By 28th March 2020 the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) pandemic leading to coronavirus disease (COVID-19) has been confirmed in 1,348,184 persons of whom 74,816 (5.5%) have died 1,2. In Europe, Italy has been particularly severely affected with 132,547 confirmed COVID-19 patients, a 16% intensive care unit (ICU) admission rate, and a 12.5% case-fatality rate (CFR) 1,3,4. Confirmed outbreaks have been reported in 184 countries or regions worldwide and therefore COVID-19 poses a serious global threat to citizens, health care systems, economies, and societies 5-9. The burden and the numeric fatalities therefore by far exceeds recent previous corona virus outbreaks such as Severe Acute Respiratory Syndrome (SARS) with 8273 cases and 775 deaths and the Middle Eastern Respiratory Syndrome (MERS) with 1139 cases and 431 deaths 10.
The transmission of SARS-CoV-2 seems to be predominantly through the respiratory route by droplets and aerosols but also via direct contact and feces contamination. In the Chinese Hubei province it has been seen that hospital-related transmission accounts for up to 41% and that vulnerable patients with chronic diseases therefore are at particular risk 10.
The clinical presentation of COVID-19 predominantly involves fever and lower respiratory tract symptoms. Among the initial 41 patients symptoms included fever (98%), cough (76%), dyspnea (55%), myalgia or fatigue (44%), sputum production (28%), headache (8%), hemoptysis (5%), and diarrhea (3%)9. In a study of 18 hospitalized patients from Singapore the six patients that required supplementary oxygen treatment were generally older and more often had underlying diseases 11. Based on the severity of symptoms COVID-19 is suggested classified into three levels - mild, severe, and critical disease 12. Mild patients only present non-pneumonia or mild pneumonia symptoms.
Severe patients have fever, respiratory symptoms, and dyspnea, respiratory frequency ≥30/min, blood oxygen saturation ≤ 93%, partial pressure of arterial oxygen to fraction of inspired oxygen ratio <300, and/or lung infiltrates >50% within 24 to 48 hours. Critical patients meet one of three criteria: (1) respiratory failure, (2) septic shock, (3) multiple organ failure. Among 72,314 cases from the Chinese Hubei province 62% were verified by testing, 22% were suspected due to symptoms and exposure, and 15% were clinically suspected only12. Most patients were 30-79 years (87%), or 20-29 years (8%). The COVID-19 were classified as mild in 81%, severe in 14%, and as critical in 5%12. In 889 (1%) patients COVID-19 was diagnosed incidentally since they were asymptomatic12. The overall case-fatality rate (CFR) was 2.3% among confirmed cases - 14.8% in patients ≥ 80 years, 8% in patients aged 70-79 years, and 49% in critical ill patients. No deaths were reported in mild or severe cases. An elevated risk of complications and fatal outcome has been observed among patients who are older with the CFR reaching 20.2% in patients who are ≥ 80 years, an age group representing more than half of the COVID-19 related deaths3. The overall CFR was elevated in patients with comorbid conditions - 10.5% for cardiovascular disease, 7.3% for diabetes, 6.3% for chronic respiratory disease, 6.0% for hypertension, and 5.6% for cancer 12. It is believed that the high rate of nosocomial transmission and hence large number affected health care professionals in this province burdened the health care system extremely, and therefore delayed relevant medical support which contributed to the high CFR10.
Approved therapeutic options for COVID-19 are currently only symptomatic treatment and management of complications since no specific anti-viral treatment exists 11,13. Anti-viral treatments and other interventions are currently being tested in 35 registered clinical trials 13,14.
Patients who are old or have haematological or oncological diseases are vulnerable to infectious diseases both due to frailty, diseases, their management, and late effects. Many haematological disorders are characterized by bone marrow failure that may be intermittent, long-lasting, or even chronic. Almost all treatments in haematology and oncology contribute to the immune deficiency.
Chemotherapeutic agents causes neutropenia, monoclonal antibodies and other drugs causes both lymfopenia and humoral immune deficiency, corticosteroids inhibits phagocytes, splenic function may be reduced or absent, high dose therapies causes long lasting barrier defects, and stem cell transplants requires long lasting immune suppression. Therefore patients with haematological disorders (cancers and non-cancer bone marrow failures etc) as well as solid tumors are expected to be particularly affected by the global COVID-19 epidemic. Patients with haematological disorders or solid tumors are furthermore often elderly and may therefore also have comorbidities both unrelated to the haematological or oncological diagnosis but also due to late effects of the disease and treatments. Elevated risks of severe COVID-19 complications are also seen in older patients in general. In previous reports older patients and patients with cancer has had the highest mortality with a CFR of 20%3.
In Denmark all patients with a haematological or oncological diagnosis and all patients who are acutely admitted to in-patient care are treated and followed in public hospitals which have universal coverage. Also all testing and management of COVID-19 is organized only through public hospitals.
With our study proposal we therefore aim to study course and complications of COVID-19 in high risk patients above 80 years or who have haematological or oncological disorders in a nationwide setting. We thereby provide knowledge on effects of immune deficiency, age, and comorbidity of the clinical course in this infectious disease. Our goal is to improve protection from and management of SARS-CoV-2. We anticipate providing results based on 1,500 patients to direct protective measures before the next wave of the epidemic strikes.