Coronavirus

Is there an association between Covid-19 and subsequent development of hypertension?

FA Manian MD, MPH, , , , , , , , , , , , Leave a comment

Although far from definite, emerging evidence suggests that adults with recently diagnosed Covid-19 are at increased risk of newly-diagnosed hypertension following the acute infection.1-4

A retrospective cohort study involving a large national healthcare data base of the Department of Veterans Affairs found that, at a median follow-up of 126 days, Covid-19 survivors had an excess burden of newly-diagnosed hypertension (15/1000 patients) and were at higher risk of initiation of antihypertensive drugs compared to controls.2

Another retrospective cohort study involving over 80,000 adults 65 years or older (median follow-up 56 days) found an increased risk of newly-diagnosed hypertension (O.R. 4.4; 95% C.I. 2.27-6.37) in the Covid-19 group. 3  Even in a younger population (18-65 years of age), the same investigators found a significant increase (81%; 95% C.I. 10-196%) in the risk of newly diagnosed hypertension in the Covid-19 group compared to that of the control cohort. 4  

Despite the inherent limitations in these retrospective studies, a cause-and-effect relationship between Covid-19 and subsequent diagnosis of hypertension is plausible given the known affinity of SARS-CoV-2 for ACE2 receptors and endothelial cells. 5   Of interest, hyperreninemia associated with reduced glomerular filtration rate has been reported in some patients with Covid-19 requiring prolonged intensive care. 6

Bonus Pearl: Did you know that Covid-19 survivors have also been reported to have an increased risk of stroke, transient ischemic attack, ischemic heart disease, pericarditis, myocarditis, heart failure, dysrhythmia, and thromboembolic disease, independently of pre-existing hypertension and other cardiovascular risk factors? 7

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References

  1. Shibata S, Kobayashi K, Tanaka M, et al. Covid-19 pandemic and hypertension: an updated report from the Japanese Society of Hypertension project team on Covid-19. Hypertens Res 2022 Dec 23:1-12. COVID-19 pandemic and hypertension: an updated report from the Japanese Society of Hypertension project team on COVID-19 – PMC (nih.gov)
  2. Al-Aly Z, Xie Y, Bowe B. High-dimensional characterization of post-acute sequelae of Covid-19. Nature 2021;594:259-64. High-dimensional characterization of post-acute sequelae of COVID-19 – PubMed (nih.gov)
  3. Daugherty SE, Guo Y, Health K, et al. Risk of clinical sequelae after the acute phase of SARS-CoV-2 infection: retrospective cohort study. BMJ 2021;373:n1098. Risk of clinical sequelae after the acute phase of SARS-CoV-2 infection: retrospective cohort study | The BMJ
  4. Guney C, Akar F. Epithelial and endothelial expressions of ACE2:SARS-CoV-2 Entry Routes.  J Pharm Pharm Sci 2021;24:84-98 Epithelial and Endothelial Expressions of ACE2: SARS-CoV-2 Entry Routes – PubMed (nih.gov)
  5. Cohen K, Ren S, Health K, et al. Risk of persistent and new clinical sequelae among adults aged 65 years and older during the post-acute phase of SARS-CoV-2 infection: retrospective cohort study. BBMJ 2022;376:e068414. Risk of persistent and new clinical sequelae among adults aged 65 years and older during the post-acute phase of SARS-CoV-2 infection: retrospective cohort study – PubMed (nih.gov) 
  6. Hulstom M, von Seth M, Frithiof R. Hyperreninemia and low total body water may contribute to acute kidney injury in coronavirus disease 2019 patients in intensive care. J Hypertens 2020 May 28. Hyperreninemia and low total body water may contribute to acute kidney injury in corona virus disease 2019 patients in intensive care – PMC (nih.gov)
  7. Xie Y, Xu E, Bowe B, et al. Long-term cardiovascular outcomes of Covid-19. Nat med 2022;28:583-90. Long-term cardiovascular outcomes of COVID-19 – PMC (nih.gov)

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Is there an association between Covid-19 and subsequent development of hypertension?

Is loss of sense of smell or taste much less common in Omicron-related Covid-19 compared to earlier strains of SARS-CoV-2?

FA Manian MD, MPH, , , , , , , , , , , , Leave a comment

Absolutely! Although loss of smell was a cardinal symptom of Covid-19 with earlier strains of SARS-CoV-2 (eg, Wuhan, alpha, delta), on average omicron causes olfactory dysfunction in only 13% of patients, 3-4 times lower than the earlier strains.1

But why is omicron less likely to causes loss of smell or taste? There may be at least 2 explanations. First explanation revolves around the solubility of omicron in the olfactory mucus. Recall that to access the olfactory epithelium, viruses and other pathogens have to first dissolve in and penetrate the mucus layer that not only allows odorants to reach the olfactory receptors but also protects the olfactory epithelium from toxins and pathogens. Hydrophilic and acid proteins can penetrate the mucus barrier more easily because they are more soluble in the mucus layer.1

What does this have to do with omicron? Well, it turns out that omicron with all its mutations in the spike protein is actually more alkaline than the Wuhan and delta strains. This means that omicron may have lower solubility in mucus and have a harder time reaching and infecting the olfactory epithelium. 1 Since the composition of olfactory mucous differs significantly from other mucus layers in the respiratory tract, omicron may still cause disease.2

Another potential mechanism may be related to the inefficiency of omicron in other steps necessary to infect nonneuronal cells of the olfactory epithelium within the nasal cavity, such as the endosomal route. 1 It turns out that cells of the olfactory epithelium express less of the endosomal membrane fusion proteases (cathepsins) which omicron prefers for cell entry! Fascinating! 

Bonus Pearl: Did you know that only 5-10% of functional olfactory neurons are required for a relatively normal sense of smell? This means that SARS-CoV-2 needs to eliminate at least 90% of all support cells of the olfactory neurons within a 3-4 day period (before their regeneration) for the host to notice anosmia?

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References

  1. Butowt R, Bilinska K, von Bartheld C. Why does the omicron variant largely spare olfactory function? Implications for the pathogenesis of anosmia in coronavirus disease 2019. J Infect Dis 2022;226:1304-1308. Why Does the Omicron Variant Largely Spare Olfactory Function? Implications for the Pathogenesis of Anosmia in Coronavirus Disease 2019 – PubMed (nih.gov)
  2. Yoshikawa K, Wang H, Jaen C, et al. The human olfactory cleft mucus proteome and its age-related changes. Sci Rep 2018;8:17170. The human olfactory cleft mucus proteome and its age-related changes – PMC (nih.gov)
  3. Harding JW, Getchell TV, Margolis FL. Degeneration of the primary olfactory pathway in mice. V. Long-term effect of intranasal ZNS04 irrigation on behavior, biochemistry and morphology. Brain Res 1978;140:271-85. Denervation of the primary olfactory pathway in mice. V. Long-term effect of intranasal ZnSO4 irrigation on behavior, biochemistry and morphology – PubMed (nih.gov)

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Is loss of sense of smell or taste much less common in Omicron-related Covid-19 compared to earlier strains of SARS-CoV-2?

Why do some patients with Covid-19 develop a rebound after completing a course of Paxlovid (nirmatrelvir/ritonavir) and how common is it?

FA Manian MD, MPH, , , , , , Leave a comment

Covid-19 rebound, characterized by the recurrence of Covid-19 symptom or a new positive viral test after having tested negative, is a poorly understood phenomenon that can occur after completion of therapy with Paxlovid, Molnupiravir (another antiviral Covid-19 drug) and even in patients with acute Covid-19 who never received any specific antiviral therapy. 1-6

Based on very limited number of studies, it appears that rebound is not caused by emergence of drug resistance or absence of neutralizing immunity, rather resumption of SARS-CoV-2 replication following completion of therapy, triggering a secondary immune-mediated response that’s associated with clinical symptoms.2,3

Recent studies suggest that rebound following Paxlovid treatment may not be as common as one may think.  In a cohort of 483 high-risk patients treated with Paxlovid for Covid-19, 0.8% experienced rebound of symptoms within 30 days of diagnosis, which were generally mild at a median of 9 days after treatment, all resolving without additional antiviral therapy.3  In this study, the median age was 63 years and 93% were fully vaccinated; there were no hospitalization related to rebound or deaths. In another study (pre-print) involving over 11,000 patients treated with Paxlovid, rebound symptoms occurred in 2.3% and 5.9% of patients  7 and 30 days following therapy, respectively, with similar rates reported in patients treated with Molnupiravir.4

Interestingly, a preprint article involving 568 untreated patients with mild-moderate Covid-19 found that 27% had symptom rebound after initial improvement with 12% having viral rebound based on nasal swabs with ≥0.5 log viral RNA copies/ml. 5 So antiviral therapy for Covid-19 is not a prerequisite for rebound symptoms.

Although some have suggested that insufficient drug exposure either due to individual pharmacokinetics or insufficient duration may be the cause of rebound in treated patients,2   there is currently no evidence that additional treatment for Covid-19 is needed in these patients.6

Despite reports of rebound, Paxlovid should still be considered in selected patients with mild-moderate Covid-19 at high risk of complications to minimize the risk of hospitalization and death from Covid-19. 

Bonus Pearl: Did you know that, according to CDC, Covid-19 rebound often occurs between 2-8 days following initial recovery? 1

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References

  1. Covid-19 rebound after paxlovid treatment. May 24, 2022. COVID-19 Rebound After Paxlovid Treatment (cdc.gov)
  2. Carlin AF, Clark AE, Chaillon A, et al. Virologic and immunologic characterization of Coronavirus Disease 2019 recrudescence after nirmatrelvir/ritonavir treatment. Clin Infec Dis 2022 (June 20). Virologic and Immunologic Characterization of Coronavirus Disease 2019 Recrudescence After Nirmatrelvir/Ritonavir Treatment | Clinical Infectious Diseases | Oxford Academic (oup.com)
  3. Ranaganath N, O’Horo JC, Challner DW, et al. Rebound phenomenon after nirmatrelvir/ritonavir treatment of Coronavirus Disease-2019 in high-risk persons. Clin Infect Dis 2022 (June 14). https://doi.org/10.1093/cid/ciac481 Rebound Phenomenon after Nirmatrelvir/Ritonavir Treatment of Coronavirus Disease-2019 in High-Risk Persons | Clinical Infectious Diseases | Oxford Academic (oup.com)
  4. Wang L, Berger NA, David PB, et al. Covid-19 rebound after Paxlovid and Molnupiravir during January-June 2022. MedRxiv 2022. COVID-19 rebound after Paxlovid and Molnupiravir during January-June 2022 | medRxiv
  5. Deo R, Choudhary MC, Moser C, et al. Viral and symptom rebound in untreated Covid-19 infection. Medrxiv 2022. Viral and Symptom Rebound in Untreated COVID-19 Infection (medrxiv.org)
  6. Covid-19 rebound after Paxlovid treatment. May 24, 2022. HAN Archive – 00467 | Health Alert Network (HAN) (cdc.gov)

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

 

Why do some patients with Covid-19 develop a rebound after completing a course of Paxlovid (nirmatrelvir/ritonavir) and how common is it?

What’s so “special” about SARS-CoV-2 Omicron subvariants BA.4 and BA.5?

FA Manian MD, MPH, , , , , , , , , , , , , , , , Leave a comment

BA.4 and BA.5 now account for the majority of Covid cases in the U.S.1  Several concerning features of BA.4 and BA.5 when compared to earlier strains of SARS-CoV-2 include:2-6

  1. High reproductive rate or R0 ie, the average number of new infections generated by an infectious person in a totally naïve population. BA.4/5 has an estimated R0 of 18.6, according to a one report.  For comparison, the R0 for the original Wuhan variant was estimated at 3.3, for Delta  5.1, early Omicron  9.5, BA.1 13.3, mumps 12, and measles 18.  So, it’s not surprising that we are currently experiencing higher rates of SARS-CoV-2 transmission in the population than just a few weeks ago.3
  2. Suboptimal existing immunity following prior infections due to Omicron variants BA.1 and BA.2, or prior vaccinations (including 3 doses of Pfizer vaccine).2,4
  3. More efficient spread than BA.2 when studied in human lung cells invitro. 2
  4. More pathogenic than BA.2 in hamsters. 2
  5. Reduced activity of SARS-CoV-2 therapeutic monoclonal antibodies.4
  6. Antigenically distant from other SARS-CoV-2 variants, with 50 mutations, including more than 30 on the spike protein, the viral protein targeted by Covid vaccines to induce immunity.5,6

Despite these potentially ominous traits, currently there is no evidence that  BA.4 or BA.5 is inherently more likely to cause severe disease than that caused by other Omicron subvariants.   The sheer number of infected persons in the population due to high transmission rates, however, will likely translate into higher hospitalization and deaths which has already happened in many areas.

High transmission rates also mean that we should not abandon the usual public health measures (eg, social distancing, masking indoors in public spaces) and vaccination with boosters for eligible persons with the aim of reducing hospitalization and death, if not infections.  

Bonus Pearl: Did you know that BA.4 and BA.5 became dominant in South Africa in April, 2022, despite 98% of the population reportedly having some antibodies from vaccination or previous infection or both?  

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References

  1. Leatherby L. What the BA.5 subvariant could mean for the United States. NY Times, July 7, 2022. https://theconversation.com/australia-is-heading-for-its-third-omicron-wave-heres-what-to-expect-from-ba-4-and-ba-5-185598
  2. Kimura I, Ymasoba D, Tamura T, et al. Virological characteristics of the novel SARS-CoV-2 Omicron variants including BA.2.12.1, BA.4 and BA.5. bioRxiv, preprint doi: https://doi.org/10.1101/2022.05.26.493539 , posted May 26, 2022. Accessed July, 13, 2022.
  3. Esterman D. The Conversation. Australia is heading for its third Omicron wave. Here’s what to expect from BA.4 and BA.5. July 4, 2022. https://theconversation.com/australia-is-heading-for-its-third-omicron-wave-heres-what-to-expect-from-ba-4-and-ba-5-185598
  4. Tuekprakhon A, Nutalai R, Dijokaite-Guraliuc A, et al. Antibody escape of SARS-COV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum.
  5. Katella K. Omicron and BA.5: A guide to what we know. YaleMedicine, July 6, 2022. https://www.yalemedicine.org/news/5-things-to-know-omicron
  6. Topol E. The BA.5 story. The takeover by this Omicron sub-variant is not pretty. Ground Truths. June 27, 2022. https://erictopol.substack.com/p/the-ba5-story

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

What’s so “special” about SARS-CoV-2 Omicron subvariants BA.4 and BA.5?

What’s the latest on second Covid vaccine boosters and should I recommend them to my adult patients?

FA Manian MD, MPH, , , , , , , , , Leave a comment

On March 29, 2022, the CDC and the FDA approved second booster shots of Pfizer and Moderna Covid vaccines for everyone 50 years of age or older as well as people 12 years of age or older with moderate to severe immune deficiencies to be given at least 4 months following the first booster.1-3  This means a 4th dose of an mRNA vaccine for many adults and a 5th dose for those with moderate to severe immune deficiencies. 

Admittedly, these recommendations are made in the context of many uncertainties, including when the next Covid surge will arrive, what will be the predominant variant, and how will our immunity hold up if a surge occurs. 

Nevertheless, in discussing the merits of a 2nd booster, I would emphasize several “talking points”:

  • Covid hasn’t gone away with new cases still diagnosed daily, some still  requiring hospitalization, albeit at lower frequency than recent past. 
  • Our immunity against Covid wanes in the absence of boosters or natural infection.
  • SARS-CoV-2 has been unpredictable in its surges, as well as emergence of new variants with frequent changes in its virulence and ease of transmission. This means we don’t know when the next surge will hit us (summer, fall or later) and how the predominant variant will behave.
  • But let’s not get too hung up on surges! The fact is that as long as Covid is circulating around, maintaining a robust immunity against infection is the best way to avoid getting infected and the best way to do this is through boosters!
  • As more people go around without masks, the risk of unprotected exposure to SARS-CoV-2 is also likely to increase, particularly in indoor public gatherings.  Boosters may allow us the freedom to go maskless more often!
  • The risk of Long Covid even following mild infection is still real even between surges. This means even if we don’t get very sick from Covid, we are placing ourselves at risk of Long Covid. Remember, no Covid, no Long Covid!
  • Irrespective of whether it’s mild or even asymptomatic, Covid infection  can cause significant disruption in our lives, whether it be isolation at home, not being allowed to return to work or just the anxiety of having it or having passed it to others. This means that, at least currently, it’s premature to consider this virus as “just another respiratory virus.”  It’s impact on our everyday lives is still a lot different than typical respiratory viruses. 
  • mRNA vaccine boosters have been proven to be as safe as primary series. 
  • Last, but not the least, a preprint Israeli study involving volunteers 60 to 100 years old found a 78% reduction in mortality from Covid following a 2nd booster dose of Pfizer mRNA vaccine compared to those who only had 1 booster.4  This study has several limitations including self-selected volunteers who may already be at lower risk of Covid mortality due to their healthier lifestyle. Nevertheless, the data is very encouraging!

Ultimately, the decision to get a second booster, particularly during non-surge periods, will depend a lot on not only available facts but the individual’s threshold for acceptable risk of even mild disease, concern over transmission to others and more recently the cost of the vaccine, among other factors.  

Bonus Pearl: Did you know that each year there are plenty of uncertainties around which influenza A or B subtypes will be the predominant seasonal strain or what month they may surge but these questions never keep us from recommending the annual flu vaccine to the public as a means of reducing influenza cases and saving lives?   

 

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References

  1. D.A. Allows Second Covid Boosters for Everyone 50 and Older – The New York Times (nytimes.com)
  2. Coronavirus (COVID-19) Update: FDA Authorizes Second Booster Dose of Two COVID-19 Vaccines for Older and Immunocompromised Individuals | FDA
  3. CDC Recommends Additional Boosters for Certain Individuals | CDC Online Newsroom | CDC
  4. Arbel R, Sergienko R, Friger M, et al. Second booster vaccine and Covid-19 mortality in adults 60-100 years old. Preprint, posted March 24, 2022. 24514bba-2c9d-4add-9d8f-321f610ed199.pdf (researchsquare.com)

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

What’s the latest on second Covid vaccine boosters and should I recommend them to my adult patients?

Should healthy adults receive a Covid vaccine booster shot and why?

FA Manian MD, MPH, , , , , , , , , Leave a comment

A booster shot of Covid vaccine (eg, mRNA, Pfizer or Moderna) is now recommended by the CDC even for healthy adults as follows:1

  • If you received Pfizer vaccine as your primary series, are ≥12 years old and at least 5 months after your 2nd dose
  • If you received Moderna vaccine as your primary series, are ≥18 years old and at least 5 months after your 2nd dose
  • If you received J&J vaccine, are ≥18 years old and at least 2 months after your 1st dose

There are at least 3 reasons for receiving a Covid vaccine booster: 1

  • Waning immunity after primary vaccine series
  • Emergence of Omicron variant which seems to be less responsive to the existing immunity from the vaccine
  • Recent data from clinical trials showing that a booster shot increased the immune response in trial participants who completed an either Pfizer or Moderna mRNA vaccine primary series 6 months earlier or had J&J vaccine single dose 2 months earlier

Here is the data from CDC on the vaccine effectiveness against Covid based on epidemiologic data on emergency department (ED)/urgent care (UC) encounters or hospitalization during the recent Omicron-predominant period:2

 Vaccine effectiveness against ED/Urgent care encounters 

  • 2 doses of mRNA vaccine: 41% (69% <2 months vs 37% ≥5 months after last dose)
  • 3 doses of mRNA vaccine: 83% (87% < 2 months vs 66% 4 months vs 31% ≥5 months)

Vaccine effectiveness against hospitalization 

  • 2 doses of mRNA vaccine: 55% (71% < 2months vs 54% ≥5 months)
  • 3 doses of mRNA overall 88% (91% if < 2 months, 78% if ≥4 months)

So take full advantage of available Covid vaccines and maximize your chance of not getting Covid!

 

Bonus Pearl: Did you know that a recent CDC study found that people 18 years and older who received the same mRNA vaccine brand for all their vaccinations experienced fewer adverse reactions following the booster dose than they did after their second dose of mRNA vaccine, with 92% of reported reactions not considered serious?3

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References

  1. Covid-19 vaccine booster shots. Feb 2, 2022. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/booster-shot.html#:~:text=It%20depends.,after%20the%20J%26J%2FJanssen%20vaccine. Accessed Feb 24, 2022
  2. Waning 2-dose and 3-dose effectiveness of mRNA vaccines against Covid-19-associated emergency department and urgent care encounters and hospitalizations among adults during periods of delta and omicron variant predominance-VISION network, 110 states, August 2021-Jan 2022. Feb 18, 2022 https://www.cdc.gov/mmwr/volumes/71/wr/mm7107e2.htm#T1_down. Accessed Feb 24, 2022.
  3. New CDC studies: Covid-19 boosters remains safe, continue to offer high levels of protection against severe disease over time and during Omicron and delta waves. Feb 11, 2022. https://www.cdc.gov/media/releases/2022/s0211-covid-19-boosters.html. Accessed Feb 24, 2022

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Should healthy adults receive a Covid vaccine booster shot and why?

My middle-age immunocompromised patient receiving immunosuppressants has had 3 doses of mRNA Covid vaccine and is now 4 months out from her 3rd dose.  Should she consider a fourth dose of Covid vaccine?

FA Manian MD, MPH, , , , , , , , , , , , , Leave a comment

Yes! According to the Centers for Disease Control and Prevention (CDC) of the U.S.,1 persons who are “moderately or severely immunocompromised” and have received 3 doses of an mRNA vaccine (either Pfizer [12+ years old) or Moderna (18+ years old]) should receive a 4th dose (“booster”) at least 3 months after the 3rd dose.  Similarly, those who initially received a J&J vaccine followed by one of the aforementioned mRNA vaccines and are at least 2 months from the 2nd dose should also receive a 3rd dose (booster. 

The following are considered moderately or severely immunocompromised conditions by CDC: 

  • Active cancer treatment for tumors or cancers of the blood
  • Organ transplant with immunosuppressants on board
  • Stem cell transplant within the last 2 years or taking immunosuppressants
  • Moderate or severe primary immunodeficiency (eg, DiGeorge or Wiskott-Aldrich syndromes)
  • Advanced or untreated HIV infection
  • Active treatment with high-dose corticosteroids or other immunosuppressants

A published study2 of Covid-19-associated emergency department (ED) and urgent care (UC) encounters and hospitalization among adults during a period including Omicron variant predominance in 10 states found vaccine effectiveness for ED/UC visits dropping to 66% and for hospitalization to 78% by the 4th month after a 3rd dose (vs 87% and 91%, respectively during the 2 months after a 3rd dose).  This study did not distinguish immunocompromised from non-immunocompromised persons, however.  More data on the vaccine effectiveness in non-immunocompromised persons at high risk of Covid-19 related complications would be welcome.

Bonus Pearl: Did you know that of American adults who are fully vaccinated against Covid-19, only about 30% have received an additional Covid vaccine dose beyond the primary series ? 3 

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References

  1. Covid-19 vaccines for moderately or severely immunocompromised people (Updated Feb 17, 2022). Accessed Feb 21, 2022.  https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/immuno.html?s_cid=10483:immunocompromised%20and%20covid%20vaccine:sem.ga:p:RG:GM:gen:PTN:FY21
  2. Waning 2-doe and 3-dose effectiveness of mRNA vaccines against Covid-10-associated emergency department and urgent care encounters and hospitalizations among adults during periods of delta and omicron variant predominance—Vision Network, 10 states, August 2021-January 2022. MMWR 2022; 71:255-63. https://www.cdc.gov/mmwr/volumes/71/wr/mm7107e2.htm?s_cid=mm7107e2_w
  3. Hubler S, Harman A. As Cov id surges, experts say U.S. booster effort is falling behind. NY Times, December 18, 2021. https://www.nytimes.com/2021/12/18/us/omicron-booster-shots-americans.html

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

My middle-age immunocompromised patient receiving immunosuppressants has had 3 doses of mRNA Covid vaccine and is now 4 months out from her 3rd dose.  Should she consider a fourth dose of Covid vaccine?

Should patients with prior Covid receive Covid vaccine?

FA Manian MD, MPH, , , , , Leave a comment

Yes, as recommended by the CDC.  The weight of the evidence to date suggests that previously infected individuals should receive Covid vaccine to minimize their risk of acquiring Covid again for many reasons, including the following:

First, depending on the population and the variant of SARS-CoV-2 (the agent of Covid) studied, a significant proportion of infected individuals— from 5% to >35% based on some studies— fail to produce antibodies against SARS-CoV-2.1 In 1 study, lack of antibody production was associated with younger age, lower viral load and a trend toward milder symptoms.1

Second, the body of the evidence for infection-induced immunity is much more limited with less consistent findings than that for vaccine-induced immunity.2

Third, vaccination against Covid has been shown to enhance the immune response and reduce the risk of infection even in those with prior Covid.2 In fact, 1 study reported that the risk of reinfection is more than twice among those who were previously infected but not vaccinated compared to those who got vaccinated after having Covid.3  In another study, the risk of infection in adults was more than 5 times higher in unvaccinated but previously infected individuals compared to the vaccinated person who had not had an infection previously.4

Some authors5 who oppose routine vaccination of individuals previously infected with Covid have invoked a recent CDC study6 which showed that when Delta was the predominant strain, persons with prior Covid had lower rates of infection than persons who were vaccinated alone.  However, this study was performed when booster doses of Covid vaccine were not yet available to most people and before Omicron became the predominant variant. 

Bonus Pearl: Did you know that following Covid infection, neutralizing antibodies  have a biphasic decline with an initial half-life of 2-3 months followed by a slower decline thereafter?2

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References

  1. Liu W, Russell RM, Bibollet-Ruche F, et al. Predictors of nonseroconversion after SARS-CoV-2 infection. Emerg Infect Dis 2021;27:2454-58. Predictors of Nonseroconversion after SARS-CoV-2 Infection – Volume 27, Number 9—September 2021 – Emerging Infectious Diseases journal – CDC
  2. Science brief: SARS-CoV-2 infection-induced and vaccine-induced immunity. October 29, 2021. Science Brief: SARS-CoV-2 Infection-induced and Vaccine-induced Immunity | CDC
  3. Cavanaugh AM, Spicer KB, et al. Reduced risk of reinfection with SARS-CoV-2 after Covid-9 vaccination-Kentucky, may-June 2021. MMWR 2021;70:1081-83. Reduced Risk of Reinfection with SARS-CoV-2 After COVID-19 Vaccination – Kentucky, May-June 2021 – PubMed (nih.gov)
  4. Laboratory-confirmed Covid-19 among adults hospitalized with Covid-19-like illness with infection-induced or mRNA vaccine-induced SARS-CoV-2 immunity—Nine states, January-September 2021. MMWR 2021;70:1539-44. Laboratory-Confirmed COVID-19 Among Adults Hospitalized with COVID-19–Like Illness with Infection-Induced or mRNA Vaccine-Induced SARS-CoV-2 Immunity — Nine States, January–September 2021 | MMWR (cdc.gov)
  5. Makary M. The high cost of disparaging natural immunity to Covid. Wall Street Journal. January 26, 2022. The High Cost of Disparaging Natural Immunity to Covid – WSJ
  6. Leon Tm, Drabawila V, Nelson L, et al. Covid-19 cases and hospitalizations by Covid-19 vaccination status and previous Covid-19 diagnosis-California and New York, May -November 2021.  MMWR 2022;71:125-31 COVID-19 Cases and Hospitalizations by COVID-19 Vaccination Status and Previous COVID-19 Diagnosis — California and New York, May–November 2021 (cdc.gov)

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Should patients with prior Covid receive Covid vaccine?

Why is Paxlovid (nirmatrelvir/ritonavir) a promising new drug in our fight against Covid-19?

FA Manian MD, MPH, , Leave a comment

Based on the manufacturer’s (Pfizer’s) report, there are several reasons why Paxlovid may be a promising drug:1

  • It’s the first oral drug approved by the FDA for Emergency Use Authorization (EUA)
  • It reduces risk of hospitalization or death by ~ 90% (when taken within 3-5 days of symptom onset) in patients at high risk of complications from Covid-19
  • It reduces viral load at day 5 of treatment by 10-fold compared to placebo, theoretically reducing infectivity at least in household settings 2
  • Serious adverse events were comparable to placebo; possible side effects include liver disease, diarrhea, altered sense of taste, hypertension and muscle aches
  • Nirmatrelvir component of Paxlovid has been found to be active against a variety of SARS-CoV-2 variants of concern such as alpha, beta, delta as well as the newer omicron variant. This finding is in contrast to significantly reduced or loss of neutralizing activity of many commercially-available monoclonal antibody products against the omicron variant (eg, Casirivimab/Imdevimab-REGEN-COV, Bamlanivimab/Etesevimab, but not Sotrovimab)  designed to reduce serious Covid-19 complications in mild to moderate disease. 3-4

Few caveats to keep in mind when prescribing Paxlovid at this time:

  • It’s only approved for adults and children 12 years of age or older weighing at least 88 lbs (40kg) who test positive for SARS-CoV-2
  • Patients should be at high risk for progression to severe Covid-19 such as hospitalization or death
  • Per manufacturer (Pfizer), Paxlovid should not be taken if a patient is on certain medications due to the possibility of adverse drug interactions. The list includes colchicine, lovastatin, simvastatin, sildenafil for pulmonary arterial hypertension, some anti-epileptics (eg, carbamazepine, phenytoin), rifampin and St. John’s Wort.
  • There is no experience with treating pregnant women or breastfeeding mothers.
  • Pfizer recommends effective barrier contraception or refraining from sexual activity while taking Paxlovid

Paxlovid comes in a box of blister packs containing 5 days’ worth of medications (two 150 mg tablets of nirmatrelvir plus one 100 mg tablet of ritonavir to be taken 2x/day).  

Bonus Pearl: Another preliminary study of Paxlovid, this time including unvaccinated adults at low risk of hospitalization or death, has found a 70% reduction in hospitalization and no death compared to placebo with marginal statistical significance (P=0.051) but still with a 10-fold drop in viral load. 1

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References

  1. Pfizer announces additional phase 2/3 study results confirming robust efficacy of novel COVID-19 oral antiviral treatment candidate in reducing risk of hospitalization or death. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-additional-phase-23-study-results . Accessed Dec 23, 2021.
  2. Marc A, kerioui M, Blanquart F, et. al. Quantifying the relationship between SARS-CoV-2 viral load and infectiousness. eLife 2021;10:e69302. https://elifesciences.org/articles/69302#:~:text=Based%20on%20the%20current%20knowledge,24%25%20to%2058%25%20in%20household  
  3. Aggarwal A, Stell AO, Walker G, et al. SARS-CoV-2 Omicron:evasion of potent humoral responses and resistance to clinical immunotherapeutics relative to viral variants of concern. MedRxiv 2021. Doi:https://doi.org/10.1101/2021.12.14.21267772. https://www.medrxiv.org/content/10.1101/2021.12.14.21267772v1
  4. Planas D, Saunders N, Maes P, et al. Considerable escape of SARS-CoV-2 variant Omicron to antibody neutralization. MedRxiv 2021. https://www.biorxiv.org/content/10.1101/2021.12.14.472630v1

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Why is Paxlovid (nirmatrelvir/ritonavir) a promising new drug in our fight against Covid-19?

Who should get tested after a holiday indoor gathering with family members?

FA Manian MD, MPH, , , , , , , , , , , , Leave a comment

Whether you should get tested after holiday gatherings depends a lot on factors such as the level of transmission of Covid-19 within your region, the vaccination status of all the attendees, the likelihood of Covid-19 in any of the attendees, and your threshold for risk of either contracting or transmitting of Covid-19 to others, particularly immunocompromised persons. 

The following discussion assumes a scenario that is common to most indoor holiday gatherings: 1. You are getting together with people outside of your household; 2.  You or your family members don’t wear a face mask at all or certainly not all the time during the gathering; and 3. You find it impossible or don’t wish to socially distance from others during the get-together.1,2

First, let’s start with 2 situations where you should get tested following a holiday get-together, irrespective of your (or the attendees’) vaccination status: 1. if you have symptoms of Covid-19; and 2. If you were in close contact of an infected person (ie, commonly defined as within 6 feet of that person for a minimum of 15 minute during a 24-hour period).3

In the absence of known exposure or symptoms, you should consider getting tested if you are not fully immunized since you will be at higher risk of contracting and transmitting Covid-19 to others as long as there is still significant Covid-19 transmission in the region.  In contrast, if you and other attendees are fully immunized already, routine testing for Covid-19 after the gathering is hard to justify given the effectiveness of FDA-authorized Covid-19 vaccines and the costs and impracticalities associated with routine testing of millions of fully vaccinated persons.  

It goes without saying that holiday gatherings with family members outside of one’s immediate houseshold is not a zero-risk proposition for contracting or transmitting Covid-19 because people can have no symptoms and be infectious and vaccinated individuals can on occasion become infected.   Even the tests are not perfect. However, if you are concerned that you might have been exposed to Covid-19  and knowledge of a negative Covid-19 test (with its inherent limitations) gives you peace of mind, you should consider getting tested. The over-the-counter rapid Covid-19 tests may be particularly useful in assessing the likelihood of being contagious.4

For further recommendations on when you should consider getting tested for Covid-19 in general, I highly recommend an NIH-sponsored online calculator called “When to Test”.  This calculator is based on mathematical modelling that takes into account an individual’s vaccination status, transmission rates in the geographic area, and mitigation behaviors (eg, masks and social distancing).1

Bonus Pearl: Did you know that persons with Covid-19 are considered infectious 2 days before they develop symptoms or 2 days before the date of their positive test if they don’t have symptoms?5

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References:

  1. When to test offers free online tool to help individuals make informed Covid-19 testing decisions. https://www.nih.gov/news-events/news-releases/when-test-offers-free-online-tool-help-individuals-make-informed-covid-19-testing-decisions. Accessed November 26, 2021.
  2. Covid-19 testing overview. https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/testing.html. Accessed November 26, 2021.
  3. Covid-19. https://www.cdc.gov/coronavirus/2019-ncov/php/contact-tracing/contact-tracing-plan/appendix.html#contact. Accessed November 26, 2021.
  4. Schuit E, Venekamp RP, Pas SD, et al. Diagnostic accuracy of rapid antigen tests in asymptomatic and presymptomatic close contacts of individuals with confirmed SARS-CoV-2 infection: cross sectional study. BMJ 2021;374:n1676.  https://www.bmj.com/content/374/bmj.n1676
  5. Quarantine and isolation. https://www.cdc.gov/coronavirus/2019-ncov/your-health/quarantine-isolation.html#:~:text=Get%20tested%205%2D7%20days%20after%20their%20first%20exposure.,the%20person%20with%20COVID%2D19. Accessed November 26, 2021.

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

Who should get tested after a holiday indoor gathering with family members?