— By Dr KK Aggarwal

375: Viral load

Dr Edward Parker of the London School of Hygiene and Tropical Medicine explains how a high viral load can impact humans.

He said: “After we are infected with a virus, it replicates in our body’s cells. The total amount of virus a person has inside them is referred to as their ‘viral load’. For Covid-19, early reports from China suggest the viral load is higher in patients with more severe disease, which is also the case for Sars and influenza.

376: Infectious dose

The amount of virus we are exposed to at the start of an infection is referred to as the ‘infectious dose’. For influenza, we know that that initial exposure to more virus — or a higher infectious dose — appears to increase the chance of infection and illness.

377: Can repeated small doses be more infectious

Studies in mice have also shown that repeated exposure to low doses may be just as infectious as a single high dose.

So, all in all, it is crucial for us to limit all possible exposures to Covid-19, whether these are to highly symptomatic individuals coughing up large quantities of virus or to asymptomatic individuals shedding small quantities. And if we are feeling unwell, we need to observe strict self-isolation measures to limit our chance of infecting others.

378: What is the similiarity between load and dose

Viral load, on the other hand, relates 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,” says Edward Parker at the London School of Hygiene and Tropical Medicine.

379: Infectious dose and health care workers

Professor Wendy Barclay, the head of the Department of Infectious Disease at Imperial College London, said existing knowledge of viral load means healthcare workers can be at greater risk of infection.

In general, with respiratory viruses, the outcome of infection — whether you get severely ill or only get a mild cold — can sometimes be determined by how much virus actually got into your 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.

So, standing further away from someone when they breathe or cough out virus likely means fewer virus particles reach you and then you get infected with a lower dose and get less ill. Doctors who have to get very close to patients to take samples from them or to intubate them are at higher risk so need to wear masks.

380: What is minimum infectious dose of COVID 19

Dr Michael Skinner, Reader in Virology, Imperial College London, said: Viruses are not poisons, within the cell they are self-replicating. That means an infection can start with just a small number of articles (the ‘dose’). The actual minimum number varies between different viruses and we don’t yet know what that ‘minimum infectious dose’ is for COVID-19, but we might presume it’s around a hundred virus particles.

381: How many cells are infected to start with

When that dose reaches our respiratory tract, one or two cells will be infected and will be re-programmed to produce many new viruses within 12-24 hours (for COVID-19, we don’t yet know how many or over how long). The new viruses will infect many more nearby cells (which can include cells of our immune defence system too, possibly compromising it) and the whole process goes around again, and again, and again.

382: What is inmate and acquired immune responses

At some time quite early in infection, our ‘innate immune system’ detects there’s a virus infection and mounts an innate immune response. This is not the virus-specific, ‘acquired immune response’ with which people are generally familiar (i.e. antibodies) but rather a broad, non-specific, anti-viral response (characterised by interferon and cytokines, small proteins that have the side effect of causing many of the symptoms: fever, headaches, muscle pain).

This response serves two purposes: to slow down the replication and spread of the virus, keeping us alive until the ‘acquired immune response’ kicks in (which, for a virus we haven’t seen, is about 2 to 3 weeks) and to call-up and commission the ‘acquired immune response’ which will stop and finally clear the infection, as well as laying-down immune memory to allow a faster response if we are infected again in the future (this is the basis of the expected immunity in survivors and of vaccination).

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

383: What happens in older people

In older people, or people with immunodeficiencies, the activation of the acquired immune system may be delayed. This means that the virus can carry on replicating and spreading in the body, causing chaos and damage as it does, but there’s another consequence.

Another job of the acquired immune system is to stand-down the innate immune system; until that’s done the innate immune response will keep increasing as the virus replicates and spreads.

Part of the innate immune response is to cause ‘inflammation’. That is useful in containing the virus early in an infection but can result in widespread damage of uninfected tissue (we call this a ‘bystander effect’) if it becomes too large and uncontrolled, a situation named ‘cytokine storm’ when it was first seen with SARS and avian influenza H5N1. It is difficult to manage clinically, requiring intensive care and treatment and carries with it high risk of death.

384: What following infection with ‘normal’ doses of virus

The scenarios described above describe what happens following infection with ‘normal’ doses of virus, both in those who make a recovery, those who require intensive care and those (mainly elderly and/or immunosuppressed) who might succumb. Those with other comorbidities probably succumb due to additional stress of their already compromised essential systems by virus and/or cytokine storm.

385: Does getting exposed to multiple COVID positive patients matter

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

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

386: What about a massive viral dose inhalation

Under such circumstances the virus receives a massive jump start, leading to a massive innate immune response, which will struggle to control the virus to allow time for acquired immunity to kick-in while at the same time leading to considerable inflammation and a cytokine storm.

For most of us, it’s hard to see how we could receive such a high dose; it’s going to be a rare event.

In the COVID-19 clinic, the purpose of PPE is to prevent such large exposures leading to high dose infection. Situations we should be concerned about are 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 only came about because lung cancer patients (not known to be infected) had lobectemies. There have been suggestions that such situations contributed to the deaths of medics in Wuhan, who were conducting normal procedures (including some that could generate aerosols of infected fluids) before the spread and risk had been appreciated.

388: What is the link between army and viral load

Prof Wendy Barclay, Action Medical Research Chair Virology, and Head of Department of Infectious Disease, Imperial College London, said: “In general with respiratory viruses, the outcome of infection – whether you get severely ill or only get a mild cold – can sometimes be determined by how much virus actually got into your 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.

389: What is the difference between doctors and patients viral dose

Standing further away from someone when they breathe or cough out virus likely means fewer virus particles reach you and then you get infected with a lower dose and get less ill. Doctors who have to get very close to patients to take samples from them or to intubate them are at higher risk so need to wear masks.

The fewer people in the room, the less likely it is than one person is coughing or breathing out infectious virus at any one time, so mixing with as few people as possible is the safest way.

390: Can two persons with same covid disease stay in one place

“But there is no evidence for any suggestion that if everyone in a family is already sick they can they reinfect each other with more and more virus. In fact for other viruses once you are infected it’s quite hard to get infected with the same virus on top.”

391: What is minimal infective dose

Professor Willem van Schaik, Professor in Microbiology and Infection at the University of Birmingham, said: “The minimal infective dose is defined as the lowest number of viral particles that cause an 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 but because SARS-CoV-2 is a new pathogen we lack data. For SARS, the infective dose in mouse models was only a few hundred viral particles. It thus seems likely that we need to breathe in something like a few hundred or thousands of SARS-CoV-2 particles to develop symptoms. This would be a relatively low infective dose and could explain why the virus is spreading relatively efficiently.

392: 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.

In the lockdown situation this seems even less likely as gatherings of more than two individuals are banned.

Because the infectious dose is probably quite low, it is more likely that you will be infected by a single source rather than from multiple sources. Transmission can take place through small droplets in the air (like the ones that are produced after sneezing and which stay in the air for a few seconds). You can breathe in these droplets or they can land on surfaces. Unfortunately, SARS-CoV-2 survives reasonably well on most surfaces, so if somebody touches these and then touches their mouth or nose, there is a very real risk that they will be infected with the viruses. This is the main reason why hand washing is promoted as a precautionary measure.

393: Why does the amount of virus shed matter?

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

The virus will survive and remain infectious outside the body, as viruses do; BUT infectivity will fall away 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 for this virus is measured in hours. In fact 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, cardboard is 3 and 1/2 hours, plastic and steel T1/2 is around 6 hours.

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

“Of course, when one deals 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.”

394: 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 are makeshift facilities. These may be set up in hostels, hotels, schools, stadiums, lodges etc., both public and private. If need be, 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, are to be maintained.
• Wherever a COVID Care Center is designated for admitting both the confirmed and the suspected cases, these facilities must have separate areas for suspected and confirmed cases with preferably separate entry and exit. Suspect and confirmed cases must not be allowed to mix under any circumstances.
• 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 Centre must necessarily be mapped to one or more Dedicated COVID Health Centres and at least one Dedicated COVID Hospital for referral purpose (details given below).
• Every Dedicated COVID Care Centre must also have a dedicated Basic Life Support Ambulance (BLSA) equipped with sufficient oxygen support on 24×7 basis, for ensuring 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 Centre facilities may also be drawn from AYUSH doctors. Training protocols developed by AIIMS is uploaded on MoHFW website. Ministry of AYUSH has also carried out training sessions. The State AYUSH Secretary/ Director should be involved in this deployment. State wise details of trained AYUSH doctors has been shared with the States. Their work can be guided by an Allopathic doctor.

395: Dedicated COVID Health Centre (DCHC)

• The Dedicated COVID Health Centre 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 entry\exit/zoning.
• Private hospitals may also be designated as COVID Dedicated Health Centres.
• 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 would have beds with assured Oxygen support.
• Every Dedicated COVID Health Centre must necessarily be mapped to one or more Dedicated COVID Hospitals.
• Every DCHC must also have a dedicated Basic Life Support Ambulance (BLSA) equipped with sufficient oxygen support for ensuring safe transport of a case to a Dedicated COVID Hospital if the symptoms progress from moderate to severe.

396: Dedicated COVID Hospital (DCH)

• The Dedicated COVID Hospitals are hospitals 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 entry\exit.
• 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 should 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, 7th April, 2020)

397: What is Joshua Santarpia study

The report cited several studies it said 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 gotten 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.

398: how safe are toilets in hospitals

Another study in preprint looking at hospitals and public areas in Wuhan found 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, stating 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.

399: What is a covid puff

The report did not cite a recent overview in the Journal of the American Medical Association by Lydia Bourouiba, PhD, of the Massachusetts Institute of Technology in Cambridge. The report noted that recent research has found that “exhalations, sneezes, and coughs not only consist of mucosalivary droplets following short-range semiballistic emission trajectories but, importantly, are primarily made of a multiphase turbulent gas (a puff) cloud that entrains ambient air and traps and carries within it clusters of droplets with a continuum of droplet sizes.”

400: Can smoker covid positive patient shed more viruses 

There is no study as yet.

((The writer is President, CMAAO, HCFI and Past national President IMA))