CME INDIA Presentation by Admin.
In many cases, it looks mysterious how transmission occurs. Knowledge gap is wide. Read the interesting scenario.
Dr Awadhesh Kumar Singh, DM (Endo), Kolkata asks:
- Case history of COVID in a family next to my door: family of 4 members – husband, wife and 2 daughters (22 and 13 year). No one stepped out of house – didn’t meet with anyone – since lockdown. No outsiders ever entered in to house but service of Swiggy, Zomato, Amazon etc. delivered goods to security guards – later handed over to house – handled by husband or wife with all extreme precautions.
- Elder daughter had fever and loss of taste and smell for 2-weeks – took nothing except Paracetamol, recovered fully. Entire family fully mixing with each other – no isolation of any manner done during daughters’ illness.
- IgG and Total antibodies (both qualitative and quantitative) test done to entire family. Elder daughter IgG is 4-fold high while other 3 members had undetectable titre.
- Explain – what did we learn so far about COVID ?
CME INDIA Discussion:
Dr Chandra Bhushan Prasad, Bihar:
It’s not amazing, I have sent many patients for anti-body testing and wondered to see that 90% have antibody titre high (means they suffered and recovered without knowing that they suffered from it (COVID), experts should explain the Nature of this disease 🙄🙄
Dr Awadhesh K Singh:
That’s a generalised statement. Concentrate about this family profile and explain Not so easy to explain Sir ji. No mild antibody even detected with any other family members!
Dr Chandra Bhushan Prasad:
Loss of taste and smell proves she got mild infection and other family members too low to show any complain and recovered with mild antibody.
Dr Rajiv Kovil, Diabetologist, Mumbai:
Is it that anosmia is usually with a low viral load? And the other members may get positive later but a PCR plus antibody should have been done in all of them?
Dr Vasanth Kumar, President Elect RSSDI, Hyderabad:
One explanation can be that the girl who was mildly symptomatic developed antibodies and others were either asymptomatic or some of them did not contact disease and they did not develop antibodies.
Dr D P Khaitan, Sr Consultant Physician, Gaya:
The immune orchestra of human body is having B-Lymphocytes dependent antibodies production and T cell dependent cellular immunity. I think, the secrecy would be revealed by unveiling this secrecy.
Dr Swati Srivastava, Sr Prof of Med, SMS medical college, Jaipur:
- Could it be like this?
- The elder daughter had fever and loss of smell and taste. She had COVID infection, which is endorsed by her high antibody levels. Others were freely coming in contact, so less likely they did not contact, unless the house is huge and they are all in separate rooms.
- Still unlikely, since must be coming close at meals etc. Meaning others had asymptomatic infection. Primary case in house developed antibodies whereas others didn’t, implying the kinetics of antibodies are highly variable in symptomatic versus asymptomatic.
https://onlinelibrary.wiley.com/doi/10.1002/cti2.1182 – this study shows:
3 major findings:
- Asymptomatic patients, mostly young females ≤ 60 years, were observed in approximately 12% of no severely ill patients infected with SARS‐CoV‐2
- >90% patients experienced IgM/IgG seroconversion at the time of virus clearance, whereas the median time from the first virus‐positive screening to IgG/IgM seroconversion was significantly shorter in asymptomatic than in symptomatic patients
- At the time of virus clearance, asymptomatic patients had lower IgG/IgM titres and plasma neutralisation capacity than symptomatic patients.
If not, much duration has lapsed, PCR may help, in this scenario no member got PCR done.
Dr Awadhesh K Singh, DM endo., Kolkata:
- Elder girl shares bed with mother and younger sister – pretty close contact thus all assumptions are still unexplained. Asymptomatic people should have some antibodies in quantitative test.
- Antibody test was done exactly on day 21 from first day of fever. No point doing PCR to anyone at the moment as almost 3/4 week has happened to first day of fever.
- Later means when? – 25 days has already past from the fever of index case.
Dr N K Singh:
I do not think, this can be explained. It simply echoes that transmission trends are largely unknown. The pathogenicity of SARS‐CoV‐2 is possibly associated with certain viral subtypes or strains, some studies showed. Asymptomatic and symptomatic patients exhibited different kinetics of IgG/IgM responses to SARS‐CoV‐2 in above mentioned reference by Dr Swati. I have, experience of few cases. Husband and wife got affected but other members not in same house, although, isolation and masking were followed.
But, seen, many instances, one person got severely affected Same house. No masking. No distancing. But, all other escaped. Like this case:
35 yr. male came to me with history of travel to Mumbai. Developed fever and cough for 10 days, did not consult to any physician. I told to do rtPRCR and HRCT thorax. COVID -Positive. For past 10 days all his family members were in contact, as none were aware. Wife was sharing the room too. After 21 days, none of the 4 members developed IgG antibodies.
Dr Awadhesh K Singh, DM endo., Kolkata:
Nothing explains – the Qs remain:
- How did elder daughter contracted the COVID when she didn’t venture outside?
- Even if one assumes it could be due to fomites from outside food or any non-living material – why did the parents who handled those things didn’t contract COVID?
- Despite all we’re in very close contact – no one of them basically had any suggestion of past contact – as evident by undetectable (quantitative) IgG Ab (100% sensitivity and 99.6% specificity)?
Both parents still run on treadmill for 45 min without any issues!
Dr N K Singh:
Agree. CDC says, transmission trends are not fully known.
Dr D P Khaitan, Gaya:
- The peptide: MHC class II complex can be recognized by antigen-specific armed helper T cells, stimulating them to make proteins that, in turn, cause the B cell to proliferate and its progeny to differentiate into antibody-secreting cells.
- If cellular immunity is good enough – antibodies production. Might be negligible to be detected.
Dr N K Singh:
How to know T cell immunity status in routine cases?
Dr Harish Darla, Mysore:
Would it be useful to check CD4/ 8 count to see if its elevated?
Dr D P Khaitan, Gaya:
Dr Awadhesh K Singh, DM endo., Kolkata:
The peculiar problem in this case is – while fomites induced transmission could be likely with index case but airborne transmission to the family has not happened.
Did you mean T cell immunity protected all family member without any Ab rise (B cell) while daughter showed both T and B cell immunity? 😩😃😁
Dr D P Khaitan, Gaya:
There might be some individual variation.
Dr Swati Srivastava:
We see very unpredictable antibody positivity in COVID patients. Can we really be sure that the others did not contact COVID on the basis of absence of antibodies? Particularly as they were quite close contacts.
Dr Basab Ghosh, Agartala:
We learn the unpredictability of this virus.
Dr Awadhesh K Singh, DM endo., Kolkata:
Similarly, how do we declare anyone in the family except index case as COVID positive?? That’s the dilemma 😀😁
Dr D P Khaitan, Gaya:
With due respect, may I clear one doubt in my mind – MHC 11 which lines the membrane of immune cells – Lymphocytes and macrophages interaction with helper T Lymphocytes due to innate immune variability is having the unpredictable response of B cells induced antibody production – responsible for unpredictable antibody positivity in COVID patient or some else mechanism is responsible
Dr Somnath, Hyderabad:
Fact about COVID is that still we are groping in the dark. I am not able to correlate patho-physiologically many symptoms and laboratory findings. Like one of my patients discharged in September and even today he is having CORAD 3 on HRCT chest. Mildly raised inflammatory markers but patient is asymptomatic and even doing normal work. Admitted with rtpcr+ve. If IgG and IgM normal. What is the explanation?
Dr Ravi A, Prof Med Stanley Med College, Chennai:
What we learned about COVID:
- It has multiple manifestations, from asymptomatic to severe ARDS.
- Clinical features are attributable to both the virus and more importantly host immune system.
- Depending upon the time of presentation, immunomodulatory agents & Oxygen Therapy scored over antivirals & multivitamins.
- Mortality rate is higher in senior citizens and people with comorbid.
- Early Oxygen Therapy found to have better outcomes along with the sheet anchor, Dexamethasone.
- Heparin became an indispensable agent.
- Awake prone breathing/ventilation hitherto less known manoeuvre proved useful.
- Importance of Medical Nutrition Therapy, especially in critical care patients became evident.
- Follow up for late complications especially thrombotic episodes are essential.
- Discordant between Radiology findings and clinical picture.
What we don’t know are:
- Why majority are asymptomatic & didn’t develop adequate protective antibodies?
- Why some young people without any comorbid succumbed?
- Why people from low socioeconomic backgrounds & children had lesser incidence?
- Men from fisherman community of North Chennai lesser affected than women.
CME INDIA Learning Points
- Several recent studies have revealed that SARS-CoV-2 antibodies deplete over time following infection and recovery.
- Some studies have reported that memory B-cells could provide durable humoral immunity even when serum antibody titers decline.
- New research has investigated the durability of B-cell immunity following SARS-CoV-2 infection and recovery.
(Ref link:https://www.medrxiv.org/content/10.1101/2020.10.28.20220996v)
- One recent study in NEJM shows that in a group of predominantly young male military recruits, approximately 2% became positive for SARS-CoV-2, as determined by qPCR assay, during a 2-week, strictly enforced quarantine
- Multiple, independent virus strain transmission clusters were identified.
- Shared rooms and shared platoon membership were risk factors for transmission. Most study participants with positive qPCR tests were asymptomatic, and all cases among participants and nonparticipants were identified as the result of scheduled testing rather than clinical qPCR testing performed as a result of daily screening.
- Participants who were associated with the two largest transmission clusters were identified by means of sequencing and were either roommates or members of the same platoons, which indicates that double-occupancy rooming and shared platoon membership were important contributors to transmission.
(November 11, 2020/DOI: 10.1056/NEJMoa2029717)
- In another new study in NEJM: Transmission was facilitated by close-quarters conditions and by asymptomatic and presymptomatic infected crew members. Nearly half of those who tested positive for the virus never had symptoms. DOI: 10.1056/NEJMoa2019375
- Still, science is chasing the mystery of transmission.
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I am reminded of an incident that happened in the early days of the Pandemic. A family friend reported to me with cough for a week. His RT PCR was negative but HRCT Chest showed Corad 5 mild Covid Pneumonia. Subsequent RT PCR was positive.
I admitted him and advised other 5 members to get tested. All turned out to be negative on RT PCR and their HRCTs were also normal.
I asked the wife whether the 2 had been quareling lately. Her head went down and she said that they were sleeping separately. Well, since then, all of us have received pts similar to one described in this post and we have no reply but to accept that we still do not know the dynamics of spread completely.
Antibodies may not be seen in asymptomatc patients and the duration for which they last is also not very clear.
There is this example of a post Covid patient who had donated plasma after recovering. When he went back to donate plasma again after 2 mths, antibodies were not seen in his blood.
Such examples also create uncertainty about the vaccine also.