Public health medicine

Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1

A novel human coronavirus that is now named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (formerly called HCoV-19) emerged in Wuhan, China, in late 2019 and is now causing a pandemic.1 We analyzed the aerosol and surface stability of SARS-CoV-2 and compared it with SARS-CoV-1, the most closely related human coronavirus.2 We evaluated the stability of SARS-CoV-2 and SARS-CoV-1 in aerosols and on various surfaces and estimated their decay rates using a Bayesian regression model (see the Methods section in the Supplementary Appendix, available with the full text of this letter at NEJM.org). SARS-CoV-2 nCoV-WA1-2020 (MN985325.1) and SARS-CoV-1 Tor2 (AY274119.3) were the strains used. Aerosols (<5 μm) containing SARS-CoV-2 (105.25 50% tissue-culture infectious dose [TCID50] per milliliter) or SARS-CoV-1 (106.75-7.00 TCID50 per milliliter) were generated with the use of a three-jet Collison nebulizer and fed into a Goldberg drum to create an aerosolized environment. The inoculum resulted in cycle-threshold values between 20 and 22, similar to those observed in samples obtained from the upper and lower respiratory tract in humans. Our data consisted of 10 experimental conditions involving two viruses (SARS-CoV-2 and SARS-CoV-1) in five environmental conditions (aerosols, plastic, stainless steel, copper, and cardboard). All experimental measurements are reported as means across three replicates.

van Doremalen, Neeltje and Bushmaker, Trenton and Morris, Dylan H. and Holbrook, Myndi G. and Gamble, Amandine and Williamson, Brandi N. and Tamin, Azaibi and Harcourt, Jennifer L. and Thornburg, Natalie J. and Gerber, Susan I. and Lloyd-Smith, James O. and de Wit, Emmie and Munster, Vincent J.march 2020

Public health medicine

Hydroxychloroquine and azithromycin as a treatment of COVID‐19: results of an open‐label non‐ randomized clinical trial.

Background: Chloroquine and hydroxychloroquine have been found to be efficient on SARS-CoV-2, and reported to be efficient in Chinese COV-19 patients. We evaluate the role of hydroxychloroquine on respiratory viral loads. Patients and methods: French Confirmed COVID-19 patients were included in a single arm protocol from early March to March 16th, to receive 600mg of hydroxychloroquine daily and their viral load in nasopharyngeal swabs was tested daily in a hospital setting. Depending on their clinical presentation, azithromycin was added to the treatment. Untreated patients from another center and cases refusing the protocol were included as negative controls. Presence and absence of virus at Day6-post inclusion was considered the end point. Results: Six patients were asymptomatic, 22 had upper respiratory tract infection symptoms and eight had lower respiratory tract infection symptoms. Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration than reported of untreated patients in the literature. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination. Conclusion: Despite its small sample size our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin.

Gautret et al.march 2020

Public health medicine

Coronavirus Disease 2019 (COVID-19): A Systematic Review of Imaging Findings in 919 Patients

OBJECTIVE. Available information on CT features of the 2019 novel coronavirus disease (COVID-19) is scattered in different publications, and a cohesive literature review has yet to be compiled. MATERIALS AND METHODS. This article includes a systematic literature search of PubMed, Embase (Elsevier), Google Scholar, and the World Health Organization database. RESULTS. Known features of COVID-19 on initial CT include bilateral multilobar ground-glass opacification (GGO) with a peripheral or posterior distribution, mainly in the lower lobes and less frequently within the right middle lobe. Atypical initial imaging presentation of consolidative opacities superimposed on GGO may be found in a smaller number of cases, mainly in the elderly population. Septal thickening, bronchiectasis, pleural thickening, and subpleural involvement are some of the less common findings, mainly in the later stages of the disease. Pleural effusion, pericardial effusion, lymphadenopathy, cavitation, CT halo sign, and pneumothorax are uncommon but may be seen with disease progression. Follow-up CT in the intermediate stage of disease shows an increase in the number and size of GGOs and progressive transformation of GGO into multifocal consolidative opacities, septal thickening, and development of a crazy paving pattern, with the greatest severity of CT findings visible around day 10 after the symptom onset. Acute respiratory distress syndrome is the most common indication for transferring patients with COVID-19 to the ICU and the major cause of death in this patient population. Imaging patterns corresponding to clinical improvement usually occur after week 2 of the disease and include gradual resolution of consolidative opacities and decrease in the number of lesions and involved lobes. CONCLUSION. This systematic review of current literature on COVID-19 provides insight into the initial and follow-up CT characteristics of the disease. Read More: https://www.ajronline.org/doi/abs/10.2214/AJR.20.23034

Sana Salehi, Aidin Abedi, Sudheer Balakrishnan, Ali Gholamrezanezhadfebruary 2020

Public health medicine

Epidemiological Characteristics of 2143 Pediatric Patients With 2019 Coronavirus Disease in China

OBJECTIVES: To identify the epidemiological characteristics and transmission patterns ofpediatric patients with COVID-19 in China.METHODS: Nationwide case series of 2143 pediatric patients with COVID-19 reported to theChinese Center for Disease Control and Prevention from January 16 to February 8, 2020 wereincluded. The epidemic curves were constructed by key dates of disease onset and case diagnosis.Onset-to-diagnosis curves were constructed by fitting a log-normal distribution to data on bothonset and diagnosis dates.RESULTS: There were 731 (34.1%) laboratory-confirmed cases and 1412 (65.9%) suspectedcases. The median age of all patients was 7 years (interquartile range: 2-13), and 1213 cases(56.6%) were boys. Over 90% of all patients were asymptomatic, mild, or moderate cases. Themedian time from illness onset to diagnoses was 2 days (range: 0 to 42 days). There was a rapidincrease of disease at the early stage of the epidemic and then there was a gradual and steadydecrease. Disease rapidly spread from Hubei Province to surrounding provinces over time. Morechildren were infected in Hubei province than any other province.CONCLUSIONS: Children at all ages appeared susceptible to COVID-19, and there was nosignificant gender difference. Although clinical manifestations of children’s COVID-19 caseswere generally less severe than those of adults’ patients, young children, particularly infants, werevulnerable to infection. The distribution of children’s COVID-19 cases varied with time and space,and most of the cases concentrated in Hubei province and surrounding

Dong Y, Mo X, Hu Y, et al.march 2020

Public health medicine

The response of Milan's Emergency Medical System to the COVID-19 outbreak in Italy

The number of people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease 2019 (COVID-19), is dramatically increasing worldwide. The first person-to-person transmission in Italy was reported on Feb 21, 2020, and led to an infection chain that represents the largest COVID-19 outbreak outside Asia to date. Here we document the response of the Emergency Medical System (EMS) of the metropolitan area of Milan, Italy, to the COVID-19 outbreak. On Jan 30, 2020, WHO declared the COVID-19 outbreak a public health emergency of international concern. Since then, the Italian Government has implemented extraordinary measures to restrict viral spread, including interruptions of air traffic from China, organised repatriation flights and quarantines for Italian travellers in China, and strict controls at international airports' arrival terminals. Local medical authorities adopted specific WHO recommendations to identify and isolate suspected cases of COVID-19. Such recommendations were addressed to patients presenting with respiratory symptoms and who had travelled to an endemic area in the previous 14 days or who had worked in the health-care sector, having been in close contact with patients with severe respiratory disease with unknown aetiology. Suspected cases were transferred to preselected hospital facilities where the SARS-CoV-2 test was available and infectious disease units were ready for isolation of confirmed cases.

Stefano Spina, Francesco Marrazzo, Maurizio Migliari, et al.february 2020

Public health medicine

Diagnostic Testing for the Novel Coronavirus

Controversies over diagnostic testing have dominated US headlines about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus responsible for coronavirus disease 2019 (COVID-19). Technical challenges with the first test developed by the Centers for Disease Control and Prevention (CDC) left the nation with minimal diagnostic capacity during the first few weeks of the epidemic. The CDC also initially limited access to testing to a narrow group of individuals with known exposure. The delayed discovery of a case of COVID-19 in California, followed quickly by evidence of community transmission in multiple states, revealed the shortcomings of this strategy. In the early stages, COVID-19 has spread beyond the nation’s ability to detect it. On February 29, the US Food and Drug Administration (FDA) moved to expand testing capacity by eliminating a requirement that advanced laboratories obtain prior FDA authorization before using their own, laboratory-developed tests. Then, on March 3, Vice President Pence announced the removal of all federal limits on testing, stating that “subject to doctors’ orders, any American can be tested.” These steps left many with questions about what had happened with testing and what should happen next. Unraveling this situation requires understanding how the regulatory structure for diagnostic tests interacts with public health emergencies. It also involves appreciating the distinction between testing capacity for public health surveillance and clinical care. While the public may want extensive testing, the usefulness of testing is greater in some scenarios than others. It is important to balance 2 concepts: remedying testing gaps is imperative, yet more testing is not always better.

Joshua M. Sharfstein, Scott J. Becker, Michelle M. Mellomarch 2020

Public health medicine

Clinical Characteristics and Intrauterine Vertical Transmission Potential of COVID-19 Infection in Nine Pregnant Women: A Retrospective Review of Medical Records

Background: Previous studies on the pneumonia outbreak caused by the 2019 novel coronavirus disease (COVID-19) were based on information from the general population. Limited data are available for pregnant women with COVID-19 pneumonia. This study aimed to evaluate the clinical characteristics of COVID-19 in pregnancy and the intrauterine vertical transmission potential of COVID-19 infection. Methods: Clinical records, laboratory results, and chest CT scans were retrospectively reviewed for nine pregnant women with laboratory-confirmed COVID-19 pneumonia (ie, with maternal throat swab samples that were positive for severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) who were admitted to Zhongnan Hospital of Wuhan University, Wuhan, China, from Jan 20 to Jan 31, 2020. Evidence of intrauterine vertical transmission was assessed by testing for the presence of SARS-CoV-2 in amniotic fluid, cord blood, and neonatal throat swab samples. Breastmilk samples were also collected and tested from patients after the first lactation. Findings: All nine patients had a caesarean section in their third trimester. Seven patients presented with a fever. Other symptoms, including cough (in four of nine patients), myalgia (in three), sore throat (in two), and malaise (in two), were also observed. Fetal distress was monitored in two cases. Five of nine patients had lymphopenia (<1·0×10⁹ cells per L). Three patients had increased aminotransferase concentrations. None of the patients developed severe COVID-19 pneumonia or died, as of Feb 4, 2020. Nine livebirths were recorded. No neonatal asphyxia was observed in newborn babies. All nine livebirths had a 1-min Apgar score of 8–9 and a 5-min Apgar score of 9–10. Amniotic fluid, cord blood, neonatal throat swab, and breastmilk samples from six patients were tested for SARS-CoV-2, and all samples tested negative for the virus. Interpretation: The clinical characteristics of COVID-19 pneumonia in pregnant women were similar to those reported for non-pregnant adult patients who developed COVID-19 pneumonia. Findings from this small group of cases suggest that there is currently no evidence for intrauterine infection caused by vertical transmission in women who develop COVID-19 pneumonia in late pregnancy.

Huijun Chen, Juanjuan Guo, Chen Wang, Fan Luo, Xuechen Yu, Wei Zhang, Jiafu Li, Dongchi Zhao, Dan Xu, Qing Gong, Jing Liao, Huixia Yang Wei Hou, Yuanzhen Zhangfebruary 2020

Public health medicine

Clinical analysis of 10 neonates born to mothers with 2019-nCoV pneumonia

Background: The newly identified 2019-nCoV, which appears to have originated in Wuhan, the capital city of Hubei province in central China, is spreading rapidly nationwide. A number of cases of neonates born to mothers with 2019-nCoV pneumonia have been recorded. However, the clinical features of these cases have not been reported, and there is no sufficient evidence for the proper prevention and control of 2019-nCoV infections in neonates. Methods: The clinical features and outcomes of 10 neonates (including 2 twins) born to 9 mothers with confirmed 2019-nCoV infection in 5 hospitals from January 20 to February 5, 2020 were retrospectively analyzed. Results: Among these 9 pregnant women with confirmed 2019-nCoV infection, onset of clinical symptoms occurred before delivery in 4 cases, on the day of delivery in 2 cases, and after delivery in 3 cases. In most cases, fever and a cough were the first symptoms experienced, and 1 patient also had diarrhea. Of the newborns born to these mothers, 8 were male and 2 were female; 4 were full-term infants and 6 were born premature; 2 were small-for-gestational-age (SGA) infants and 1 was a large-for-gestational-age (LGA) infant; there were 8 singletons and 2 twins. Of the neonates, 6 had a Pediatric Critical Illness Score (PCIS) score of less than 90. Clinically, the first symptom in the neonates was shortness of breath (n=6), but other initial symptoms such as fever (n=2), thrombocytopenia accompanied by abnormal liver function (n=2), rapid heart rate (n=1), vomiting (n=1), and pneumothorax (n=1) were observed. Up to now, 5 neonates have been cured and discharged, 1 has died, and 4 neonates remain in hospital in a stable condition. Pharyngeal swab specimens were collected from 9 of the 10 neonates 1 to 9 days after birth for nucleic acid amplification tests for 2019-nCoV, all of which showed negative results. Conclusions: Perinatal 2019-nCoV infection may have adverse effects on newborns, causing problems such as fetal distress, premature labor, respiratory distress, thrombocytopenia accompanied by abnormal liver function, and even death. However, vertical transmission of 2019-nCoV is yet to be confirmed.

Huaping Zhu, Lin Wang, Chengzhi Fang, Sicong Peng, Lianhong Zhang, Guiping Chang, Shiwen Xia, Wenhao Zhoufebruary 2020

Public health medicine

Posição da Sociedade Portuguesa de Cardiologia sobre a utilização de IECA e ARA II no contexto da pandemia do COVID-19

No contexto da actual pandemia, a segurança dos IECA e ARA II foi questionada em dois artigos de opinião, tendo os autores sugerido que os doentes sob tratamento com estes fármacos poderiam estar sujeitos a uma evolução mais grave da doença, em caso de infecção pelo coronavírus 1,2. Na origem destas preocupações há razões teóricas legítimas apoiadas em dados epidemiológicos; no conhecimento disponível dos mecanismos patogénicos da infecção pelos coronavírus; na resposta inflamatória do hospedeiro às infecções e das complexas vias de sinalização envolvidas; e no mecanismo de acção dos IECA e ARA II. Algumas das extrapolações publicadas baseiam-se em resultados de estudos que mostraram, entre os doentes com o COVID-19, ser a prevalência de hipertensão (HTA) mais elevada nos que desenvolveram doença grave, incluindo ARDS e morte, do que nos que tiveram uma evolução mais favorável3,4. Porém, à excepção de um estudo com 191 casos5, não foram feitas análises ajustadas dos resultados, razão por que os estudos não permitem, com segurança, associar o pior prognóstico dos doentes à presença de HTA, cuja prevalência variou entre 23,7% e 58%3-5. Apesar de o tratamento anti-hipertensivo prévio não ter sido avaliado em qualquer dos estudos em causa3-5 , os autores procuraram estabelecer uma relação de causalidade entre a terapêutica anti-hipertensiva e o pior prognóstico observado nos hipertensos infectados pelo COVID-19. Dado os bloqueadores do Sistema Renina-Angiotensina-Aldosterona (SRAA) - IECA e ARA II serem dos fármacos mais utilizados no tratamento da HTA, admitiram aqueles autores que estes fármacos poderiam ter tido um efeito facilitador da invasão viral e das suas complicações1, notavelmente a ARDS6. Não foi considerada a hipótese alternativa de a hiperactividade do SRRA, presente nos hipertensos e agravada pelo SARS-CoV, ser um dos determinantes major da amplificação do processo inflamatório desencadeado pelo hospedeiro em resposta à invasão viral. Acontece que na China, onde 37% da população entre os 37 e os 75 anos é hipertensa e 44% das mortes são atribuídas às doenças cardiovasculares, apenas 23% dos hipertensos estão sob tratamento anti-hipertensivo7. Como a taxa de prescrição dos ARAII /IECA na China é inferior a 7.5%7 e porque a associação das duas classes não está recomendada, dos mais de 250 milhões de hipertensos existentes, menos de 4,5 milhões estarão em tratamento com um ARA II ou IECA7. Desta forma, pela força dos números, não é possível estabelecer-se uma relação de causalidade entre o pior prognóstico observado nos hipertensos com infecção pelo COVID-19 e o tratamento com ARA II ou IECA.

António Pedro Machado, Carlos Rabaçalmarch 2020

Public health medicine

Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents.

Currently, the emergence of a novel human coronavirus, SARS-CoV-2, has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described with incubation times between 2-10 days, facilitating its spread via droplets, contaminated hands or surfaces. We therefore reviewed the literature on all available information about the persistence of human and veterinary coronaviruses on inanimate surfaces as well as inactivation strategies with biocidal agents used for chemical disinfection, e.g. in healthcare facilities. The analysis of 22 studies reveals that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days, but can be efficiently inactivated by surface disinfection procedures with 62-71% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite within 1 minute. Other biocidal agents such as 0.05-0.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. As no specific therapies are available for SARS-CoV-2, early containment and prevention of further spread will be crucial to stop the ongoing outbreak and to control this novel infectious thread.

Kampf, Todt, Pfaender, Steinmannfebruary 2020

Public health medicine

A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19

BACKGROUND: No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2. METHODS: We conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao2) to the fraction of inspired oxygen (Fio2) of less than 300 mm Hg. Patients were randomly assigned in a 1:1 ratio to receive either lopinavir–ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care, or standard care alone. The primary end point was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever came first. RESULTS: A total of 199 patients with laboratory-confirmed SARS-CoV-2 infection underwent randomization; 99 were assigned to the lopinavir–ritonavir group, and 100 to the standard-care group. Treatment with lopinavir–ritonavir was not associated with a difference from standard care in the time to clinical improvement (hazard ratio for clinical improvement, 1.24; 95% confidence interval [CI], 0.90 to 1.72). Mortality at 28 days was similar in the lopinavir–ritonavir group and the standard-care group (19.2% vs. 25.0%; difference, −5.8 percentage points; 95% CI, −17.3 to 5.7). The percentages of patients with detectable viral RNA at various time points were similar. In a modified intention-to-treat analysis, lopinavir–ritonavir led to a median time to clinical improvement that was shorter by 1 day than that observed with standard care (hazard ratio, 1.39; 95% CI, 1.00 to 1.91). Gastrointestinal adverse events were more common in the lopinavir–ritonavir group, but serious adverse events were more common in the standard-care group. Lopinavir–ritonavir treatment was stopped early in 13 patients (13.8%) because of adverse events. CONCLUSIONS: In hospitalized adult patients with severe Covid-19, no benefit was observed with lopinavir–ritonavir treatment beyond standard care. Future trials in patients with severe illness may help to confirm or exclude the possibility of a treatment benefit.

Bin Cao, Yeming Wang, Danning Wen, Wen Liu, et al.march 2020

Public health medicine

Combination of RT‐qPCR testing and clinical features for diagnosis of COVID‐19 facilitates management of SARS‐CoV‐2 outbreak

Quantitative real‐time reverse transcriptase‐polymerase chain reaction (RT‐qPCR) assay has routinely been used for the detection of causative viruses from respiratory secretions and final pathogenic diagnostics of COVID‐19. More than seven types of SARS‐CoV‐2 nucleic acid test kit have been developed and approved rapidly, while a large number of the “suspected” cases with typical clinical COVID‐19 features and identical specific computed tomography (CT) images were not diagnosed. Unfortunately, due to an overwhelming situation in local hospitals, many “suspected” cases and diagnosed cases cannot efficiently be separated or treated. Recently, one patient was not confirmed by RT‐qPCR testing for SARS‐CoV‐2 infection for the first three times within 3 weeks before bronchoalveolar lavage fluid (BALF) was acquired, results from both RT‐qPCR and next‐generation sequencing (NGS) testing were positive for SRAS‐CoV‐2. These largely affected efficiency to control viral spreading and outbreak. Indeed, several factors have been proposed to explain the inconsistency or the high false‐negative rate (FNR). For example, results from RT‐qPCR testing using primers in the ORF1ab gene and N genes can be affected by the variation of viral RNA sequences. In terms of the natural history of the disease and viral load in different anatomic sites of the patients, sampling procedures largely contribute to high FNR. By estimate, FNR from one‐time testing was as high as 30% to 50% in real COVID‐19 cases.

Yishan Wang, Hanyujie Kang, Xuefeng Liu, Zhaohui Tongfebruary 2020

Dermatology

Upadacitinib in adults with moderate to severe atopic dermatitis: 16-week results from a randomized, placebo-controlled trial

Atopic dermatitis is a chronic inflammatory skin disease characterized by pruritic skin lesions. \n \n Objective \n We sought to evaluate the safety and efficacy of multiple doses of the selective Janus kinase 1 inhibitor upadacitinib in patients with moderate to severe atopic dermatitis. \n \n Methods \n In the 16-week, double-blind, placebo-controlled, parallel-group, dose-ranging portion of this 88-week trial in 8 countries (ClinicalTrials.gov, NCT02925117; ongoing, not recruiting), adults with moderate to severe disease and inadequate control by topical treatment were randomized 1:1:1:1, using an interactive response system and stratified geographically, to once-daily upadacitinib oral monotherapy 7.5, 15, or 30 mg or placebo. The primary end point was percentage improvement in Eczema Area and Severity Index from baseline at week 16. Efficacy was analyzed by intention-to-treat in all randomized patients. Safety was analyzed in all randomized patients who received study medication, based on actual treatment. \n \n Results \n Patients (N = 167) enrolled from November 21, 2016, to April 20, 2017. All were randomized and analyzed for efficacy (each upadacitinib group, n = 42; placebo, n = 41); 166 were analyzed for safety (each upadacitinib group, n = 42; placebo, n = 40). The mean (SE) primary efficacy end point was 39% (6.2%), 62% (6.1%), and 74% (6.1%) for the upadacitinib 7.5-, 15-, and 30-mg groups, respectively, versus 23% (6.4%) for placebo (P = .03, <.001, and <.001). Serious adverse events occurred in 4.8% (2 of 42), 2.4% (1 of 42), and 0% (0 of 42) of upadacitinib groups (vs 2.5% [1 of 40] for placebo). \n \n Conclusions \n A dose-response relationship was observed for upadacitinib efficacy; the 30-mg once-daily dose showed the greatest clinical benefit. Dose-limiting toxicity was not observed.

Emma Guttman-Yassky, Diamant Thaçi, Aileen L. Pangan, H. Chih-ho Hong, et al.february 2020

Public health medicine

Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China

Importance: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. Risk factors for the clinical outcomes of COVID-19 pneumonia have not yet been well delineated. Objective: To describe the clinical characteristics and outcomes in patients with COVID-19 pneumonia who developed acute respiratory distress syndrome (ARDS) or died. Design, Setting, and Participants: Retrospective cohort study of 201 patients with confirmed COVID-19 pneumonia admitted to Wuhan Jinyintan Hospital in China between December 25, 2019, and January 26, 2020. The final date of follow-up was February 13, 2020. Exposures: Confirmed COVID-19 pneumonia.Main Outcomes and Measures: The development of ARDS and death. Epidemiological, demographic, clinical, laboratory, management, treatment, and outcome data were also collected and analyzed. Results: Of 201 patients, the median age was 51 years (interquartile range, 43-60 years), and 128 (63.7%) patients were men. Eighty-four patients (41.8%) developed ARDS, and of those 84 patients, 44 (52.4%) died. In those who developed ARDS, compared with those who did not, more patients presented with dyspnea (50 of 84 [59.5%] patients and 30 of 117 [25.6%] patients, respectively [difference, 33.9%; 95% CI, 19.7%-48.1%]) and had comorbidities such as hypertension (23 of 84 [27.4%] patients and 16 of 117 [13.7%] patients, respectively [difference, 13.7%; 95% CI, 1.3%-26.1%]) and diabetes (16 of 84 [19.0%] patients and 6 of 117 [5.1%] patients, respectively [difference, 13.9%; 95% CI, 3.6%-24.2%]). In bivariate Cox regression analysis, risk factors associated with the development of ARDS and progression from ARDS to death included older age (hazard ratio [HR], 3.26; 95% CI 2.08-5.11; and HR, 6.17; 95% CI, 3.26-11.67, respectively), neutrophilia (HR, 1.14; 95% CI, 1.09-1.19; and HR, 1.08; 95% CI, 1.01-1.17, respectively), and organ and coagulation dysfunction (eg, higher lactate dehydrogenase [HR, 1.61; 95% CI, 1.44-1.79; and HR, 1.30; 95% CI, 1.11-1.52, respectively] and D-dimer [HR, 1.03; 95% CI, 1.01-1.04; and HR, 1.02; 95% CI, 1.01-1.04, respectively]). High fever (≥39 °C) was associated with higher likelihood of ARDS development (HR, 1.77; 95% CI, 1.11-2.84) and lower likelihood of death (HR, 0.41; 95% CI, 0.21-0.82). Among patients with ARDS, treatment with methylprednisolone decreased the risk of death (HR, 0.38; 95% CI, 0.20-0.72). Conclusions and Relevance: Older age was associated with greater risk of development of ARDS and death likely owing to less rigorous immune response. Although high fever was associated with the development of ARDS, it was also associated with better outcomes among patients with ARDS. Moreover, treatment with methylprednisolone may be beneficial for patients who develop ARDS.

Chaomin Wu, Xiaoyan Chen, Yanping Cai, et al.march 2020

Public health medicine

Critical Care Utilization for the COVID-19 Outbreak in Lombardy, Italy

On February 20, 2020, a patient in his 30s admitted to the intensive care unit (ICU) in Codogno Hospital (Lodi, Lombardy, Italy) tested positive for a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19). He had a history of atypical pneumonia that was not responding to treatment, but he was not considered at risk for COVID-19 infection. The positive result was immediately reported to the Lombardy health care system and governmental offices. During the next 24 hours, the number of reported positive cases increased to 36. This situation was considered a serious development for several reasons: the patient (“patient 1”) was healthy and young; in less than 24 hours, 36 additional cases were identified, without links to patient 1 or previously identified positive cases already in the country; it was not possible to identify with certainty the source of transmission to patient 1 at the time; and, because patient 1 was in the ICU and there were already 36 cases by day 2, chances were that a cluster of unknown magnitude was present and additional spread was likely. On February 21, an emergency task force was formed by the Government of Lombardy and local health authorities to lead the response to the outbreak. This Viewpoint provides a summary of the response of the COVID-19 Lombardy ICU network and a forecast of estimated ICU demand over the coming weeks (projected to March 20, 2020).

Giacomo Grasselli, Antonio Pesenti, Maurizio Cecconimarch 2020