乌鸦传媒

Updated May 11

What about mild or asymptomatic cases of COVID-19?

Asymptomatic transmission has not only been confirmed in China, but recent modeling data found that mild or asymptomatic cases that went undetected ("undocumented") accounted for 85% of total infections in the earliest stages of the outbreak. The study found these cases were less infectious on a per-contact basis, but because those individuals weren't isolated they infected more people in total.

The big unknown, however, is how common it may be for people to become infected but with symptoms too mild to seek treatment. Currently, detection is based on molecular testing, which is performed only on individuals who come into contact with the healthcare system. The prevalence of such mild or asymptomatic infections won't be known until an inexpensive serological test, detecting antibodies to the virus that signal previous exposure, is available for use with routine blood draws. Thus, the extent of exposure in the population may not be known for years.

How do you contract COVID-19?

Research points to droplet and fomite transmission, with recent data suggesting the virus can survive on surfaces such as plastic and stainless steel for up to several days. It can also survive in the air for a few hours, indicating it may also potentially be aerosol transmissible.

The virus may also be transmitted through the fecal-oral route, with research suggesting some patients develop gastrointestinal symptoms, and that the virus is shed through stool.

A small cohort study in China found the virus present in two patients' tears, indicating it might be transmissible through eye secretions.

How infectious is the COVID-19 coronavirus?

Research from China found a similar viral load in symptomatic and asymptomatic patients, which may suggest patients can transmit the virus whether they have mild or severe disease.

Latest data from the , meaning infected individuals transmit it to 2-2.5 others on average. By contrast, the R0 for measles is 12-18, while for seasonal influenza it's a little over 1.

How virulent is COVID-19?

According to JAMA, global mortality for COVID-19 is reported to be 4.7%, , though the authors emphasized this was not an accurate case-fatality rate due to the uncertain denominator.

CDC examined , and found 508 (12%) of patients were hospitalized, and of those, 121 were known to be admitted to an intensive care unit, and 44 patients died. Similar to China, both hospitalization and mortality rates increased with increasing age, though this data indicated 20% of hospitalized patients and 12% of patients admitted to an ICU were ages 20-44. Nine patients ages 20-44 died, though in the entire group most deaths were among adults ages 65 and older.

Notably, however, mortality rates vary dramatically from one country to another, raising more questions about case-finding and record-keeping than there are answers.

What are early symptoms of COVID-19?

In addition to fever, cough and shortness of breath, chills, repeated shaking with chills, new loss of taste or smell, muscle aches, headache and sore throat.

Examining data from patients admitted in New York City, prior to respiratory symptoms, including about three-quarters presented with cough or fever, and almost 60% with shortness of breath. Gastrointestinal symptoms seem to be more common in U.S. patients, with about a quarter reporting diarrhea and 20% reporting vomiting.

It appears not all patients present with symptoms, with research out of Germany in February finding patients testing positive for COVID-19 despite being afebrile and otherwise normal-seeming.

How is COVID-19 diagnosed?

include hospitalized patients with symptoms of COVID-19, older symptomatic adults with chronic medical conditions and/or who are immunocompromised, and anyone who has been in close contact with a suspected or confirmed COVID-19 case within 14 days, including healthcare professionals, or anyone who has traveled to affected geographic areas within 14 days of symptom onset.

A patient is swabbed, then the sample is tested via reverse transcription polymerase chain reaction (RT-PCR) to determine presence of viral RNA.

The FDA recently authorized the first serology test to detect IgM and IgG antibodies under Emergency Use Authorization, for diagnosing COVID-19 infection in combination with other clinical and lab data.

What are risk factors for more severe disease?

Reports from China indicate disease is much more severe in older patients, with the highest mortality rate among adults age 80 and older. Patients with other comorbidities are also the most at risk, with U.S. data finding hypertension and obesity were the most common chronic medical conditions among patients hospitalized with COVID-19, followed by chronic lung conditions, diabetes and cardiovascular disease.

Data out of New York City found obesity as a risk factor for mechanical ventilation. Patients requiring mechanical ventilation were also more likely to need vasopressors, and experienced other complications such as atrial arrhythmias and new renal replacement therapy.

What does severe disease look like?

JAMA detailed , 15 of whom needed mechanical ventilation. All 15 had acute respiratory distress syndrome, and eight developed severe ARDS by 72 hours. Vasopressors were used for 14 patients, though most patients did not present with evidence of shock, and seven patients developed cardiomyopathy. Mortality among this group was 67%, 24% remained critically ill and 9.5% were discharged from the ICU, as of March 17.

In New York City, a third of patients required intubation, and of these, 30% did not get supplemental oxygen, meaning they deteriorated quickly.

However, U.K. research indicated compared to patients with non-COVID-19 viral pneumonia (52.1% vs 77.8%, respectively).

How is the disease treated?

Treatment , according to CDC recommendations. The most common complications of severe disease include pneumonia, hypoxemic respiratory failure/ARDS, shock, multiorgan failure.

Since pneumonia is common, IV antibiotic use has been widely reported, along with supplemental oxygen, with anecdotal reports of proning and ultimately, mechanical ventilation, including some patients who receive extra corporeal membrane oxygenation (ECMO).

Although corticosteroids were widely used in China, the CDC generally recommends against them except in patients with steroid-responsive comorbidities such as septic shock. "[P]atients with MERS-CoV or influenza who were given corticosteroids were more likely to have prolonged viral replication, receive mechanical ventilation, and have higher mortality," whereas reports from China in COVID-19 were uncontrolled and observational, the CDC explained.

Research indicates patients hospitalized with COVID-19 often develop blood clots, leading some international societies to call for patients to receive prophylactic anticoagulant treatment to prevent this complication. Additional research found longer duration of anticoagulation therapy tied to reduced risk of mortality in certain mechanically ventilated patients.

What are potential therapeutic options for treating the virus?

There are currently no approved therapies to treat COVID-19, although some have emergency use authorization (EUA), including hydroxychloroquine and remdesivir. The , which noted both insufficient clinical data to recommend for or against use of both remedisivir and hydroxychloroquine and chloroquine. Specifically, the agency noted monitoring patients who receive HCQ for adverse effects, especially prolonged QTc interval. The FDA recently issued a warning about the heart risks of the drug.

NIH also said there is insufficient clinical data to recommend use of convalescent plasma or hyperimmune globulin, as well as interleukin-6 inhibitors and interleukin-1 inhibitors.

The agency recommended against the use of hydroxychloroquine plus azithromycin, lopinavir/ritonavir (Kaletra) or other HIV protease inhibitors, interferons and Janus kinase inhibitors.

For remdesivir, an interim analysis of a formal trial from the National Institute of Allergy and Infectious Diseases including data from U.S. patients found remdesivir met its primary endpoint in severe COVID-19 patients, a significantly faster time to recovery versus controls, and trended towards a survival benefit. Manufacturer Gilead Sciences also reported comparing two dosing regimens in severe cases, but without a usual-care control group, showing a trend favoring a 5- versus 10-day treatment period.

What is the status of clinical trials for potential therapies?

Remdesivir

Many hospitals have begun to use hydroxychloroquine or chloroquine, which is most commonly used to treat patients with malaria, as well as arthritis and systemic lupus erythematosus, although the supporting evidence is anecdotal at best. The FDA has held in the National Strategic Stockpile, although that does not make COVID-19 an approved indication. Research found no difference in risk of ventilation the drug in male veterans with severe COVID-19, and data out of New York City found no difference in the risk of intubation or death in hospitalized patients treated with hydroxychloroquine.

A small case series in China found three of five patients treated with convalescent plasma were later discharged from the hospital, though questions about scaling this as a potential therapy remain.

Small trials overseas found improvements in overall survival of hospitalized patients with cytokine-targeting therapy, anakinra (Kineret) in Italy, and a three-drug regimen including lopanivir-ritonavir (Kaletra), ribavirin and interferon beta-1b shortened time to virus elimination in mild to moderate hospitalized cases in Hong Kong.

For anti-cytokine agents such as tocilizumab (Actemra) but . Controlled trials with tocilizumab are now underway, including one sponsored by drugmaker Genentech/Roche.

Sanofi and Regeneron announced a , another anti-interleukin-6 agent, for patients with severe COVID-19.

The Milken Institute has collated on its website.

What are the vaccine prospects?

Several companies and public health agencies have vaccines in development, including the National Institute of Allergy and Infectious Diseases. are underway, with a timeline of 12-18 months for a vaccine to be ready for wide-scale deployment.

As of April 21, the Milken Institute counted 115 vaccine candidates in development, including .

What is the prognosis for patients with COVID-19?

Older patients and those with other comorbidities are the most at risk, whereas the disease appears to be less severe among younger patients. U.S. data seems to indicate fewer children contract severe disease than adults, and hospitalization in this population is most common among infants and children with underlying conditions.

Research is starting to come from China that COVID-19 vertical transmission from mother to baby is possible, given several isolated case reports, and reports of miscarriage related to placental infection, and maternal death from cardiopulmonary complications are also starting to emerge.

What are some potential complications of COVID-19?

Data from New York City indicated ST-segment elevation on the EKG was complex, and confirmed COVID-19 cases were complicated by ST-segment elevation, which could have indicated potential acute MI.

Neurologic complications have been reported, with limited case reports from Italy linking COVID-19 infection to Guillain-Barré syndrome. And in China, more than a third of confirmed COVID-19 cases had neurologic symptoms, such as acute cerebrovascular events, impaired consciousness and muscle injury, which were more common among patients who required mechanical ventilation.

Acute ischemic stroke can be another complication of COVID-19, with reports out of the U.K. indicating a series of patients with large vessel occlusion, and U.S. reports finding acute ischemic large vessel stroke even among younger adult patients.

What are the long-term sequelae of COVID-19?

It is unclear whether or how often COVID-19 survivors will experience persistent pulmonary or other problems, or for how long. Many patients have remained hospitalized with the illness for weeks outside of China, out of an abundance of caution and for public health reasons.

Researchers from China pointed to cardiovascular system abnormalities in nearly half of a small group of SARS patients in a 12-year follow-up cohort, as well as about two-thirds with high lipids and 60% with glucose metabolism problems. They suggested COVID-19 may also cause chronic damage to the cardiovascular system, as the virus has a similar structure to SARS.

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