In a new study, researchers identified the most common characteristics of 85 COVID-19 patients who died in Wuhan, China in the early stages of the coronavirus pandemic.
The study reports on commonalities of the largest group of coronavirus patient deaths to be studied to date.
The paper was published online in the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.
In “Clinical Features of 85 Fatal Cases of COVID-19 From Wuhan: A Retrospective Observational Study,” researchers from China and the United States report on an analysis of the electronic health records of patients with COVID-19 who died despite treatment at two hospitals in Wuhan: Hanan Hospital and Wuhan Union Hospital between Jan. 9 and Feb. 15, 2020. Wuhan, in China’s Hubei Province, was the epicenter of the COVID-19 outbreak.
“The greatest number of deaths in our cohort were in males over 50 with non-communicable chronic diseases,” stated the authors.
“We hope that this study conveys the seriousness of COVID-19 and emphasizes the risk groups of males over 50 with chronic comorbid conditions including hypertension (high blood pressure), coronary heart disease and diabetes.”
The researchers examined the medical records of 85 patients who had died, and recorded information on their medical histories, exposures to coronavirus, additional chronic diseases they had (comorbidities), symptoms, laboratory findings, CT scan results and clinical management. Statistical analyses were then done.
The median age of these patients was 65.8, and 72.9 percent were men. Their most common symptoms were fever, shortness of breath (dyspnea) and fatigue.
Hypertension, diabetes and coronary heart disease were the most common comorbidities.
A little over 80 percent of patients had very low counts of eosinophils (cells that are reduced in severe respiratory infections) on admission.
Complications included respiratory failure, shock, acute respiratory distress syndrome (ARDS) and cardiac arrhythmia, among others. Most patients received antibiotics, antivirals and glucocorticoids (types of steroids).
Some were given intravenous immunoglobulin or interferon alpha-2b.
The researchers noted: “The effectiveness of medications such as antivirals or immunosuppressive agents against COVID-19 is not completely known.
Perhaps our most significant observation is that while respiratory symptoms may not develop until a week after presentation, once they do there can be a rapid decline, as indicated by the short duration between time of admission and death (6.35 days on average) in our study.”
Based on their findings, eosinophilopenia – abnormally low levels of eosinophils in the blood – may indicate a poor prognosis.
The scientists also noted that the early onset of shortness of breath may be used as an observational symptom for COVID-19 symptoms.
In addition, they noted that a combination of antimicrobial drugs (antivirals, antibiotics) did not significantly help these patients.
The majority of patients studied died from multiple organ failure.
“Our study, which investigated patients from Wuhan, China who died in the early phases of this pandemic, identified certain characteristics.
As the disease has spread to other regions, the observations from these areas may be the same, or different.
Genetics may play a role in the response to the infection, and the course of the pandemic may change as the virus mutates as well.
Since this is a new pandemic that is constantly shifting, we think the medical community needs to keep an open mind as more and more studies are conducted.”
The study authors are affiliated with a number of medical centers and departments of the Chinese PLA General Hospital; Wuhan Union Hospital; Renmin Hospital of Wuhan University; China’s National Clinical Research Center for Geriatric Diseases; Wuhan Hannan Hospital; Tongji Medical College, Huazhong University of Science & Technology; Joe DiMaggio Children’s Hospital, Hollywood, FL; and University of California, Davis.
All ages are susceptible. Infection is transmitted through large droplets generated during coughing and sneezing by symptomatic patients but can also occur from asymptomatic people and before onset of symptoms .
Studies have shown higher viral loads in the nasal cavity as compared to the throat with no difference in viral burden between symptomatic and asymptomatic people . Patients can be infectious for as long as the symptoms last and even on clinical recovery.
Some people may act as super spreaders; a UK citizen who attended a conference in Singapore infected 11 other people while staying in a resort in the French Alps and upon return to the UK .
These infected droplets can spread 1–2 m and deposit on surfaces. The virus can remain viable on surfaces for days in favourable atmospheric conditions but are destroyed in less than a minute by common disinfectants like sodium hypochlorite, hydrogen peroxide etc. .
Infection is acquired either by inhalation of these droplets or touching surfaces contaminated by them and then touching the nose, mouth and eyes.
The virus is also present in the stool and contamination of the water supply and subsequent transmission via aerosolization/feco oral route is also hypothesized . As per current information, transplacental transmission from pregnant women to their fetus has not been described .
However, neonatal disease due to post natal transmission is described . The incubation period varies from 2 to 14 d [median 5 d]. Studies have identified angiotensin receptor 2 (ACE2) as the receptor through which the virus enters the respiratory mucosa .
The clinical features of COVID-19 are varied, ranging from asymptomatic state to acute respiratory distress syndrome and multi organ dysfunction. The common clinical features include fever (not in all), cough, sore throat, headache, fatigue, headache, myalgia and breathlessness. Conjunctivitis has also been described.
Thus, they are indistinguishable from other respiratory infections. In a subset of patients, by the end of the first week the disease can progress to pneumonia, respiratory failure and death. This progression is associated with extreme rise in inflammatory cytokines including IL2, IL7, IL10, GCSF, IP10, MCP1, MIP1A, and TNFα .
The median time from onset of symptoms to dyspnea was 5 d, hospitalization 7 d and acute respiratory distress syndrome (ARDS) 8 d. The need for intensive care admission was in 25–30% of affected patients in published series.
Complications witnessed included acute lung injury, ARDS, shock and acute kidney injury. Recovery started in the 2nd or 3rd wk. The median duration of hospital stay in those who recovered was 10 d.
Adverse outcomes and death are more common in the elderly and those with underlying co-morbidities (50–75% of fatal cases). Fatality rate in hospitalized adult patients ranged from 4 to 11%. The overall case fatality rate is estimated to range between 2 and 3% .
Interestingly, disease in patients outside Hubei province has been reported to be milder than those from Wuhan . Similarly, the severity and case fatality rate in patients outside China has been reported to be milder .
This may either be due to selection bias wherein the cases reporting from Wuhan included only the severe cases or due to predisposition of the Asian population to the virus due to higher expression of ACE2 receptors on the respiratory mucosa .
Disease in neonates, infants and children has been also reported to be significantly milder than their adult counterparts. In a series of 34 children admitted to a hospital in Shenzhen, China between January 19th and February 7th, there were 14 males and 20 females.
The median age was 8 y 11 mo and in 28 children the infection was linked to a family member and 26 children had history of travel/residence to Hubei province in China. All the patients were either asymptomatic (9%) or had mild disease. No severe or critical cases were seen.
The most common symptoms were fever (50%) and cough (38%). All patients recovered with symptomatic therapy and there were no deaths. One case of severe pneumonia and multiorgan dysfunction in a child has also been reported . Similarly the neonatal cases that have been reported have been mild .
A suspect case is defined as one with fever, sore throat and cough who has history of travel to China or other areas of persistent local transmission or contact with patients with similar travel history or those with confirmed COVID-19 infection. However cases may be asymptomatic or even without fever. A confirmed case is a suspect case with a positive molecular test.
Specific diagnosis is by specific molecular tests on respiratory samples (throat swab/ nasopharyngeal swab/ sputum/ endotracheal aspirates and bronchoalveolar lavage). Virus may also be detected in the stool and in severe cases, the blood. It must be remembered that the multiplex PCR panels currently available do not include the COVID-19. Commercial tests are also not available at present.
In a suspect case in India, the appropriate sample has to be sent to designated reference labs in India or the National Institute of Virology in Pune. As the epidemic progresses, commercial tests will become available.
Other laboratory investigations are usually non specific. The white cell count is usually normal or low. There may be lymphopenia; a lymphocyte count <1000 has been associated with severe disease. The platelet count is usually normal or mildly low. The CRP and ESR are generally elevated but procalcitonin levels are usually normal.
A high procalcitonin level may indicate a bacterial co-infection. The ALT/AST, prothrombin time, creatinine, D-dimer, CPK and LDH may be elevated and high levels are associated with severe disease.
The chest X-ray (CXR) usually shows bilateral infiltrates but may be normal in early disease. The CT is more sensitive and specific. CT imaging generally shows infiltrates, ground glass opacities and sub segmental consolidation. It is also abnormal in asymptomatic patients/ patients with no clinical evidence of lower respiratory tract involvement. In fact, abnormal CT scans have been used to diagnose COVID-19 in suspect cases with negative molecular diagnosis; many of these patients had positive molecular tests on repeat testing .
Differential Diagnosis 
The differential diagnosis includes all types of respiratory viral infections [influenza, parainfluenza, respiratory syncytial virus (RSV), adenovirus, human metapneumovirus, non COVID-19 coronavirus], atypical organisms (mycoplasma, chlamydia) and bacterial infections. It is not possible to differentiate COVID-19 from these infections clinically or through routine lab tests. Therefore travel history becomes important. However, as the epidemic spreads, the travel history will become irrelevant.
Treatment is essentially supportive and symptomatic.
The first step is to ensure adequate isolation (discussed later) to prevent transmission to other contacts, patients and healthcare workers. Mild illness should be managed at home with counseling about danger signs. The usual principles are maintaining hydration and nutrition and controlling fever and cough.
Routine use of antibiotics and antivirals such as oseltamivir should be avoided in confirmed cases. In hypoxic patients, provision of oxygen through nasal prongs, face mask, high flow nasal cannula (HFNC) or non-invasive ventilation is indicated. Mechanical ventilation and even extra corporeal membrane oxygen support may be needed.
Renal replacement therapy may be needed in some. Antibiotics and antifungals are required if co-infections are suspected or proven. The role of corticosteroids is unproven; while current international consensus and WHO advocate against their use, Chinese guidelines do recommend short term therapy with low-to-moderate dose corticosteroids in COVID-19 ARDS [24, 25].
Detailed guidelines for critical care management for COVID-19 have been published by the WHO . There is, as of now, no approved treatment for COVID-19. Antiviral drugs such as ribavirin, lopinavir-ritonavir have been used based on the experience with SARS and MERS.
In a historical control study in patients with SARS, patients treated with lopinavir-ritonavir with ribavirin had better outcomes as compared to those given ribavirin alone .
In the case series of 99 hospitalized patients with COVID-19 infection from Wuhan, oxygen was given to 76%, non-invasive ventilation in 13%, mechanical ventilation in 4%, extracorporeal membrane oxygenation (ECMO) in 3%, continuous renal replacement therapy (CRRT) in 9%, antibiotics in 71%, antifungals in 15%, glucocorticoids in 19% and intravenous immunoglobulin therapy in 27% .
Antiviral therapy consisting of oseltamivir, ganciclovir and lopinavir-ritonavir was given to 75% of the patients. The duration of non-invasive ventilation was 4–22 d [median 9 d] and mechanical ventilation for 3–20 d [median 17 d].
In the case series of children discussed earlier, all children recovered with basic treatment and did not need intensive care .
There is anecdotal experience with use of remdeswir, a broad spectrum anti RNA drug developed for Ebola in management of COVID-19 . More evidence is needed before these drugs are recommended. Other drugs proposed for therapy are arbidol (an antiviral drug available in Russia and China), intravenous immunoglobulin, interferons, chloroquine and plasma of patients recovered from COVID-19 [21, 28, 29]. Additionally, recommendations about using traditional Chinese herbs find place in the Chinese guidelines .
American Thoracic Society