Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review.

This article by Wiersinga and colleagues was first published online in JAMA in July 2020.
Importance:  The coronavirus disease 2019 (COVID-19) pandemic, due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease. This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19.
Observations:  SARS-CoV-2 is spread primarily via respiratory droplets during close face-to-face contact. Infection can be spread by asymptomatic, presymptomatic, and symptomatic carriers. The average time from exposure to symptom onset is 5 days, and 97.5% of people who develop symptoms do so within 11.5 days. The most common symptoms are fever, dry cough, and shortness of breath. Radiographic and laboratory abnormalities, such as lymphopenia and elevated lactate dehydrogenase, are common, but nonspecific. Diagnosis is made by detection of SARS-CoV-2 via reverse transcription polymerase chain reaction testing, although false-negative test results may occur in up to 20% to 67% of patients; however, this is dependent on the quality and timing of testing. Manifestations of COVID-19 include asymptomatic carriers and fulminant disease characterized by sepsis and acute respiratory failure. Approximately 5% of patients with COVID-19, and 20% of those hospitalized, experience severe symptoms necessitating intensive care. More than 75% of patients hospitalized with COVID-19 require supplemental oxygen. Treatment for individuals with COVID-19 includes best practices for supportive management of acute hypoxic respiratory failure. Emerging data indicate that dexamethasone therapy reduces 28-day mortality in patients requiring supplemental oxygen compared with usual care (21.6% vs 24.6%; age-adjusted rate ratio, 0.83 [95% CI, 0.74-0.92]) and that remdesivir improves time to recovery (hospital discharge or no supplemental oxygen requirement) from 15 to 11 days. In a randomized trial of 103 patients with COVID-19, convalescent plasma did not shorten time to recovery. Ongoing trials are testing antiviral therapies, immune modulators, and anticoagulants. The case-fatality rate for COVID-19 varies markedly by age, ranging from 0.3 deaths per 1000 cases among patients aged 5 to 17 years to 304.9 deaths per 1000 cases among patients aged 85 years or older in the US. Among patients hospitalized in the intensive care unit, the case fatality is up to 40%. At least 120 SARS-CoV-2 vaccines are under development. Until an effective vaccine is available, the primary methods to reduce spread are face masks, social distancing, and contact tracing. Monoclonal antibodies and hyperimmune globulin may provide additional preventive strategies.
Conclusions and Relevance:  As of July 1, 2020, more than 10 million people worldwide had been infected with SARS-CoV-2. Many aspects of transmission, infection, and treatment remain unclear. Advances in prevention and effective management of COVID-19 will require basic and clinical investigation and public health and clinical interventions.
This article is freely available to all via this link

Critical Care Reviews Newsletter 448 12th June 2020

The Critical Care Reviews Newsletter, provides you with the best critical care research and open access articles from across the medical literature.
“Once again, this week’s edition is dominated by COVID-19. The highlights are systematic reviews and meta analyses on hospital‑ and ICU‑treated sepsis & sepsis acquired in hospitals and intensive care units; observational studies on persistent symptoms in patients after acute COVID-19, the emerging spectrum of COVID-19 neurology, the association between discharge delay from intensive care and patient outcomes & the prevalence of SARS-CoV-2 in Spain. There are also two COVID-19 – related guidelines on the management of critically ill adults with COVID-19s & antithrombotic management in COVID-19; three excellent COVID-19 – related narrative reviews, including a general review, emerging pharmacological therapies & extrapulmonary manifestations; editorials on critical care journals during the COVID-19 pandemic & when data interpretation should not rely on the magnitude of P values; and commentaries on whether a different approach is required for COVID-19 related ARDS, airborne transmission of COVID-19 & COVID-19 clinical trials; as well as correspondence on frailty in COVID-19 patients & patient-self-inflicted lung injury in COVID-19.
The full text of the issue is available via this link

Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study

This article from the UK Obstetric Surveillance System SARS-CoV-2 Infection in Pregnancy Collaborative Group was published online in the BMJ (Clinical research ed.) at the end of June 2020.
Objectives:  To describe a national cohort of pregnant women admitted to hospital with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the UK, identify factors associated with infection, and describe outcomes, including transmission of infection, for mothers and infants.
Design:  Prospective national population based cohort study using the UK Obstetric Surveillance System (UKOSS).
Setting:  All 194 obstetric units in the UK.
Participants:  427 pregnant women admitted to hospital with confirmed SARS-CoV-2 infection between 1 March 2020 and 14 April 2020.
Main Outcome Measures:  Incidence of maternal hospital admission and infant infection. Rates of maternal death, level 3 critical care unit admission, fetal loss, caesarean birth, preterm birth, stillbirth, early neonatal death, and neonatal unit admission.
Results:  The estimated incidence of admission to hospital with confirmed SARS-CoV-2 infection in pregnancy was 4.9 (95% confidence interval 4.5 to 5.4) per 1000 maternities. 233 (56%) pregnant women admitted to hospital with SARS-CoV-2 infection in pregnancy were from black or other ethnic minority groups, 281 (69%) were overweight or obese, 175 (41%) were aged 35 or over, and 145 (34%) had pre-existing comorbidities. 266 (62%) women gave birth or had a pregnancy loss; 196 (73%) gave birth at term. Forty one (10%) women admitted to hospital needed respiratory support, and five (1%) women died. Twelve (5%) of 265 infants tested positive for SARS-CoV-2 RNA, six of them within the first 12 hours after birth.
Conclusions:  Most pregnant women admitted to hospital with SARS-CoV-2 infection were in the late second or third trimester, supporting guidance for continued social distancing measures in later pregnancy. Most had good outcomes, and transmission of SARS-CoV-2 to infants was uncommon. The high proportion of women from black or minority ethnic groups admitted with infection needs urgent investigation and explanation.
This article is freely available to all via this link

Intensive Care Medicine Volume 46 Number 7 July 2020

intensive-care-medicineTo view Intensive Care Medicine’s July issue’s contents page follow this link.
Articles published in this issue include: Managing ICU surge during the COVID-19 crisis: rapid guidelines, “Interventions for oropharyngeal dysphagia in acute and critical care: a systematic review and meta-analysisand “Acute kidney injury in critically ill patients with COVID-19”.
Together with other articles on COVID 19 these are freely available in full text to everyone.
To read the full text of any of these articles via the journal’s homepage requires a personal subscription to “Intensive Care Medicine” though some are available open access.  Individual articles can be ordered from the Rotherham NHS Foundation Trust Library and Knowledge Service.  Registered members of the library can make article requests online via this link.
The full text of articles from issues older than one year ago is available via this link to an archive of issues of Intensive Care Medicine.  A Rotherham NHS Athens password is required.  Eligible staff can register for an Athens password via this link.  Please speak to the library staff for more details.

Critical Care Reviews Newsletter 446 28th June 2020

The highlights of this week’s edition are the pre-print of the randomised controlled RECOVERY trial, reporting a huge mortality benefit in critically ill COVID-19 patients, & another RCT comparing resident physician ICU shifts of ≤ 16 hours with longer shifts; systematic reviews and meta analyses on physical distancing, face masks, and eye protection to prevent transmission of SARS-CoV-2, & rehabilitation interventions in critically ill patients; and observational studies on ultra-rapid exome sequencing in critically ill infants, & adverse events after transition from ICU to hospital ward. There are also guidelines on venous thromboembolism prophylaxis in trauma patients, & pediatric airway management in COVID-19 patients; narrative reviews on emerging therapies in acute ischemic stroke, & ventilation-induced lung injury; editorials on making the case for clinical trials and against off-label drug use in COVID-19, & editorial evaluation and peer review during a pandemic; and commentaries on the identification of pathophysiological patterns for triage and respiratory support in COVID-19, & COVID-19 and ethnicity: who will research results apply to?.
The full text of the issue is available via this link

Intensive Care Medicine Volume 46 Number 6 June 2020

To view Intensive Care Medicine’s June issue’s contents page follow this link.
Articles published in this issue include: High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study”, COVID-19 pneumonia: different respiratory treatments for different phenotypes? and “No dose” lung ultrasound correlation with “low dose” CT scan for early diagnosis of SARS-CoV-2 pneumonia.
Together with other articles on COVID 19 these are freely available in full text to everyone.
To read the full text of any of these articles via the journal’s homepage requires a personal subscription to “Intensive Care Medicine” though some are available open access.  Individual articles can be ordered from the Rotherham NHS Foundation Trust Library and Knowledge Service.  Registered members of the library can make article requests online via this link.
The full text of articles from issues older than one year ago is available via this link to an archive of issues of Intensive Care Medicine.  A Rotherham NHS Athens password is required.  Eligible staff can register for an Athens password via this link.  Please speak to the library staff for more details.

Incidence, clinical outcomes, and transmission dynamics of severe coronavirus disease 2019 in California and Washington: prospective cohort study.

This article by Lewnard and colleagues was first published in the BMJ in May 2020.
Objective:  To understand the epidemiology and burden of severe coronavirus disease 2019 (covid-19) during the first epidemic wave on the west coast of the United States.
Design:  Prospective cohort study.
Setting:  Kaiser Permanente integrated healthcare delivery systems serving populations in northern California, southern California, and Washington state.
Participants:  1840 people with a first acute hospital admission for confirmed covid-19 by 22 April 2020, among 9 596 321 healthcare plan enrollees. Analyses of hospital length of stay and clinical outcomes included 1328 people admitted by 9 April 2020 (534 in northern California, 711 in southern California, and 83 in Washington).
Main Outcome Measures:  Cumulative incidence of first acute hospital admission for confirmed covid-19, and subsequent probabilities of admission to an intensive care unit (ICU) and mortality, as well as duration of hospital stay and ICU stay. The effective reproduction number (RE ) describing transmission dynamics was estimated for each region.
Results:  As of 22 April 2020, cumulative incidences of a first acute hospital admission for covid-19 were 15.6 per 100 000 cohort members in northern California, 23.3 per 100 000 in southern California, and 14.7 per 100 000 in Washington. Accounting for censoring of incomplete hospital stays among those admitted by 9 April 2020, the estimated median duration of stay among survivors was 9.3 days (with 95% staying 0.8 to 32.9 days) and among non-survivors was 12.7 days (1.6 to 37.7 days). The censoring adjusted probability of ICU admission for male patients was 48.5% (95% confidence interval 41.8% to 56.3%) and for female patients was 32.0% (26.6% to 38.4%). For patients requiring critical care, the median duration of ICU stay was 10.6 days (with 95% staying 1.3 to 30.8 days). The censoring adjusted case fatality ratio was 23.5% (95% confidence interval 19.6% to 28.2%) among male inpatients and 14.9% (11.8% to 18.6%) among female inpatients; mortality risk increased with age for both male and female patients. Reductions in RE were identified over the study period within each region.
Conclusions:  Among residents of California and Washington state enrolled in Kaiser Permanente healthcare plans who were admitted to hospital with covid-19, the probabilities of ICU admission, of long hospital stay, and of mortality were identified to be high. Incidence rates of new hospital admissions have stabilized or declined in conjunction with implementation of social distancing interventions.
The full text of this article is freely available via this link

Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study

This article by Docherty and other members of the ISARIC4C investigators group was first published in BMJ during May 2020.
Objective:  To characterise the clinical features of patients admitted to hospital with coronavirus disease 2019 (covid-19) in the United Kingdom during the growth phase of the first wave of this outbreak who were enrolled in the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) World Health Organization (WHO) Clinical Characterisation Protocol UK (CCP-UK) study, and to explore risk factors associated with mortality in hospital.
Design:  Prospective observational cohort study with rapid data gathering and near real time analysis.
Setting:  208 acute care hospitals in England, Wales, and Scotland between 6 February and 19 April 2020. A case report form developed by ISARIC and WHO was used to collect clinical data. A minimal follow-up time of two weeks (to 3 May 2020) allowed most patients to complete their hospital admission.
Participants:  20 133 hospital in-patients with covid-19.
Main Outcome Measures:  Admission to critical care (high dependency unit or intensive care unit) and mortality in hospital.
Results:  The median age of patients admitted to hospital with covid-19, or with a diagnosis of covid-19 made in hospital, was 73 years (interquartile range 58-82, range 0-104). More men were admitted than women (men 60%, n=12 068; women 40%, n=8065). The median duration of symptoms before admission was 4 days (interquartile range 1-8). The commonest co-morbidities were chronic cardiac disease (31%, 5469/17 702), uncomplicated diabetes (21%, 3650/17 599), non-asthmatic chronic pulmonary disease (18%, 3128/17 634), and chronic kidney disease (16%, 2830/17 506); 23% (4161/18 525) had no reported major comorbidity. Overall, 41% (8199/20 133) of patients were discharged alive, 26% (5165/20 133) died, and 34% (6769/20 133) continued to receive care at the reporting date. 17% (3001/18 183) required admission to high dependency or intensive care units; of these, 28% (826/3001) were discharged alive, 32% (958/3001) died, and 41% (1217/3001) continued to receive care at the reporting date. Of those receiving mechanical ventilation, 17% (276/1658) were discharged alive, 37% (618/1658) died, and 46% (764/1658) remained in hospital. Increasing age, male sex, and comorbidities including chronic cardiac disease, non-asthmatic chronic pulmonary disease, chronic kidney disease, liver disease and obesity were associated with higher mortality in hospital.
Conclusions:  ISARIC WHO CCP-UK is a large prospective cohort study of patients in hospital with covid-19. The study continues to enrol at the time of this report. In study participants, mortality was high, independent risk factors were increasing age, male sex, and chronic comorbidity, including obesity. This study has shown the importance of pandemic preparedness and the need to maintain readiness to launch research studies in response to outbreaks.
The full text of this article is freely available via this link.

Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy.

This article in JAMA by Grasselli and colleagues was first published online in April 2020.
Importance:  In December 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) emerged in China and has spread globally, creating a pandemic. Information about the clinical characteristics of infected patients who require intensive care is limited.
Objective:  To characterize patients with coronavirus disease 2019 (COVID-19) requiring treatment in an intensive care unit (ICU) in the Lombardy region of Italy.
Design, Setting, and Participants:  Retrospective case series of 1591 consecutive patients with laboratory-confirmed COVID-19 referred for ICU admission to the coordinator center (Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy) of the COVID-19 Lombardy ICU Network and treated at one of the ICUs of the 72 hospitals in this network between February 20 and March 18, 2020. Date of final follow-up was March 25, 2020.
Exposures:  SARS-CoV-2 infection confirmed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay of nasal and pharyngeal swabs.
Main Outcomes and Measures:  Demographic and clinical data were collected, including data on clinical management, respiratory failure, and patient mortality. Data were recorded by the coordinator center on an electronic worksheet during telephone calls by the staff of the COVID-19 Lombardy ICU Network.
Results:  Of the 1591 patients included in the study, the median (IQR) age was 63 (56-70) years and 1304 (82%) were male. Of the 1043 patients with available data, 709 (68%) had at least 1 comorbidity and 509 (49%) had hypertension. Among 1300 patients with available respiratory support data, 1287 (99% [95% CI, 98%-99%]) needed respiratory support, including 1150 (88% [95% CI, 87%-90%]) who received mechanical ventilation and 137 (11% [95% CI, 9%-12%]) who received non-invasive ventilation. The median positive end-expiratory pressure (PEEP) was 14 (IQR, 12-16) cm H2O, and Fio2 was greater than 50% in 89% of patients. The median Pao2/Fio2 was 160 (IQR, 114-220). The median PEEP level was not different between younger patients (n = 503 aged ≤63 years) and older patients (n = 514 aged ≥64 years) (14 [IQR, 12-15] vs 14 [IQR, 12-16] cm H2O, respectively; median difference, 0 [95% CI, 0-0]; P = .94). Median Fio2 was lower in younger patients: 60% (IQR, 50%-80%) vs 70% (IQR, 50%-80%) (median difference, -10% [95% CI, -14% to 6%]; P = .006), and median Pao2/Fio2 was higher in younger patients: 163.5 (IQR, 120-230) vs 156 (IQR, 110-205) (median difference, 7 [95% CI, -8 to 22]; P = .02). Patients with hypertension (n = 509) were older than those without hypertension (n = 526) (median [IQR] age, 66 years [60-72] vs 62 years [54-68]; P < .001) and had lower Pao2/Fio2 (median [IQR], 146 [105-214] vs 173 [120-222]; median difference, -27 [95% CI, -42 to -12]; P = .005). Among the 1581 patients with ICU disposition data available as of March 25, 2020, 920 patients (58% [95% CI, 56%-61%]) were still in the ICU, 256 (16% [95% CI, 14%-18%]) were discharged from the ICU, and 405 (26% [95% CI, 23%-28%]) had died in the ICU. Older patients (n = 786; age ≥64 years) had higher mortality than younger patients (n = 795; age ≤63 years) (36% vs 15%; difference, 21% [95% CI, 17%-26%]; P < .001).
Conclusions and Relevance:  In this case series of critically ill patients with laboratory-confirmed COVID-19 admitted to ICUs in Lombardy, Italy, the majority were older men, a large proportion required mechanical ventilation and high levels of PEEP, and ICU mortality was 26%.
The full text of this article is available freely via this link.  A copy of this issue is also available in Rotherham Hospital Library on D Level.

Intensive Care Medicine Volume 46 Number 4 April 2020

To view Intensive Care Medicine’s May issue’s contents page follow this link.
Articles published in this issue include: COVID-19: a novel coronavirus and a novel challenge for critical care”, “Critical care crisis and some recommendations during the COVID-19 epidemic in China” and “Imaging changes of severe COVID-19 pneumonia in advanced stage”.
Together with other articles on COVID 19 these are freely available in full text to everyone.
To read the full text of any of these articles via the journal’s homepage requires a personal subscription to “Intensive Care Medicine” though some are available open access.  Individual articles can be ordered from the Rotherham NHS Foundation Trust Library and Knowledge Service.  Registered members of the library can make article requests online via this link.
The full text of articles from issues older than one year ago is available via this link to an archive of issues of Intensive Care Medicine.  A Rotherham NHS Athens password is required.  Eligible staff can register for an Athens password via this link.  Please speak to the library staff for more details.