Challenges for NHS hospitals during covid-19 epidemic

Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)

China and the rest of the world are experiencing an outbreak of a novel betacoronavirus known as severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). 1 By Feb 12, 2020, the rapid spread of the virus had caused 42 747 cases and 1017 deaths in China and cases have been reported in 25 countries, including the USA, Japan, and Spain. WHO has declared 2019 novel coronavirus disease (COVID-19), caused by SARS-CoV-2, a public health emergency of international concern. In contrast to severe acute respiratory system coronavirus and Middle East respiratory syndrome coronavirus, more deaths from COVID-19 have been caused by multiple organ dysfunction syndrome rather than respiratory failure, 2 which might be attributable to the widespread distribution of angiotensin converting enzyme 2—the functional receptor for SARS-CoV-2—in multiple organs.3, 4 Patients with cancer are more susceptible to infection than individuals without cancer because of their systemic immunosuppressive state caused by the malignancy and anticancer treatments, such as chemotherapy or surgery.5, 6, 7, 8 Therefore, these patients might be at increased risk of COVID-19 and have a poorer prognosis. On behalf of the National Clinical Research Center for Respiratory Disease, we worked together with the National Health Commission of the People's Republic of China to establish a prospective cohort to monitor COVID-19 cases throughout China. As of the data cutoff on Jan 31, 2020, we have collected and analysed 2007 cases from 575 hospitals (appendix pp 4–9 for a full list) in 31 provincial administrative regions. All cases were diagnosed with laboratory-confirmed COVID-19 acute respiratory disease and were admitted to hospital. We excluded 417 cases because of insufficient records of previous disease history. 18 (1%; 95% CI 0·61–1·65) of 1590 COVID-19 cases had a history of cancer, which seems to be higher than the incidence of cancer in the overall Chinese population (285·83 [0·29%] per 100 000 people, according to 2015 cancer epidemiology statistics 9 ). Detailed information about the 18 patients with cancer with COVID-19 is summarised in the appendix (p 1). Lung cancer was the most frequent type (five [28%] of 18 patients). Four (25%) of 16 patients (two of the 18 patients had unknown treatment status) with cancer with COVID-19 had received chemotherapy or surgery within the past month, and the other 12 (25%) patients were cancer survivors in routine follow-up after primary resection. Compared with patients without cancer, patients with cancer were older (mean age 63·1 years [SD 12·1] vs 48·7 years [16·2]), more likely to have a history of smoking (four [22%] of 18 patients vs 107 [7%] of 1572 patients), had more polypnea (eight [47%] of 17 patients vs 323 [23%] of 1377 patients; some data were missing on polypnea), and more severe baseline CT manifestation (17 [94%] of 18 patients vs 1113 [71%] of 1572 patients), but had no significant differences in sex, other baseline symptoms, other comorbidities, or baseline severity of x-ray (appendix p 2). Most importantly, patients with cancer were observed to have a higher risk of severe events (a composite endpoint defined as the percentage of patients being admitted to the intensive care unit requiring invasive ventilation, or death) compared with patients without cancer (seven [39%] of 18 patients vs 124 [8%] of 1572 patients; Fisher's exact p=0·0003). We observed similar results when the severe events were defined both by the above objective events and physician evaluation (nine [50%] of 18 patients vs 245 [16%] of 1572 patients; Fisher's exact p=0·0008). Moreover, patients who underwent chemotherapy or surgery in the past month had a numerically higher risk (three [75%] of four patients) of clinically severe events than did those not receiving chemotherapy or surgery (six [43%] of 14 patients; figure ). These odds were further confirmed by logistic regression (odds ratio [OR] 5·34, 95% CI 1·80–16·18; p=0·0026) after adjusting for other risk factors, including age, smoking history, and other comorbidities. Cancer history represented the highest risk for severe events (appendix p 3). Among patients with cancer, older age was the only risk factor for severe events (OR 1·43, 95% CI 0·97–2·12; p=0·072). Patients with lung cancer did not have a higher probability of severe events compared with patients with other cancer types (one [20%] of five patients with lung cancer vs eight [62%] of 13 patients with other types of cancer; p=0·294). Additionally, we used a Cox regression model to evaluate the time-dependent hazards of developing severe events, and found that patients with cancer deteriorated more rapidly than those without cancer (median time to severe events 13 days [IQR 6–15] vs 43 days [20–not reached]; p<0·0001; hazard ratio 3·56, 95% CI 1·65–7·69, after adjusting for age; figure). Figure Severe events in patients without cancer, cancer survivors, and patients with cancer (A) and risks of developing severe events for patients with cancer and patients without cancer (B) ICU=intensive care unit. In this study, we analysed the risk for severe COVID-19 in patients with cancer for the first time, to our knowledge; only by nationwide analysis can we follow up patients with rare but important comorbidities, such as cancer. We found that patients with cancer might have a higher risk of COVID-19 than individuals without cancer. Additionally, we showed that patients with cancer had poorer outcomes from COVID-19, providing a timely reminder to physicians that more intensive attention should be paid to patients with cancer, in case of rapid deterioration. Therefore, we propose three major strategies for patients with cancer in this COVID-19 crisis, and in future attacks of severe infectious diseases. First, an intentional postponing of adjuvant chemotherapy or elective surgery for stable cancer should be considered in endemic areas. Second, stronger personal protection provisions should be made for patients with cancer or cancer survivors. Third, more intensive surveillance or treatment should be considered when patients with cancer are infected with SARS-CoV-2, especially in older patients or those with other comorbidities.

The threat to health of the COVID‐19 infection (caused by the novel zoonotic SARS‐CoV‐2 coronavirus) is now established. 1 , 2 As widespread community transmission becomes likely, it is necessary to urgently consider the unique impact this may have on haematology patients and the practical steps that can be taken to reduce their risk during ongoing care. The importance of personal hygiene, the use of protective equipment and the investigation, isolation and treatment of infected patients are well documented elsewhere (https://www.england.nhs.uk/ourwork/eprr/coronavirus/), and are not discussed here. From its emergence in China, the virus has spread to involve 100 000 confirmed cases across 82 countries as of 4th March 2020; there are currently 116 confirmed cases in the UK. Spread from symptomatic as well as asymptomatic patients leads to clusters of local outbreaks, and as community transmission increases, the current policy of contact tracing and containment will move to one designed to slow disease transmission. Without natural immunity in the population, isolation and quarantine will slow, rather than significantly reduce, the ultimate spread of disease. The proportion of the population likely to contract the virus during the outbreak is currently unknown. The UK Government's COVID‐19 action plan is preparing for up to 80% of the population to become infected (https://www.gov.uk/government/publications/coronavirus-action-plan). Initial large series of patients with confirmed COVID‐19 infection have suggested a case fatality rate of between 1·4% 3 and 2·3% 2 although estimates of this are complicated by factors likely to cause both over and under estimation of the true figure. Cases of COVID‐19 in those aged 80 years are over‐represented amongst diagnosed cases of the disease (3·2% of those diagnosed, despite making up 1·8% of the affected population) 2 It is unclear whether these age discrepancies reflect differences in infection rates, or whether they are due to detection bias, as older patients may be more likely to have symptoms and present for medical attention. The case fatality rate in the elderly is clearly increased however, being 14·8% in those aged >80 years, and 8% between 70 and 80 years. Given the immunosuppressive nature of most cancer therapies, it is expected that patients with cancer will be at higher risk of severe infection than the normal population. Data from China show that patients with cancer have a statistically higher incidence of severe events (including intensive care unit admission/ventilation/death) after contracting the virus (39% vs. 8% in patients without cancer 4 ). However, this was a small series of elderly patients and there are no data available yet on patients with haematological malignancies. In responding to increased viral circulation in the population in a timely and proportionate manner, it is necessary to consider the risks to the patient of deviating from current standards of care (e.g. reducing chemotherapy intensity or frequency of phlebotomy) in an attempt to potentially reduce their risk of COVID‐19 infection and its complications. Furthermore, it is possible that as an epidemic worsens, healthcare provision will be critically stretched, and therefore all activities that place further burden on those resources will have to be justified. For this reason, the delivery of treatments likely to increase immunosuppression, or increase the risk of intensive care support being required may not be possible in some healthcare settings. There is therefore a need to consider the practical steps that can be taken, in the event of widespread community transmission, to reduce the risk to our vulnerable patient groups. The steps below aim to reduce the chances of patient exposure, and to consider reducing the degree of immunosuppression when possible. The following represent our own thoughts, rather than official guidance and we hope will act as a stimulus for the provision of official centralised recommendations from national bodies in the UK, in the now likely event of a global pandemic. Communication and remote working Contact details of all patients, including e‐mail address and mobile telephone number, should be confirmed and strategies developed to enable rapid updates of the patient population en masse with the latest advice via e‐mail and/or text. Patients should be advised that normal communication channels may be unavailable depending upon staff capacity. Healthcare workers and administrators should be provided with Information Technology (IT) support to enable them to work remotely, such that they can continue to work if fit but self‐isolating, or if not required to be on site. Outpatient clinics Self‐isolation may enable patients to delay, or avoid, infection by COVID‐19, and this may be of critical importance, particularly following chemotherapy. As the number of cases in the community and hospitals rise, so will the risks to the patient of leaving their home to attend clinic appointments. Bringing potentially immunosuppressed, and often elderly, patients with cancer into this environment should be avoided where possible. Outpatient clinics should move to telephone appointments or video‐conferencing arrangements wherever this is felt to be acceptable. Patients attending in person could be asked to wait in their car until the clinician is available to see them, reducing their exposure to other patients. Phlebotomy Clustering large groups of vulnerable and potentially unwell patients into waiting areas for phlebotomy has the potential to facilitate the spread of the infection. Consideration should be given to extending the interval between monitoring blood tests, as the risks, and burdens on the health service of their provision increases. The establishment of off‐site phlebotomy facilities, e.g. in car parks, where patients can queue within their cars, would minimise their contact with other patients. Supportive treatments delivered in a hospital setting Routine, in hospital, provision of supportive treatments aimed at minimising longer term side‐effects should be paused. Such treatments would include: the use of bisphosphonates to reduce skeletal‐related events in patients with myeloma, venesection to reduce iron burden in patients after allogeneic transplant or in selected patients with erythrocytosis and hereditary haemochromatosis. Therapies that can easily be paused should be nationally agreed and circulated. Maintenance and non‐curative chemotherapy Individualised decisions on the benefits and risks of continuation of maintenance chemotherapy will have to be taken if the infection rates in the community rise. The benefit of tight disease control should be balanced against the immunosuppressive effects of the treatment, and the theoretical increased risk of harm from COVID‐19 that this may carry. Examples where treatment could be deferred may include maintenance rituximab in follicular and mantle cell lymphoma. Ideally, oral chemotherapy should be used where possible to avoid unnecessary hospital visits. Curative chemotherapy If pressures on hospitals increase, and rates of community infection climb, the balance in favour of delaying or abandoning cycles of chemotherapy will increase, to such an extent that, in the worst‐case scenario, only immediately life‐saving chemotherapy may be considered. This problem may be exacerbated by potential absence due to illness amongst the pool of specialist nurses trained to deliver chemotherapy. Life‐saving chemotherapy that will continue should be nationally agreed to ensure equity amongst patients. Bone marrow transplantation In the case of widespread community infection and substantial pressures on hospitals, it will be hard to justify the prolonged immunosuppression, close follow‐up and additional demands on hospital services that come with performing allogeneic (and to a lesser extent, autologous) bone marrow transplants. In this scenario, it is plausible that many transplants will have to be deferred. It may be necessary to ration transplants, and arrange for transfer of patients to areas with sufficient capacity to support delivery and recovery from these regimes. Close liaison amongst the transplant community nationally will be vital. The appropriate management and deferral of planned transplant recipients and donors who have had, or been exposed to, COVID‐19 has been covered in pragmatic guidelines by the European Society for Blood and Bone Marrow Transplantation and will be updated as new evidence emerges (https://www.ebmt.org/ebmt/news/ebmt-recommendation-coronavirus-disease-covid-19). Visitors If community spread increases then relatives and friends should be discouraged from visiting inpatients, and from accompanying patients to clinic appointments; it may prove necessary to strictly enforce this. Provision of medicines Due to the global nature of this infection outbreak, it is possible that pathways of drug manufacture may be compromised, and shortages of medicines may develop. Co‐ordination of response to this will require national oversight. To reduce potential viral exposure at pharmacy departments, consideration should be given to the use of a drive‐through medicine collection facility, where patients are alerted by telephone when their medicine is available. Some hospitals may alternatively choose a courier service. Workforce Hospitals should ensure that consideration is given to maintaining functional healthcare systems during periods of high workforce absence due to infection, and the potential consequences of disruption to schools and transport links. The UK Government has proposed drafting in volunteers, and recently retired medical personnel. It may prove necessary to re‐deploy haematologists outside of their sub‐speciality interest to maintain core services. Summary There is great uncertainty surrounding the burden that managing COVID‐19 will place on global healthcare systems. It is prudent to plan for a scenario of maximal disruption, and consider how this would affect haematology patients, and the departments managing them, in the hope that many of the measures outlined may not need to be implemented. Clear guidance and communication from governments and hospital leaders regarding COVID‐19 will be essential. In addition, strong leadership within haematology teams nationally and locally will be needed to ensure timely and proportionate implementation of contingency plans, which balance risks and protect patients as infections rise. Disclosures No authors have relevant disclosures to declare.