Covid-19

Is it just my imagination or are Covid-19 cases going down as influenza cases are surging out of control during this flu season?

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

No, you are not imagining! Although during respiratory tract infection (RTI) season several viruses such as rhinovirus, respiratory syncytial virus (RSV) and coronavirus may cocirculate, influenza virus frequently outcompetes many RTI viruses, likely through a phenomenon called “viral interference.” 1-4

A negative viral interference is observed when a virus that has already infected a host makes that host resistant to infection by the second virus (isn’t that fascinating?). Although there a lot of virus, host and environmental variables that affect infection risk, potential mechanisms for this interference include a rapid and robust innate immune response to the first virus such as through upregulation of interferon (IFN) production which can protect against unrelated viruses, thereby creating a temporary “antiviral state.” 1-4

A negative viral interference has been shown between influenza-A virus (IAV) and SARS-CoV-2 by a cool 2024 study using the air-liquid interface culture model of the differentiated human airway epithelium. 4 Replicating IAV induced a robust interferon response and suppressed SARS-CoV-2 replication in both sequential and simultaneous infections. In contrast, SARS-CoV-2 did not demonstrate significant viral interference with IAV.  The researchers took their experiment a step further and found that oseltamivir (Tamiflu), an anti-IAV agent, restored SARS-CoV-2 replication with IAV coinfection by reducing induction of IFN!

One explanation for the inability of SARS-CoV-2 to interfere with the production of influenza virus is its slower induction of IFN stimulating genes likely due to its more effective mechanisms of antagonizing the IFN response with infected cells.4 Another explanation is that SARS-CoV-2 has a slower growth rate than IAV, making it more susceptible to being “outgunned” by faster growing viruses. Some strains of IAV may also cause more damage to the epithelial cells than SARS-CoV-2 thus reducing the number of host cells available for SARs-CoV-2 infection.2 Last, secreted IFNs (eg, IFN λ) can also bind to receptors present at the surface of infected and neighboring state blocking the second virus from infecting the host.1

So, it looks like competition among living forms in this world also applies to the world of viruses!

Bonus Pearl: Did you know that the concept of viral interference was first described in the 1960s following observation that oral administration of live enterovirus vaccines decreased detection of several unrelated respiratory viruses such as influenza virus, RSV and human adenovirus?1

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References

  1. Piret J, Bolvin G. Viral interference between respiratory viruses. Emerg Infect Dis 2022;28:273-280. Viral Interference between Respiratory Viruses – PubMed
  2. Gilbert-Girard S, Piret J, Carbonneau J, et al. Viral interference between severe acute respiratory syndrome coronavirus 2 and influenza A viruses. PLOS Pathogens 2024;20(7):e1012017. Viral interference between severe acute respiratory syndrome coronavirus 2 and influenza A viruses – PubMed
  3. Kaaijk P, Swaans N, Nicolaie AM, et al. Contribution of influenza viruses, other respiratory viruses and viral co-infections to influenza-like illness in older adults. Viruses 2022;14, 797. Contribution of Influenza Viruses, Other Respiratory Viruses and Viral Co-Infections to Influenza-like Illness in Older Adults – PubMed
  4. Cheemarla NR, Watkins TA, Mihaylova VT, et al. Viral interference during influenza A-SARS-CoV-2 coinfection of the human airway epithelium and reversal by oseltamivir. J Infect Dis 2024;229:1430-4. Viral Interference During Influenza A-SARS-CoV-2 Coinfection of the Human Airway Epithelium and Reversal by Oseltamivir – PubMed

Disclosures/Disclaimers: 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 it just my imagination or are Covid-19 cases going down as influenza cases are surging out of control during this flu season?

How common is hyponatremia in patients with Covid-19 and what’s its significance?  

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

Hyponatremia has been reported between 20% and 35% of patients hospitalized for Covid-19, 1-5 with low serum sodium levels on admission often associated with progression to severe illness, mechanical ventilation, increased length of stay and death.1,2,4,5

A 2023 retrospective multicenter study involving over 2,600 hospitalized Covid-19 patients (between February 2020 and August 2022) found hyponatremia in 34.2%: Mild (Na 131-134 mmol/L) 25.1%, moderate (Na 126-130 mmol/L) 7.5% and severe (<126 mmol/L) 1.8%.3 There was a significant association between male sex at birth, hypertension, chronic kidney disease, immunosuppressives, thiazide diuretics and hyponatremia.3

Similarly, another retrospective study of hospitalized Covid-19 patients found an association between hyponatremia and several common chronic diseases, such as diabetes, hypertension, ischemic heart disease, chronic liver disease and chronic kidney disease.4 It’s important to note that since older age has also been found to be a risk factor for hyponatremia in Covid-19, the independent contribution of these conditions to hyponatremia is unclear.3

As with many other infectious diseases, the mechanism of hyponatremia in patients with Covid-19 likely has multiple causes, including hypovolemia, syndrome of inappropriate anti-diuretic hormone secretion (SIADH), diuretic use and corticosteroid deficiency, particularly in the critically ill. 1-4  

Interestingly, a study performed early in the pandemic (March 2020) found that the majority (57%)  of hospitalized Covid-19 patients with hyponatremic were euvolemic and that the administration of isotonic saline to such patients was independently associated with increased hospital mortality (cause unclear).2 The authors suggested closer attention to the volume status of Covid-19 patients with hyponatremia (eg, through closer attention to the jugular venous pressure on physical exam) before considering treatment with isotonic saline.

Last, Covid-19 may be associated with hyponatremia during the post-discharge period as well.  An intriguing 2024 study found nearly 25% of patients with Covid-19 developed hyponatremia (<135 mmol/L) during the 1-year follow-up period after discharge with most not reported to have hyponatremia during their index hospitalization.5 In the same study, hyponatremia was associated with older age, male sex, diabetes, hypertension, heart failure, previous invasive ventilatory support and increased rate of readmission.5

Bonus Pearl: Did you know that there is an inverse relationship between interleukin-6, a key pro-inflammatory cytokine, and plasma sodium levels in Covid-19 and that this association may be stronger than that of other viral or bacterial respiratory infections?2  

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References

  1. Ayus JC, Klantar-Zadeh K, Tantisattamo E, et al. Is hyponatremia a novel marker of inflammation in patients with Covid-19? Nephrol Dial Transplant 2023;38:1921-24. Is hyponatremia a novel marker of inflammation in patients with COVID-19? – PubMed (nih.gov)
  2. Pazos-Guerra M, Ruiz-Sanchez JG, Perez-Candel X, et al. Inappropriate therapy of euvolemic hyponatremia, the most frequent type of hyponatremia in SARS-CoV-2 infection, is associated with increased mortality in COVID-19 patients. Front Endocrinol 2023; 14:1227058. Inappropriate therapy of euvolemic hyponatremia, the most frequent type of hyponatremia in SARS-CoV-2 infection, is associated with increased mortality in COVID-19 patients – PubMed (nih.gov)
  3. De Haan L, ten Wolde, Beudel M, et al. What is the aetiology of dynatreaemia in COVID-19 and how is this related to outcomes in patients admitted during earlier and later COVID-19 waves? A multicentre, restrospective observational study in 11 Dutch hospitals. BMJ Open 2023;13:e075232. Original research: What is the aetiology of dysnatraemia in COVID-19 and how is this related to outcomes in patients admitted during earlier and later COVID-19 waves? A multicentre, retrospective observational study in 11 Dutch hospitals – PMC (nih.gov)
  4. Rehman F, Rehan ST, Rind BJ, et al. Hyponatremia causing factors and its association with disease severity and length of stay in Covid-19 patients: A retrospective study from tertiary care hospital. Medicine 2023; 102:45(e35920) Hyponatremia causing factors and its association with disease severity and length of stay in COVID-19 patients: A retrospective study from tertiary care hospital – PubMed (nih.gov)
  5. Biagetti B, Sanchez-Montalva A, Puig-Perez A, et al. Hyponatremia after COVID-19 is frequent in the first year and increases re-admissions. Scientific Reports 2024:14:595. Hyponatremia after COVID-19 is frequent in the first year and increases re-admissions – PubMed (nih.gov)

 

Disclosures/Disclaimers: 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!

How common is hyponatremia in patients with Covid-19 and what’s its significance?  

My patient with Covid-19-related generalized weakness has rhabdomyolysis. How common is rhabdomyolysis in Covid-19?

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

Covid-19-associated rhabdomyolysis has been reported since the early years of the pandemic with an overall prevalence ranging from 4%-20% among hospitalized patients and nearly 50% in ICU patients.1-5

In a 2023 scoping review of Covid-19-associated rhabdomyolysis involving 117 cases (January 2020-July 2022),1 68.4% had at least one reported non-Covid-19 risk factor (excluding hypoxemia), including age 65 years or older, metabolic syndrome features, hypothyroidism, previous rhabdomyolysis, hemoglobinopathy, trauma/compression or selected rhabdomyolysis-associated medications.  Presenting symptoms did not always include myalgias or weakness with some patients only presenting with fever, back pain, respiratory symptoms, or fatigue. Mortality was high (32% and 21% in those with or without other risk factors, respectively).  Routine creatine kinase (CK) testing was suggested for hospitalized patients with a low threshold for testing outpatients with Covid-19.

A 2024 cross-sectional study involving hospitalized Covid-19-patients (March 2020-March 2021) reported the following independent factors for concurrent rhabdomyolysis: male gender, dyspnea, hyponatremia, myalgia, elevated D-dimer, aspartate transaminase-AST (3x higher than normal) and platelet count >450,000 (cells/L).2 In the same study, myalgia was reported in only 30% of patients with rhabdomyolysis.   

Potential mechanisms explaining the association between Covid-19 and rhabdomyolysis include hypoxemia, viral myositis (either directly or immune-mediated), viral-induced mitochondrial dysfunction, cytokine storm, hypovolemia and Covid-related coagulopathies.1,2,4

Bonus Pearl: Did you know that although the 3 most common symptoms of patients with rhabdomyolysis are myalgias, muscle weakness and dark urine, the triad is present in only 10% of patients? 6

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References

  1. Preger A, Wei R, Berg B, et al. Covid-19-associated rhabomyolysis: A scoping review. Intern J Infect Dis 2023:136:115-126. COVID-19-associated rhabdomyolysis: A scoping review – PubMed (nih.gov)
  2. Hashemi B, Farhangi N, Toloul A, et al. Prevalence and predictive factors of rhabydomyolysis in Covid-19 patients: A cross-sectional study. Indian J of Nephrol 2024;34:144-48. Prevalence and Predictive Factors of Rhabdomyolysis in COVID-19 Patients: A Cross-sectional Study – PubMed (nih.gov)
  3. Samardzic T, Muradashvill T, Guirguis S, et al. Relationship between rhabdomyolysis and SARS-CoV-2 disease severity. Cureus 16:e53029 (January 27, 2024). Relationship Between Rhabdomyolysis and SARS-CoV-2 Disease Severity – PubMed (nih.gov)
  4. Haroun MW, Dielev V, Kang J, et al. Rhabdomyolysis in Covid-19 patients: A retrospective observational study. Cureus 13:e12552. Rhabdomyolysis in COVID-19 Patients: A Retrospective Observational Study – PubMed (nih.gov)
  5. Albaba I, Chopra A, Al-Tarbsheh AH, et al. Incidence, risk factors, and outcomes of rhabdomyolysis in hospitalized patients with Covid-19 infection. Cureus 13:e19802. Incidence, Risk Factors, and Outcomes of Rhabdomyolysis in Hospitalized Patients With COVID-19 Infection – PubMed (nih.gov)
  6. Lu W, Li X, You W, et al. Rhabdomyolysis in a patient with end-stage renal disease and SARS-CoV-2 infection: A case report. Medicine 2023;102:48(e36360). Rhabdomyolysis in a patient with end-stage renal disease and SARS-CoV-2 infection: A case report – PMC (nih.gov)

 

Disclosures/Disclaimers: 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 patient with Covid-19-related generalized weakness has rhabdomyolysis. How common is rhabdomyolysis in Covid-19?

When should I consider treating my adult ambulatory patient with newly diagnosed Covid-19 with an antiviral drug?

FA Manian MD, MPH, , , , , , , , , , , , , , , 1 Comment

You should seriously consider prescribing an antiviral agent either oral nirmatrelvir-ritonavir (Paxlovid) (within 5 days of onset of symptoms) or IV remdesivir (within 7 days of onset of symptoms) in all your ambulatory patients with mild/moderate Covid-19 at high risk of progression (ie, ≥1 risk factors) to severe disease (Figure). 1-3 Both of these drugs reduce hospitalization and mortality from Covid-19 by over 85%!1 Oral molnupiravir may be prescribed as a second-line agent (within 5 days of onset of symptoms), if neither Paxlovid or remdesivir is an option and the patient is not pregnant. There is no indication for the use of  dexamethasone or systemic steroids in the treatment of Covid-19 in ambulatory settings. As with all drugs, you should be familiar with adverse-effects and contraindications of these anti-viral agents before prescribing them. 

Couple of questions to ask when managing a patient with newly diagnosed Covid-19 in ambulatory setting:

  1. Does your patient truly have mild/moderate disease (eg, Sp02 on room air ≥94% on room air and not tachypneic) or severe disease (eg, Sp02 on room air <94%)?4 If severe disease is likely, you should refer your patient to a hospital for evaluation and treatment as soon as possible. If your patient is not symptomatic from Covid-19, no antiviral treatment is indicated. 
  2. Once you decide your patient has mild/moderate disease and doesn’t need to go to hospital, ask whether your patient has any risk factor associated with progression to severe Covid-19.2 Recall that there are numerous risk factors, including age over 50 and many physical disabilities, smoking (current or former) and mental health disorders, such as depression, ADHD, autism and depression that may be present even in the younger population.2
    • In the absence of any risk factor for progression, no antiviral therapy is indicated.

In the presence of 1 or more risk factors for progression or contraindications, you should consider initiation of Paxlovid x 5 days, if within 5 days of onset of Covid-19 symptoms or IV remdesivir x 3 days, if within 7 days of onset of Covid-19 symptoms.  

  • Remember that although Paxlovid may potentially interact with numerous drugs, fewer such drugs are absolutely contraindicated. Convenient online resources are available to help you decide if your patient can still receive Paxlovid safely.
  • Also don’t forget that remdesivir can now be given without dosage adjustment in renal insufficiency, including those on dialysis. 

If for some reason neither Paxlovid nor remdesivir is an option, oral molnupiravir can be considered with some caveats, including recommendations against its use during pregnancy and use of effective contraception during and following treatment in people who engage in sexual activity that may result in conception. 

Irrespective of treatment, it is prudent to monitor for any deterioration of sp02 at home when managing patients with mild/moderate Covid-19.  

Bonus pearl: Did you know that despite its high efficacy (89% reduction in hospitalization and death) against Covid-19,1,5 Paxlovid is severely underutilized in the outpatient setting with fewer than 25% of eligible patients with Covid-19 receiving it?6

Figure: Covid-19 management in ambulatory adult patients

 

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References

  1. Rubin R. Paxlovid Is Effective but Underused—Here’s What the Latest Research Says About Rebound and More | Infectious Diseases | JAMA | JAMA Network Published online January 31, 2024. doi:10.1001/jama.2023.28254
  2. Interim Clinical Considerations for COVID-19 Treatment in Outpatients | CDC. Accessed Feb 1, 2024
  3. Molnupiravir | COVID-19 Treatment Guidelines (nih.gov). Accessed Feb 1, 2024.
  4. Clinical Spectrum | COVID-19 Treatment Guidelines (nih.gov). Accessed Feb 1, 2024
  5. Appaneal HJ, LaPlante KL, Lopes VV, et al. Nirmatrelvir/ritonavir utilization for the treatment of non-hospitalized adults with Covid-10 in the National Veterans Affairs (VA) Healthcare System. Infectious Diseases and Therapy 204;13:155-172. Nirmatrelvir/Ritonavir Utilization for the Treatment of Non-hospitalized Adults with COVID-19 in the National Veterans Affairs (VA) Healthcare System | Infectious Diseases and Therapy (springer.com)
  6. Hammond J, Leister-Tebbe H, Gardner A, et al. Oral Nirmatrelvir for high-risk, nonhospitalized adults with Covid-19. N Engl J Med 2022; 386:397-408. Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19 – PubMed (nih.gov)

 

Disclosures/Disclaimers: 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!

 

 

When should I consider treating my adult ambulatory patient with newly diagnosed Covid-19 with an antiviral drug?

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?

How is Monkeypox different than Covid-19?

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

Just like Covid-19, Monkeypox (MP) is caused by a virus (this time related to smallpox), but there are major differences between these 2 diseases. 1-11

First, in contrast to Covid-19 which can easily be transmitted by casual contact through air, MP is primarily transmitted by close skin-to-skin contact (or possibly through contaminated clothing/bed linens) and sexual contact,  with great majority of current cases occurring among men who have sex with men (MSM); airborne transmission does not appear to be an important source of spread. 2

Although there is an overlap, the incubation period of MP tends to be longer (3-17 days) than that of Covid-19 which can be as few as 2 days.  Common to both diseases are flu-like symptoms such as fever, chills, muscle aches and headache, but MP is characterized by a rash that may be located on or near the genitals or anus or other areas, including hands, feet, chest face or mouth. 4

The rash (Figure) can look like pimples or blisters initially and may be painful or itchy as well. MP rash can either precede or follow flu-like symptoms after 1-4 days, or be the sole manifestation of the disease. Lymph node swelling or eye involvement (advise infected patients not to touch their eyes) may occur.  Although respiratory symptoms such as sore throat, nasal congestion and cough may occur with both diseases, shortness of breath would be unusual in MP.  A person with MP is considered contagious from onset of illness until the rash scabs over completely, which usually takes 2-4 weeks. 4,5,7,8

In contrast to Covid-19, currently there are no specific proven effective therapy against MP. However, several therapeutic agents with known activity against smallpox may be considered for those particularly at high risk of complications (eg, immunosuppressed patients, those with severe disease, exfoliative skin conditions [eg, eczema, psoriasis, Darier disease] children <8 years of age, pregnant or breast feeding patients, those with complications {eg, bacterial skin infection, pneumonia, gastroenteritis) or concurrent comorbidities.  These include an antiviral drug, Tecovirimat (TPOXX, ST-246) which can be obtained under an expanded-access protocol through the CDC in the U.S. (https://www.cdc.gov/poxvirus/monkeypox/clinicians/obtaining-tecovirimat.html. opens in new tab) — and Vaccinia Immune Globulin Intravenous (VIGIV) also through the CDC. 3,10

There are some “good news” related to MP when compared to Covid-19. First, in contrast Covid-19, hospitalization or death from MP due to the current circulating West African strain of the virus are extremely uncommon to rare.   In fact, of more than 12,000 cases of MP in 68 countries during the first few weeks of the epidemic, only 3 deaths have been reported, none in the U.S. thus far. 2

Second, in contrast to Covid-19, a person with MP is not considered infectious before onset of symptoms. So from a public health standpoint, it may be easier to control the spread of MP in the population following identification of a case. 9

Third, vaccination of contacts with one of the 2 available vaccinia/smallpox vaccines following significant exposure to MP may prevent disease altogether or render the disease milder. Vaccines should be administered within 4 days of exposure and no longer than 14 days after.  The generally preferred vaccine against MP is a modified vaccinia virus Ankara vaccine (MVA; JYNNEOS in the U.S., Imvanex in the European Union, and Imamune in Canada) which is live but non-replicative and is associated with fewer adverse events and contraindications than the alternative, ACAM2000, a live smallpox vaccine. 3

Last, in contrast to lack of pre-existing immunity to Covid-19 in virtually everyone  when the pandemic hit over 2 years ago, a large proportion of the population who received smallpox vaccine as part childhood vaccination (ending in 1972 in the U.S.) may have at least partial immunity against MP, resulting in either no or milder disease.6,11  

Bonus Pearl: Did you know that despite its name, monkeys are not a natural host of Monkeypox, with the causative virus having been isolated from a wild monkey in Africa only once? Instead, the virus first got its name after it was identified in a colony of Asian monkeys in a laboratory in Denmark in 1958. Squirrels, rats and shrew species serve as its natural host.1

Figure: Monkeypox rash (Courtesy CDC). 

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References

  1. Cohen J. Monkeypox is a new global threat. African scientists know what the world is up against. Science. June 1 2022. Monkeypox is a new global threat. African scientists know what the world is up against | Science | AAAS
  2. Osterholm MT. Gellin B. Confronting 21st-century monkeypox. Science 2022;377:349. Confronting 21st-century monkeypox | Science
  3. Medical countermeasures available for the treatment of monkeypox. Treatment Information for Healthcare Professionals | Monkeypox | Poxvirus | CDC. Accessed August 2, 2022.
  4. Key characteristics for identifying monkeypox. Clinical Recognition | Monkeypox | Poxvirus | CDC. Accessed August 6, 2022
  5. Monkeypox signs and symptoms. Signs and Symptoms | Monkeypox | Poxvirus | CDC. Accessed August 6, 2022.
  6. Karem KL, Reynold M, Hughes C, et al. Monkeypox-induced immunity and failure of childhood smallpox vaccine to provide complete protection. Clin Vaccine Immunol 2007;14:1318-27. Monkeypox-induced immunity and failure of childhood smallpox vaccination to provide complete protection – PubMed (nih.gov)
  7. Monkeypox: Key facts. Monkeypox (who.int). Accessed August 6, 2022.
  8. Clinical presentations of Covid-19. Clinical Presentation | Clinical Care Considerations | CDC. Accessed August 6, 2022.
  9. How monkeypox spreads. How it Spreads | Monkeypox | Poxvirus | CDC. Accessed August 6, 2022.
  10. Sherwat A, Brooks JT, Birnkrant D, et al. Tecovirimat and the treatment of monkeypox—past, present, and future. N Engl J Med 2020. August 3, 2022. Tecovirimat and the Treatment of Monkeypox — Past, Present, and Future Considerations | NEJM
  11. Mandavilli A. Who is protected against monkeypox. NY Times. May 26, 2022. Who Is Protected Against Monkeypox? – The New York Times (nytimes.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!

How is Monkeypox different than Covid-19?

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 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?