Viral load: Dr Edward Parker of the London School of Hygiene and Tropical Medicine has explained how high viral load can impact humans.

He stated that when a virus infects us, it replicates in our body’s cells. The total amount of virus present inside a person is referred to as their ‘viral load’. For COVID-19, early reports from China suggested that the viral load is higher in patients with more severe disease, which is also noted for SARS and influenza.

Infectious dose

The amount of virus one is exposed to at the onset of an infection is referred to as the ‘infectious dose’. For influenza, it is known that initial exposure to more virus, or a higher infectious dose, tends to increase the chance of infection and illness.

Can repeated small doses be more infectious

Studies in mice have revealed that repeated exposure to low doses could be as infectious as a single high dose.

It is, therefore, essential to limit all possible exposures to COVID-19. This includes exposure to highly symptomatic individuals coughing up large quantities of virus as well as to asymptomatic individuals shedding small quantities. If one is feeling unwell, he/she should observe strict self-isolation measures to limit the chance of infecting others.

[Excerpts from: The Independent]

What is the similarity between load and dose

Viral load refers to the number of viral particles being carried by an infected individual and shed into their environment. “The viral load is a measure of how bright the fire is burning in an individual, whereas the infectious dose is the spark that gets that fire going,” said Edward Parker at the London School of Hygiene and Tropical Medicine. [Source: New Scientist]Infectious dose and health care workers

Professor Wendy Barclay, the head of the Department of Infectious Disease at Imperial College London, stated that the current knowledge of viral load suggests that healthcare workers can be at greater risk of infection.

With respiratory viruses, the outcome of infection, whether severe illness or mild cold, can sometimes be determined by how much virus actually got into the body and started the infection off.  “It’s all about the size of the armies on each side of the battle, a very large virus army is difficult for our immune systems army to fight off,” stated Professor Barclay.

Standing away from a person when he/she breathes or coughs out virus possibly translates to fewer virus particles reaching you and then you getting infected with a lower dose and getting mildly ill.  Doctors who have to get very close to patients to take samples from them or to intubate them have increased risk so they need to wear masks. [Source: The Independent]

What is minimum infectious dose of COVID-19

Dr Michael Skinner, Reader in Virology, Imperial College London, has stated that viruses are not poisons. They self-replicate within the cell. This points out that an infection can start with just a small number of articles (the ‘dose’). The actual minimum number differs for different viruses and it is not yet known what that ‘minimum infectious dose’ is for COVID-19. We might presume that it’s around a hundred virus particles.

How many cells are infected to start with

When that particular dose reaches the respiratory tract, one or two cells get infected and are re-programmed to produce many new viruses within 12-24 hours (for COVID-19, it is not known as to how many or over how long). The new viruses go on to infect several more nearby cells, which could include cells of our immune defense system as well, possibly compromising it. The entire process goes around again, and again.

What is innate and acquired immune responses

At some point, early in the infection, our innate immune system detects a virus infection and builds an innate immune response. This is not the virus-specific, ‘acquired immune response’ but a broad, non-specific, anti-viral response. This is characterized by interferon and cytokines, small proteins that have the side effect of causing symptoms like fever, headaches, muscle pain.

This response slows the replication and spread of the virus, and keeps us alive until the ‘acquired immune response’ starts (which, for a virus we haven’t seen, is about 2 to 3 weeks). Additionally, the response commissions the ‘acquired immune response’ which will stop and finally clear the infection. This lays down immune memory enabling a faster response if we are infected again in the future.

With COVID-19, these two arms of the immune system work well for nearly 80% of the population who recover from more or less mild influenza-like illness.

What happens in older people

In older people, or people with immunodeficiencies, there may be a delay in the activation of the acquired immune system. The virus goes on replicating and spreading in the body, causing damage.

Additionally, the acquired immune system does another job, that is, to stand-down the innate immune system. Until then, the innate immune response will keep increasing as the virus replicates and spreads.

A part of the innate immune response is to cause inflammation. This helps in containing the virus early in an infection but can result in widespread damage of uninfected tissue. This is known as the ‘bystander effect.’ If it becomes uncontrolled, a situation termed as ‘cytokine storm’ arises. It is difficult to manage clinically, requiring intensive care and treatment and is associated with high risk of death.

What happens following infection with ‘normal’ doses of virus

The situations described above indicate what happens after infection with ‘normal’ doses of virus, both in those who recover, those who require intensive care and those (mainly elderly and/or immunosuppressed) who might succumb. People with other comorbidities likely succumb due to additional stress on their already compromised essential systems by virus and/or cytokine storm.

Does getting exposed to multiple COVID positive patients matter

It is unlikely that higher doses acquired by being exposed to multiple infected sources would affect the course of disease or the outcome much.

It’s hard to see how the dose would vary by more than 10 fold. Differences have been seen; however, in lab animal infections with some viruses. But those animals are inbred (genetically similar to respond in the same way).

What about a massive viral dose inhalation

In such situations, the virus receives a massive jump start, leading to an extensive innate immune response, which strives to control the virus to allow time for acquired immunity to kick-in while simultaneously leading to considerable inflammation and a cytokine storm.

It is hard to see how we could receive such a high dose; it’s going to be a rare event.

In the COVID-19 clinic, PPE is used to prevent such large exposures leading to high dose infection. We should be concerned about potential high dose exposure of clinical staff conducting procedures on patients who are not known to be infected.

There is a Chinese description of an early stage COVID-19 infection of the lung, which occurred because lung cancer patients (not known to be infected) had lobectemies. It has been suggested that such situations led to the deaths of healthcare workers in Wuhan, who were conducting normal procedures (including some that could generate aerosols of infected fluids) before the spread and risk had been appreciated.

What is the link between army and viral load

Prof Wendy Barclay has stated that with respiratory viruses, the outcome of infection could be guided by how much virus gets into the body and starts the infection.  It’s all about the size of the armies on each side of the battle, a very large virus army makes it difficult for our immune systems army to fight off.

What is the difference between doctors and patients viral dose

Standing away from someone who breathes or coughs out virus could mean fewer virus particles reaching you and you contracting the infection with a lower dose and getting less ill.  However, doctors getting very close to patients to take samples or to intubate them have higher risk, and therefore, need to wear masks.

Can two persons with same COVID-19 disease stay in one place

There is no evidence to suggest that if everyone in a family is already sick, they can reinfect each other with more and more virus.  For other viruses, once you are infected, it’s quite hard to get infected with the same virus on top.

What is minimal infective dose

Professor Willem van Schaik, Professor in Microbiology and Infection at the University of Birmingham, has pointed out that the minimal infective dose refers to the lowest number of viral particles that cause infection in 50% of individuals (or ‘the average person’). For many bacterial and viral pathogens we have a general idea of the minimal infective dose. However, SARS-CoV-2 is a new pathogen, and therefore, data is limited.

For SARS, the infective dose in mouse models was found to be only a few hundred viral particles. Therefore, it seems likely that we need to breathe in a few hundred or thousands of SARS-CoV-2 particles to develop symptoms. This is a relatively low infective dose and could thus explain why the virus is spreading relatively efficiently.

What about the crowd

“It seems unlikely that people can pick up small numbers of viruses from others (e.g. in a crowd) and that will tip the infection over the edge to become symptomatic as that must happen around the same time,” said Professor Willem.

In the lockdown situation, this becomes even less likely.

As the infectious dose is quite low, it is more likely that you will be infected by a single source rather than from multiple sources. Transmission can occur through small droplets in the air, for instance,  the ones that are produced after sneezing and stay in the air for a few seconds. One may breathe in these droplets or they can land on surfaces. SARS-CoV-2 has been reported to survive reasonably well on most surfaces. If someone touches these and then touches their mouth or nose, there is a high risk that they will be infected with the viruses. This is the main reason why hand washing is a crucial precautionary measure.

 Why does the amount of virus shed matter?

The inoculum, or the infecting dose of virus, is more likely to cause infection in the “recipient” the higher the amount of the virus there is in the excreta.

The virus can survive and remain infectious outside the body; however, the infectivity will regress with time. How quickly this fall occurs is measured as the time taken for virus infectivity to reduce by half. This is termed ‘half-life’ or T1/2 and is measured in hours. This is best thought of as ‘rate of decay’.

The rate of decay is fastest on copper with a T1/2 around 1 hour, in air as an aerosol T1/2 is also around 1 hour, on cardboard is 3 and 1/2 hours, plastic and steel T1/2 is around 6 hours.

To understand this, if one million viruses were placed on various surfaces, it would require 20 half lives to become undetectable and non-infectious, 20 hours if in an aerosol, 20 hours on copper, 60-70 hours on cardboard and finally 120-130 hours on plastic and steel.

While dealing with infectivity rather than detectability, extinguishing infectivity is far quicker. Studies with cultured virus starting at relatively high levels have shown loss of infectivity within around 12-15 hours on copper, under 10 hours on cardboard, around 50 hours on steel and 70 hours on plastic. The data for infectivity in aerosols were not comparable and were of a different time course.

[Source: Science Media Centre]

COVID Care Center (CCC)

• The COVID Care Centers shall offer care only for cases that have been clinically assigned as mild or very mild cases or COVID suspect cases.
• The COVID Care Centers serve as makeshift facilities. These may be set up in hostels, hotels, schools, stadiums, lodges etc., both public and private. If need arises, existing quarantine facilities could also be converted into COVID Care Centers. Functional hospitals like CHCs, etc, which may be handling regular, non-COVID cases should be designated as COVID Care Centers as a last resort. This is important as essential non-COVID Medical services like those for pregnant women, newborns etc, need to be maintained.
• Wherever a COVID Care Center is designated for admitting both the confirmed and the suspected cases, the facilities must have separate areas for suspected and confirmed cases preferably with separate entry and exit. Suspect and confirmed cases must not be allowed to mix.
• As far as possible, wherever suspect cases are admitted in the COVID Care Center, preferably individual rooms should be assigned for such cases.
• Every Dedicated COVID Care Center must necessarily be mapped to one or more Dedicated COVID Health Centers and at least one Dedicated COVID Hospital for referral (details given below).
• Every Dedicated COVID Care Center must have a dedicated Basic Life Support Ambulance (BLSA) equipped with sufficient oxygen support on 24x7 basis, to ensure safe transport of a case to Dedicated higher facilities if the symptoms progress from mild to moderate or severe.
• The human resource to man these Care Center facilities may also be drawn from AYUSH doctors. Training protocols developed by AIIMS have been uploaded on MoHFW website. Ministry of AYUSH has also conducted training sessions. The State AYUSH Secretary/Director should be involved in this deployment. State wise details of trained AYUSH doctors have been shared with the States. Their work can be guided by an Allopathic doctor.

Dedicated COVID Health Center (DCHC)

The Dedicated COVID Health Centers are hospitals that shall offer care for all cases that have been clinically assigned as moderate.

• These should either be a full hospital or a separate block in a hospital with preferably separate entryexit/zoning.
• Private hospitals may also be designated as COVID Dedicated Health Centers.
• Wherever a Dedicated COVID Health Center is designated for admitting both the confirmed and the suspect cases with moderate symptoms, these hospitals must have separate areas for suspect and confirmed cases. Suspect and confirmed cases must not be allowed to mix under any circumstances.
• These hospitals need to have beds with assured oxygen support.
• Every Dedicated COVID Health Center has to be mapped to one or more Dedicated COVID Hospitals.
• Every DCHC must have a dedicated Basic Life Support Ambulance (BLSA) equipped with sufficient oxygen support to ensure safe transport of a case to a Dedicated COVID Hospital if the symptoms progress from moderate to severe.

Dedicated COVID Hospital (DCH)

• The Dedicated COVID Hospitals are those that shall offer comprehensive care primarily for those who have been clinically assigned as severe.
• The Dedicated COVID Hospitals should either be a full hospital or a separate block in a hospital with preferably separate entryexit.
• Private hospitals may also be designated as COVID Dedicated Hospitals.
• These hospitals would have fully equipped ICUs, Ventilators and beds with assured Oxygen support.
• These hospitals will have separate areas for suspect and confirmed cases. Suspect and confirmed cases must not be allowed to mix under any circumstances.
• The Dedicated COVID Hospitals would also be referral centers for the Dedicated COVID Health Centers and the COVID Care Centers.

(Source: Guidance document on appropriate management of suspect/confirmed cases of COVID-19.Ministry of Health & Family Welfare, Directorate General of Health Services, EMR Division, 7^th April, 2020)

What is Joshua Santarpia study

A recent report has cited several studies that supported the idea that SARS-CoV-2 is airborne. One study (still in preprint and not yet peer reviewed) by Joshua Santarpia, PhD, and colleagues at the University of Nebraska Medical Center in Omaha, has received a lot of attention. The researchers collected air and surface samples from 11 rooms of patients with COVID-19, and found viral RNA in the air both inside and outside the rooms and on ventilation grates. [Medscape]

How safe are toilets in hospitals

A study, currently in preprint, looked at hospitals and public areas in Wuhan. It was noted that the highest concentrations of virus were in toilet facilities and in PPE removal rooms. Doffing of the PPE may potentially have aerosolized the virus, the researchers hypothesized.

 Fineberg and colleagues; however, approached the finding with caution, and have stated that "it may be difficult to re-suspend particles of a respirable size." More likely, "fomites could be transmitted to hands, mouth, nose, or eyes without requiring direct respiration into the lungs," they write. [Medscape]

What is a COVID puff

Recent research has shown that exhalations, sneezes, and coughs not only consist of mucosalivary droplets following short-range semiballistic emission trajectories but are largely made up of a multiphase turbulent gas, or a puff, cloud that climbs on ambient air and traps and carries within it clusters of droplets with a continuum of droplet sizes. [Medscape]

Can smoker COVID-positive patient shed more viruses at more distance

There is no study as yet.

Dr K K Aggarwal,

President Confederation of Medical Associations of Asia and Oceania