vrijdag 3 april 2020

FAQ Coronavirus on symptoms, viabililty on surfaces and in aerosols, prolonged faecal shedding and the need for serological testing

What symptoms of SARS-CoV-2 are common?
Of 99 patients, 83% presented with fever, 82% with a cough and 31% with shortness of breath. Symptoms such as muscle ache, confusion, headache, sore throat, diarrhoea, nausea and vomiting were also observed. The NHS, RIVM and other health autorities seem to present rhinorrhoea and sneezing as main symptoms of COVID. Rhinorrhoea was observed in 4% of COVID cases (Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, The Lancet, 30 January 2020).

Another case study, Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study, confirms the abovementioned. Of 30 patients, the most common symptom was fever (96%), followed by cough (22%) and dyspnoea (17%). In severe cases, serum alkaline phosphatase was significantly higher than in mild cases. Multifocal ground-glass lung opacities were seen in 74%.

According to a study involving 191 patients the median time from illness onset until discharge is 22 days. The median duration of viral shedding for survivors is 20 days. Among 29 patients receiving lopinavir/ritonavir treatment, the median time of viral shedding is 22 days. In critical patients, the median duration of viral shedding is 24 days, the longest viral shedding observed being 30 days (Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study, The Lancet, published online on 9 March 2020).

How viable is SARS-CoV-2 on materials and in aerosols?
Viability refers to the time a virus can 'survive' on materials and in aerosols. Airborne transmission is the transmission route of viral particles through air. In aerosols, SARS-CoV-2 proved to remain stable up to 3 hours. The virus remains stable for up to 72 hours on plastic, up to 48 hours on stainless steel,  24 hours on cardboard and 4 hours on copper (Aerosol and Surface Stability of SARS-CoV-2 as compared to SARS-CoV-1, The New England Journal of Medicine, 17 March 2020).

Air samples taken from airborne infection isolation rooms in Singapore were all negative (Air, Surface, Environmental and Personal Protective Equipment Contamination by SARS-CoV-2 From a Symptomatic Patient, JAMA, 4 March 2020), indicating that inducing air flow by regular ventilation of rooms is important. A preprint claims that air samples taken at the Nebraska Medical Center contained SARS-CoV-2. The highest concentration was recovered from an air handling grate. Air samples were found to be 63.2% positive by RT-PCR, while none of the patients were observed to cough. The highest airborne concentration was observed while a patient was receiving oxygen through a nasal cannula (Transmission potential of SARS-CoV-2 in viral shedding observed at the University of Nebraska Medical Center, preprint available via MedRxiv).

Caution is recommended. What has to be proven yet is:
1. The infection of in vivo cells through airborne transmission;
2. Given that airborne transmission proves to be a route to infect hosts' cells, how concentration of viable loads, expelled through aerosols, relates to severity of SARS-CoV-2.

Why is hand hygiene important?
The fecal-oral route and respiratory droplet-oral route are two possible transmission routes. Note that contamination through surfaces and faeces is not the only transmission route, but the fecal route must not be understated as a shedding route of SARS-CoV-2 (Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes, Emerging Microbes and Infections, 17 February 2020).

One study supplied evidence that some SARS-CoV-2-infected patients can harbor the virus in the intestines during the early stage of the infection, whereas in SARS-infected patients, intestinal infection was observed during the late stage of the infection. A study involving 1099 patients confirms that asymptomatic people might be shedding virus through stool. Eight out of ten children tested positive on rectal swabs, even after testing negative on nasopharyngael surveillance (COVID-19: faecal-oral transmission?, Nature Reviews Gastroenterology & Hepatology, 25 March 2020).

There is evidence for prolonged presence of SARS-CoV-2 in feces. For 5 weeks after the patients' respiratory samples tested negative for viral RNA, virus was detected on faecal sampling. One patient had positive faecal samples for 33 days after testing negative on respiratory sampling; another patient had a prolonged faecal shedding for 47 days after first symptom onset (Prolonged presence of SARS-CoV-2 viral RNA in faecal samples, The Lancet Gastroenteroloy & Hepatology, 19 March 2020).

Is routine surveillance sufficient?
No: routine surveillance typically involves oral sampling, which is not accurate in respect of the difference in viral loads during different stages of a SARS-CoV-2 infection. In a January 2020 molecular study, of the patients with viremia blood, none tested oral or anal positive, indicating that patients should not be discharged on oral negative swabbing alone. This confirms the necessity of serological testing using IgM and IgG (Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes, Emerging Microbes and Infections, 17 February 2020).

Moreover, in a SARS-CoV-2 infected patient with mild symptoms, ASC peaked on day 8 after onset. Antibodies are observed until day 20 (Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19, Nature Medicine, 16 March 2020). Rebound of viral load after 5 days was observed in one cohort study (Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2, The Lancet, 23 March 2020).

Thus: a policy that demands discharging a patient on oral negative swabbing is contrary to findings concerning patients testing positive on viremia blood sampling. Add a health policy of anal swabbing and serological testing. One should be aware of the fact that feces of a SARS-CoV-2 patient might test positive until a median of 5 weeks after onset. Awareness and adjustment of health policies should reduce the risk of contamination with faecal shedding of SARS-CoV-2.