance to combat the COVID-19 outbreak. Guangdong Second Provincial General Hospital plans to incorporate artificial intelligence image recognition into the observing system, aiming to enhance the sensitivity and accuracy of instant detection. Implementing and improving the observing system might be a promising endeavor for controlling nosocomial infection of the COVID-19 outbreak and other acute infectious diseases.

Convalescent plasma as a potential therapy for COVID-19.

Extracorporeal membrane oxygenation (ECMO): does it have a role in the treatment of severe COVID-19?

Extracorporeal membrane oxygenation (ECMO) has been increasingly used for severe neonatal respiratory failure refractory to conventional treatments. To systematically evaluate the complications and mortality of venovenous ECMO (VV ECMO) in the treatment of neonatal respiratory failure, we performed a systematic review and meta-analysis of all the related studies. PubMed, Embase, and Cochrane Library were searched. The retrieval period was from the establishment of the database to February 2019. Two investigators independently screened articles according to the inclusion and exclusion criteria. The quality of article was assessed by the Newcastle-Ottawa scale (NOS). The meta-analysis was performed by Stata 15.0 software. Four observational studies were included, with a total of 347 newborns. VV ECMO was used for neonates with refractory respiratory failure unresponsive to maximal medical therapy. Median ages of the newborns at cannulation were 43.2 h, 23 h, 19 h, and 71 h in the included four studies, respectively. The overall mortality at hospital charge was 12% (5–18%) with a heterogeneity of I2 = 73.8% (p = 0.01). Two studies reported mortality during ECMO and after decannulation, with 10% (0.8–19.2%) and 6.1% (2.6–9.6%), respectively. The most common complications associated with VV ECMO were: pneumothorax (20.6%), hypertension (20.4%), cannula dysfunction (20.2%), seizure (14.9%), renal failure requiring hemofiltration (14.7%), infectious complications (10.3%), thrombi (7.4%), intracranial hemorrhage or infarction (6.6%), hemolysis (5.3%), cannula site bleeding (4.4%), gastrointestinal bleeding (3.7%), oxygenator failure (2.8%), other bleeding events (2.8%), brain death (1.9%), and myocardial stun (0.9%). The overall mortality at discharge of VV ECMO in the treatment of neonatal respiratory failure was 12%. Although complications are frequent, the survival rate during hospitalization is still high. Further larger samples, and higher quality of randomized controlled trials (RCTs) are needed to clarify the efficacy and safety of this technique in the treatment of neonatal respiratory failure.

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Complications and mortality of venovenous extracorporeal membrane oxygenation in the treatment of neonatal respiratory failure: a systematic review and meta-analysis.

https://journals.sagepub.com/doi/pdf/10.1177/0963689721995455

Mesenchymal Stromal Cell-Based Therapy: A Promising Approach for Severe COVID-19.

A novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged in Wuhan, China since the end of December 2019 and has quickly spread all over the world in a matter of two months. To date, no specific treatment has been proven to be effective for coronavirus disease 2019 (COVID-19). With the rapid increase of infected patients and deaths, it is urgent to explore an effective treatment for COVID-19. Current studies suggest that there exists cytokine storm in SARS-CoV-2-infected patient, some of the patients will develop to acute respiratory distress syndrome (ARDS) and multiple organ dysfunction, even death. Mesenchymal stem cells (MSCs) possess the property of immunomodulation. Given the previous preclinical and clinical studies, MSCs therapy has been shown safety and efficacy in the treatment of respiratory failure or ARDS. Based on similar principles, MSCs therapy may also be an effective therapy in the treatment of COVID-19. In this study, we summarized the clinical outcomes of MSCs for ARDS patients in some preclinical and clinical studies, and discussed the application of MSCs for patients with COVID-19 in China and the related important issues with MSCs use during the outbreak.

Jing Xiong

Papers

Convalescent plasma as a potential therapy for COVID-19.

Extracorporeal membrane oxygenation (ECMO): does it have a role in the treatment of severe COVID-19?

Complications and mortality of venovenous extracorporeal membrane oxygenation in the treatment of neonatal respiratory failure: a systematic review and meta-analysis.

Mesenchymal Stromal Cell-Based Therapy: A Promising Approach for Severe COVID-19.

Mesenchymal Stem Cell-based Therapy for COVID-19: Possibility and Potential.